Omer Uzel

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.

Multivariate analysis of prognostic factors in 75 patients with soft tissue sarcoma

The results of 75 patients with soft-tissue sarcomas treated by the combination of local surgical excision plus postoperative radiotherapy are reported. Thirty-five tumors were situated in the extremities, 32 in the trunk, and eight in the head and neck. Twenty-eight tumors were high grade, 33 intermediate and 14 low grade. Sixty-two patients had complete resections (wide or marginal) and 13 incomplete resections (intralesional). Radiation was administered with a shrinking-field technique (median total dose, 64 Gy; range, 50-78). Twenty-five patients developed local recurrence (33%). The 5-year local control rate was 67%. On univariate analysis, a tumor site other than extremity (p < 0.05), unfavorable histology (p < 0.01), and incomplete resection (p < 0.01) were poor risk factors for local recurrence. When multivariate analysis were performed, only incomplete resection (relative risk (RR) 7.2) remained a poor risk factor. The 5-year overall survival rate was 50.5% for the entire group. Following a univariate analysis of host tumor and treatment-related factors, a tumor site other than extremity (p < 0.05), high tumor grade (p < 0.01) unfavorable histology (p < 0.05), and incomplete tumor resection (p < 0.01) were found to significantly increase the risk of further tumor death. Multivariate analysis found high tumor grade (RR 5.6), and incomplete resection (RR 7) to be independent poor risk factors for survival.

Retinoblastoma in Turkey: survival and clinical characteristics 1981 - 2004

Background: In this study, the authors aim to describe the survival and clinical characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004.

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.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1, 69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours (p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA (p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients (p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion (p = 0.01), 34.8% for positive margins versus 78.1 for negative margins (p < 0.0001). After a multivariate analysis, tumour grade (p = 0.026) and presence of positive margins (p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

Toxic Epidermal Necrolysis after Cranial Radiotherapy and Phenytoin Treatment

Background: There are few reports about Stevens-Johnson syndrome, a bullous form of erythema multiforme, that can develop in patients treated with cranial irradiation and antiepileptic drugs, especially with phenytoin. We present a patient who developed toxic epidermal necrolysis, a rare and severe form of Stevens-Johnson syndrome, during cranial radiotherapy and phenytoin treatment. Case Report: A 65-year-old male patient with stage IIIB non-small cell lung carcinoma developed a brain metastasis. The patient was treated with phenytoin and dexamethasone. Palliative total cranial irradiation was performed. On the 23rd day of phenytoin administration, erythema and edema in the radiotherapy area and lips, as well as widespread maculopapular eruptions and rashes in the upper thoracic area were observed. The dermal lesions progressed to bullae and subsequently toxic epidermal necrolysis covering 70% of the whole body surface developed. The patient died within 15 days of appearance of the lesions due to secondary infections, despite supportive and symptomatic treatment. Conclusion: Although toxic epidermal necrolysis is a rare toxicity it must always be considered during cranial irradiation and antiepileptic prophylaxis.

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.

Is FDG -PET-CT A Valuable Tool in Prediction of Persistent Disease in Head and Neck Cancer

OBJECTIVES To evaluate accuracy of FDG-PET CT in prediction of persistent disease in head and neck cancer cases and to determine prognostic value of metabolic tumor response. MATERIALS AND METHODS Between 2009 and 2011, 46 patients with squamous cell carcinoma of head and neck receiving PET-CT were treated with definitive radiotherapy, with or without chemotherapy. There were 29 nasopharyngeal, 11 hypopharyngeal, 3 oropharyngeal and 3 laryngeal cancer patients, with a median age of 50.5 years (range 16-84), 32 males and 14 females. All patients were evaluated with PET-CT median 3-5 months (2.4-9.4) after completion of radiotherapy. RESULTS After a median 20 months of follow up, complete metabolic response was observed in 63% of patients. Suspicious residual uptake was present in 10.9% and residual metabolic uptake in 26.0% of patients. The overall sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET-CT for detection of residual disease was 91% and 81%, 64% and 96% respectively. Two year LRC was 95% in complete responders while it was 34% in non-complete responders. CONCLUSIONS FDG PET CT is a valuable tool for assessment of treatment response, especially in patients at high risk of local recurrence, and also as an indicator of prognosis. Definitely more precise criteria are required for assessment of response, there being no clear cut uptake value indicating residual disease. Futhermore, repair processes of normal tissue may consume glucose which appear as increased uptake in control FDG PET CT.

