Faysal Dane

Vascular endothelial growth factor, hypoxia-inducible factor 1 alpha and CD34 expressions in early-stage gastric tumors: relationship with pathological factors and prognostic impact on survival.

Background: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) and CD34 expressions as markers of angiogenesis in gastric cancer. Patients and Methods: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1α and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. Results: Thirty out of 51 patients were males. The median age was 63 years (range 34–81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1α were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3–68). VEGF, HIF-1α and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1α expression (p = 0.00, p = 0.00). HIF-1α expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1α, CD34 expressions and other pathological characteristics were found to have no impact on survival. Conclusion: VEGF, HIF-1α and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1α might be more effective at earlier stages of gastric cancer.

Bevacizumab + Capecitabine as Maintenance Therapy after Initial Bevacizumab + XELOX Treatment in Previously Untreated Patients with Metastatic Colorectal Cancer: Phase III ‘Stop and Go' Study Results - A Turkish Oncology Group Trial

Objective: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). Methods: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 twice daily on days 1-14 + oxaliplatin 130 mg/m2 on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). Conclusions: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizumab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX.

Causes and risk factors for liver injury following bone marrow transplantation.

Goals: A retrospective study of pretransplantation risk factors predisposing to liver injury following bone marrow transplantation (BMT). Background: Liver complications are a major cause of morbidity and mortality following BMT. Determination of the pretransplantation factors that are likely to lead to liver injury may allow earlier diagnosis after BMT and may possibly improve prognosis. Study: Medical records of BMT patients were reviewed, and results of serial liver function tests and HBV/HCV serology during the pre‐ and posttransplantation 1‐year period were noted. Presence of liver injury was defined as alanine aminotransferase levels twice the upper limit of normal. Forty‐four allogeneic and 17 autologous BMTs, performed between 1990 and 2000, were analyzed in the study. Results and Conclusion: One‐year survival was 77% (34 of 44 patients) for allogeneic BMT and 52% (9 of 17 patients) for autologous BMT. Seventy‐two percent (32 of 44) of allogeneic transplant recipients and 47% (8 of 17) of autologous transplant recipients had liver injury during the first year of BMT. The most frequent causes of liver injury were graft‐versus‐host disease and drug hepatotoxicity for allogeneic BMT and drug hepatotoxicity for autologous BMT. Fulminant hepatic failure occurred in one allogeneic transplant recipient who was a pretrans‐plantation HBV carrier and led to death. Multivariate regression analysis showed that pretransplantation HBV/HCV positivity and pretransplantation elevated liver enzyme levels of any cause were predictive risk factors for post‐BMT liver injury, and close follow‐up, early diagnosis, and treatment are highly recommended for BMT patients with these risk factors.

Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer.

The long-term use of subcutaneous implanted ports for chemotherapy in cancer patients has been associated with the occurrence of thrombosis and infection. In this study, we compared the safety and efficacy of administration of 1000 U of heparin flushes in prolonged interval (every 6 weeks) with standard dose and schedule (500 U every 4 weeks) for port-related infections and thrombosis during periods of non-use. Data were collected retrospectively from patients treated for various cancer types (matched as 2:1 for age, gender, stage of the disease). Patients who had diseases that could cause thrombosis or bleeding in their past medical history, or were taking oral anticoagulants, or had contraindications for heparin usage were excluded. After completing their chemotherapy, 59 patients received prolonged interval, while 30 patients received standard schedule. All patients were followed for at least 1 year. No clinically documented port-related infection or thrombosis has been found in both groups. Also, none of the devices was removed during this time. Prophylactic flushing of central venous ports with 1000 U of heparin in every 6 weeks might be a safe, easy, cheaper, comfortable and effective alternative to standard dose and schedule for preventing thrombosis and infections.

Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials.

Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone. Menopausal symptoms are significant but are not worse than those seen in older premenopausal women.

Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology.

Purpose: To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). Methods: Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. Results: Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028). Conclusions: Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.

Doxycycline-induced ulceration mimicking esophageal cancer

IntroductionDoxycycline-induced esophageal ulcer patients are mostly young persons with no history of esophageal dysfunction. Heartburn, midsternal pain and dysphagia are the most common symptoms. It has generally a benign course. The present case is the first report of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments alongside, in the literature.Case presentationThis report describes a 16-year-old Caucasian girl who, while taking doxycycline capsules100 mg twice a day for acne vulgaris for 3 months, developed these symptoms. An upper endoscopy revealed multiple circumferential deep ulcerations surrounding fragile, irregular, hyperemic and hypertrophic mucosa at the level of the mid-esophagus and concomitantly in the lower esophageal sphincter. The lesions were biopsied to exclude esophageal carcinoma because of the suspicious appearance in the endoscopic examination. The histopathological examination, haematoxylin and eosin stained sections showed ulceration with a mixed inflammatory infiltrate. Doxycycline was discontinued and she was given sucralfate 1 g qid and omeprazole 20 mg bid orally. All symptoms of the patient were resolved on the third day of the treatment. After 4 weeks of the therapy, an upper endoscopic control examination demonstrated normal findings.ConclusionThe present case has been an uncommon presentation of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments, concomitantly. Even the lesions were biopsied to exclude esophageal carcinoma. A modification on the behavior of taking drugs can prevent these unpleasant complications.

