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PostPosted: Sat Nov 06, 2010 9:35 am 
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This is one question that I had when I was first diagnosed. The grade of my cancer was wrongly diagnosed and I was slightly relieved not to have a high grade, but what did this mean in terms of prognosis?

My cancer is at high risk of turning into a higher grade. However, these statistics can only give you an indication. Just as I am not into bucket lists, so I am no longer as interested but I realise that others newly diagnosed will be.

One question that remains unanswered is the translation of lifestyle into prognostic advantage. I remain convinced that it is a significant factor, however there remain some unanswered questions.

Why do low grade tumours remain unchanged for a period? Why is the average progression free survival (PFS) around 5 years?

Some possible answers are that, apart from high grade tumours, cancers grow at a far slower rate than previously thought. That cancer being a chronic disease, when risk factors are addressed by patients then this has an effect on prognosis. Maybe that is why the median is followed by a long tail - does this mean that those who reduce their risk survive longer (ie prevent recurrence)?

Obviously, these questions remain largely unanswered by science. This the approach I have chosen and while one person's experience isn't statistically significant, the more of us that follow an approach like David Servan-Schreiber the more evidence there will be on whether it works.

If 80% of cancer can be prevented due to lifestyle, that gives us a fighting chance. My intuition tells me there are two groups within the statistics - those who don't change with a lower PFS and those who make the right changes and form part of that long tail.


Last edited by kenobewan on Sat Nov 06, 2010 10:20 am, edited 1 time in total.

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PostPosted: Sat Nov 06, 2010 9:53 am 
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Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic

Abstract

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month–38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free of recurrence 10 years after diagnosis. Postoperative RT was associated with improved OS and PFS and is recommended for patients after subtotal resection or biopsy.

Low-grade gliomas (LGGs) are primary brain tumors classified as grade I and II by the WHO grading system.1 Treatment goals for patients with LGG include prolongation of both progression-free survival (PFS) and overall survival (OS). Even with prospective trials,2–5 many questions remain about management of LGG, including the role for and extent of surgical resection and the optimal timing of radiotherapy (RT), either immediately postoperatively or as a salvage strategy at progression. We analyzed a cohort of consecutive patients with nonpilocytic WHO grade II LGG to assess long-term outcomes and impact of tumor, patient, and treatment characteristics.

We used the Mayo Clinic tumor registry to perform a retrospective review of 314 consecutive patients aged 18 years or older with newly diagnosed, nonpilocytic LGG who presented between 1960 and 1992. To be included, biopsy confirmation and pathologic review by the Mayo Clinic Department of Pathology was required, as was a detailed operative report. Patients who had tumors in the optic tract or lower brainstem were excluded. Data were retrieved concerning patient presentation, extent of surgical resection, histologic type, adjuvant therapy, and other pertinent prognostic factors as well as type of recurrence, PFS, and OS.

No attempt was made to define an epicenter if multiple sites of brain were involved, but all involved sites were recorded. The extent of resection was assessed by the operative report, neurosurgeon's impression, and postoperative imaging when available. A surgical procedure was designated as radical subtotal resection (rSTR) first, when the operative report described “radical subtotal resection”; second, when gross total resection (GTR) was clearly the goal of the operation but minimal known tumor was left in situ; or third, when imaging reports indicated small, questionable amounts of residual tumor after GTR.

The label “low grade” is assigned to tumors of astrocytic lineage solely on the basis of their microscopic appearance. The numerical grade assigned to a given tumor, however, can vary depending on which grading system is used (Table 1). Therefore, it is important to specify the grading system with which a tumor has been labeled. In the present analysis, all patients were classified by histologic type and grade according to WHO criteria and the Kernohan grading system.6–8 The Kernohan system allows for labeling of well-differentiated tumors as grade 1, thus dividing the WHO grade II tumors, which are recognized to display a spectrum of nuclear features and mitotic activity, into more favorable and less favorable groups. Because pilocytic tumors were excluded, no WHO grade I tumors were reported in this analysis.

Materials and Methods

We used the Mayo Clinic tumor registry to perform a retrospective review of 314 consecutive patients aged 18 years or older with newly diagnosed, nonpilocytic LGG who presented between 1960 and 1992. To be included, biopsy confirmation and pathologic review by the Mayo Clinic Department of Pathology was required, as was a detailed operative report. Patients who had tumors in the optic tract or lower brainstem were excluded. Data were retrieved concerning patient presentation, extent of surgical resection, histologic type, adjuvant therapy, and other pertinent prognostic factors as well as type of recurrence, PFS, and OS.

No attempt was made to define an epicenter if multiple sites of brain were involved, but all involved sites were recorded. The extent of resection was assessed by the operative report, neurosurgeon's impression, and postoperative imaging when available. A surgical procedure was designated as radical subtotal resection (rSTR) first, when the operative report described “radical subtotal resection”; second, when gross total resection (GTR) was clearly the goal of the operation but minimal known tumor was left in situ; or third, when imaging reports indicated small, questionable amounts of residual tumor after GTR.

The label “low grade” is assigned to tumors of astrocytic lineage solely on the basis of their microscopic appearance. The numerical grade assigned to a given tumor, however, can vary depending on which grading system is used (Table 1). Therefore, it is important to specify the grading system with which a tumor has been labeled. In the present analysis, all patients were classified by histologic type and grade according to WHO criteria and the Kernohan grading system.6–8 The Kernohan system allows for labeling of well-differentiated tumors as grade 1, thus dividing the WHO grade II tumors, which are recognized to display a spectrum of nuclear features and mitotic activity, into more favorable and less favorable groups. Because pilocytic tumors were excluded, no WHO grade I tumors were reported in this analysis.

Recurrence information was collected using all available data in the medical record. Specifically, imaging, clinical signs and symptoms, pathologic information, or initiation of any additional intervention such as surgery, RT, or chemotherapy were used to declare progression.
This study was approved by the Mayo Clinic Institutional Review Board. Patients who refused to allow their data to be used for medical research were excluded from this analysis.

Statistical Analysis

Thirteen possible prognostic factors were analyzed for their association with both OS and PFS on univariate analysis. These variables (age, sex, midline/bilateral involvement, size, histology, extent of resection, RT, chemotherapy, sensory motor symptoms at presentation, supratentorial location, Kernohan grade, enhancement on computed tomography [CT] and/or magnetic resonance imaging [MRI]) were chosen because of their prognostic importance in prior studies.3–5,9–29
PFS and OS curves were calculated using the Kaplan-Meier method30 and compared with the log-rank test.31 Multivariate analysis for both recurrence and survival was performed using the Cox proportional hazards model, including variables that were statistically significant (p < .05) on univariate analysis.32 Deaths without documented recurrence were considered censored observations for recurrence at time of death. This method assumes that all patients who had unknown disease status at the time of death or last follow-up died of disease. All tests were 2 tailed. The χ2 test was used to analyze prognostic factors with the likelihood of surgical extent or postoperative RT use.

Patient, Tumor, and Treatment Characteristics

Patient and tumor characteristics are cataloged in Table 2. Tumor characteristics were identifed from the operative and radiographic report (CT, MRI, angiography) as well as electroencephalograms. Because the starting point of the study interval (1960) predated the modern neuroimaging era (1975), CT data were available for 155 patients (49%) and MRI data were available for 61 patients (19%). Enhancement on imaging was evident for 75 patients (48%) with CT information and 17 patients (28%) with MRI information. Of note, after 1975, CT data were available for 68% of patients.

The majority of patients (301/314; 96%) had supratentorial tumors, most commonly involving the frontal lobe (163 patients [52%]) and temporal lobe (126 patients [40%]).

Surgery and Pathology

GTR was achieved in 41 patients (13%), rSTR in 33 (11%), subtotal resection (STR) in 130 (41%), and biopsy only in 110 (35%).

Histologic subtype for the entire group showed pure astrocytoma in 181 tumors (58%), mixed oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Operative pathology revealed that of the 314 WHO grade II tumors, 285 (91%) were Kernohan grade 2. As pilocytic tumors were excluded, the majority of Kernohan grade 2 tumors were pure astrocytomas (18/29 [62%]).

Postoperative RT and Chemotherapy

Eighty-three patients (26%) were observed and did not receive adjuvant therapy in the immediate postoperative period. Postoperative RT was given to 231 patients (74%) and chemotherapy was given to 21 patients (7%); of the latter, 16 (5%) received chemotherapy in conjunction with RT and 5 (2%) received chemotherapy alone. Twelve patients received carmustine and nine received combination therapy with procarbazine, lomustine, and vincristine.

The total dose, calculated at midplane for opposed treatments or at isocenter for nonopposed treatments, ranged from 28.5 Gy to 70.2 Gy, with a median dose of 54 Gy delivered in a median of 28 fractions over a median 40 days. The three most common total doses delivered were 50 or 50.4 Gy (83 patients [26%]), 54 Gy (31 patients [10%]), and 60 Gy (50 patients [16%]). Whole-brain RT (WBRT) was administered to 53 patients (17%), WBRT plus partial brain boost to 41 patients (13%), and a partial brain only field to 220 patients (70%).

Recurrence/Progression Outcomes

Overall, the median follow-up was 13.6 years. Recurrence was documented in 174 patients who had a median time to progression of 7.2 years and a median PFS of 5.0 years. The 5-, 10-, and 15-year PFS rates were 50%, 27%, and 17%, respectively (Fig. 1).

Adverse prognostic factors identified on univariate analysis for PFS included age 40 years or older (p < .001), presentation with sensory motor symptoms (p < .004), tumor size 5 cm or larger (p < .001), Kernohan grade 2 disease (p < .01), astrocytoma histology (p < .02), and undergoing less than an rSTR (p < .001). Neither postoperative RT nor chemotherapy was associated with PFS (p < .92 and p < .47, respectively). On multivariate analysis (Table 3), only size 5 cm or larger and undergoing less than an rSTR remained statistically significant (both p < .001).

