A pilot study of hypofractionated radiation therapy with temozolomide for adults with glioblastoma multiforme

To evaluate the safety and efficacy of hypofractionated radiotherapy (RT) with a standard temozolomide (TMZ) regimen for adults with newly diagnosed glioblastoma multiforme (GBM), twenty-six consecutive adults (range 39–79 years) who met our enrollment criteria received short courses of hypofractionated RT (45 Gy in 15 fractions over three weeks) with concomitant TMZ at 75 mg/m²/d. After 28 days, TMZ was maintained at 150–200 mg/m²/d on five days for 12 cycles or until tumor progression or unacceptable toxicity. The primary end point was determined by overall survival (OS) and toxicity. Secondary assessed end points were: progression-free survival (PFS) at six months, health-related quality of life (HRQOL), and pseudo-progression. We assessed HRQOL by use of the Karnofsky performance status (KPS) and the Functional Assessment of Cancer Therapy–Brain (FACT-Br) Subscale. All 26 patients were evaluated for OS, PFS, and HRQOL. At a median follow-up of 20 months, the median OS was 15.6 months (95% confidence interval 9.0–22.2 months) with acceptable toxicity. PFS rate at six months was 65%. KPS and FACT-Br Subscale scores did not decline after this procedure. Pseudo-progression occurred in two (8%) patients. Adult patients with GBM benefitted from favorable OS and PFS rate as a result of the hypofractionated RT with TMZ. An additional advantage is that this procedure may reduce the course of treatment. Further studies using this procedure are warranted.     

Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience

The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60–86), median KPS was 80 (range 30–100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5–8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9–11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9–19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.     

Health-related quality of life,cognitive screening,and functional status in a randomized phase III trial (EF-14) of tumor treating fields with temozolomide compared to temozolomide alone in newly diagnosed glioblastoma

We characterized health-related quality of life (HRQoL), cognitive, and functional status in newly diagnosed glioblastoma (GBM) patients receiving Tumor treating fields (TTFields) with temozolomide (TMZ) versus TMZ alone in a planned interim analysis of a randomized phase III trial [NCT00916409], which showed significant improvement in progression-free and overall survival with TTFields/TMZ. After radiotherapy with concomitant TMZ, newly diagnosed GBM patients were randomized (2:1) to TTFields/TMZ (n?=?210) or TMZ (n?=?105). Interim analysis was performed in 315 patients with ≥18 months of follow-up. HRQoL, a secondary endpoint, was evaluated in per-protocol patient population and expressed as change from baseline (CFB) at 3, 6, and 9 months for each subscale in the EORTC QLQ-C30/BN20. Karnofsky performance scores (KPS) and Mini-Mental State Examination scores (MMSE) were assessed. CFB in HRQoL was balanced in treatment groups at the 12-month time point. Initially, HRQoL improved in patients treated with TTFields/TMZ (CFB3: 24% and CFB6: 13%) versus TMZ (CFB3: ?7% and CFB6: ?17%), though this difference was no longer evident at the 9-month point. General scales, including physical and social functioning, showed no difference at 9 and 12 months. TTFields/TMZ group reported higher concerns of “itchy skin”. KPS over 12 months was just below 90 in both groups. Cognitive status (MMSE) was stable over time. HRQoL, KPS, and MMSE were balanced in both groups over time. There was no preliminary evidence that HRQoL, cognitive, and functional status is adversely affected by the continuous use of TTFields.     

Abbreviated course of radiation therapy with concurrent temozolomide for high-grade glioma in patients of advanced age or poor functional status

