The results of concomitant and sequential chemoradiotherapy with cisplatin and etoposide in patients with locally advanced non-small cell lung cancer.

PURPOSE: To report on the treatment results and demographic characteristics of patients with locally advanced non small cell lung carcinoma (NSCLC) who were treated with concomitant or sequential chemoradiotherapy. PATIENTS AND METHODS: 132 patients with locally advanced NSCLC (stage IIIB) were evaluated. Their median age was 60 years (range 33-80). Histopathological diagnosis was epidermoid carcinoma in 96 (73%) patients, adenocarcinoma in 33 (25%) patients and large cell carcinoma in 3 (2%) patients. Karnofsky performance status (KPS) score was >/= 70 in 112 (85%) patients. Weight loss was greater than 5% in 34 (26%) patients at presentation. One hundred and six (80%) patients were treated with sequential chemoradiotherapy which consisted of 3 monthly cycles of cisplatin (100 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3) before radiotherapy. Radiotherapy consisted of a total dose of 60 Gy in 30 fractions (2 Gy / fraction), given to a volume including primary tumor and mediastinum. Two to 4 cycles of chemotherapy were administered after completion of radiotherapy to patients whose disease had not progressed after initial chemotherapy. Twenty-six patients were treated with concomitant chemoradiotherapy. The same radiotherapy regimen was started with the 2nd cycle of chemotherapy which consisted of cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3). Chemotherapy was completed after 4 cycles in all patients. RESULTS: Overall survival (OS) was 14.5 months in 106 patients treated with sequential chemoradiotherapy and 14.6 months in 26 patients treated with concomitant chemoradiotherapy (p=0.99). Median time to progression was 9.77 months in the concomitant group and 11.6 months in the sequential group (p=0.47). However, progression-free survival was better in patients of both groups whose KPS was >70 (12.4 months versus 11.5 months, p= 0.02). While presence of anemia was found as an adverse prognostic factor only in univariate analysis, non-epidermoid histology, KPS less than 70 and presence of N2-N3 disease were found as adverse prognostic factors in both univariate and multivariate analysis. CONCLUSION: The addition of chemotherapy to radiation concomitantly or sequentially prolongs survival in locally advanced NSCLC patients with acceptable adverse event profiles in both arms compared with results of the trials in the literature in which radiotherapy is used as single treatment modality.

Effectiveness of brachytherapy in the treatment of lip cancer: a retrospective study at the istanbul university oncology institute.

Stage T1 through T3 lip cancers can be treated primarily by brachytherapy (BRTX), with or without external radiotherapy (ERT), with adequate safety margins and good results. In this study, the outcomes of BRTX were reviewed for patients treated at the Brachytherapy Department of the Istanbul University Oncology Institute (IUOE). The medical records of 41 patients registered at IUOE with a diagnosis of lip cancer between 1988 and 2003 were reviewed. The median follow-up time was 88 months (24-160 mo). Among these patients, 21 patients with a primary tumor, 14 with tumors arising postoperatively, and 6 with postoperative recurrence of tumor were treated using BRTX. A total of 33 patients (80%) received BRTX alone and 8 (20%) received BRTX and ERT. The 10-year local control rate was 100%, 93%, and 67% for patients treated with BRTX alone, BRTX and surgery, and those treated for postoperative recurrence, respectively (P<.02). For patients treated with BRTX only and BRTX plus surgery, specific disease-free survival was 95% and 94%, respectively, and overall survival was 93% and 100%, respectively; these differences were not statistically significant. One patient with a postoperative recurrence who had been treated with BRTX died as a result of lip cancer. No patients developed any ulcerations, intra-oral complications, or mandibular necrosis. In the BRTX only group, 83% had excellent or good cosmetic results. In the surgery group, 62% had a contour deformity. In lip cancer management, BRTX results were comparable for local control, survival, and minimal late effects in normal tissue. This is in accordance with current reports in the medical literature. Satisfactory results were observed in patients with stage T1 and T2 lesions who had been treated with BRTX only and in patients with stage T3 lesions who had been treated with BRTX plus ERT, without a need for additional treatment modalities.

