Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be deferred?

Whole brain radiotherapy (WBRT) has been increasingly omitted as the first treatment of primary central nervous system lymphoma (PCNSL) because of neurotoxicity risks. However, neurotoxicity risks are lower in young (<60 years) patients; deferring WBRT may not be necessary and may compromise disease control. To investigate this question, we report a consecutive series of young (<60 years) PCNSL patients uniformly treated with a response-adjusted approach, with WBRT omitted in patients with chemosensitive disease. Treatment started with induction chemotherapy consisting of methotrexate (3 g/m(2)), CCNU, procarbazine, methylprednisolone and intrathecal methotrexate, cytarabine, and methylprednisolone. Patients achieving complete response (CR) received five additional chemotherapy cycles and no further treatment. Patients with less than CR were treated on an individual basis, typically with WBRT or high-dose chemotherapy (HDC) with stem cell rescue. Sixty-four patients were included (median age: 47; median KPS: 70). Median progression-free survival (PFS) was 12 months; median overall survival (OS) was 63 months (median follow-up: 108 months). Objective response after induction was 87% (CR: 54%; PR: 33%). To date, salvage WBRT has been given to a total of 27 patients and HDC to 29. Neurotoxicity developed in five patients (none in patients treated with chemotherapy only). Deferring WBRT in chemosensitive patients seems to compromise PFS but not OS. Neurotoxicity was reduced but not eliminated, as salvage WBRT was frequently required. HDC and WBRT were effective salvage treatments. As the objective of treatment in this population is a cure, withholding WBRT may not be the best strategy and deserves further investigation. Ongoing studies are investigating whether upfront treatment with HDC can replace WBRT in this setting.

How accurate are physicians in the prediction of patient survival in advanced lung cancer?

BACKGROUND: Because most cases of non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage with a poor prognosis, patient inclusion in clinical trials is critical. Most trials require an estimated life expectancy >3 months, based on clinician estimates of patient survival probability, without providing formal guidelines. The aim of this study was to assess the accuracy of clinicians' predictions of survival in NSCLC patients (stages IIIB, and IV) and the possible impact of patient quality of life on survival estimation. METHODS: At diagnosis, clinical, biological, and quality of life data (QLQ-C30 questionnaire) were recorded, and doctors "forecast" each patient's estimated survival. Concordance between predicted and actual survival was assessed with the intraclass correlation coefficient. RESULTS: Eighty-five patients with a mean age of 62.2 years, 81.1% male, were included (squamous cell carcinoma, 33; adenocarcinoma, 42; large cell carcinoma, 8; neuroendocrine carcinoma, 2). The mean follow-up was 40 months and median survival time was 11.7 (range, 0.4-143.7) weeks. All clinicians (residents, registrars, and consultants) overestimated patient survival time, with a moderate concordance between predicted and actual survival time. A worse global health status was associated with a lower discrepancy between estimated and actual patient survival, and a worse role functioning was associated with a larger difference between estimated and actual patient survival. CONCLUSION: The absence of specific recommendations to estimate patient survival may introduce major selection in clinical studies. Further research should investigate whether the accuracy of patient survival estimates by clinicians would be improved by taking into account patient quality of life.

Is there a relationship between the presence of lung mucosa preinvasive lesions and lung cancer incidence? Influence of tobacco consumption.

UNLABELLED: Although studied for years, the nature of the relationships between tobacco consumption, bronchial preinvasive lesions and lung cancer are still not completely elucidated. Objectives were to determine the relationship between tobacco consumption and lung mucosa preinvasive and invasive lesions and to describe patients' evolution according to baseline characteristics. METHODS: Bronchial biopsy specimens were taken at six predetermined sites in 156 males, current smokers, aged above 18 years. Relationships between smoking characteristics and preinvasive lesions indexes and between baseline characteristics and lung cancer occurrence during a prospective follow-up were examined. RESULTS: Maximum grade was hyperplasia for 16.7% of patients, metaplasia 33.3%, dysplasia 25.0%, and carcinoma in situ 1.3%. For 23.7% of patients, all biopsies were considered normal. Preinvasive lesion indexes were related to smoking intensity (cigarettes/day). Lung cancer incidence during the follow-up was 19.9%. No association between severity of mucosa lesions at baseline and incidence of cancer during the follow-up period was observed. CONCLUSION: The majority of smokers had mucosa lesions, but a relatively small number of them would have a cancer, and there was a poor correlation between severity of mucosalesions and incidence of cancer. Even if an evolution from preinvasive lesions to an invasive cancer is plausible and coherent with current concepts, this link does not appear strong enough to recommend the use of systematic classic endoscopy for targeting of a sub-group of higher risk smokers who would require a closer follow up.

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy.

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.

Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004.

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly.

BACKGROUND: Treatment for primary CNS lymphoma (PCNSL) in the elderly is associated with lower response rates and higher risks of acute and late delayed toxicity as compared to younger patients. Temozolomide has emerged as a new alternative treatment for PCNSL and constitutes an attractive option for the elderly because of its favorable toxicity profile. In this study we report outcomes of a consecutive series of PCNSL elderly patients initially treated with an innovative regimen combining methotrexate and temozolomide without radiotherapy or intra-thecal chemotherapy. METHODS: Histologically confirmed newly-diagnosed PCNSL patients older than 60 years were included. An induction chemotherapy was initially given (methotrexate 3 g /m(2) on days 1, 10, and 20, and temozolomide 100 mg/m(2) on days 1-5). Patients achieving a partial or complete response proceeded to a maintenance phase (up to 5 monthly cycles of methotrexate 3 g/m(2) on day 1, and temozolomide 100 mg/m(2 )days 1-5). Non-responders were treated on an individual basis. RESULTS: Among the 23 included patients, a complete response was observed in 55%, and disease progressed in the other 45%. Median event-free survival was 8 months, and median overall survival was 35 months. Grades 3 or 4 toxicities included nephrotoxicity in three patients, and hematotoxicity in five; no neurotoxicity has been observed to date. One patient died while on treatment from complications of intestinal obstruction. CONCLUSION: Our efficacy results are comparable to other reported regimens, with the advantages of a favorable toxicity profile, and absence of intra-thecal chemotherapy. Prospective, controlled studies are warranted to confirm such results.