We analyzed extent of resection using four categories of surgical treatment (GTR, rSTR, STR, and biopsy only). Patients who underwent at least rSTR had improved PFS (p < .001). When comparing GTR with rSTR, no significant differences were noted in PFS. These patients (GTR/rSTR) were considered to have more aggressive surgical resection and were combined for the remainder of this analysis. Similarly, no difference in PFS was noted between patients who underwent biopsy only or STR. Patients who underwent more limited surgery (STR/biopsy only) were also combined for the remainder of the analysis. Extent of resection was strongly associated with PFS outcome. The 10-year PFS was 47% vs. 21% for those who underwent GTR/rSTR vs. STR/biopsy only (p < .001). A χ2 analysis was performed to assess factors associated with extent of resection. Patients with unfavorable characteristics such as 5 cm or larger (p < .001), sensory motor symptoms (p < .05), or CT enhancement (p < .02) were less likely to undergo aggressive surgery (GTR/rSTR).
Postoperative RT did not affect PFS overall. However, by χ2 analysis, use of RT was statistically significantly associated with factors shown to be adverse. RT was preferentially delivered to patients with more aggressive histologies such as astrocytoma (p < .001) and Kernohan grade 2 pathology (p < .001) and to those who underwent less aggressive surgical procedures such as STR/biopsy only (p < .001).

Survival Outcomes

The median OS was 6.9 years (range, 1 month–38.5 years), representing 250 deaths. The 10- and 15-year OS rates were 36% and 23%, respectively (Fig. 1). One hundred forty-four patients (46%) died from or with disease, 102 (32%) died from unknown or undocumented causes, 4 (1%) died without known evidence of disease, and 42 (13%) were alive without evidence of disease at last follow-up.

Adverse prognostic factors identified on univariate analysis included age 40 years or older (p < .008), size 5 cm or larger (p < .001), astrocytoma histology (p < .008), undergoing less than an rSTR (p < .001), Kernohan grade 2 disease (p < .004), presentation with sensory motor symptoms (p < .001), supratentorial location (p < .007), and enhancement on CT (p < .03). Neither postoperative RT nor chemotherapy affected OS (p < .96 and p < .87, respectively). Again, when extent of resection was analyzed, those who underwent at least an rSTR had improved OS (p < .001). The 10-year OS was 57% vs. 30% for those who underwent GTR/rSTR vs. STR/biopsy alone (p < .001).

On multivariate analysis (Table 3), statistical significance remained for size 5 cm or larger (p < .05), pure astrocytoma histology (p < .05), Kernohan grade 2 disease (p < .05), presentation with sensory motor symptoms (p < .001), and undergoing less than an rSTR (p < .03). The use of RT did not show a statistically significant association on multivariate analysis for OS (risk ratio [RR], 0.75; 95% confidence interval [CI], 0.62–1.1; p < .34). Because CT data were unavailable for 159 patients, we conducted an exploratory multivariate analysis without using CT enhancement as a potential interacting factor. Similar results were seen with this analysis in that size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2 disease, presentation with sensory motor symptoms, undergoing less than an rSTR, and supratentorial location were significantly associated with a decline in OS (all p values < .05). In addition, use of postoperative RT was associated with a statistically significant improvement in OS (RR, 0.81; 95% CI, 0.69–0.96; p < .01).

Outcomes for STR/Biopsy Alone

Overall, patients treated with STR/biopsy only combined with RT had intermediate rates of 10-year PFS and OS (Fig. 2). Specifically, 10-year OS was 34% for STR/biopsy alone combined with RT, compared with 11% for STR/biopsy alone and 57% for GTR/rSTR with or without RT (Fig. 2B). A separate analysis was done for patients who underwent STR/biopsy alone. For this group, the median OS was 5.4 years and PFS was 4.2 years.

On univariate analysis, adverse prognostic factors for PFS included size 5 cm or larger (p < .004), age 40 years or older (p < .005), presentation with sensory motor symptoms (p < .02), and lack of postoperative RT (p < .001). The median PFS was 5.0 years for those who received RT and 2.69 years for those who did not (Fig. 2C).

On univariate analysis, adverse prognostic factors for OS included age 40 years or older (p < .05), presentation with sensory motor symptoms (p < .02), enhancement on CT scan (p < .01), size 5 cm or larger (p < .002), astrocytoma histology (p < .002), and lack of postoperative RT (p < .001). The median OS were 6.3 years for those who received RT and 3.2 years for those who did not (Fig. 2D).

On multivariate analysis, age 40 years or older (p < .002), presentation with sensory motor symptoms (p < .01), and use of postoperative RT (RR, 0.67; 95% CI, 0.58–0.94; p < .04) remained statistically significantly associated with OS.

Outcomes by Histology

Median survival ranged from 5.1 to 9.5 years, depending on histologic type (p < .008). Patients with oligoastrocytomas experienced intermediate outcomes compared with those with astrocytomas (lower survival) and oligodendrogliomas (higher survival). Specifically, survival at 15 years was 18% for patients with astrocytoma, 25% for those with oligoastrocytoma, and 41% for those with oligodendroglioma.

Radiation Dose and Volume

Median dose of 54 Gy was chosen as a cut-off to assess for dose response. When patients who received RT were compared, there was a trend toward improved OS for those who received 54 Gy or more vs. those who did not (10-year OS 39% vs. 24%; p < .06). For patients who underwent STR/biopsy only, there was no significant difference in outcome for those treated with 54 Gy or more (10-year OS 36% vs. 23%; p < .14).

Recurrence: Findings and Treatment

One hundred seventy-four patients experienced a presumed recurrence. Symptoms were present in 158 patients (91%) at the time of recurrence, and 141 (81%) had documented radiographic disease recurrence. Ninety-two patients (53%) underwent a biopsy, and 76 patients (44%) underwent at least an STR at the time of recurrence. Pathologic data were available for 151 patients whose specimens were reviewed by Mayo Clinic. In 19 (13%) of 151 patients, radiation necrosis was noted in the specimen, and in 4 (3%) of 151 specimens, neither tumor nor necrosis was identified. Thus, these 23 patients were not counted as having recurrences in our statistical analysis. In 66 (44%) of 151 patients, the tumor had progressed to a higher grade than at diagnosis. The remaining 62 patients (41%) had pathologic findings consistent with their initial diagnosis. Thirty patients had RT for recurrence and 83 patients received chemotherapy. Median survival after recurrence was 1.2 years.

Discussion

The indolent natural course of LGGs has resulted in uncertainties and controversies regarding the role, timing, and technique of both surgery and RT. Subjects of debate include more aggressive vs. more limited resection such as biopsy (or even observation), timing of RT as adjuvant therapy immediately after surgery vs. delayed until recurrence, and the role for chemotherapy. Long-term follow-up is paramount to make such evaluations of PFS and OS. With a median follow-up of 13.6 years, the current study is among the largest with such long-term follow-up. Additionally, this study is unique in accomplishing a separate analysis of patients undergoing STR and biopsy alone. Table 4 outlines data from the present series alongside results of the European Organisation for Research and Treatment of Cancer (EORTC) protocol 22845 and other randomized trials.2–5

Surgery at the time of diagnosis provides tissue diagnosis in addition to a potential therapeutic debulking benefit. Similar to other investigations, our study displayed improved outcomes for patients who underwent more aggressive resections. However, GTR is often not possible without serious risk of neurologic injury because of tumor location or infiltration. We found that aggressive resections were more likely to have been performed in patients with more favorable tumor characteristics, such as size smaller than 5 cm, lack of enhancement on CT scan, and lack of sensory motor symptoms. To date, no randomized trials have specifically compared “up-front” surgery with a more conservative approach of delayed surgery. However, considering both retrospective and prospective data, many neurosurgeons favor maximally safe resection.3,4,10,12,16,22,27,29,33 Although not randomized, three prospective studies correlated aggressive surgery (GTR or near GTR) and improved prognosis.3,4,34 Additionally, an intraoperative MRI study found that patients undergoing STR experienced 1.4 and 4.9 times the risk of recurrence and death, respectively, compared with GTR (12). Another recent study, using MRI volumetric analysis, correlated resection of 90% or more with improved OS and PFS (27).

Retrospective data are inconsistent relative to the effect of postoperative RT. Due to perceived toxicities with RT and the disease's indolent nature,35,36 some advocate delaying RT until there is evidence of progression, symptoms, or high-grade transformation.14,17,37–48 EORTC 22845 evaluated the timing of RT in a phase 3 trial of immediate RT (54 Gy) or observation until progression. With follow-up just over 7 years, postoperative RT significantly prolonged PFS (median, 5.3 vs. 3.4 years) without affecting OS (median, 7.4 vs. 7.2 years).2,5 These results are inconsistent with the present study's findings of improved OS on multivariate analysis but no impact on PFS for adjuvant RT. In addition, in the present study, the benefit of postoperative RT was most clearly seen, in terms of improved OS and PFS, in patients undergoing more limited resections.

The most likely explanation for differences in PFS outcomes between studies is the imbalance in patient groups who did or did not receive postoperative RT. In the present study, treatment decisions were not randomized, and as noted, RT was preferentially delivered to higher-risk patients, such as those with more aggressive tumors and, most important, after less aggressive resections. The strong effect the extent of resection had on OS and PFS in this study likely confounds the PFS data. An alternate interpretation of the current data is that RT can improve outcomes in high-risk patients to approximate the PFS outcomes seen in more favorable risk categories. The differences in OS outcomes between the studies may be attributable to the significantly longer follow-up in this study than in EORTC 22845 (13.6 vs. 7.7 years). Furthermore, in the EORTC trial, 44% of patients underwent GTR (>90% resection), a much higher percentage than in this report, where only 23% of patients underwent GTR/rSTR. In light of our findings, it is therefore possible that the EORTC trial was not able to show a survival benefit because it included a large percentage of patients at lower risk of progression and death who were less likely to benefit from RT. This is further supported by the current results in which the patients who underwent more limited resections benefited most, in terms of OS and PFS, from postoperative RT (Fig. 2A,B).

Because diagnostic and surgical techniques evolved over the period of the present evaluation, and in order to offer a more relevant comparison to the modern-era EORTC and NCCTG trials (which both began enrolling patients in 1986), we analyzed the present data of the 95 patients (30%) who presented in 1986 or later. Median follow-up in this group was 12 years. Patients who presented in 1986 or later, compared with patients who presented before 1986, had improved OS (median, 9.2 vs. 6 years; p < .02) but not PFS (median, 5.3 vs. 4.4 years; p < .17). Of these 95 patients, 24 (25%) underwent GTR/rSTR. Similarly, of the 219 patients whose disease was diagnosed before 1986, 49 (22%) underwent GTR/rSTS. Therefore, it does not seem likely that the extent of surgical resection varied on the basis of decade of presentation when the EORTC and NCCTG trials' time frames are used. Similar to the results of the entire study cohort, the extent of resection was strongly predictive of both OS and PFS in the cohort of patients whose disease was diagnosed in 1986 or later (univariate analysis data not shown). Use of RT was not associated with either OS or PFS in this modern cohort (univariate analysis data not shown). For the 71 patients whose disease was diagnosed in 1986 or later and who underwent more limited surgical procedures (biopsy/STR), postoperative RT showed a trend toward PFS on univariate analysis (5-year PFS, 51% vs. 13%; 10-year PFS, 21% vs. 11%). However, this difference was not statistically significant (p < .18). The use of postoperative RT was not associated with improved OS (p < .65) in this subgroup.