Unusual metastases from rectal adenocarcinoma; report of two cases with literature review.

Two case reports of patients with skin and orbital metastasis from rectal carcinoma are described. The reasons for the rarity of this kind of metastases are considered. The survival of these cases was very short.

Protective effects of DL-alpha-tocopherol acetate and sodium selenate on the liver of rats exposed to gamma radiation.

The aim of this study is to investigate whether vitamin E (as DL-alpha-tocopherol acetate) and selenium (as sodium selenate) exert a protective effect against radiation damage. The liver tissue of rats irradiated with a single dose of 1,000 cGy 60Co-gamma-irradiation was examined for morphological changes after the intraperitoneal (ip) administration DL-alpha-tocopherol acetate and sodium selenate as compared to controls. Also, the amounts of blood glutathione and serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and total protein were determined by spectrophotometric methods. Degenerative changes were observed under light and electron microscopy in the liver tissue of the control (radiation only) group. In the group receiving radiation and ip doses of DL-alpha-tocopherol acetate and sodium selenate, the damage to the liver tissue was minimal or absent. In the radiation-only group, a reduction of the blood glutathione level and increases in serum values of AST, ALT, ALP, and LDH activity were observed, whereas in the irradiation-treated group, the reverse was found to occur. Based on these morphological and biochemical observations, it was concluded that the ip administration of DL-alpha-tocopherol acetate and sodium selenate exerts a protective effect against liver radiation damage.

Preliminary analysis of a phase II study of Paclitaxel and CHART in locally advanced non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb) is one of the most active single agents for non-small cell lung cancer (NSCLC), and ideal in combination with radiation therapy. We designed a phase II study to determine the efficacy and toxicity of continuous hyperfractionated accelerated radiotherapy (CHART) and concurrent weekly Paclitaxel (T) in good performance status patients with unresectable stage III A and B NSCLC. T (60 mg/m2) was given as a 3-h infusion on days 1, 8, 15, 22, 29 and 36; CHART was started on day 15 with 150 cGy/fraction given three times a day for a total dose of 54 Gy in 12 days with no weekend break. Twenty patients were evaluable for acute toxicity. The major acute toxicities were esophagitis and pulmonary toxicity; 70% of the patients experienced grade 2-3 esophagitis and 50% experienced grade > or = 3 pulmonary toxicity. Grade 3 anemia developed in only one patient. Of the 17 patients evaluable for late toxicity, 12% of the patients had grade 3 pulmonary toxicity, one patient developed grade 4 esophagitis. Nineteen patients were evaluable response. The overall response rate was 84% (95% confidence interval, 60-97). CHART with concurrent weekly T seems to be an effective regimen, but tolerability needs to be documented with a larger number of patients and longer follow-up.

Nitric oxide and radiation enteritis.

OBJECTIVE: To investigate the changes in intestinal nitric oxide (NO) and myeloperoxidase (MPO) concentrations, the rate of endotoxaemia, and intestinal mucosal structure in rats after irradiation of the abdomen and to find out the effect of Nomega-nitroarginine methyl ester (L-NAME) inhibition NO synthesis. SETTING: Medical school, Turkey. DESIGN: Experimental study. MATERIAL: 46 Wistar-albino rats. INTERVENTIONS: In Group I (n = 12), rats underwent abdominal irradiation alone. In Group II (n = 12), they underwent abdominal irradiation and were given L-NAME orally for 3 days before and 3 days after irradiation. In Group III (n = 12), rats had abdominal irradiation and were given L-NAME orally for 3 days after irradiation. Group IV (n = 10) were controls and were untreated. The irradiation procedure consisted of a single shot of 1000 cGy to the abdomen and L-NAME was given 30 mg/kg/day orally in the drinking water. MAIN OUTCOME MEASURES: Intestinal mucosal MPO and nitrite, and plasma endotoxin concentrations. Changes in villous height and number were recorded. RESULTS: In groups II and III, MPO and NO2- concentrations decreased significantly compared with group I. Mucosal integrity was protected in both groups treated with L-NAME (groups II and III) in contrast to the group given irradiation without treatment (group I). CONCLUSION: These results suggest that the NO pathway contributes to the inflammatory response of radiation enteritis. Inhibition of NO synthesis may have a beneficial effect in the treatment of inflammation caused by irradiation.

