Bunyamin Kaplan

Preliminary results of a phase II study of weekly paclitaxel (PTX) and carboplatin (CBDCA) administered concurrently with thoracic radiation therapy (TRT) followed by consolidation chemotherapy with PTX/CBDCA for stage III unresectable non-small-cell lung cancer (NSCLC).

Concurrent chemoradiotherapy plays an important role in the treatment of unresectable NSCLC. This phase II study was conducted to evaluate the efficacy and toxicity of paclitaxel (PTX) and carboplatin (CBDCA) at a recommended dose, based on other previous phase I studies. Twenty-two unresectable stage III NSCLC patients participated in this trial. Of those 22 patients, 19 were evaluable, with a median age of 57 (with ages ranging between 42 and 74), in stages IIIA/IIIB: 6/13. Every patient displayed adequate organ functions. Treatment consisted of a 1-hour i.v. infusion of 50 mg/m2 of PTX followed by a half-hour infusion of CBDCA AUC 2 administered weekly concurrently with radiation treatment, every first day of those weeks in which the patient underwent radiotherapy. Concurrent thoracic radiation therapy was performed in daily doses of 2 Gy to a total dose of 66 Gy over a period of 6.5 weeks. After completion of chemoradiotherapy, consolidation chemotherapy was administered via a 3-hour i.v. infusion of 175 mg/2 PTX on days 1 and 22, in combination with a 1-hour i.v. infusion of CBDCA AUC 6 on days 1 and 22, q 4 weeks for 4 cycles. The overall response rate was 78.9% (95% CI: 62–87.7) with 5 CR (26.3%), 10 PR (52.6%), 2 SD (15.8%), and 1 PD (5.3%). The median survival rate of the patients was 13.9 months, and the 1-year survival rate was 65.1%. Toxicity was moderate: grade 2 neutropenia was seen in 8, and grade 3 neutropenia in 5 patients. Grade 2 thrombocytopenia was seen in 3 patients, and grade 3 thrombocytopenia was not observed. Nonhematologic toxicities were moderate: esophagitis was the most common, and significant toxicity was noted in this study (89.4%). Grade 1 asthenia/fatigue was observed in 5, and grade 2 asthenia/fatigue in 3 patients; furthermore, grade 1 peripheral neuropathy was seen in 4 of the cases and grade 2 peripheral neuropathy in 3 of the cases. Concurrent chemoradiotherapy with weekly PTX/CBDCA, followed by consolidation chemotherapy with the same regimen in patients with stage III unresectable NSCLC is feasible and well tolerated.

Gamma radiation sensitivity of larvae and adults of the red flour beetle, Tribolium castaneum Herbst

In this study, the susceptibility of larvae and adults of Tribolium castaneum (Herbst) to gamma radiation was investigated in the laboratory in Turkey. Gamma radiation was applied at 6 dose levels between 20 and 200 Gy to 13–15 day-old adults and at 5 dose levels between 20 and 180 Gy to 18–20 day-old larvae of T. castaneum. All experiments were performed in growth chambers maintained at 27 ± 1 °C and 70 ± 5 % r.h. The larvae proved to be the more susceptible stage, survival to the adult stage being prevented by exposure of the eggs to 100 Gy; the adult stage was less susceptible. LD50 and LD99 values were determined as 19,75 and 42,97 Gy for larvae and 33,21 and 64,50 Gy for adult stage, respectively. It was concluded that 100 Gy is the effective dose for both larval and adult stages.