The disparity in these results, compared with those for the whole group, may be attributed to insufficient follow-up and patient numbers to detect a statistical difference. Furthermore, even though a similar percentage of patients underwent GTR/rSTR, improvements in imaging and surgical techniques that allow for earlier detection, more aggressive yet safe resection, and more accurate classification of surgical extent could certainly be affecting the data. Also, the limitations of referral bias are likely to be even more pronounced in the modern series with more high-risk patients being referred for RT. Because the OS in the more modern group is improved and extent of surgery is the strongest predictor for survival in our series, it is likely that all these factors contribute to the differences in results. Overall, the data presented herein from the subset of more modern patients are not unlike the findings of the EORTC trial for which postoperative RT showed improved PFS2,5 but no improvement in OS.

A minority of patients received chemotherapy at the time of diagnosis, combined with RT in only 5%, and 1% received chemotherapy alone. Chemotherapy was much more frequently given to patients at the time of recurrence (48% of recurrences). No strong evidence exists for routine use of postoperative chemotherapy, especially in light of two phase 3 trials that showed no significant improvement in OS or PFS.34,49 Temozolomide is a promising oral alkylating agent with proven benefit in high-grade gliomas.50,51 Thus, temozolomide has been used in some small trials to delay RT in patients with newly diagnosed LGG.52,53 Ongoing trials by the EORTC, the Eastern Cooperative Oncology Group, and the Radiation Therapy Oncology Group will evaluate temozolomide's role for those deemed at high risk for early progression. Until these results are known, the current findings suggest careful consideration for the use of temozolomide as a means of delaying RT because it may have a detrimental effect on PFS and OS, especially in patients with minimal surgical resection.

In summary, analysis of a large series of patients with nonpilocytic WHO grade II LGG with long-term follow-up from a single institution indicates that for the majority of patients prognosis is poor (15-year OS 23%), especially recognizing that these patients are frequently young adults. However, there are subsets of patients who do significantly better, such as those undergoing an aggressive surgical resection. Our results favor performing a maximally safe resection, and in patients who have undergone STR/biopsy alone, we favor early use of RT, given the observed benefits in OS and PFS.

http://neuro-oncology.oxfordjournals.or ... 4/437.full


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PostPosted: Sat Nov 06, 2010 10:59 am 
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Management of Low-Grade Glioma

Abstract

The optimal management of patients with low-grade glioma (LGG) is controversial. The controversylargely stems from the lack of well-designed clinical trialswith adequate follow-up to account for the relatively longprogression-free survival and overall survival of patientswith LGG. Nonetheless, the literature increasingly suggeststhat expectant management is no longer optimal. Rather,there is mounting evidence supporting active managementincluding consideration of surgical resection, radiotherapy,chemotherapy, molecular and histopathologic characteriza-tion, and use of modern imaging techniques for monitoringand prognostication. In particular, there is growing evidencefavoring extensive surgical resection and increasing interest in the role of chemotherapy (especially temozolomide) in themanagement of these tumors. In this review, we criticallyanalyze emerging trends in the literature with respect tomanagement of LGG, with particular emphasis on reportspublished during the past year.

Introduction

Despite their initially indolent nature, low-grade gliomas(LGGs) may cause considerable morbidity and inevitablylead to death. Whereas expectant management once wasacceptable and the norm, current trends and mountingevidence now favor more active management, includingconsideration of surgical resection, radiotherapy, chemo-therapy, molecular and histopathologic characterization,and use of modern imaging techniques for monitoring andprognostication. Some of these changes have gainedsignificant momentum and support, whereas others remaininvestigational and controversial. In this review, wecritically analyze emerging trends in the literature withrespect to management of LGGs, with particular emphasison reports published during the past year.Definition and EpidemiologyThe term LGG technically includes all World HealthOrganization (WHO) grade I and II gliomas. However, thisbroad grouping contains tumors that are clinically, histologically, and molecularly diverse. For example, themanagement of WHO grade I gliomas is dramaticallydifferent from that of WHO grade II gliomas, the formerbeing amenable to surgical cure while the role of surgeryfor the latter is still being justified. Therefore, in the contextof this review, LGG refers only to WHO grade II diffuseastrocytomas, oligodendrogliomas, and oligoastrocytomas,all of which have similar invasive and malignant potential.Approximately 2,000 to 3,000 LGGs are diagnosed in theUnited States every year, accounting for nearly 15% of allprimary brain tumors. Peak incidence occurs in peoplebetween 35 and 44 years of age, and there is an increasedprevalence among white people and men [1]. Despite apreponderance of astrocytomas, there has been an increas-ing diagnosis and/or incidence of pure oligodendrogliomasand mixed oligoastrocytomas in recent years [2]. Low-grade astrocytomas have a predilection for “secondary”functional areas, such as the supplementary motor area andthe insular lobe, whereas oligodendrogliomas are seen mostcommonly along the convexity in subcortical areas,particularly in the frontal lobe [3].

The patient’s presenting symptoms and imaging character-istics are critical guides for management. Seizure is the mostcommon presenting symptom, occurring in up to 80% ofpatients [4]. Other less common modes of presentationinclude headache, lethargy, and personality changes. In stillothers, the slow-growing nature of the tumor may concealthe diagnosis for years. When patients present with symp-toms related to mass effect or intracranial hypertension,surgical treatment often is necessary and undisputed. Incontrast, patients who do not have evidence of radiographictumor growth and whose symptoms are well controlledmedically are the ones in whom management becomesdifficult and controversial. This controversy largely stemsfrom the lack of well-designed clinical trials with adequatefollow-up to account for the relatively long progression-freesurvival (PFS, 36–95 months) and overall survival (OS,≥7 years) some patients with LGG enjoy [4–6, 7•]

Prognostic Factors

The most important negative prognostic factors to emergefrom the literature include increasing age, astrocytichistology, large tumor diameter (>4–6 cm), tumors crossingthe midline, neurologic deficits, and poor performancestatus [2, 4–6, 7•, 8, 9]. In contrast, presentation withseizures, which generally occur in patients who areotherwise neurologically intact, often is identified as apositive prognostic factor [5, 8, 9]. (Schiff et al. [9] providea more extensive review of prognostic factors for LGG.) In2002, Pignatti et al. [4] described a simple scoring systemto account for these important prognostic factors so that physicians could better counsel patients and stratify patientsfor subsequent trials (Table 1). Based on a multivariateanalysis of data from one prospective European Organisa-tion for Research and Treatment of Cancer (EORTC) trialand validated on the data from another, they assigned onepoint each for age ≥40 years, astrocytoma histology,maximal tumor diameter ≥6 cm, tumor crossing themidline, and presence of neurologic deficit before surgery.Low-risk patients (scores 0–2) had a median OS of7.72 years, compared with 3.20 years for high-risk patients(scores 3–5) [4]. The University of California, SanFrancisco (UCSF) group recently introduced a new LGGscoring system that uses a four-point scoring system topredict OS and PFS, assigning one point each for agegreater than 50 years, Karnofsky performance score (KPS)≤80, maximum tumor diameter greater than 4 cm, andeloquent involvement of the tumor (Table 1) [7•]. Whenstratified according to low-risk (scores 0–1), medium-risk(score 2), and high-risk (scores 3–4) groups, 5-year OS was97%, 81%, and 56%, respectively, and 5-year PFS was76%, 49%, and 18%, respectively [7•]. This newer scoringsystem is unique in that it is the first such system toconsider eloquence as a poor independent prognostic factor.The importance of eloquence may be attributable to beingat higher risk of neurologic deficits but also may speak tothe resectability of a tumor, as patients with noneloquenttumors are more likely to have more extensive resections.

The impact of increasing age on the LGG prognosis has received particular attention during the past year because older patients (ie, those ≥55–60 years of age) are increasingly being diagnosed with LGG. As might be expected, older patients with LGG have a poorer prognosis, with a 5-year OS of 30% to 40% [10, 11]. Moreover, eachadditional year of age has a negative impact on prognosis,suggesting that reports from investigators studying age as abinomial likely have understated the impact of increasingage on outcomes [10, 11]. Despite the poorer prognosis,however, patients who survive 2 years beyond the initialdiagnosis may experience prolonged PFS [10].

Imaging

Besides the prognostic factors already reviewed, there isincreasing interest in the role of imaging in the managementof LGG. Several studies have been published touting theprognostic significance of various imaging findings, in-cluding contrast enhancement, tumor growth rates, cholineand creatinine peaks on magnetic resonance (MR) spec-troscopy, relative cerebral blood volume (rCBV), andabsolute diffusion coefficients (ADCs) [12–15]. Unfortu-nately, studies directly comparing these various MRI-basedimaging modalities are limited. In one comparative study,MR spectroscopy was shown to be superior to tumorgrowth rates and rCBV measurements for predictinganaplastic transformation [15]. On the other hand, inanother study, tumor growth rate was superior to initialvolume, rCBV, and ADC for predicting PFS and OS [14].

The relative importance of imaging findings comparedwith known prognostic factors is difficult to ascertain becausestudies rarely simultaneously account for known prognosticfactors and imaging findings. The study by Chaichana et al.[16] of the prognostic significance of contrast enhancementis an exemplary exception. Before concluding that contrastenhancement portends decreased survival and increasedrecurrence, the authors demonstrated that the two groupsstudied (those with and without contrast enhancement) werewell matched with respect to all known prognostic factors(eg, KPS and age) [16]. Further prospective studiesincorporating clinically important prognostic factors andimaging findings will need to be conducted to understandthe true importance of these novel imaging modalities.

Molecular Pathogenesis

Further advances in the management of LGG will be madeonly by developing a more thorough understanding of thepathogenesis of these tumors. Recent reports have dramat-ically altered our conceptual framework of LGG moleculargenetics, suggesting that isocitrate dehydrogenase (IDH)mutations are an early event in LGG pathogenesis. IDH1,found in the cytoplasm and peroxisome, catalyzes theoxidative decarboxylation of isocitrate to α-ketoglutarate, reducing NADP+ to NADPH.