A phase II trial, feasibility of combination of daily cisplatinum and accelerated radiotherapy via concomitant boost in stage III non-small cell lung cancer.

PURPOSE: A prospective phase II trial was conducted by the Institute of Oncology, Istanbul University in December 1994 on patients with locally-advanced non-small cell lung cancer to assess acute toxicity and the feasibility of a combination of radiosensitizer and accelerated radiotherapy with concomitant boost. MATERIALS AND METHODS: Patients were irradiated using 'large' fields (primary tumour and locoregional lymph nodes) with 1.8 Gy per fraction, five fractions a week. Reduced 'boost' fields (primary and involved nodes only) were also irradiated twice-weekly 1.8 Gy per fraction in ten fractions concomitantly 6 h after the administration of large field. Total radiation dose was 63 Gy in 5 weeks (45 Gy 'large' fields and 18 Gy 'boost'). The maximum allowed dose to the spinal cord was 3750 cGy. Cisplatinum, 6 mg/m2 was given daily just before 'large' field irradiation. RESULTS: As of January 1997, 15 patients were evaluated (median follow-up of 12.5 months with a range of 5.5-23 months). The overall acute toxicity rate was 38% and Grade 3 acute toxicity was 8%. Grade 4 or greater acute toxicities were not observed. The overall rate of cisplatinum-induced nausea and vomiting was 80% (severe in 60%), but all were easily treated with antiemetics. Complete response rate (clinical and radiological) was 40% and an overall response rate was 73%. Median survival was 16 months and progression-free survival was 5.5 months (range of 2.5-21 months). CONCLUSIONS: Toxicity was well tolerated and no treatment-related death occurred with this combined treatment regimen. Although it appears that better local control rates can be achieved, additional phase II/III studies are needed.

Plastic surgery in irradiated areas: analysis of 200 consecutive cases.

Reconstructive surgery in previously irradiated areas is more difficult than in non-irradiated cases. A retrospective analysis of the outcome of 200 previously irradiated patients who had skin graft or flap reconstruction performed by the same surgeon is presented, and the most suitable surgical technique in irradiated areas is discussed. One hundred and fifty-six patients had skin and oral cavity cancer, and were operated on after local recurrence. Twenty patients had breast cancer; 15 were operated on for local recurrence and five for breast reconstruction. Twenty-four patients had soft tissue sarcomas. Eighty-five patients had a skin graft (group 1), 35 had a skin flap (group 2), 10 had a fascia/muscle flap plus skin graft and 70 had a myocutaneous flap (group 3). Analysis of complications revealed statistically significant differences in terms of incomplete graft/flap necrosis between group 1 and 2 (P < 0.001) and groups 1 and 3 (P < 0.001), and in terms of infection between groups 1 and 3 (P < 0.01). We conclude that the method of reconstruction is determined by the characteristics of the defect such as size and localization; the quality, fractionation, total dose, and energy of radiation used; skin and subcutaneous tissue changes due to radiation; and operation time. However, it is reasonable to choose fascia/muscle or myocutaneous flaps for reconstruction in previously irradiated areas. These methods are more resistant to bacterial inoculation, more prone to clean residual infection, and provide better vascularized tissue and volume replacement for contour defects.

Total vermilionectomy; indications and technique.

In this study, total vermilionectomy, indications and technique are discussed. The results of 33 cases are presented with review of the literature.