Lapatinib plus Capecitabine for HER2-Positive Advanced-Stage Breast Cancer in Elderly Women: Review of the Anatolian Society of Medical Oncology (ASMO) Experience.

Background: The efficacy and safety of the lapatinib and capecitabine combination remain elusive in elderly patients with metastatic breast cancer (MBC), who progress after trastuzumab-based therapy. Patients and Methods: A total of 26 patients with HER2-positive MBC were included in this retrospective multicenter study. Median age was 69 years (range 65-82 years). All patients were treated with the combination of lapatinib (1,250 mg/day, continuously) and capecitabine (2,000 mg/m2 on days 1-14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. Results: The median follow-up was 10 months (range 2-31 months). An overall response rate of 33.4% was achieved, including 1 complete response (3.8%), and 8 partial responses (30.8%). Median progression-free survival was 7 months (95% confidence interval (CI) 5-8), and the median overall survival was 15 months (95% CI 11-19). Most common side effects were fatigue (53.8%), diarrhea (46%), vomiting (36.3%), hand-foot syndrome (34.5%), and anorexia (34.6%). Grade 3-4 toxicities were identified as hand-foot syndrome (3.8%), diarrhea (7.6%), and fatigue (11.5%). There were no symptomatic cardiac events. Conclusion: Lapatinib and capecitabine combination therapy was effective and well tolerated in elderly patients with MBC, who had progressive disease after trastuzumab-based therapy.

Efficacy and Safety of Concomitant Chemoradiotherapy with Cisplatin and Docetaxel in Patients with Locally Advanced Squamous Cell Head and Neck Cancers

BACKGROUND Chemoradiation (CRT) using cisplatin-based regimens has become the standard of care in the treatment of squamous cell head and neck cancers (SCHNC). The impact of taxanes as radiosensitizing agents with concurrent CRT regimens is unknown. We therefore retrospectively evaluated the efficacy and tolerability of a weekly cisplatin+docetaxel combination with CRT in locally advanced SCHNC. METHODS Sixty-six patients with locally advanced SCHNC (39.4% stage IV, 53% stage III, and 7.6% stage II) were assessed retrospectively. Total radiation dose to the PTV of gross disease (primary and/or node) was 70 Gy/ 35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to PTVs of elective high risk and low risk disease, respectively. Chemotherapy (CT) consisted of weekly cisplatin (20 mg/m2) +docetaxel (20 mg/m2) concurrently with RT. RESULTS The median age of the patients was 58 years (range, 32-77). Objective response rate was 83.3%. The 2-year progression-free survival (PFS) and overall survival (OS) were 75.7% and 78.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (36.4%), nausea and vomiting (12.1%), neutropenia (4.5%). CONCLUSION Weekly cisplatin and docetaxel concurrent with RT for locally advanced SCHNC was found tolerable with high efficacy.

Comparison of WHO, RECIST 1.1, EORTC, and PERCIST criteria in the evaluation of treatment response in malignant solid tumors.

AimTo compare response assessment according to the WHO, RECIST 1.1, EORTC, and PERCIST criteria in patients diagnosed with malignant solid tumors and who had received cytotoxic chemotherapy to establish the strength of agreement between each criterion. Materials and methodsSixty patients with malignant solid tumors were included in this retrospective study. The baseline and the sequential follow-up fluorine-18-fluorodeoxyglucose PET/computed tomography (CT) of each patient were evaluated according to the WHO, RECIST 1.1, EORTC, and PERCIST criteria. PET/CT images were used for both metabolic and anatomic evaluation. The concurrent diagnostic CT and MRI images (performed within 1 week of PET/CT) were also utilized when needed. The results were compared using the &kgr;-statistics. ResultsThe response and progression rates according to the WHO criteria were 37 and 38%, respectively. The same ratios were also found for RECIST 1.1 (&kgr;=1). The response and progression rates according to the EORTC criteria were 47 and 40%, respectively. When PERCIST criteria were used, one patient with progressive disease was upgraded to stable disease (&kgr;=0.976). As we found the same results with WHO and RECIST 1.1 criteria, we used WHO criteria to compare the anatomic and metabolic criteria. When we compared the WHO and EORTC criteria, there was an agreement in 80% of the patients (&kgr;=0.711). With WHO and PERCIST criteria, there was an agreement in 81.6% of the patients (&kgr;=0.736). ConclusionSignificant agreement was detected when the WHO, RECIST 1.1, EORTC, and PERCIST criteria were compared both within as well as between each other.