Ahmet Ober

Medulloblastoma in adults: Treatment results and prognostic factors

PURPOSE To investigate the treatment outcome and prognostic factors of adult medulloblastoma patients who received postoperative craniospinal irradiation (RT). METHODS AND MATERIALS Between 1983 and 2000, 30 adult patients (17 men and 13 women, age >or=16 years, median 27, range 16-45) underwent postoperative RT. The median duration of symptoms was 2 months (range 1-9). The tumor location was lateral in 16 (53%). A desmoplastic variant was seen in 12 (40%). Tumor resection was complete in 20 (67%) and incomplete in 10 (33%). All patients received craniospinal RT. The median dose to the whole brain was 40 Gy (range 36-51), to the posterior fossa 54 Gy (range 49-56), and to the spinal axis 36 Gy (range 24-40). The median interval between surgery and the start of RT was 31 days (range 12-69), and the median duration of RT was 45 days (range 34-89). Ten patients (33%) received adjuvant chemotherapy. The median follow-up was 51 months (range 5-215). RESULTS The 5- and 8-year overall survival and disease-free survival rates were 65% and 51% and 63% and 50%, respectively. Twelve patients (40%) developed relapse, with a median follow-up of 51 months. The posterior fossa was the most common site of relapse (6 patients). The median time to relapse was 26 months (range 4-78). Fifty percent of the relapses occurred after 2 years, 17% after 5 years. In univariate analysis, M stage and the interval between surgery and the start of RT were significant prognostic factors for disease-free survival. At 5 years, 70% of M0 patients were estimated to be disease-free, but none of the 3 M3 patients reached 5 years without recurrence (p = 0.0002). The 5-year disease-free survival rate for the patients whose interval between surgery and the start of RT was <3 weeks, between 3 and 6 weeks, and >6 weeks was 0%, 85%, and 75%, respectively (p = 0.002). The 5-year posterior fossa control rate for patients who received >or=54 Gy or <54 Gy to the posterior fossa was 91% and 33%, respectively (p = 0.05). CONCLUSION The survival results for medulloblastomas in adults compare favorably with those in children. However, late relapses, lateral tumor location, and desmoplastic histologic features are more frequent in adults. Spinal seeding at presentation is a poor prognostic factor for disease-free survival. A minimal dose of 54 Gy to the posterior fossa is essential for adequate tumor control. The interval between surgery and the start of RT, which was found to be a significant prognostic factor, is an interesting issue that requires further study.

The Effect of Treatment Interruptions in the Postoperative Irradiation of Breast Cancer

Objective: There is much evidence for the detrimental effect of treatment interruptions on tumor control, particularly in head and neck cancer. In order to determine the outcome of the treatment interruptions in postoperative irradiation of breast cancer, 853 female patients treated between 1990 and 1999 inclusive were retrospectively analyzed. Methods: Locally advanced breast cancer patients who received neoadjuvant chemotherapy were not included in the study. Five hundred and forty-six patients (64%) treated with mastectomy and 307 patients (36%) with breast-conserving surgery were analyzed. A total dose of 50 Gy (46–54 Gy) was given to the chest wall/breast and regional lymph nodes in 1.8- to 2-Gy daily fractions, 5 times per week. A 14-Gy (10- to 20-Gy) photon or electron boost was given to the tumor bed of the patients with breast-conserving surgery. Unplanned treatment interruptions occurred in 741 (87%) of the patients and the median duration of the gaps was 13 days (1–91 days). A total of 348 patients (41%) had no treatment break or interruptions of 1 week or less, whereas 505 patients (59%) had treatment interruptions of more than 1 week. The locoregional control (LC) and overall survival (OS) rates were estimated with the Kaplan-Meier method. A Cox proportional hazard regression model was used to evaluate the influence of host- and treatment-related factors on LC and OS (age, menopausal status, histological subtype, grade, hormonal receptor status, pT stage, pN stage, type of surgery, adjuvant treatment, number of gaps and duration of gaps). Results:For all patients LC rates for 5 and 10 years were 95 and 87%, respectively, and OS rates were 78% for 5 years and 62% for 10 years. LC rates for the group of patients with no treatment break or interruptions of 1 week or less, for 5 and 10 years were 94 and 90%, whereas the LC rates for 5 and 10 years were 89 and 86%, for the group of patients with interruptions of more than 1 week (p = 0.019). Treatment interruptions of more than 1 week and premenopausal status appeared to be independent adverse prognostic factors in multivariate analyses affecting the LC (p = 0.043 and p = 0.005, respectively). The OS rates for the patients without treatment interruptions or interruptions of 1 week or less were also significantly better than for the patients with treatment interruptions of more than 1 week (p = 0.026) in multivariate analyses. Conclusion:Interruptions more than 1 week during postoperative irradiation of breast cancer adversely affect the treatment outcome.

Skeletal muscle: An unusual site of distant metastasis in gastric carcinoma

Gastric cancer metastatic to skeletal muscle is an unusual entity. Surgery, systemic chemotherapy, or radiotherapy to the metastatic mass can be treatment options for achiving palliation. Case Report: A patient with multiple skeletal muscle metastases that occurred during follow-up after gastrectomy and adjuvant chemo-radiotherapy is reported. Magnetic resonance imaging (MRI) demonstrated soft-tissue masses involving the posterior right paralumbar and posterior left paradorsal muscles. Biopsy showed metastatic infiltrating adenocarcinoma. The patient did not respond to palliative chemotherapy. Palliative radiotherapy was administered to the painful mass. Based on this case, the diagnosis of muscle metastases and treatment options for palliation are discussed.