Prealbumin is a more sensitive marker than albumin to assess the nutritional status in patients undergoing radiotherapy for head and neck cancer

Aim of the study The aim of this prospective study was to determine the prevalence of malnutrition and to evaluate a more sensitive marker to assess the nutritional status in patients undergoing RT for head and neck cancer. Material and methods The prospective study included 51 (mean age of 57.6 ±11.2 years) patients undergoing RT for head and neck cancer. Malnutrition was defined as weight loss > 5% of baseline. Results Forty-six (90.2%) of 51 patients were male. Malnutrition developed in 33 (64.7%) patients during RT. Mean prealbumin level was significantly lower in patients with malnutrition than in those without malnutrition (17 ±5 g/dl vs. 22 ±5 g/dl, respectively, p = 0.004). On the other hand, there was no significant difference between the two groups in terms of other nutrition parameters including total protein, albumin, total cholesterol, triglyceride, and glucose (p > 0.05). The percentage of weight loss negatively correlated with prealbumin (r = –0.430, p = 0.002), but not with other nutrition parameters including total protein, albumin, triglyceride, total cholesterol, HDL cholesterol, LDL cholesterol, and glucose (p > 0.05). Conclusions The prevalence of malnutrition was high in patients with head and neck cancer. Prealbumin was a more sensitive marker than albumin to assess the nutritional status in these patients.

Clinicopathologic characteristics and therapeutic outcomes of primary gastrointestinal non-Hodgkin's lymphomas in central Anatolia, in Turkey.

Primary gastrointestinal lymphoma is a common presentation of non-Hodgkins lymphoma. The main controversy arises when many aspects of its classification and management are under discussion, particularly regarding roles for surgical resection. The aim of this study was to evaluate clinicopathologic characteristics and the therapeutic outcome of primary gastrointestinal non-Hodgkins lymphoma. We carried out a retrospective analysis of 74 patients who were presented to our center with histopathological diagnosis of primary gastro-intestinal non-Hodgkins lymphoma between 1990 and 2001. All patients have been staged according to Lugano Staging System. For histopathological classification, International Working Formulation was applied. The treatment choice concerning the surgical or non-surgical management was decided by the initially acting physician. Treatment modalities were compared using the parameters of age, sex, histopathological results, stage, and the site of disease. Of the 74 patients, 31 were female and 43 were male, with a median age of 49 years (range 15-80). The stomach was the most common primary site and was seen in 51 of 74 patients (68.9%). The intermediate and high grade lymphomas constituted 91.9% of the all cases. In a median follow-up of 29 months (range 2-128), 20 out of 74 patients died. There was a three year overall survival rate in 65.4% of all patients. The three year overall survival rate was better in stage I and II1 patients who were treated with surgery plus chemotherapy (+/-RT) than those treated with chemotherapy alone (93.7% vs. 55.6%, p < 0.05). The stage and presence of B symptoms affected the disease free survival and overall survival significantly, but the histopathologic grade only affected the overall survival. On the basis of these results, we suggest that surgical resection is necessary before chemotherapy in early stage (stage I and II1) patients with gastrointestinal non-Hodgkins lymphomas because of the significant survival advantage it would bring to the patient.

ABO Blood Groups are Not Associated with Treatment Response and Prognosis in Patients with Local Advanced Non-Small Cell Lung Cancer

BACKGROUND Lung cancer is the leading cause of cancer death, late diagnosis being the main obstacle to improving the outcomes with stage at diagnosis as an important prognostic factor. Relationships between ABO blood groups and risk of benign or malignant diseases have been observed and in this study, we aimed to investigate whether they might affect prognosis and response to chemoradiotherapy in patients with local advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Eighty-one patients with non-metastatic local advanced NSCLC were included in the study. ABO blood groups were A in 45 (55.6%), B in 7 (8.6%), AB in 8 (9.9%), and O in 21 (25.9%) patients. The patients were also divided two groups according to blood group A (45 patients) and non-A (B, AB and O; 36 patients). Response to chemoradiotherapy was complete remission in 10 (12.3%), disease regression in 42 (51.9%), stable disease in 12 (14.8%), and disease progression in 17 (21.0%) patients. RESULTS There was no significant difference among ABO blood group categories or between patients with A blood group and those with non-A blood group in terms of responses to chemoradiotherapy (p>0.05). There were also no significant differences regarding overall and disease-free survival rates. CONCLUSION The ABO blood group system has no significant effect on prognosis and response to chemoradiotherapy in patients with non-metastatic NSCLC.

Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer

OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m2 docetaxel and 20 mg/m2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.

Post-Operative Sequential Chemo-Radiotherapy in High-Grade Cerebral Gliomas with Fotemustine

Abstract High-grade gliomas are the most common primary brain tumors in adults. Twenty-seven patients with histopathologically proven anaplastic astrocytoma and glioblastoma multiforme were enrolled in this study from November 1998 to August 2002. Radiotherapy was administered after surgery and fotemustine (100 mg/m2) was sequentially administered every 3 weeks for 6 cycles. Overall, 111 cycles were administered to the 27 patients (median, 5 cycles; range, 1 to 6 cycles). Myelosuppression was mild to moderate. The median overall survival and progression free survival were 11±3.1 months (95%CI, 4.9-17.1) and 8±0.5 months (95%CI 7.1-8.9), respectively. One-year and two-year survivals were calculated at 48% and 7%, respectively. Significant prognostic factors (P<0.05) via univariateanalysis were divided into two groups: completion of 6 cycles of chemotherapy versus incompletion of 6 cycles of chemotherapy. This trial demonstrates that postoperative radiotherapy and sequential fotemustine therapy is feasible, well tolerated, and may prolong survival in patients with newly diagnosed high-grade gliomas.

Is Human Kallikrein 11 in Non-small Cell Lung Cancer Treated Chemoradiotherapy Associated with Survival?

Purpose Involvement of human kallikreins (hKs) in human cancers has been reported and several hKs are promising biomarkers of various cancers. The aim of this study was to evaluate the prognostic significance of hK11 expression in patients with non-metastatic non-small cell lung cancer (NSCLC). Materials and Methods The study included 44 patients with NSCLC. hK11 expression was determined by immunohistochemical staining. Results The estimation of disease-free and overall survival by Kaplan-Meier was 11 months and 17 months, respectively. The estimation of overall survival by Kaplan-Meier was significantly higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not statistically different, the estimation of disease-free survival by Kaplan-Meier was higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox regression analysis showed that the overall survival rates were significantly associated with response to chemoradiotherapy and the degree of staining with hK11. Conclusion The stronger hK11 expression in NSCLC appears to be associated with better survival rates. hK11 may be a prognostic biomarker of NSCLC.

Prognostic Value of SPARC Expression in Unresectable NSCLC Treated with Concurrent Chemoradiotherapy

BACKGROUND The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. MATERIALS AND METHODS The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel (20 mg/m2) and cisplatin (20 mg/m2). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. RESULTS Median overall survival was 16±2.73 (11.55-20.46) months for low expression vs 7±1.79 months (7.92-16.08) months for high expression (p=0.039), while median local control was 13±2.31 (8.48-17.5) months for low expression vs 6±0.85 (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was 10±2.31 (5.48-14.5) months for low expression vs 6±1.10 (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. CONCLUSIONS High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.

The effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy.

The aim of this study was to examine the effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy and chemotherapy. In this study 152 patients were evaluated. Radiotherapy dose was 45 Gy given in 5 weeks. 5-FU 425 mg/m(2) and folinic acid 20 mg/m(2) were administered weekly during the radiotherapy and four cycles with 4-week intervals as consolidation chemotherapy after radiotherapy. Patients were assigned into two groups according to their body mass index: overweight (body mass index ≥25 kg/m(2)) and normal weight (body mass index <25.0 kg/m(2)). The median overall survival was 39 months vs. 18 months and median disease-free survival was 27 months vs. 13 months in the overweight and normal-weight groups respectively (P = 0.004 and P = 0.006 respectively). The 5-year survival was better in the patients with overweight than those with normal weight (42% vs. 17%; P = 0.004). The overall survival was significantly better with being overweight and early pathological stage (P = 0.016 and P = 0001 respectively). Overall survival, disease-free survival and long-term survival in patients with gastric cancer undergoing adjuvant treatment were better in overweight than normal-weight patients. Moreover, it was shown that body mass index and pathological stage were associated to survival and prognosis.