Increase in the Rate of HPV Positive Oropharyngeal Cancers During 1996-2011 in a Case Study in Turkey

BACKGROUND Primary aim of this study is to assess whether or not there is an increase at rate of HPV positive oropharyngeal cancers during 1996-2011 in Turkey, for comparison with prior reports from Western countries. MATERIALS AND METHODS A total of 138 newly diagnosed patients with oropharyngeal cancer were identified, 39 of which had no primary tumor specimen available and 18 patients with invalid HPV status, therefore HPV status for remaining 81 patients was evaluated. The presence and type of HPV DNA were determined with formalin- fixed paraffin embedded specimens, using an HPV DNA-based multiplex PCR assay. Associations between HPV status and clinicopathological characteristics were evaluated using a two-sample t-test for the continuous variables and the categorical variables were compared by chi-square test. Overall survival (OS) periods were calculated with Kaplan-Meier method. RESULTS The proportion of HPV-positive cancer has continued to increase during 2004-2011 as compared with 1996-2003. Notably, 33% (6/18) of the cases were HPV-positive in 1996-1999, 43% (9/21) in 2000-2003, 55% (11/20) in 2004-2007 and 70% (16/23) in 2008-2011. Thus, when we compared the results obtained during the 2004-2011with results of 1996-2003 period, we found that increase at HPV-positivity ratio was statistically significant (38% vs 64% p=0.012). CONCLUSIONS This study demonstrated that HPV positive oropharyngeal cancers are increasing in Turkish patients as in the Western world.

Acute Toxicity in Nasopharyngeal Carcinoma Patients Treated with IMRT/VMAT

PURPOSE To evaluate acute toxicity in nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) with or without cisplatin-based chemotherapy. MATERIALS AND METHODS A total of 45 newly diagnosed, histologically proven non-metastatic NPC patients treated with IMRT between May 2010 and December 2012, were evaluated retrospectively, 37 planned with Eclipse and 8 with Prowess Panther treatment planning system. The doses to the planning target volumes of primary tumor and involved lymph nodes, high risk region, and uninvolved regional nodal areas were 70 Gy, 60 Gy, and 54 Gy respectively and delivered simultaneously over 33 fractions to 39 patients. Another 6 patients irradiated with sequential boost technique. Some 84.4% of patients received chemotherapy. Acute toxicities were graded according to the Radiation Therapy Oncology Group scoring criteria and Common Terminology Criteria for Adverse Events (CTCAE) for chemotherapy side effects. RESULTS Median age was 43 years (14-79) and all patients were WHO type II. Grade 1 mucositis and dysphagia were observed in 17 (37.8%), and 10 (22.2%) patients, respectively. The incidence of acute grade 2 mucositis and dysphagia was 55.6% and 68.9%, respectively. The most common chemoradiotherapy related acute toxicities were nausea, leucopenia and thrombocytopenia. Grade 3 toxicity was detected in 13 (28.8%) cases. No grade 4 toxicity was occurred. Mean weight loss was 9%. None of the patients required the insertion of percutaneous endoscopic gastrostomy for nutritional support. Radiation therapy was completed without interruption in all patients. CONCLUSIONS IMRT is a safe and effective treatment modality, and well tolerated by patients in the treatment of nasopharyngeal carcinoma. No unexpected side effects were observed.