Sedat Turkan

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.

Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial

BACKGROUND AND PURPOSE Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC. MATERIAL AND METHODS Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms. RESULTS The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01). CONCLUSIONS The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.

Insufficiency Fractures After Pelvic Radiotherapy in Patients With Prostate Cancer

PURPOSE To assess the incidence, predisposing factors, and clinical characteristics of insufficiency fractures (IF) in patients with prostate cancer, who received pelvic radiotherapy as part of their definitive treatment. METHODS AND MATERIALS The charts of 134 prostate cancer patients, who were treated with pelvic radiotherapy between 1998 and 2007 were retrospectively reviewed. IF was diagnosed by bone scan and/or CT and/or MRI. The cumulative incidence of symptomatic IF was estimated by actuarial methods. RESULTS Eight patients were identified with symptomatic IF after a median follow-up period of 68 months (range, 12-116 months). The 5-year cumulative incidence of symptomatic IF was 6.8%. All patients presented with lower back pain. Insufficiency fracture developed at a median time of 20 months after the end of radiotherapy and was managed conservatively without any need for hospitalization. Three patients were thought to have metastatic disease because of increased uptake in their bone scans. However, subsequent CT and MR imaging revealed characteristic changes of IF, avoiding any further intervention. No predisposing factors for development of IF could be identified. CONCLUSIONS Pelvic IF is a rare complication of pelvic radiotherapy in prostate cancer. Knowledge of pelvic IF is essential to rule out metastatic disease and prevent unnecessary treatment, especially in a patient cohort with high-risk features for distant spread.

Nasopharyngeal carcinoma in childhood: long-term results of 32 patients

PURPOSE To evaluate treatment results and prognostic factors, pediatric patients with nasopharyngeal carcinoma were reviewed. MATERIALS AND METHODS Thirty-two patients at the age of 16 and younger were treated for nasopharyngeal carcinoma. One patient had WHO type I, 15 had WHO type II, and 14 had WHO type III histology. All patients were treated with radiotherapy, median dose to nasopharynx and involved nodes was 70 Gy (range 60-70.4 Gy), three patients received intracavitary booster dose of 24 Gy in three fractions, 12 patients were also given from two to four courses of platinum based neo-adjuvant chemotherapy. RESULTS Twenty-three patients are alive and well with a median follow-up of 107 months. Ten and 15 years loco-regional control (LRC) and overall survival (OS) rates were 82.5, 68.7 and 72.7, 62.4%, respectively. Patient age, size of the lymph node and prolongation of overall external radiotherapy time were found to be the prognostic factors in univariate analysis, however the only factor remained significant after multivariate analysis was the size of the lymph node on LRC. Almost all long-term survivors experienced moderate to severe complications yielding complication free survival rate of 10.9% at 15 years.

Results and complications of high dose rate and low dose rate brachytherapy in carcinoma of the cervix: Cerrahpaşa experience

PURPOSE To evaluate the results and complications of treatment with high dose rate (HDR) compared to low dose rate (LDR) brachytherapy in cervical carcinoma. METHODS Three hundred and seventy patients who were treated with external irradiation and intracavitary brachytherapy and followed for more than 2 years between 1978 and 1998 have been recently updated. The low dose rate group consisted of 77 cases treated between 1978 and 1982 and HDR group consisted of 293 cases treated between 1982 and 1998. All patients first received external irradiation with 60Co or 9-18 MV photons and a median dose of 54 Gy was given in 6 weeks. In the LDR group, intracavitary treatment was given with Manchester applicators loaded with radium (30 mg) in an intrauterine tube and 20 mg in vaginal ovoids. The dose delivered to point A was on average 32 Gy in one application. In the HDR group, a total dose of 24 Gy was given to point A in three insertions 1 week apart. The dose rate was 0.62 Gy at point A. RESULTS The 5-year pelvic control rate was found to be 73% in the HDR group, compared with 86% in the radium group for stage I cases. In stage IIB and IIIB cases, the rates were 68% and 45% for HDR and 65% and 53% for LDR, respectively. In all stages, there was no statistical difference in pelvic control and survival rates between the two groups. Overall incidence of late complications was found as 31.1% and 31.9% in HDR and LDR groups, respectively. The grade 2-4 late complication rate was 14% in the HDR group compared to 19% in the LDR group (P>0.05). CONCLUSION HDR brachytherapy in the management of the cervix appears to be a safe and efficacious approach. Pelvic control, survival and complications rates are quite similar when compared with LDR.

Continuous hyperfractionated accelerated radiotherapy in the treatment of high-grade astrocytomas

Between May 1993 and January 1995, 36 patients with high-grade astrocytomas were treated with 1.05 Gy continuous hyperfractionated accelerated radiotherapy three times daily to a total target dose of 59.85 Gy in 19 days with 6-h intervals. The median age of the patients was 51 years and the median follow-up was 58 weeks. The median survival rate was 58 weeks and the cumulative survival rate was 22% at 2 years. No severe toxicity occurred in patients treated with this fractionation scheme. These results suggest that continuous hyperfractionated accelerated radiotherapy is an altered fractionation schedule for high-grade astrocytomas with tolerable acute toxicity and survival rates comparable to conventional fractionation and to other altered fractionation schedules.

Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration.

Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.

Fight against cancer around the Mediterranean area: “Many hands make light work!”

The geopolitical and strategic importance of the Mediterranean area is evident since a long time. In terms of health programs and means for cancer care, significant disparities have been reported between countries that borders the Mediterranean basin. AROME project began modestly in 2006 with a group of leaders who recognized the need to promote practical training of young people and, thus, contribute to reduce these inacceptable inequalities in terms of early diagnosis and management. Moreover, our project has been built from our belief that the socio-cultural specificity of this region, its epidemiology, availability of means for diagnosis and treatment, should impose a sustained regional research and better knowledge of tumor biology and identify the specificities that may require particular strategies of care that should not be based only on Western and Asian research data. We must thus take advantage of advances in the identification of intimate biological tumors to provide answers to our ignorance of the specific Mediterranean biology. In this paper, we illustrate this issue describing some particular cancers in this region such as breast and nasopharyngeal cancers.

Nasopharyngeal cancer around the Mediterranean area: Role of newer radiation techniques

Primary radiotherapy has been the mainstay of treatment of patients with nondisseminated nasopharyngeal cancer (NPC). Novel techniques, such as intensity modulated and image guided radiotherapy has the capability to generate steep dose gradients, leading to an improved therapeutic index, especially in NPC. Although it is widely accepted as the treatment of choice in NPC in the modern world, in developing countries the financing of these innovative delivery systems still continues to be a major problem. The purpose of this article is to discuss the difficulties one may experience during the transition from 2D way of thinking to the 3D conformal era and to review the clinical outcome and toxicity profile of these promising new radiation techniques.