Ahmet Kizir

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.

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.

Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0+ rectal cancer: Istanbul R-01 study

BACKGROUND AND PURPOSE The optimum duration between neoadjuvant radiochemotherapy and transmesorectal excision in locally advanced rectal cancer has not been defined yet. This randomized study was designed to compare the efficacy of four-week versus eight-week delay before surgery. METHODS One-hundred and fifty-three patients with locally advanced low- or mid-rectum rectal adenocarcinoma were included in this single center prospective randomized trial. Patients were assigned to receive surgical treatment after either four weeks or eight weeks of delay after chemoradiotherapy. Patients were followed for local recurrence and survival, and surgical specimens were examined for pathological staging and circumferential margin positivity. RESULTS 4-week and 8-week groups did not differ with regard to lateral surgical margin positivity (9.2% vs. 5.1%, P=0.33, respectively), pathological tumor regression rate (P=0.90), overall survival (5-year, 76.5% vs. 74.2%, P=0.60) and local recurrence rate (11.8% vs. 10.3%, 0.77). Overall survival was better in patients with negative surgical margins (78.8% vs. 53.0%, P=0.04). Local recurrence rate was significantly higher among patients with positive surgical margin (28.5% vs. 9.3%, P=0.02). CONCLUSIONS Intentional prolongation of the chemoradiotherapy-surgery interval does not seem to improve clinical outcomes of patients with locally advanced rectal cancer. Surgical margin positivity seems to be more important with this regard.

Protective effects of dl-α-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-α-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 1000 cGy 60Co-γ-irradiation was examined for morphological changes after the intraperitoneal (ip) administration dl-α-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-α-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-α-tocopherol acetate and sodium selenate exerts a protective effect against liver radiation damage.

Factors affecting progression-free survival in non-HIV-related Kaposi sarcoma

Abstract Background: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. Methods: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. Results: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28–85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. Conclusions: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study

AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers

Purpose: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. Methods: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. Results: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). Conclusions: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.