Haldun Şükrü Erkal

Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome

PURPOSE The present study reviews the experience in treatment of 447 patients with nasopharyngeal carcinomas, analyzing patient, tumor and treatment characteristics determining outcome. MATERIALS AND METHODS There were 322 males and 125 females, their ages ranging from 7 to 85 years (median, 45 years). Two-hundred and seventy-two patients had World Health Organization (WHO) type 3 carcinomas, 123 patients had T4 tumors and 320 patients had metastatic cervical lymph nodes. Three-hundred and eight patients were treated with radiation therapy alone and 139 patients with chemotherapy in combination with radiation therapy. Cumulative radiation dose to primary tumor ranged from 50 to 76Gy (median, 70Gy) and radiation dose to metastatic cervical lymph nodes ranged from 46 to 74Gy (median, 66Gy). RESULTS Follow-up ranged from 0.1 to 19.5 years (mean, 7.6 years). Local complete response was achieved in 357 patients. In multivariate analysis, T-classification, cumulative radiation dose to primary tumor and treatment with chemotherapy in combination with radiation therapy predicted local response. Nodal complete response was achieved in 272 patients. In multivariate analysis, N-classification and radiation dose to metastatic cervical lymph nodes predicted nodal response. Local failure was observed in 70 patients, nodal failure in 35 patients and systemic failure in 114 patients. Overall survival, disease-free survival and disease-specific survival were 33, 32 and 37%, respectively, at 10 years. In multivariate analysis, age, T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted overall survival whereas T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted both disease-free survival and disease-specific survival. CONCLUSIONS Radiation therapy alone appears to be an adequate and viable treatment for patients with early-stage nasopharyngeal carcinomas, whereas treatment with chemotherapy in combination with radiation therapy appears to improve outcome for patients with advanced-stage nasopharyngeal carcinomas.

The histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy in a rat model

Purpose: This study presents the histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy. Materials and methods: Thirty-two Wistar rats were divided into four groups. The rats in Group 1 received melatonin and underwent radiation therapy. The rats in Group 2 received no melatonin and underwent radiation therapy. The rats in Group 3 received melatonin and underwent sham radiation therapy. The rats in Group 4 received no melatonin and underwent sham radiation therapy. Melatonin was administered at a dose of 100 mg/kg using an intraperitoneal injection. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 18 Gy through an anterior portal covering the right lung in entirety. The rats underwent euthanasia at 6 weeks following radiation therapy. The lungs were dissected and blinded histopathological evaluation was performed. Results: Concerning the right lung, a decrease in intra-alveolar edema and intra-alveolar erythrocytes was observed despite an increase in activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. Concerning the left lung, a decrease in alveolar neutrophils and intra-alveolar erythrocytes was evident despite an increase in activated macrophages, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. Conclusions: This study puts forward the histopathological evidence regarding the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy through restrained inflammation, regrettably at the expense of promoted fibrosis. The effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy needs to be evaluated further for the unresolved concerns regarding the safety.

Squamous cell carcinomas of the head and neck: descriptive analysis of 1293 cases

Medical reports of 1293 patients with squamous cell carcinoma (SCC) of the head and neck were retrospectively evaluated. The patients were classified according to their age, sex, primary tumour localization and tumoral stage. There were 1181 males (91.3 per cent) and 112 females (8.7 per cent), with a male to female ratio of 10.5:1. The peak incidences for all primary tumour localizations were observed in the fifth decade. Most common primary tumour localizations were the larynx (71.1 per cent), the nasopharynx (10.1 per cent) and the oral cavity (8.8 per cent). Of all patients in whom staging was complete, 43.1 per cent presented at early and 56.9 per cent at advanced stages. The proportion of patients presenting with metastatic neck nodes was 34.4 per cent and the incidence of metastatic neck nodes increased with increasing T stage. The supraglottic region was the most common primary site among all laryngeal SCC, with a supraglottic to glottic SCC ratio of 1.5:1. Glottic SCC presented at earlier stages compared to supraglottic SCC. The incidence of nodal metastases increased with increasing T stage for SCC of the larynx, the oral cavity and the oropharynx.

Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model.

INTRODUCTION Melatonin is a hormone which is known to be a powerful cardioprotective agent due to its free radical-scavenging properties. This study was carried out to evaluate whether melatonin administration prior to irradiation would have a protective effect on cardiac histopathological changes in an experimental rat model. METHODS Rats were divided into four groups. Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. 50mg/kg dose of melatonin were injected intraperitonally 15 min prior to radiation exposure. Analyses and assessments were performed 6 months after radiation exposure. RESULTS Severe myocardial fibrosis was observed prominently in three regions: the apex, tips of papillary muscles and adjacent to the atrioventricular valves. Inflammation was found to be more in irradiated groups. Increased inflammation and fibrosis were in concordance. The number of mast cells was found to be decreased in irradiated groups. Myocyte necrosis and fibrosis were diminished with melatonin while vasculitis was prevented. CONCLUSIONS Elementary pathological lesions of radiation-induced heart disease (RIHD) are fibrosis, vascular damage, vasculitis and myocyte necrosis. Development of vasculitis was prevented by the use of melatonin. Fibrosis and necrosis were prominently decreased. Prevention of RIHD with the use of melatonin at the long term is encouraging according to the histopathological results.

Radiation therapy for stage I primary orbital non-Hodgkin's lymphomas.

Aims and Background The orbit is an uncommon primary site for non-Hodgkins lymphomas (NHL), and it accounts for less than 1% of all sites of primary presentations. We report the experience of the Department of Radiation Oncology at Ankara University Faculty of Medicine with radiation therapy in treatment of patients with stage I primary orbital NHL. Methods From February 1978 through August 1993, 14 patients with stage I primary orbital NHL were treated with radiation therapy. According to the Working Formulation classification, 8 patients had low-grade and 6 had intermediate-grade lymphomas. The most commonly used radiation therapy technique was a single anterior field with a Cobalt-60 unit, delivering 40 Gy in 2 Gy daily fractions. Two patients with intermediate-grade lymphomas received the CHOP regimen following radiation therapy. Results Follow-up ranged from 0.8 to 18.3 years (median, 10.3 years). Local control was achieved in all patients. Two patients with low-grade lymphomas relapsed locally and were successfully salvaged with radiation therapy. Three patients with intermediate-grade lymphomas failed systemically. Salvage therapy consisted of combination chemotherapy for 2 of them but was unsuccessful. Overall survival probabilities at 2, 5 and 10 years were 78.6%, 61.1% and 52.4%, respectively, for the entire group of 14 patients. Overall, cause-specific and disease-free survival probabilities were higher for patients with low-grade lymphomas than for those with intermediate-grade lymphomas (P = 0.03, P = 0.03 and P = 0.06, respectively). Cataracts were observed in 9 and lacrimal disorders in 4 patients. Conclusions The study suggests that among stage I primary orbital NHL, low-grade lymphomas could be treated with radiation therapy alone, whereas combination chemotherapy could accompany radiation therapy for intermediate-grade lymphomas.

Assessment of early and late dysphagia using videofluoroscopy and quality of life questionnaires in patients with head and neck cancer treated with radiation therapy

BackgorundThe aim of this study was to evaluate dysphagia in patients with head and neck cancer (HNC) undergoing three-dimensional conformal radiation therapy using objective and subjective tools simultaneously and to associate the clinical correlates of dysphagia with dosimetric parameters.MethodsTwenty patients were included in the study. The primary tumor and the involved lymph nodes (LN) were treated with 66-70 Gy, the uninvolved LN were treated with 46-50 Gy. Six swallowing structures were identified: the superior pharyngeal constrictor muscle (SPCM), the middle pharyngeal constrictor muscle (MPCM), the inferior pharyngeal constrictor muscle (IPCM), the base of tongue (BOT), the larynx and the proximal esophageal sphincter (PES). Dysphagia was evaluated using videofluoroscopy and European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ-C30) and supplemental EORTC QoL module for HNC (QLQ-H&N35). The evaluations were performed before treatment, at 3 months and at 6 months following treatment.ResultsOn objective evaluation, the Dmax for the larynx and the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness and proximal esophageal stricture at 3 months, whereas the V65, the V70and the Dmax for the larynx was correlated with BOT weakness and the V65, the V70, the Dmax or the Dmean for the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness, reduced laryngeal elevation, reduced epiglottic inversion and aspiration at 6 months following treatment. On subjective evaluation, the V60, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 3 months, whereas the V70 for SPCM were correlated with QoL scores for HNPA and the V60, the V65, the V70, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 6 months following treatment.ConclusionsThe use of multiple dysphagia-related endpoints to complement eachother rather than to overlap with one another, as well as the use of multiple evaluations over time to represent a scale of early to late findings might provide a better insight in terms of the association of the clinical correlates of dysphagia with the dose-volume data for the dysphagia-related anatomical structures.