Elderly or frail patients with high-grade gliomas (HGG) can be effectively treated with an abbreviated course of radiation therapy (RT) consisting of 40?Gy in 15 fractions. Concurrent temozolomide (TMZ) improves survival in non-elderly patients with glioblastoma treated with standard schedule of 60?Gy in 30 fractions. We describe our institutional experience of combining abbreviated RT with concurrent TMZ for treatment of HGG. Between 1/1/2004 and 2/5/2010 31 patients were treated. Survival was estimated with the Kaplan?CMeier method. Toxicity was scored according to CTCAE 3.0. Median age was 66?years (range 32?C90), and 17 patients had Karnofsky performance score <70. At the time of analysis, 30 patients (98?%) had died, with a followup of 14?months in the surviving patient. Median survival was 11?months (range 1?C20), and 41?% of patients were alive at 12?months. Thirty patients (97?%) had a decreased corticosteroid requirement after completion of therapy. Only one new hospitalization for worsening neurologic status was required during therapy. Grade 3?C4 hematologic toxicity occurred in 11 patients. Abbreviated RT with concurrent TMZ provides a clinical benefit, is safe and tolerable in patients of advanced age or poor functional status.     

Failure to complete standard radiation therapy in glioblastoma patients: Patterns from a national database with implications for survival and therapeutic decision making in older glioblastoma patients

IntroductionIt is estimated that 5%–10% of patients with newly diagnosed glioblastoma (GBM) fail to complete standard chemoradiation (CRT). We sought to determine the impact of failure to complete CRT on survival and to identify risk factors.MethodsWe queried the National Cancer Database and identified a cohort of 17,451 adults with GBM diagnosed from 2005 to 2012. The cohort was restricted to patients that started conventionally fractionated adjuvant chemoradiation of 1.8 to 2.0 Gy per fraction to a dose of ≤66Gy. Patients were stratified by RT dose: a) completed RT ≥ 58Gy, b) nearly completed RT ≥ 50Gy - <58Gy, and c) did not complete RT ≤ 50Gy.ResultsThe CRT completion rate correlated with survival, 87% of patients completed CRT and had a median OS of 13.5 months, 4% were near completers (median OS 5.7 months), and 9% did not complete RT (median OS 1.9 months). Older age was associated with a higher risk of non-completion. Twenty-eight percent of patients ≥80 years old did not complete standard CRT (OR 2.99) and 19% of 70–79-year olds did not complete CRT (OR 1.99). The adjusted mortality hazard ratio was greater for patients that did not complete CRT across all age categories and for nearly complete CRT patients older than 40 (non-significant for age < 40).ConclusionsFailure to complete standard chemoradiation was associated with decreased survival in our cohort. Patients with risk factors for failure (like advanced age) should be considered for alternative treatments such as hypofractionated radiotherapy.     

A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023

PURPOSE: This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: Patients with histologically confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter <60 mm were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. RESULTS: A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (p = 0.14). CONCLUSION: This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT.     

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions)?±?concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60–90). After a median follow-up of 5.8 months (IQR 3.7–13.1 months), median overall survival (OS) was 7.5 months (95?% CI 4.5–19.1) and the 1-year and 2-year OS were 39.5?% (95?% CI 21.9–71.2?%) and 6.6?% (95?% CI 1.0??43.3?%), respectively. Median progression-free survival (PFS) was 5.8 months (95?% CI 3.9–7.7 months), 1-year and 2-year PFS were 15.2?% (95?% CI 4.4–52.4) and 0?%, respectively. Overall, 16 (76.2?%) patients presented a recurrence. Overall seven patients (33.3?%) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p?相似文献   

Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme.

PURPOSE: Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. PATIENTS AND METHODS: One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m(2)/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m(2) on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). RESULTS: Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. CONCLUSION: TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.     

Treatment for primary CNS lymphoma: the next step.

PURPOSE: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease control and survival in patients with primary CNS lymphoma (PCNSL). The reported protocol was designed to optimize and enhance the chemotherapeutic component of treatment. PATIENTS AND METHODS: Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m(2), procarbazine 100 mg/m(2)/d, and vincristine 1.4 mg/m(2). Thirty patients received whole-brain RT (45 Gy). Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity; these patients are compared with 12 older patients who completed the entire treatment regimen. Most patients (n = 35) received high-dose cytarabine after RT. RESULTS: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30 patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to MTX was seen in two patients. Older patients had similar median survival with or without the addition of RT: 32 versus 33 months, respectively. However, late neurotoxicity was significantly more common in those older patients who received RT (P: =.00004). Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival. CONCLUSION: Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL. Younger patients in particular fared extremely well with this treatment regimen. In older patients, deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity.     