Previously, it was recognized that most LGGs harboredone of two mutually exclusive genetic changes: TP53mutations in most low-grade astrocytomas and deletions ofchromosomes 1p and 19q in most pure low-grade oligo-dendrogliomas (Table 2) [9]. Low-grade mixed gliomastend to have either TP53 mutation or 1p/19q codeletion.Recent studies, however, have demonstrated IDH1 muta-tions in 59% to 90% of grade II astrocytomas, 68% to 85%of grade II oligodendrogliomas, and 50% to 83% of gradeII oligoastrocytomas (Table 2) [17–19, 20•, 21]. The factthat IDH1 mutations are seen in similar frequencies intumors with TP53 mutation and 1p/19q deletion suggeststhese mutations may precede other genetic alterations [17,20•]. This is supported further by serial biopsies of LGGsshowing that when IDH1 mutations occur, they alwaysprecede and never follow TP53 mutation or loss ofheterozygosity of 1p/19q [19, 22]. Moreover, large-scalegenetic sequencing of 105 glioblastomas identified IDH1mutations in almost all secondary glioblastomas but in only7% of primary (de novo) glioblastomas [23].

IDH mutations in gliomas have some remarkablefeatures. First, every IDH1 mutation occurs in codon 132,which normally codes for an arginine in the enzyme’sactive site. All produce amino acid substitutions, which inmore than 90% is a histidine, resulting in decreasedcatalytic activity [17, 19, 20•]. IDH1 shares substantialhomology with IDH2, a mitochondrial enzyme catalyzingthe same reaction. Rare IDH2 mutations also wererecognized recently in gliomas, especially oligodendroglio-mas [18, 20•]. All IDH2 mutations are point mutations atcodon 172 in the enzyme’s active site, a position represent-ing the precise analogue of R132 in IDH1. IDH mutationsare exceedingly rare in pediatric gliomas, nonglioma braintumors, and other cancers [18].

The mechanisms by which IDH mutations predispose togliomagenesis remain mysterious. Although the mutatedprotein is catalytically less active, consistent with a loss offunction, these mutations are always heterozygous. More-over, none of the mutations is a nonsense mutation, furthersuggesting the mutations may produce a dominant negativeor gain of function [24]. Thus, IDH1 and IDH2 seem tofunction as tumor suppressor genes. Their inactivation hasbeen shown to induce genes crucial to angiogenesis,although the relevance of this finding to LGGs that lackangiogenesis remains uncertain [24].

Investigation of the role of cancer-related cell signalingpathways continues in LGG. Recent reports highlight theimportance of the MAPK pathway in pilocytic astrocyto-mas, with many of these tumors manifesting tandemduplication of 7q, resulting in a fusion gene incorporatingthe kinase domain of the BRAF oncogene with constitutiveBRAF activity [25]. However, the 7q34 duplication is notseen in grade II astrocytomas [26]. Another important oncogenic signaling pathway is the PI3K-Akt-mTORpathway, on which PTEN normally serves as a brake.Although PTEN sometimes is mutated in primary glioblasto-mas, PTEN mutations do not occur in LGG. However, mostLGGs epigenetically silence PTEN via hypermethylation [27,28].

Evidence of overactivation of the PI3K-Akt-mTORpathway manifesting as phosphorylation of downstreamproteins appeared to correlate inversely with survival,although numbers were small and this finding requiresconfirmation [28].To what extent molecular markers such as 1p/19qcodeletion status, IDH mutational status, and the presence orabsence of MGMT promotor hypermethylation, which is aprognostic factor in glioblastoma outcome, predict respon-siveness to specific therapies or overall prognosis remainsuncertain. The presence of 1p/19q deletion seems to portend abetter prognosis in LGG, although its favorable impact isweaker than in grade III gliomas. Small studies havesuggested that MGMT methylation status may predictimproved OS [29], but the small size of these studies and apotential confounding correlation between MGMT methyla-tion and 1p/19q codeletion mandate larger studies. Similarly,in univariate analyses, IDH1 mutations conferred improvedOS in low-grade and anaplastic gliomas as well as inglioblastomas, but it remains unclear whether mutationalstatus retains prognostic significance when other prognosticmarkers are incorporated into multivariate models [19, 21].

Surgical Resection

The lack of pathognomonic imaging for LGG and the need formolecular, chromosomal, and histopathologic characteriza-tion of tumors mandate tissue acquisition for accuratediagnosis, prognostication, and management. Needle biopsyspecimens have been associated with a greater than 50%misdiagnosis rate [30, 31]. Surgical resection (vs biopsyalone) affords a better opportunity to characterize, grade, andstudy tumor tissue to ensure proper diagnosis, treatment, andprognostication. Despite the lack of a randomized controlledtrial, the evidence for the benefits of extensive surgicalresection is growing. In 2001, Keles et al. [32] reviewed theliterature and concluded that a preponderance of the evidencefavored more extensive resection for patients with LGG.Since then, several additional long-term institutional studies have been published favoring extensive surgical resection [8,33, 34, 35•]. Smith et al. [35•] retrospectively analyzedoutcomes in 216 patients who underwent surgical resectionfor LGG at UCSF between 1989 and 2005, from a total ofmore than 800 patients treated for LGG during that period.Patients who underwent biopsy were specifically excludedbecause such patients usually have complicating factors andinclusion might confound the interpretation of the results. Onmultivariate analysis, extent of resection (EOR) was signif-icantly associated with improved OS but not PFS. Five-yearsurvival in patients with at least 90% EOR was 97%,whereas it was 76% in those with less than 90% EOR [35•].In 170 patients treated surgically at Johns Hopkins Hospitalbetween 1996 and 2007, McGirt et al. [33] similarly foundthat gross total resection (GTR; based on independentradiologist interpretation) was independently associated withimproved OS and PFS compared with subtotal resection(5-year OS: 95% vs 70%, P=0.017; median time toprogression: 7 vs 3.5 years, P=0.043). Although these studiessuggest GTR is desirable, not all tumors are amenable toGTR. Predictors of incomplete tumor resection includetumor involvement of the corticospinal tract, large tumorvolume, and oligodendroglioma histopathologic type [36].

Some may argue that enthusiasm for these retrospectivereports must be tempered by results from prospective trialsand other retrospective series that failed to find a significantprognostic effect of EOR. For example, the prospectiveintergroup American trial comparing low- and high-doseradiation therapy found EOR to be a significant prognosticfactor for both OS and PFS on univariate analysis but found itwas not significant on multivariate analysis [2]. Similarly,Pignatti et al. [4], who retrospectively studied the prospec-tively collected data from EORTC trials 22844 and 22845,found that extensive surgery (ie, >90%) was associated withlonger OS on univariate analysis but failed to showsignificance on multivariate analysis. Although prospective,these studies have significant shortcomings, includingneurosurgeon assessment of EOR, inclusion of biopsiedpatients in the analyses, and the fact that the studies were notprimarily designed or powered to assess the effect of EOR.

In addition to OS and PFS, cognitive and quality-of-lifeoutcomes after surgical resection must be considered,especially because concerns regarding these outcomes havethwarted the enthusiasm for radiotherapy. return to baseline or improve upon preoperative cognitivefunction within 3 months [37]. Moreover, advances inintraoperative technology (eg, neuronavigation) and pre-and intraoperative brain mapping techniques (eg, functionalMRI, magnetic source imaging, and cortical and subcorticalstimulation mapping) now allow neurosurgeons to tailorresections to individual functional brain architecture,minimizing the risk of permanent deficit to less than 2%and ensuring that patients’ quality of life is preserved [38,39]. Duffau et al. [39] found that LGG patients operated onwith the assistance of cortical stimulation had a significantlylower permanent deficit rate, a higher GTR rate, and a survivaladvantage compared with patients who were operated onwithout intraoperative mapping. In fact, the authors found thatmapping may be used to identify dynamic changes inindividual patients’ functional brain architecture, allowingmore extensive tumor resections using a multistaged surgicalapproach [40]. Besides making surgeries safer and moreextensive, advances in brain mapping also have madesurgery an option for more patients [39]. In particular, therehas been significantly increased interest in the surgicalmanagement of insular gliomas, which are challenging froman anatomic and eloquence standpoint but can be resectedwith only a 6% risk of postoperative deficit [41].

Ideally, a multicenter, multinational, prospective trialshould be conducted to address this issue, but such a trial isunlikely because of the difficulty in recruiting sufficientnumbers to demonstrate differences, the long-term follow-up that would be necessary, and ethical concerns thatsufficient data already exist supporting GTR.

Radiotherapy

Among all available treatment modalities, radiotherapy isthe only intervention shown in a randomized controlled trialto provide some benefit to LGG patients [42]. Even so, theoptimal role for radiotherapy in the management of patientswith LGG remains unclear. EORTC 22845 reported longerPFS and increased rates of seizure control in patientsreceiving upfront radiotherapy (54 Gy) compared withpatients who were treated at the time of progression (PFS:5.3 vs 3.4 years, P<0.0001; seizure control rates: 75% vs59%, P=0.0329). OS, however, was not significantlydifferent between the two groups (7.4 vs 7.2 years) [42].Despite its efficacy with respect to PFS and seizure control,the authors concluded that radiotherapy might still bedeferred in patients with LGG who are “in a goodcondition.” The ambivalence is attributable, in part, to thefact that quality of life was not studied; therefore, it wasunclear at what cost patients with LGG were realizing abenefit in PFS and seizure control without an OSadvantage. Moreover, by delaying radiotherapy, 35% of Although surgery may transiently exacerbate baseline deficits, most patients patients in the latter group (with a median follow-up of7.4 years) never required radiation therapy, sparing themthe possible adverse effects of radiation [42].