Defining the “Hostile Pelvis” for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy

PURPOSE The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to the Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (Dmin), maximum dose (Dmax), and mean dose (Dmean) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (VD) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. RESULTS According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. CONCLUSIONS Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT.

The effects of irradiation on the blood dynamics

AIM The present study evaluates the effects of irradiation on the blood dynamics. MATERIALS AND METHODS Thirty-six volunteers providing written consent participated. A blood sample was transferred into three tubes containing CPDA-1 solution while another blood sample was transferred into three tubes containing heparin. Each tube containing CPDA-1 solution was paired with another tube containing heparin. The first pair was not irradiated, not stored and analyzed immediately (Group 1). The second pair was not irradiated, stored and analyzed at seven days (Group 2). The third pair was irradiated, stored and analyzed at seven days (Group 3). The blood count was performed and the blood viscosity was determined. RESULTS The mean hemoglobin contents were 126 g/l for Group 1, 128 g/l for Group 2 and 129 g/l for Group 3. For the mean hemoglobin contents, the difference between Group 1 and Group 3 (P<0.001) and Group 2 and Group 3 (P=0.01) were significant. The mean red blood cell volumes were 81.8 fl for Group 1, 82.1 fl for Group 2 and 82.3 fl for Group 3. For the mean red blood cell volumes, the difference between Group 1 and Group 2 (P=0.003) and Group 1 and Group 3 (P=0.006) were significant. The mean blood viscosities were 2.2 mPa s for Group 1, 2.8 mPa s for Group 2 and 3.2 mPa s for Group 3. For the mean blood viscosities, the difference between Group 1 and Group 2 (P<0.001), Group 1 and Group 3 (P<0.001) and Group 2 and Group 3 (P=0.004) were significant. CONCLUSION The present study indicates that the recommended doses of irradiation for the blood products to be used in attempt to prevent the transfusion associated graft versus host disease leads to marked alterations in the blood dynamics and might decrease the viability of the red blood cells following transfusion.

High Dose Rate Transurethral Brachytherapy as a Boost Dose for Localized Adenocarcinoma of the Prostate

From September 1989 to February 1993, 11 patients with localized adenocarcinoma of the prostate were treated with pelvic external-beam radiation therapy followed by high dose rate (HDR) transurethral brachytherapy as a boost dose. External-beam radiation therapy was administered through opposed pelvic fields using a 60Co teletherapy unit to a tumor dose of 46-50 Gy in 23-25 fractions and followed by three fractions of transurethral brachytherapy, delivered using a 60Co HDR remote afterloading equipment. The treatment time was calculated using the prostatic capsule as the reference point. The dose calculated to be delivered to the capsule was 5 Gy/fraction, making a total of 15 Gy. The follow-up period ranged from 11 to 65 months, with a median follow-up time of 30 months. Local control was achieved in all patients. The prostate-specific antigen levels were normalized within 3 months of radiotherapy in 9 patients and within 3-6 months in the remaining 2. Transurethral brachytherapy appears to be a simple and feasible form of brachytherapy. Preliminary local control and radiotherapy-related morbidity rates are comparable to those of other forms of brachytherapy. Further follow-up is required for assessment of long-term local control and delayed radiotherapy-related morbidity.