Glioblastoma in the elderly

BACKGROUND:

Glioblastoma (GBM) is the most common malignant primary brain tumor, and approximately 50% of cases occur in patients aged ≥65 years. However, to the authors' knowledge, there is no accepted standard treatment for elderly GBM patients, and specific prognostic factors in the elderly GBM population have not been systematically studied to date.

METHODS:

The Memorial Sloan‐Kettering Cancer Center institutional database was used to identify patients with histologically confirmed GBM who were aged ≥65 years at the time of diagnosis.

RESULTS:

Three hundred ninety‐four GBM patients with a median age of 71.9 years (59% of whom were men) were included. Approximately 18% of patients underwent biopsy, whereas 82% underwent tumor resection; 81% received radiotherapy (RT), and 43% received adjuvant chemotherapy. The median overall survival was 8.6 months; at the time of last follow?up, 90% of patients had died, and the median follow‐up of the 39 surviving patients was 12 months. In a multivariate analysis, younger age, better Karnofsky performance status (KPS), single tumor, and surgical resection were found to be independent predictors of survival. Comparing 103 patients who received adjuvant chemotherapy with 48 who were only followed after RT, there was a 55% decrease in the risk of death (hazards ratio, 0.45; 95% confidence interval, 0.30‐0.66 [P < .0001]) after adjusting for age, KPS, extent of surgical resection, and number of lesions.

CONCLUSIONS:

Similar to studies in younger GBM patients, advancing age, KPS, and extent of tumor resection were found to be independent prognostic factors in the current study. Although survival is inferior in older GBM patients, age alone should not disqualify patients from aggressive therapy with surgical resection, RT, and chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma

Objectives The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. Patients and methods Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) ≥ 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150–200 mg/m² for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. Results The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3–4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. Conclusions Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.     

Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma

The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant’ Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6–12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m², given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.     

Treatment of recurrent glioblastoma multiforme with GliaSite brachytherapy

PURPOSE: In this study, we assess the efficacy of GliaSite brachytherapy in the treatment of patients with recurrent glioblastoma multiforme (GBM). METHODS AND MATERIALS: Between 1999 and 2004, 24 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System (RTS). The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of surgical resection. Low-dose-rate radiation is then delivered locally by temporarily inflating the balloon with an aqueous solution of organically bound (125)I (Iotrex [sodium 3-((125)I)-iodo-4-hydroxybenzenesulfonate]). Patients at the Johns Hopkins Hospital with recurrent GBM, who were previously treated with surgery and external beam radiotherapy, underwent surgical resection followed by GliaSite balloon implantation. Subsequently, the patients received radiation therapy using the GliaSite to a mean dose of 53.1 Gy. Ten patients were male, and 14 patients were female. The mean age was 48.1 years. All patients had pathologically confirmed recurrent GBM. The median Karnofsky performance status (KPS) was 80. Median follow-up time was 21.8 months. RESULTS: At the time of analysis, 18 patients (75%) had died; 6 patients (25%) were alive. Median survival from diagnosis for all patients was 23.3 months. Median survival after GliaSite brachytherapy was 9.1 months. Patients with a KPS > or =70 had a median survival of 9.3 months, whereas patients with a KPS <70 had a median survival of 3.1 months (p < 0.003). Survival was not significantly different between patients receiving 45 Gy and patients receiving a dose greater than 45 Gy. Acute side effects were minor, consisting of mild nausea and/or headache. One patient developed a wound infection. No incidents of meningitis were observed. Late sequelae were rare, but 2 incidents of symptomatic radiation necrosis were observed. One patient developed transient expressive aphasia. CONCLUSIONS: GliaSite radiotherapy confers a prolongation of survival in patients with recurrent glioblastoma multiforme compared to historical controls with recurrent GBM. GliaSite therapy leads to a favorable survival outcome of 9.3 months in patients with KPS > or =70, but only 3.1 months in patients with KPS <70. Favorable survival is observed for patients within each recursive partitioning analysis class. Treatment with GliaSite is safe and generally well tolerated. Additional data are needed to fully assess the therapeutic benefit of GliaSite brachytherapy for recurrent GBM.     