Recent studies therefore focused on quality-of-life meas-ures after radiotherapy to better define its role in managingpatients with LGG. Radiation leukoencephalopathy mayensue months to years after radiotherapy of the brain andmay include progressive deterioration in personality, gait andbalance, urinary continence, attention, memory, and executivefunction [43]. To reduce such risks, studies have beenconducted demonstrating that total dose, fractional dose,and irradiation fields can be reduced without affecting theefficacy of treatment (see Baumert and Stupp [44] for moreextensive reviews of this subject). Still, patients with LGGare at substantial risk of suffering from these complicationsbecause of their relatively long OS. Douw et al. [45] recentlyreported the most comprehensive and long-term analysis ofcognitive and quality-of-life outcomes in 65 patients withLGG, half of whom had received radiotherapy. With a meanfollow-up of 12 years, 27% of patients who had not beenirradiated had significant cognitive deficits in at least 5 of 18neuropsychological test parameters, whereas 53% of patientswho received radiotherapy had significant cognitive deficits.Deficits were most pronounced in the domains of cognitiveprocessing and attention, but nonsignificant differences alsowere observed in information processing speed, psychomotorfunctioning, and working memory [45]. These long-termsequelae of radiotherapy further challenge its upfront andsystematic use considering radiotherapy and its complica-tions can be delayed for more than a decade in some patientsand the fact that advances in other treatment domains (eg,surgery and chemotherapy) may obviate the need for upfrontradiation. Do patients who have had a GTR receive anyadditional benefit from radiotherapy? Likewise, does radio-therapy confer any advantage to patients who are treated withupfront temozolomide? As described in the “Chemotherapy”section, trials are currently under way to answer these types ofquestions.

Chemotherapy

With respect to chemotherapy, neuro-oncologists havefocused their attention largely on temozolomide, whichoffers the advantages of an oral agent with a favorabletoxicity profile compared with procarbazine, lomustine, andvincristine (PCV); crosses the blood–brain barrier well; andis more active against glioblastoma than PCV. Phase 2clinical trials indicate that temozolomide, given on either astandard 5-day schedule or a dose-dense, metronomicschedule (3 weeks on, 1 week off or 7 weeks on, 4 weeksoff), is active against both previously irradiated andunirradiated growing LGGs [29, 46, 47]. Moreover, temozolomide is associated with a favorable quality-of-lifeprofile [48].

The two major questions relating to temozolomide use in LGG are whether temozolomide can substitute for radiation therapy and whether there is benefit from combining thesetwo therapeutic modalities. Clinical trials addressing boththese questions have been launched. European and Canadianinvestigators initiated a phase 3 clinical trial randomlyassigning patients with LGG to receive either standardradiation or temozolomide. Patients are stratified based onchromosome 1p status. PFS is the primary end point, and thestudy incorporates neurocognitive and quality-of-life endpoints to assess the impacts of radiation and temozolomidein these regards.

Clinical trials are evaluating the combination of temo-zolomide with radiotherapy in high-risk LGGs previouslyuntreated with radiation or chemotherapy. The Radiation Therapy Oncology Group (RTOG) recently completedaccrual to a phase 2 clinical trial (RTOG 0424) of thiscombination; results are not expected before 2013. Underthe aegis of the Eastern Cooperative Oncology Group(ECOG), the three major US brain tumor cooperative groups have launched a phase 3 effort (ECOG E3F05)randomly assigning LGG patients to receive standardradiation therapy combined with temozolomide and fol-lowed by a year of temozolomide or to receive radiationtherapy alone. The trial design closely parallels theEuropean trial of radiation versus temozolomide; in concert,these two trials should comprehensively address the role oftemozolomide in the management of LGG.

The activity of chemotherapy in recurrent LGG postradiotherapy, as well as a growing appreciation for thechemosensitivity of tumors with an oligodendroglial com-ponent, led the RTOG to study the combination of PCV andradiation therapy. In this trial (RTOG 9802), patients withLGG deemed high risk because of age greater than 40 yearsor less than GTR were randomly assigned to receivestandard radiation therapy with or without PCV. Although the cohort receiving chemoradiation had improved PFS, OS did not differ significantly between the two groups [49], suggesting that PCV was as active as salvage therapy as incombination with radiation.

Finally, reports suggest there may be a role for neo-adjuvant therapy before surgical resection [50]. In both reported cases, although contralateral involvement via thecorpus callosum originally prohibited GTR, chemotherapyshrunk the tumors to the extent that GTR was possible. Theimpact of timing of surgery can and will be appreciatedonly when a prospective trial is performed, such as wasdone for the timing of radiation therapy for the managementof LGG [42].

Conclusions

The management of LGG is changing. New treatmentstrategies are being proposed that recognize the potentialrisks of a “wait-and-see” policy and radiotherapy as well asthe potential benefits of extensive surgical resection andupfront chemotherapy. Considering the evidence currentlyavailable, the optimal treatment strategy likely includesoffering extensive surgical resection when possible anddelaying radiotherapy until the time of progression (Fig. 1).Several trials currently under way almost surely willrevolutionize the treatment of these tumors further, definingthe role of temozolomide in the management of thesetumors and perhaps obviating the need for radiotherapy.Further multivariate investigations are necessary to definethe prognostic significance of data from novel imagingtechniques and molecular markers of pathogenesis.

Source - eScholarship UC item 5ck846qc.pdf


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PostPosted: Sat Nov 13, 2010 9:46 am 
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Confronting a cancer diagnosis: Steps to consider

Although the National Cancer Institute’s (NCI) primary mission is to conduct, support, and coordinate cancer research, it also has a role in collecting and disseminating information about cancer. In that role, NCI serves as a source of important information for patients and their family and friends, including information about how to communicate with their health care providers. Many people have never spoken with a health care professional about cancer, and knowing what to do and who to talk with from the start may be critical in get-ting the best possible treatment and outcome.

For many African Americans, a serious disease like cancer can be a shared family experience. It is not uncommon for family members to rally around a cancer patient. Family or friends can assume various roles in gathering information and in helping make decisions. These tasks include learning about the specific cancer type that has been diagnosed, selecting a physician, getting a second opinion, assessing insurance coverage, and identifying a place to receive treatment.

Here are some important things to consider when con-fronting cancer:

Learn about the disease and treatment options. The first thing to do is to educate yourself as much as possible about the type of cancer you have been diagnosed with as well as possible treatment approaches. You can do this any number of ways, starting with talking to your doctor. Information is also available through NCI. You can begin with the NCI web site, cancer.gov (cancer.gov/espanol. You can also call the NCI’s toll-free Cancer Information Service, 1-800-4-CANCER and speak to a specialist who can answer your questions about cancer and also direct you to additional information, including publications).

Learn about which physicians treat cancer patients. Most physicians who treat people with cancer are medical doctors (they have an M.D. degree) or osteopathic doctors (they have a D.O. degree). These doctors often have advanced training in a specialty or a subspecialty.

For example, medical oncologists are internal medicine doctors who manage the treatment regimen of cancer patients, and hematologists are internal medicine doctors who focus on diseases of the blood and related tissues. Radiation oncologists use radiation to treat cancer, and surgeons perform operations.

Find a doctor. Most people will get a referral from their primary care physician, but you can also consult a local hospital or cancer center, or access a list of specialists from local or national medical societies. Friends and family can also help you identify a doctor, especially if they have already dealt with cancer.

Ask questions. There are some basic questions you can ask your doctor before your treatment begins. Shock and stress after the diagnosis can make it hard to think of everything you want to ask the doctor. It often helps to make a list of questions before the appointment. To help remember what the doctor says, you may want to take notes or ask whether you may use a tape recorder.

Some people want to have a family member or a friend with them when they talk to the doctor—to take part in the discussion, to take notes, or just to listen. You do not have to ask all of your questions at once.

Suggested questions are available in the NCI publication, What You Need to Know About Cancer, available on cancer.gov (cancer.gov/espanol).

After consulting a doctor to learn about the disease and recommended treatments, consider obtaining a second opinion. Sometimes people worry about this. They are afraid it may seem like they don’t trust their first doctor. Not at all.

What they are doing is seeking an additional evaluation of their medical condition from another professional. It is quite common to seek a second opinion, and most physicians welcome another doctor’s views. Your health care plan may even require that you get a second opinion. In fact, your doctor may be able to recommend a specialist for this consultation.

Finally, when confronted with a cancer diagnosis (whether your own or that of some-one you love), just remember to collect yourself and take a deep breath. Most times, you don’t need to rush to make a decision. You will make the best decisions, if you give yourself the chance to get the best information you can.

http://www.thewestsidegazette.com/news/ ... emSource=L

[comment - becoming informed is important. Accepting some responsibility for lifestyle changes. Be reborn - this is the challenge, the way forward - accept that if it is true that 80% of cancers are preventable, you want to be among the majority. Accept that the most important things that happen from now on will be your research, decisions and actions. Simple lifestyle changes are effective without chasing some magical cure - none exists but that doesn't mean there is no hope - its up to you. Have you got the courage, determination and stamina required?]


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PostPosted: Sun Dec 19, 2010 7:47 am 
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Cell of Origin for Brain Tumors May Predict Response to Therapy

ScienceDaily (Dec. 17, 2010) — For patients with glioma, the most common primary brain tumor, new findings may explain why current therapies fail to eradicate the cancer. A UCSF-led team of scientists has identified for the first time that progenitor rather than neural stem cells underly a type of glioma called oligodendroglioma. This distinction explains why oligodendroglioma is more responsive to therapy than other brain tumors such as glioblastoma multiforme.

The finding is significant, the researchers say, because it gives cancer doctors and researchers new cellular pathways to target in developing therapies. It also updates current beliefs -- that brain tumors derive from neural stem cells -- with the indication that, since oligodendroglioma derives from progenitor cells, stem cell-specific therapies may not hold promise for treating those types of brain tumors.

Different life expectancies for two types of brain tumors were what first piqued the scientists' interest.

"With treatment, patients with oligodendroglioma can live many years longer than patients with gliobastoma multiforme. For two types of tumor that appear similar, the outcome is so different. We were interested in understanding this," said William A. Weiss, MD, PhD, corresponding author and professor in the Departments of Neurology, Pediatrics and Neurological Surgery.

"There has been a great deal of research into the molecular basis of glial tumors, but current therapies have not advanced much. Many remain ineffective and the majority of patients die from the disease, so fresh strategies are desperately needed. The ability we now have to sub-classify tumors and differentiate gliomas based on differences in cell of origin will be helpful in the search for more effective treatments," Weiss added.

Findings are described in the December 14 issue of the journal Cancer Cell.

Glioblastomas arise from the glial cells in the brain and are known to be highly aggressive, resulting in a life expectancy of just six to 12 months after diagnosis, according to the National Brain Tumor Society. Glial and neuronal cells both arise from progenitor cells, which in turn arise from neural stem cells. Oligodendrglial cells are a type of glial cell that supports neuronal cells, insulating them by producing myelin, a substance that promotes communication between neurons.

