PurposeA multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer.Methods and MaterialsT2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3.ResultsOf 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy—5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction.ConclusionsDose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811.Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy <= 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT.Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genito-urinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, PZ. 032), grade 3+ gastrointestinal, 21% (9811 36%, P = .0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations.Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials. (C) 2013 Elsevier Inc.

Purpose: We conducted a phase II multicentre study of gemcitabine in patients with anaplastic astrocytoma and glioblastoma multiforme at first relapse.Patients and methods: Patients with anaplastic astrocytoma or glioblastoma multiforme receiving a stable dose of steroids and ECOG performance status less than or equal to 3 were eligible for this study at the time of first relapse. One adjuvant chemotherapy regimen was permissible. Patients received gemcitabine 1000 mg/m(2) i.v. weekly x 3, repeated on a four-weekly cycle.Results: Of 20 patients enrolled, 15 were evaluable for response, 19 for non-hematological toxicity and 18 for hematological toxicity. Seven patients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme (GBM). Age ranged from 28-71 years (median 50). Fifteen patients discontinued therapy due to disease progression. The median number of cycles administered was 1 (range 1-11); only two patients received more than three cycles. Hematologic toxicity was acceptable and no grade 4 toxicity was seen. One patient developed Pneumocystis pneumonia and eventual pulmonary embolism; one died of gastric hemorrhage related to steroid therapy. No objective responses were seen. Nine patients had stable disease (median duration 2.7 months, range 0.9-11.2).Conclusions: Gemcitabine given in this dose and schedule seems well tolerated but is not active in patients with recurrent high-grade gliomas.

Puroose: To determine the prognostic significance of histologic grading in oligodendrogliomas.And to assess the role of postoperative radiotherapy in low-grade tumors and adjuvant chemotherapy in anaplastic tumors.Methods and Materials: The records of 38 consecutive patients with the diagnosis of oligodendroglioma were studied.Histologic grade was based on the Smith System and adjusted for the Kemohan's variables.Treatment of low-grade tnmors consisted of surgery or surgery plus postoperative radiotherapy.High-grade tumors, anaplastic and malignant, had surgeq and postoperative radiotherapy with or without adjuvant chemotherapy.&p& 23 patients with low-grade tumors showed improved S-year progression-free survival compared to 15 patients with high-grade tumors (74% and 27% respectively), and improved overall 5-year survival (70% compared to 27%).Of the low-grade group, 16 patients receiving postoperative radiotherapy showed improved 5-year progression-free survival compared to 7 patients who did not receive adjuvant radiation (80% and 24% respectively).The overall 5-year survival was similar (86%).10 patients of the high-grade group had anaplastic oligodendrogliomas.5 patients receiving adjuvant chemotherapy showed improved 5-year progression-free survival compared to 5 patients not receiving adjuvant chemotherapy (60% and 20% respectively).The overall 5-year survival was similar (40%).The remaining 5 patients of the high-grade group had malignant oligodendrogliomas.These received adjuvant chemotherapy and had similar overall survival and progression-tke survival, ie: 40% at 5 years.Conclusion: High-grade oligodendroglimas have worse prognosis than low-grade tumors.postoperative radiotherapy may offer some benefit prolonging time to progression of low-grade tumors.Similarly adjuvant chemotherapy may prolong time to progression of anaplastic oligcdendrogliomas.Prospective randomized clinical trials are needed to more Molly assess these issues.

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.8.1511 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2072151 Dose intensity and lymphoma. R MeyerxR MeyerSearch for articles by this author , M GoodyearxM GoodyearSearch for articles by this author , W HryniukxW HryniukSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.8.1511 PDF "Dose intensity and lymphoma.." Journal of Clinical Oncology, 9(8), p. 1511© 1991 by American Society of Clinical Oncology