Short-course Radiotherapy in Elderly and Frail Patients with Glioblastoma Multiforme. A Phase II Study

Purpose. To evaluate efficacy of short-course radiotherapy (RT) in elderly (60 years) and frail [Karnofsky performance status (KPS) 50–70] patients with glioblastoma multiforme (GBM).Materials and methods. Between January 1987 and June 1993, a total of 47 elderly and frail patients with histological diagnosis of GBM entered into a phase II study. RT alone was administered with tumor dose of 45 Gy in 15 daily fractions in 15 treatment days in 3 weeks to a target volume described as tumor visible on CT scan and a 2-cm margin.Results. Forty-four patients were evaluable for this analysis. There were 15 (34%) CR and 11 (25%) PR, making the overall response rate of 60%. Median duration of response was 9 months (range, 2–36 months). Improvement in pretreatment performance status was observed in 20/44 (45%) patients, 5 of which improved their KPS for 20%. Median survival time is 9 months, and 1–4 year survival rates are 39%, 6.8%, 4.5%, and 0, respectively, while median time to tumor progression is 8 months, and 1–4 year progression-free survival rates are 30%, 4.5%, 4.5%, and 0, respectively. Females did significantly better than males, patients with KPS 60–70 did significantly better than those with KPS 50, patients having tumors 4–5 cm did significantly better than those with tumors 6–8 cm as well as did those with more radical surgery when compared to those with biopsy only. On multivariate analysis, only tumor size and extent of surgery were found to independently influence survival. Acute toxicity was generally assessed as mild. One of the 12 (8%) autopsied patients had RT-induced brain necrosis.Conclusion This shortened RT appears to be an effective tool in palliation of elderly and frail patients with GBM. Further studies with more patients are needed before testing it against more aggressive treatment approaches in this patient population.     

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.     

A population-based study of glioblastoma multiforme

PURPOSE: To describe (1) the use of surgery and radiotherapy (RT) in the treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3) proportion of survival time spent in the hospital after diagnosis. METHODS AND MATERIALS: We performed a population-based cohort study of all Ontario Cancer Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR records, hospital files containing surgical procedure codes from the Canadian Institute for Health Information, and province-wide RT records. We studied the odds of treatment using multivariate logistic regression. We expressed the time spent in the hospital as the mean number of days per case, and as a proportion of the interval between diagnosis and death, or 24 months following diagnosis, whichever came first. We used the life-table method and Cox proportional hazards regression to describe survival. RESULTS: The proportion of patients with GBM undergoing any surgery directed at the tumor varied with age (p < 0.0001) and region of residence (p < 0.0001). The proportion undergoing RT varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among patients receiving RT and 3 months among those not receiving RT. The percentage of survival time spent in the hospital was similar among those who received from 49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted relative risk of death varied with age and region of residence. CONCLUSION: We observed practice variation in the treatment of patients with GBM according to age, region of residence, and year of diagnosis. Survival did not increase during the study period. The variation in RT dose between those receiving from 49.5 to < 53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival between regions where one or the other of the dose ranges predominated, nor was variation in dose ranges among the regions paralleled by variation in the proportion of survival time spent in the hospital.     

Conditional probability of survival and post-progression survival in patients with glioblastoma in the temozolomide treatment era