"Our study shows that tumors can arise from either neural stem cells or progenitor cells, which produce different types of brain cancers that exhibit different responses to therapy," Weiss said.

Using MRI and detailed analyses of both human and mouse tumors, the team discovered that tumor cells differentiate in the brain in two key ways, and the mode of differentiation impacts whether the tumor will be sensitive to therapy. Tumors that arise from neural stem cells such as astrocytomas (of which glioblastoma is the most common) are less sensitive to therapy because dormant stem cell-like tumor cells do not divide unless provoked by certain factors. Tumors that arise from progenitor cells, such as oligodendroglioma, are more sensitive to therapy because progenitor cells are actively dividing.

"These results suggest that oligodendroglioma tumor cells arise from normal oligodendrocyte progenitor cells, and that a progenitor rather than a neural stem cell origin underlies improved prognosis in patients with this tumor," said lead author Anders I. Persson, PhD, assistant professor of Neurology in UCSF's Helen Diller Family Comprehensive Cancer Center.

Since oligodendrogliomas are more sensitive to therapy, the team hypothesized that this sensitivity might be a property of the glial progenitors from which they arise. To test this, they treated stem cells, astrocytomas, progenitors and oligodendrogliomas with the chemotherapeutic used for glioma treatment, temozolomide. They found that stem cells and astrocytoma cells were largely resistant to the drug, but the growth of oligodendroglioma cells and of glial progenitors was vastly stalled.

"By studying the properties and behavior of the precursor cells, we have better clues about which cellular pathways could be effective for therapy, depending on the type of tumor," Persson said. "So for instance, now that we know to determine whether a brain tumor is a progenitor disease or stem cell disease, we could use MRI to make these diagnoses, resulting in faster, more effective treatment for glioma patients."

http://www.sciencedaily.com/releases/20 ... 141943.htm


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Tick for Australia in cancer comparison with other nations

PATIENTS stricken with four of the most common types of cancer fare as well or better in Australia than in five other developed nations.

An expert analysis tracked the survival rates of 2.5 million people, including more than 250,000 Australians, and found this country outperformed Canada, Denmark, Norway, Sweden and Britain in terms of the numbers of people still alive both one and five years after a diagnosis of colorectal cancer.

Australia was a close third in survival rates for lung cancer -- with less than a single percentage point separating it from Canada and Sweden -- and a close second in breast cancer.

In ovarian cancer, Australia came third after the same two countries, but lost the top spot by a wider margin.

Britain was consistently at the bottom in the comparison, scoring just 8.8 per cent for the proportion of lung cancer patients still alive in 2005-07 more than five years after diagnosis, compared to 17 per cent in Australia.

Five-year survival for colorectal cancer was also 53.6 per cent in Britain, compared with 63.7 per cent in Canada and 65.9 per cent in Australia.

In breast cancer, Britain scored 81.6 per cent for five-year survival, compared with 88.1 per cent in Australia.

While Sweden was consistently among the top-performing nations, fellow Scandinavian nation Denmark performed only slightly better than Britain, with Norway in the mid-range.

The results, published yesterday online by The Lancet, were based on the outcomes of 145,174 NSW patients and 110,844 in Victoria.

Cancer Council chief executive Ian Olver said the good scores reflected the existence of effective screening programs for breast and ovarian cancer, and the rapid availability of effective new treatments -- such as the breast cancer drug Herceptin.

"It's a tick for our health system, but we could do even better because the funding for the bowel cancer screening program runs out at the end of the financial year," Professor Olver said. "It's a very partial program, because they only send (bowel cancer testing) kits out to 50-, 55- and 60-year-olds, whereas the ideal is to send them to everyone aged 50 and above every two years.

"It's a rudimentary program anyway, and there's no funding for its continuation (after June)."

http://www.theaustralian.com.au/news/na ... 5975195688

[comment - if you have one of main cancers this may be good news. Not so good for brain cancers. At the risk of sounding like a broken record, prevention is better than cure - this may be true even if you already have cancer (more likely seeing there isn't a cure)]


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Victims of cancer are increasingly becoming survivors

SALT LAKE CITY — All she ever wanted was to be a grandmother and she'd been accumulating various ideas and activities to do with her prospective grandchildren for years.

But then doctors discovered a large, mass in Marion Peterson's armpit, as well as 17 (of 20) cancerous lymph nodes in the same general area.

"I cried and cried because I had never seen anyone survive with so many lymph nodes affected," Peterson said, but she was determined to make it.

The early detection and aggressive therapy, along with having good doctors, helped. But most of all, Peterson believes that prayers offered by so many, even people she didn't know, of varying religious backgrounds and in far-off places, have kept her alive to enjoy her nine grandchildren since the cancer was detected in 1998.

Peterson is not out of the woods yet, as the cancer could come back, but she joins the more than 11.7 million cancer survivors in the United States today — a number that is increasing as early detection and prevention methods are becoming more widespread.

The CDC reports that the majority of today's cancer survivors are women winning the battle against breast cancer. Prostate and colorectal cancers are also common among survivors. Nearly 65 percent of cancer survivors are now living at least five years or more after their diagnosis of cancer and 59 percent of them are over age 65.

Just 40 years ago, the numbers paled in comparison, when only 3 million were counted as survivors of cancer. Then, a much higher number became victims of the largely unexplained disease.

"It is good news that so many are surviving cancer and leading long, productive and healthy lives," said Dr. Thomas R. Frieden, director of the U.S. Centers for Disease Control and Prevention.

The CDC attributes increasing survivorship to earlier detection, improved diagnostic methods, more effective treatment, improved clinical follow-up after treatment and an aging U.S. population. If these trends continue, the number of cancer survivors is expected to increase further.

"Preventing cancer and detecting it early remain critically important as some cancers can be prevented or detected early enough to be effectively treated," Frieden said. Smoking cessation or not smoking, regular physical activity, healthy eating, and limiting alcohol use, he said, can reduce the risk of many cancers.

In Utah, the number of people who die each year from cancer, has either been stable or declining since the late 90s. With just over 2,500 lives lost per year in Utah, it is still well below the national averages. Certain types of cancer, however, seem to be rising, including melanoma of the skin and thyroid cancer, according to the National Cancer Institute.

The NCI and CDC work together to track and research statistics surrounding cancer incidence, to better understand cancer survivorship and find out what it takes to make it.

Peterson, who worked for the American Cancer Society prior to her diagnosis, said friends and family made a world of difference to her in her struggle to beat cancer. After a double mastectomy, she said she feels "really proud to be a survivor."

"I'm really glad that the world of medicine was there to help me," she said. But never knowing her own grandmother, Peterson feels her dreams kept her going.

http://www.deseretnews.com/article/7053 ... ivors.html

[comment - of course as a person with brain cancer I would feel especially fortunate to survive this disease. But I don't just want to survive I want to live well. I love health and fitness, as long as I have these things in my life I will be happy. So far so good :)]


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After a Diagnosis, Wishing for a Magic Number

When my wife, Ruth, learned she had breast cancer, friends told us not to worry. After all, they said, a lot of progress has been made.

As a cancer researcher and a doctor at Memorial Sloan-Kettering Cancer Center, where she was being treated, I knew this was true. Progress has indeed been made. Throughout my career, death rates from breast cancer in the United States have steadily declined by 1 percent to 2 percent a year.

Some experts credit mammography screening for up to half the decline; others credit it less, or not at all. But there is no dispute that much of the progress has come through better treatments for early-stage breast cancer. Chemotherapy has improved, radiation has grown more effective and additional drugs lower the risk that the cancer will come back.

All of this progress meant that the chance that Ruth’s breast cancer would come back was a lot lower than it might have been years ago. But what was that chance, anyway? It was the obvious question, and we put it to her oncologist at our first appointment with him. He paused and then offered a peculiar answer. He said we should realize that it didn’t matter. It would either happen or it wouldn’t.

I was stunned. Her oncologist, the one I had asked to see her when we found out Ruth had breast cancer, is the most quantitatively oriented and science-based doctor I know. He is one of the world’s authorities on breast cancer, has conducted many of the crucial studies of treatment and written some of the most important papers about it.

The notion that the probability didn’t matter was antithetical to everything I knew about him. Of course it’s about the probabilities — those are the things he is trying to affect every day when he gives women chemotherapy and other treatments.

More maddening still: he obviously knew the data inside and out, so it wasn’t a hard question; it was an easy one. I just expected him, in his direct way, to look at us, head slightly tilted, and say: “2 percent, which is one in 50,” or “25 percent, which is one in four,” whatever. We’d swallow hard, and then we’d go on.

His approach also didn’t make any sense because he couldn’t really keep the information from us. Never mind going on the Internet; my expertise includes the area of prognosis and cancer patient outcomes. I could find all the relevant data and figure out the answer myself. Down to the last digit.

But instead of just spitting out a number he went all philosophical on us.

In his 1985 essay “The Median Isn’t the Message,” the paleontologist and MacArthur Foundation “genius” award winner Stephen Jay Gould described the solace he felt after he learned he had a deadly cancer when he saw in the statistics that a few rare people actually lived a very long time, even though most people with his diagnosis succumbed rapidly.

He decided at that moment to be one of the rare ones; put scientifically, he planned to be in the tail of the distribution. It is a beautiful essay by one of the greatest scientific writers of our era. And it was prescient. He lived another 17 years after publishing it.

But every time I read it, I see past my admiration of the man to the conclusion that Dr. Gould chose to actively delude himself. Only in Lake Wobegon can everyone be reliably above average, and there’s merit to being realistic.

Dr. Atul Gawande, another MacArthur award winner, and perhaps an even more gifted writer than Dr. Gould, both paid tribute to and took issue with his argument in a recent essay in The New Yorker called “Letting Go,” noting that although hope has many roles, “hope is not a plan.”

So, Doc, why not just tell us our odds?

Ruth’s oncologist elaborated on his refusal, promising he would tell us the number just as soon as we told him what probability of recurrence would cause us to make different choices for our lives.

Neither of us had an answer.

What he was proposing was that we adopt neither Dr. Gould’s rosy view that our chances are somehow just better than the statistics, nor take Dr. Gawande’s implicit advice that we confront the number and plan accordingly. Because the truth is that no number, no matter how low, would have let us go skipping out of the office confident that this monster was slain for good. And no number, no matter how high, would keep us from living our lives.