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

Background and Purpose:To investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients.Patients and Methods:59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m2/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m2/day 5-FU and 25 mg/m2/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7–112 months).Results:Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment.Conclusion:Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.Hintergrund und Ziel:Untersuchung der Rolle der postoperativen Radiochemotherapie bei Patienten mit Adenokarzinom des Magens.Patienten und Methodik:59 total oder subtotal operierte Patienten mit Adenokarzinom des Magens, die eine Invasion der Serosaoberfläche, einen Befall der regionären Lymphknoten oder positive Resektionsränder aufwiesen, wurden in die Studie eingeschlossen. Postoperativ wurde eine simultane Radiochemotherapie begonnen. Die Bestrahlung wurde in „Extended-field“-Technik über zwei Felder (anterior-posterior und posterior-anterior) mit einer Gesamtdosis von 45 Gy in 25 Fraktionen zu 1,8 Gy appliziert. 28 Patienten (48%) mit positiven Resektionsrändern erhielten zusätzlich einen 10-Gy-Boost auf den Anastomosenbereich. Die adjuvante Chemotherapie mit einem 450-mg/m2-Bolus 5-Fluorouracil (5-FU) wurde an den ersten 3 Tagen verabreicht und am 20. Tag wiederholt. Nach der Strahlentherapie erhielten die Patienten 450 mg/m2 5-FU i.v. und 25 mg/m2 Leukovorin i.v. wöchentlich für weitere 6 Monate. Die Immunmodulation mit 40 mg Levamisol p.o. wurde am 1. Bestrahlungstag begonnen und für 6 Monate weitergeführt. Der mediane Nachuntersuchungszeitraum lag bei 37 Monaten (7–112 Monate).Ergebnisse:Die mediane Überlebenszeit betrug 23 Monate. Die 3- und 5-Jahres-Gesamtüberlebensraten lagen bei 35% und 14%. Patienten mit positiven Resektionsrändern wiesen eine mediane Überlebenszeit von 22 Monaten auf. Die lokoregionale Kontrollrate betrug 59% nach 3 Jahren und 55% nach 5 Jahren. Die häufigsten Nebenwirkungen der Behandlung waren gastrointestinale Beschwerden bei 42 Patienten (71%). Vier Patienten (7%) starben infolge der Nebenwirkungen. Sechs Patienten konnten die Behandlung aufgrund von Nebenwirkungen nicht beenden.Schlussfolgerung:Obwohl 48% der Patienten in dieser Studie einen mikroskopisch nachweisbaren Resttumor aufwiesen, war die beobachtete Überlebenszeit verhältnismäßig gut. Aufgrund der hohen Toxizität sollte die Behandlung jedoch sehr sorgfältig unter Einsatz angemessener supportiver Maßnahmen durchgeführt werden.

Ovarian ablation by radiation therapy: Is it still an option for the ablation of ovarian function in endocrine responsive premenopausal breast cancer patients?

Surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21-52 years). RT was given with either Co-60 or 15MV photons of the linear accelerator. The median total dose was 15Gy in 4 consecutive fractions (range 5Gy single fraction-36Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6-167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given.

Ovarian ablation by radiotherapy; is it still an option for the ovarian function suppression in endocrine responsive premenopausal breast cancer patients?.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #5137 Background ; Although surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a resonable alternative. Data regarding the use of pelvic radiotherapy (RT) for ovarian ablation is very limited and in 10thSt Gallen consensus meeting, ovarian radiation was overwhelmingly rejected. In this retrospective study we evaluated the efficacy of RT for ovarian function suppression in 118 premenopausal breast cancer patients. Materials and Methods; 153 breast cancer patients had RA between the years 1979 and 2002 at the single center where this study was performed. 19 patients who received chemotherapy within 12 months of RA, and 16 patients who were lost to follow-up within 6 months following RA, were not included into the analyses. All patients were premenopausal and the median age at the initiation of RA was 39 years (range, 21- 52 years). 96 of 118 patients (82%) underwent RA for metastatic disease, 17 patients (14%) received RA as the systemic treatment after locoregional recurrences and 5 patients (4%) had RA as an adjuvant treatment. 97 patients (82%) received only RA as their systemic treatment, 20 patients (17%) had RA with tamoxifen and one patient (1%) had RA with aromatase inhibitors. RT was given with either Co-60 or 15 MV photons of the linear accelerator. A modified pelvic volume was irradiated with opposing anterior and posterior fields, and the dose was prescribed to midplane. The median total dose used for RA was 15Gy in 4 fractions (range 5Gy single fraction-36Gy in 18 fractions). Results; As the efficacy of RA, data regarding the menstrual status were collected. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. 88 patients (75%) experienced amenorrhea in 2 months after pelvic RT. 5 patients (4%) who had still normal menstrual functioning after 6 months of RA had estrodiol and follicle stimulating hormone measurements. As they were found to have premenopausal levels, 3 of them received surgical and 2 of them received medical ablation. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24,5 months (range; 6-167 months), no late severe complications that could be attributable to RT were reported. The total RT dose (more than 15Gy) were found to be significant on the rate of ovarian ablation with Mann Whithney U-test (p=0.02). Conclusion: Ovarian ablation was achieved with a rate of 96% without any major acute and late toxicity using pelvic RT. It should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5137.