With standard treatment for glioblastoma (GBM) consisting of surgery followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ), median survival is ~14.6 months. This is not as informative to patients who have survived for some time. Conditional probability of survival may offer more relevant survival estimates. Outcomes/conditional probability of survival and post-progression survival (PPS) estimates were retrospectively reviewed in the TMZ treatment era of 882 consecutive patients with a diagnosis of GBM from January 2004 to August 2010. Median age of entire cohort was 62 years including 62 % males. Baseline performance status (PS) was 0–1 in 67, 23 % had frontal lobe tumors, 58 % received concurrent RT/TMZ ± adjuvant TMZ. Survival (OS) was similar for those with frontal lobe tumors versus other locations (P = 0.25). OS for patients receiving standard RT/TMZ ± TMZ was 14.2 months. Age, PS, extent of surgery, therapy post-surgery had significant effects on OS. OS for entire cohort at 1, 2, 3, 4, 5 years was 43.4, 17.9, 10.4, 8.4, 7.2 % respectively. Conditional probability of survival of an additional year given survival to 1, 2, 3, 4, 5 years was 41.4, 58, 80.7, 85.7, 81.5 % respectively. Conditional probability of survival for those patients receiving concurrent RT/TMZ ± adjuvant TMZ was similar. Patients who progress >18 months after their initial treatment for GBM had significantly greater 2 and 5 year PPS as well as OS. Conditional probabilities of survival may provide more meaningful life expectancy predictions for survivors of GBM than conventional survival outcomes.     

Neurological outcome of long-term glioblastoma survivors

Extended survival of 3 or more years is rare in patients with glioblastoma (GBM) but is becoming more common. Clinical outcome has not been well studied. We reviewed GBM patients at Memorial Sloan-Kettering Cancer Center between 2001 and 2003 who were seen for two or more visits. Patient characteristics and long-term clinical outcomes were reviewed for patients who had survived 3 or more years following diagnosis. Thirty-nine (11%) of 352 GBM patients were identified as long-term survivors. Median survival was 9.15 years (range: 3–18 years). Median age was 47 years (range: 16–69); 13% were 65 years or older. Median KPS was 90 (range: 50–100). One long-term survivor underwent biopsy alone; 19 patients each had either complete or subtotal resection. All received focal radiotherapy (RT) with a median dose of 5940 cGy; 18% received concurrent temozolomide. Adjuvant chemotherapy was administered to 35 (90%). Twelve patients (31%) remained in continuous remission. Twenty-seven had tumor progression a median of 29.2 months after diagnosis (range: 1.2–167 months); 18 had multiple relapses. Median KPS at last follow-up was 70 (range: 40–100); 85% of long-term survivors had at least one significant neurologic deficit. Eleven (28%) had clinically significant RT-induced leukoencephalopathy, 9 (23%) developed RT necrosis and 9 (23%) treatment-related strokes. Treatment-related complications occurred a median of 2.7 years from diagnosis (range: 0.9–11.5 years). Long-term survivors remain rare, but are found across all age groups despite multiple recurrences; clinically significant delayed complications of treatment are common.     

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.     

Efficacy of radiotherapy for malignant gliomas in elderly patients

Purpose: Age above 65 years is a strong negative prognostic factor for survival in patients with malignant gliomas (MG) treated with radiotherapy (RT) and its value has been questioned. We analyzed the effect of RT on the survival of elderly patients with malignant gliomas.

Methods and Materials: We examined 85 consecutive elderly patients with a histological diagnosis of MG. Age ranged from 65 to 81 years (median 70 years). Glioblastoma multiforme (GBM) was diagnosed in 64 patients (75.3%). Surgical treatment included needle biopsy in 32 patients (37.6%). Median postoperative Karnofsky Performance Status (KPS) was 60 (range: 30–100). Survival probability was estimated using Kaplan-Meier method and compared with the log-rank test. Crude and adjusted hazard ratios (HR) were calculated using Cox’s regression models.

Results: Median survival time for all patients was 18.1 weeks. In multivariate analysis, RT was the only independent prognostic variable for survival (HR: 9.1 [95% CI: 4.5–18.7]). Forty-two patients did not start RT mostly due to low KPS (<50). The median survival of the 43 patients who started RT was 45 weeks. In these patients, Cox multivariate analysis indicated that age was independently associated with prolonged survival (HR: 2.85 [95% CI 1.31–6.19]). Median survival of patients age 70 years and younger was 55 weeks compared with 34 weeks for patients older than 70 years.

Conclusions: The overall survival for elderly patients with MG is poor. RT seems to improve survival in patients up to 70 years, but in older patients treated with RT the survival is significantly shorter.