I never asked again.

http://well.blogs.nytimes.com/2011/03/2 ... ss&emc=rss


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PostPosted: Sat Apr 09, 2011 7:54 am 
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Addiction fed by gap between life's rewards

ARISTOTLE called it akrasia. The puzzle of self-defeating behaviours. Why do we persist in doing things we know are against our interests? Things that we say we do not want to do.

Why is it when one leaves the beach at Yuurrgubarraalbigu for the five-hour drive back to Cairns one swears there will be no stopping at the KFC in the main street of Mareeba, four hours away? The recollection of how ill the last indulgence left one is vivid. What was irresistibly finger-licking good before the fatal capitulation soon turns into bilious recrimination. The regret starts before the indulgence is complete.

What was firm resolve back at Lakeland Downs starts dissolving down the straight at Biboohra and by the time you zoom past the "Welcome to Mareeba: More than 300 sunny days a year" sign, the Devil has seized the steering wheel. The cues are unavoidable, the final being the Colonel's beneficent but evil smile saying in his Kentucky drawl: "You thought you were going to dodge me n-n-native, but where I come from black folks eat fried chicken and watermelon and I'm gonna make every one of you n-n-natives down under join 'em!"

So under compulsion, natives stuff the red and white buckets into the overhead lockers heading north to Cape York and the Torres Strait, filling the plane with the alluring if faintly nauseating perfume of fried chicken.

The layman may call it gluttony, but the ancient Greeks called it akrasia. Weakness of will.

The scientific literature on food compulsions increasingly points to common hedonic mechanisms underlying obesity and drug addiction. Whether alcohol, drugs or fatty food, a wide range of disorders remind us no matter how much we may intellectually appreciate the larger costs associated with certain indulgences, such compulsions are immune to reason. The smoker is aware that smoking kills, but even the highest medical awareness of future costs is no match.

There are two ways to look at the apparent inability of addicts to resist temptation. The old disease model championed by Alcoholics Anonymous and others emphasise that addicts are powerless over the addiction.

In recent decades, theories of addiction have burgeoned around the role of choice. Addicts seem not completely bereft of choice. The literature on addictions is divided between those who urge a visceral view of addiction and those who say that we make choices around our addictions.

There is not yet a scientific consensus on the nature of addiction. My layman's view is that a synthesis needs to reflect a thorough understanding of choice theory.

The literature in psychology and behavioural economics on the role of choice in addiction started with Nobel Laureate Gary Becker's 1988 theory of rational addiction. With a colleague from the Chicago School of Economics, Becker argued that addicts seek to maximise their future utility from their drug use.

In 1937, economist Paul Samuelson first brought precision to the measurement of utility in economics, and Becker applied rational choice theory to the analysis of addiction. That addicts are rational utility maximisers is the idea. According to this theory humans discount the value of a future reward according to an exponential curve over time. The exponential rate of discounting has been central to microeconomics ever since Samuelson.

The meaning of exponential discounting is as follows: imagine a reward that we can obtain in the future. But we value any reward higher if we get it sooner. We therefore discount the value of the reward by a constant factor per unit time.

However George Ainslie, an American research psychiatrist, published experimental evidence in the 1970s that showed the rate of discounting of future rewards followed a hyperbolic rather than exponential curve. Since then an accumulation of research involving a range of human and animal subjects confirms the hyperbolic discount rather than the exponential rate assumed in standard economics. Hyperbolic discounting means that we don't discount the value of a reward by a constant factor per unit time of delay before we can get it. The further into the future a reward lies, the less sensitive we are to delays.

The important consequence of hyperbolic discounting is as follows. There is a time when a larger but later future reward is more attractive than a smaller, sooner reward; there is a point in time where both rewards are equally attractive; and there is a time - just before you can get the smaller reward - when the smaller, sooner reward is more attractive. If we draw two curves that show the valuations of the two rewards over time, the point of equal valuation is the point where these two curves intersect.

Which mathematics do we intuitively follow in our everyday decisions? Exponential or hyperbolic discounting?

It appears that exponential discounting of a future reward is limited to circumstances where humans are at their most rational: calculating the value of money over time. Perhaps it is when we engage in mathematical calculation that our choices are the coolest. In other circumstances we probably make much hotter and less rational calculations.

Hyperbolic discounting represents a challenge to conventional economics. Research evidence and theories emanating in psychology and neuroscience have messed up the clean lines of rational economic theory. Microeconomics does not presently know how to contend with what Ainslie dubbed the picoeconomics of human motivation and brain functioning.

One of the strengths of Ainslie's hyperbolic discounting is that it predicts an important feature of animal and human behaviour: preference reversal. Standard economics provides no explanation for preference reversal.

In standard economic theory, if we place a high valuation on our long-term health (the larger, later reward) then we will discount that value exponentially according to a curve with the same shape as we discount the low valuation we place on an indulgence in fried chicken.

If our valuation of future indulgence is lower than our valuation of future health at a certain point in time, it should be lower at every point in time, including the 30 seconds before we drive past KFC. This would be true if our valuation curves were exponential.

Yet while we might hold to the larger, later reward for a long period of time, there comes a point when the sooner reward is imminent, and we flip our preference!

Ainslie's hyperbolic discount curves explain why we change our preference driving down the main street of Mareeba and we see the KFC Colonel chuckling at our impotence. When indulgence and health are both perceived to be distant rewards, health is valued higher. Close to the opportunity for gluttony the curves intersect. And in the final seconds the temptation is irresistible.

We often anticipate preference reversal, and we try to devise strategies to deal with anticipated weakness of will.

We can, earlier in the journey, when our preferences for health v fried chicken have not yet been reversed, choose a strategy of detouring through the back streets of Mareeba, thereby avoiding temptation. This is the strategy of pre-commitment.

It is one of the measures proposed by the Productivity Commission to curb problem gambling. Andrew Wilkie and Nick Xenophon are now pushing the Gillard government to introduce pre-commitment devices to poker machines, against opposition from clubs and state governments. Wilkie and Xenophon are dead right: without pre-commitment devices, no amount of "responsible gambling" education and awareness campaigns will match the power of addiction and preference reversal.

Which is why I am sceptical of the national marketing campaign aimed at tackling the appalling rates of tobacco smoking among indigenous Australians. If it helps to get the conversation going in communities, then fine, but the water-off-a-duck's-back effect of education and awareness campaigns is well known. Much more decisive interventions will need to accompany the campaign.

If we are susceptible to subverting larger, later rewards in favour of smaller, sooner rewards, then one strategy that appears to avoid compromising our long-term wellbeing is to construct what I will call valuable rewards in the near-term.

This happens when employees who value their jobs are able to arrest their substance abuse problems when subjected to random drug testing as part of workplace health and safety requirements. This was evident in a trial of young indigenous workers from Cape York Peninsula who relocated to Victoria to work in abattoirs.

While many were habitual marijuana users, most readily adjusted to the random drug testing regime thanks to an appropriate amnesty by the meat processing company. In this case the calculation facing the young men was whether to give in to the smaller, sooner reward of indulging in marijuana, or to preserve their jobs and high incomes that were visible and valuable when they made their calculations.

The use of random drug testing in workplaces for health and safety reasons represents an effective intervention for thousands of people who would otherwise be struggling with drug addictions.

For similar reasons, programs enabling the reinstatement of practising certificates to doctors provided they comply with drug testing over an extended period, have proven highly effective in the rehabilitation of drug-addicted medical practitioners.

The discourse between visceral motivations involved in addiction and choice remains to be resolved. I am conscious that laymen such as me follow such interesting intellectual developments as if following a horse race. I expect Ainslie will ultimately perform the required synthesis and receive a Nobel for illuminating the picoeconomics of human motivation and choice.

http://www.theaustralian.com.au/news/op ... 6036211618

[comment - while adopting the right lifestyle is no guarantee, I believe that these addictions, particularly to junk food, you are much more likely to end up on the lefthand side of the median curve - the wrong side]


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PostPosted: Sun Apr 10, 2011 2:28 pm 
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The cancer industry is failing us

We are asked to give generously to every cancer cause - and do, often in the hope that the disease won't touch us. But when cancer strikes your family or friends you soon find out how primitive the tools are to detect and treat it. And the commitment to prevention seems secondary.

Last year 174,000 Canadians heard the dreaded words, "You have cancer." More than 76,000 lost their lives to this chronic disease. It is expected that nearly half of all males and four in ten females will eventually contract cancer. One in four of us will die from it.

The lives of those who have been diagnosed are changed forever. It becomes a life of trying to defy the odds. The emotional, physical and financial strain on them and their families is profound and unyielding.

Countless billions have been spent in this country over the last half century on cancer screening, treatment and research. Last year cancer accounted for about 10% of our total health care spending - nearly $20- billion.

According to the Canadian Cancer Society the average cost of a single course of treatment is $65,000 - almost as much as our average annual household income.

The results? Not particularly impressive. The self-perpetuating cancer industry seems to be doing all right. But what about the rest of us?

A 2009 Conference Board of Canada study found that 180 Canadians for every 100,000 died of cancer in 1960. Fifty years later the muchtrumpeted "War on Cancer" has only managed to reduce this mortality rate by about 5%. The elusive "cure" for cancer has been "just around the corner" for decades. And it is still out of sight.

We remain dependent on the same three primary treatments that have been used for generations: surgery to remove the tumour, chemotherapy and radiation to try to kill any remaining cancer cells. Anyone who has gone through this torturous "treatment" knows how medieval it can be.

Months of injecting a cocktail of drugs into your system, which kills both healthy and cancerous cells, followed by a period of intense radiation are still the basic responses. But both these treatments can have debilitating side effects, both short and long-term.

Fortunately there is an army of medical professionals and volunteers in cancer agencies and hospitals who are caring and dedicated. They work hard and optimistically to lessen the physical and psychological burden of these brutal treatments. And there has been progress with cancer drugs and procedures to make them more targeted and tolerable.

As for a cure for cancer - a silver bullet that will stop the suffering and deaths - don't count on that happening any time soon, if ever. Leading researchers like Dr. Bert Vogelstein of the Howard Hughes Medical Institute believe, "it is going to be even more difficult perhaps than previously expected to derive real cures from such (drug) therapies." He suggests that redirecting research funds into detection and prevention would be a more sensible strategy.

A much greater emphasis on aggressive prevention is a common theme with critics of the current cancer strategy. They maintain that "Prevention is the Cure." It is widely acknowledged that over half of all cancers can be prevented - stopped before they start. But the present allocation of funds makes it clear that the cancer establishment isn't buying into the old axiom about 'an ounce of prevention.'

According to the Canadian Cancer Research Alliance less than two per cent of the billions spent on cancer research in this country go to primary prevention.

And yet, where cancer rates have dropped, there is a clear connection to prevention. Anti-smoking campaigns helped lower cancer rates for men. Reduced use of hormone replacement therapy did the same thing for breast cancer.

We all know the major lifestyle choices that contribute to cancer:

smoking, obesity, inactivity, poor nutrition, and sun and radiation exposure. It's often within our own personal power to manage these risks.

However, viewed more broadly, cancer is an environmental disease. It is becoming increasingly apparent that the air we breathe, the water we drink, the food we eat, and the products we use contain a wide range of cancer-causing substances - pesticides, solvents, phthalates, heavy metals, hormones, and others.

Dr. Devra Davis of the University of Pittsburgh Cancer Institute is a strong believer in prevention. She maintains that there have been millions of preventable cancer deaths in the U.S.

over the last 30 years. She attributes them to "an obsessive, militaristic focus on beating the disease," rather than removing carcinogens from our environment.

Of the hundred-plus cancer organizations in Canada, only a few focus primarily on prevention. None of them have much influence, or are among the big players.

The newest mega-cancer agency is the Canadian Partnership Against Cancer (CPAC). It was formed in 2007 to implement a national cancer control strategy. It's a worthy and overdue initiative. Part of its mandate is prevention.

But don't expect the CPAC - supported entirely by $500-million federal funding - to be at the forefront of political advocacy for improvements in our environmental safety.

They are all about "collaboration and consultation."

The Canadian Cancer Society does an admirable job of helping those who already have cancer. But their prevention initiatives don't go much beyond providing information on healthier lifestyles and the environmental risks that surround us.

Fighting for public policies that will significantly reduce the probability and prevalence of cancer will take more than pseudo-activism. Canadians need a truly independent cancerprevention coalition.

We need advocacy that isn't afraid to take on foot-dragging governments and conflicting commercial interests.

We need an alliance capable of rallying the public behind the knowledge we already have, to bring prevention to the forefront of the fight against cancer.

http://www.lfpress.com/comment/2011/04/08/17927831.html


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PostPosted: Fri May 27, 2011 5:32 pm 
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How to educate and motivate yourself - instead of getting medicated

(NaturalNews) Sick and miserable again, you go to the doctor, and invariably you leave with a prescription of pharmaceutical medication and maybe the dire words that there is no other option: you`ll have to take the tablets for the rest of your life. Instead of handing over your personal responsibility and future to others though, your educational research initiative can allow fresh air in, which is superior over being passive and stuck with recommendations by well-meaning professionals of whom you don`t know the extent of their medical education and approach. Few doctors have been trained in nutrition or natural health. Motivation is the next step; it`s the key to applying what you have thoroughly investigated and found to be beneficial. It moves you to action despite other people`s raised eyebrows and criticism as well as your own deeply ingrained habits. Motivation helps towards better health and the confidence that you`re genuinely doing the best that`s possible, given your personal circumstances.

You may have looked up a few websites in your quest for relief from your chronic complaint, and you may already know that natural treatments are safer. When you bring up the subject with your well-meaning GP or specialist - oncologist consultant - however, s/he might be less than encouraging about your choice. Consequently you yourself might start doubting the prospect of a positive outcome (other than relieving symptoms) when using natural medicine. That`s if you`ve allowed your research to leave any doubts in your mind.

To make a wise health decision, first of all you need to be fully aware of the source of any and all information: 1) from the medical, pharmaceutical side of things; 2) from the well-educated, well-informed, well-researched natural health scene; 3) from the experienced or otherwise just anecdotal field of grass-root home remedies; 4) from the perhaps borderline supernatural area of energy healing, reiki, angels, and hypnotism etc.; or 5) from outright quacks.

You`ll probably decide right here and now to what you wish to pre-limit yourself. Don`t be surprised, however, if you find opposing opinions on the Internet about everything. The more you research, though, the more you`ll recognise the ring of genuine medical truth. Take ample time, and analyse thoroughly. It`s your body, your health, your life, and your future.

On an A4 paper write down what treatments, advantages, and disadvantages there are. You need to have an accurate knowledge of your choices and their consequences. Then weigh up the pros and cons.

Take for example, cancer treatments. The choices include chemotherapy, radiation therapy, operation, hormonal therapy, bowel detoxing, building up the immune system, a plant-based cancer diet, and going to a health institute for natural treatment, to mention just a few options. For answers, examine websites that shed light on the subject from different angles, and in normal, non-scientific English. Try also to recognise any side effects and risks, plus possible money agendas behind the options. The advertised goal is always to minimise pain and to maximise pleasure in life, but consider what you may have to sacrifice on the way.

Once you have gathered your information, weighed up everything, and made an informed choice, you might see a need to make some serious lifestyle changes.

With your motivation based on solid facts, you can direct your behaviour towards particular goals. The motivation from within will provide the increased energy you need for special efforts. Old habits die hard, but in order to change, reminders are invaluable. So put notes on your fridge and in other appropriate places. And then just be consistent. You`re worth it.

http://www.naturalnews.com/032530_drugs_motivation.html

[comment - energy equals light - it also equals health]


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PostPosted: Fri Nov 18, 2011 5:18 pm 
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Hmmmm thanks for sharing this i really like ur post it was quite helpful quite interesting i got so many new things in this post u really have the knowledge thanks.........


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PostPosted: Fri Nov 18, 2011 5:19 pm 
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There are so many types of physical therapy which will really help while in the treatment i have personally experience of physical therapy its a really helpful treatment......


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PostPosted: Fri Apr 06, 2012 6:53 am 
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Change, not cancer, is the C-word

Jess Rossie doesn't even want to think about all the changes her two-month-old son, Mason, is likely to live through.

''Because it means I'm going to have to try to keep up,'' said the 28-year-old. ''I don't even know how to use an iPhone.''

The mother of three from Rozelle says her greatest concern for her son is that he will become consumed by technology. ''I don't want him to have two mobile phones to his ears [or have] too many computer and Xbox games.''

She did not want him to become a technology ''hermit'' and ''waste his life away''.

Rossie also fears that she won't be able to keep up with the rapid rate of change. ''The kids will have some fandangle gadgets with a thousand passwords and I won't be able to access [them] or do anything about it,'' she said.

''I'll probably hide it and they'll find it with GPS tracking.''

Rossie and her partner, Shannon Weller, already have a two-year-old daughter, Matilda, and a four-year-old daughter, Mikayla. She says the couple are optimistic about their children's future.

''We'll probably find the cure for AIDS and cancer,'' she said. ''So who knows, our children could live to over 100.''

Rebecca Griffith, of Carlingford, hopes cancer will become a non-life-threatening illness much like a common cold in the lifetime of her son, Deacon, who was born on New Year's Day. ''Influenza used to kill people and now you just go to the doctor and have a shot or some antibiotics and rest for a few days, and you're fine,'' she said.

The 37-year-old says that she and her husband Chris have had many friends and family who have been affected by cancer.

''I'd love my children not to have to worry about the dreaded 'C', '' she said.

Griffith, whose first-born child, Adelaide, is almost two, says the main concern she has for her children is that the Australian economy is in good shape.

''But there are a lot of things in the world that are wrong and [Deacon has] been born into a very fortunate country, so I'm fairly optimistic,'' she said.

http://www.smh.com.au/national/change-n ... z1rCYKmkiR


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PostPosted: Wed May 02, 2012 7:27 am 
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Terminal breast cancer leads woman to pick palliative care, not aggressive therapy

The day I found out that I was terminally ill, it was misty, just barely raining, appropriately gray and damp. I was 51 years old. My life was normal — wonderful, in fact.

My mother and I, both in our raincoats, both carrying umbrellas, were walking down a city sidewalk miles from home when my cellphone rang. It was my oncologist calling to give me test results; she knew I’d want them before a medical appointment the next day. She told me gently. I hung up.

“It’s stage four,” I told my mother. “The bone biopsy showed that the cancer has spread. It’s in my lower spine.” The diagnosis seemed to drop from the sky, rain clouds turned to lead, crashing down on us. We hugged, crying, my tiny mother, her tall daughter. One wet, raincoated shape as we held one another, our umbrellas forgotten.

“Take three deep breaths,” I finally managed to say to her. We tried. But as we inhaled, suddenly both of us began laughing, uncontrolled belly laughs, despite — and in defiance of — the damp death sentence that had just fallen from the sky.

That was more than 18 months ago. Now, the medical countdown toward the end of my life continues. And I’ve done a lot of thinking about how best to live the limited time I have left.

I had felt fine. But a small, red, rough-textured spot (not a lump) about the size of a pea had appeared on my right breast. I was educated as a registered nurse, led quality-improvement efforts as a health-care administrator and now am at a foundation focused on improving the health of our nation’s older adults. But even without that background, I’d have known something was wrong. Anyone would.

My primary-care physician quickly arranged for me to have scans and a biopsy at a local hospital. Both of us were aware that the red spot might be cancerous.

The night before my hospital appointment, I was wide awake, reading. Breast cancer, in general, has a five-year survival rate nearing 90 percent. But inflammatory breast cancer, which I suspected the spot might be, is different. It’s an especially aggressive form of cancer where the breast itself eventually can become red and swollen, and even develop a diseased open wound. But most frightening is that it tends to spread to other parts of the body. Of those who receive diagnoses of inflammatory breast cancer, at which point it’s usually stage III or IV, only 40 percent live to five years.

That night my research revealed that despite all the funding going toward curing breast cancer, what seemed an insignificant amount goes toward finding a cure for inflammatory breast cancer. The next morning, before most people had had their first cup of coffee, I was in the hospital, watching as a radiologist extracted “core samples” of my breast tissue. In a clear, informational way, she explained what she was doing and what she was seeing. She noted eventually that the samples appeared to be malignant. I appreciated her honesty.

When the biopsy results were back, I met with an oncologist in New York, where I work. After she gave me a physical exam, we sat quietly in her office, lined with its reassuring books and diplomas. She looked me in the eye and in a soft voice told me the diagnosis: inflammatory breast cancer. Hearing it said out loud was almost anticlimactic. I’d thought so. And the radiologist who had taken the biopsy had gently helped prepare me for the news.

http://www.washingtonpost.com/national/ ... tid=pm_pop


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