Prognostic factors in gastrointestinal stromal tumors: multicenter experience of 333 cases from Turkey.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22-102 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.

Bevacizumab plus irinotecan-based therapy in metastatic colorectal cancer patients previously treated with oxaliplatin-based regimens.

BACKGROUND: Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. PATIENTS AND METHODS: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). RESULTS: Three patients achieved a complete response (7.5%), 5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). CONCLUSION: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.

Synchronous bilateral breast cancer in an aged male patient.

BACKGROUND: Male breast cancer is an uncommon disease. Moreover, synchronous bilateral breast cancer is extremely rare in men. The management is still undefined, although it shows similarities to breast cancers in women. CASE REPORT: We report the case of a 66-year-old male patient who presented with palpable bilateral breast masses. Synchronous bilateral breast cancer was diagnosed with imaging studies and tru-cut biopsy. Histopathological examination revealed bilateral early-stage breast cancer. None of the possible predisposing factors, including hormonal and hereditary history, could be detected. Following bilateral modified radical mastectomy, the patient received adjuvant chemotherapy with tamoxifen. The pertinent literature is reviewed. CONCLUSION: More studies are warranted to better identify possible risk factors for male breast cancers.

Docetaxel combined with oral etoposide as second-line treatment for advanced gastric carcinoma after failure of platinum- and fluoropyrimidine-based regimens.

BACKGROUND: Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC. METHODS: Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m(2) as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m(2) once daily on days 1-5, every 3 weeks until disease progression or unacceptable toxicities. RESULTS: Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32-77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5-3.5). Median overall survival was 6 months (95% CI, 3.8-8.2) with 16.9% 1-year survival rate. Grade 3-4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%). CONCLUSION: Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

Cisplatin plus docetaxel combination in the first-line treatment of metastatic non-small cell lung cancer.

AIMS: To evaluate activity and toxicity of cisplatin plus docetaxel combination in the first-line treatment of chemotherapy-naive patients with metastatic non-small cell lung cancer. PATIENTS AND METHODS: Between October 2004 and July 2008, 186 patients with metastatic non-small cell lung cancer treated with first-line cisplatin plus docetaxel were retrospectively evaluated in 7 centers. The chemotherapy schedule consisted of cisplatin, 75 mg/m(2) iv infusion, and docetaxel, 75 mg/m(2) iv infusion on day 1, every 3 weeks. RESULTS: Median age was 56 years (range, 28-75). Eighteen patients (9.7%) were females and 168 (90.3%) were males, with a median ECOG performance status of 1 (range, 0-2). A total of 833 cycles of chemotherapy was administered (median, 4 cycles; range, 1-6). Two patients (1.1%) achieved clinical complete response, 77 patients (41.4%) partial response, and 66 patients (35.5%) stable disease. Median time to disease progression was 6 months (95% CI, 5.54-6.46). Median overall survival was 14.6 months (95% CI, 11.47-17.73). One- and 2-year overall survival was 55.2% and 19.7%, respectively. The most common grade 3-4 hematological toxicities were neutropenia (n = 32, 17.2%) and anemia (n = 4, 2.2%). CONCLUSIONS: The cisplatin plus docetaxel combination was effective and safe in the first-line treatment of patients with metastatic non-small cell lung cancer.

Non-gestational uterine choriocarcinoma in a postmenopausal woman.

BACKGROUND: Gestational trophoblastic disease occurs rarely in postmenopausal women. CASE REPORT: We report on a 65-year-old woman with uterine choriocarcinoma developing 16 years after menopause and 25 years after her last pregnancy. She was found to have a uterine tumor on laparotomy after presenting with uterine bleeding and abdominal pain. Histopathological examination demonstrated malignant syncytiotrophoblastic and cytotrophoblastic cells with extensive necrosis and hemorrhage, consistent with pure choriocarcinoma. Chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) was started. The treatment was changed to methotrexate and folinic acid because of severe hypersensitivity reaction after etoposide infusion. After 4 cycles, the serum beta-human chorionic gonadotropin (beta-hCG) level had decreased to normal. The patient remains disease free 20 months after the treatment. CONCLUSIONS: This case further illustrates that choriocarcinoma may be seen in older women after a long menopausal period. Accurate diagnosis and treatment are essential, because the tumor is very chemosensitive and curable even in advanced stages.

Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis.

AIMS AND BACKGROUND: Glioblastoma is the most common primary brain tumor in adults. The standard treatment is surgery and radiotherapy. In this study, the results of radiotherapy plus concomitant and adjuvant temozolomide are reported. In addition, the efficiency of adjuvant temozolomide is evaluated. METHODS AND STUDY DESIGN: Forty-one patients were analyzed. All patients received radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after surgery. Thirty-one patients received an average of 6 cycles (range, 1-8 cycles) of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose of 200 mg/m2/day. The primary end point was overall survival. RESULTS: The median overall survival was 16.7 months. The overall survival significantly increased in the adjuvant temozolomide group compared to the group with no adjuvant therapy (18.9 vs 9.8 months). The difference in overall survival between adjuvant temozolomide cycles of < or = and > 3 was significant (8.7 vs 20 months). On multivariate analyses, the important prognostic factors were type of surgery and application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy, respectively. CONCLUSIONS: The study confirmed the effectiveness of radiotherapy plus temozolomide in newly diagnosed glioblastoma. It was established that the application of adjuvant temozolomide for at least 4 cycles is required to obtain a benefit from adjuvant therapy. However, further studies are needed to confirm these data.

Opportunistic cytomegalovirus infection in a patient receiving temozolomide for treatment of malignant glioma.

Treatment of malignant gliomas has changed substantially over the last few years. An oral alkylating agent, temozolomide, has become the standard agent for glioma management. Although it is generally well tolerated, it can cause lymphopenia and may lead to opportunistic infections. We report on a patient with malignant glioma who developed opportunistic cytomegalovirus (CMV) pneumonia following the termination of temozolomide therapy. The patient was admitted with acute dyspnea, fever and hypoxia, and she was diagnosed with CMV pneumonitis using a PCR-based CMV-DNA analysis. After treatment with ganciclovir, she recovered dramatically. To our knowledge, although there have been reported cases of Pneumocystis carinii infection associated with temozolomide therapy, there has only been one other case of CMV infection. We also review this report.

Gemcitabine-induced acute coronary syndrome: a case report.

OBJECTIVES: To report a case of metastatic leiomyosarcoma, in which a patient developed chest pain accompanied by acute left bundle-branch block (LBBB) after gemcitabine infusion. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old woman admitted with bilateral pulmonary nodules had classic risk factors for coronary heart disease and coronary stenosis as demonstrated by previous coronary angiography. She was treated with gemcitabine infusion, and 30 min later she experienced severe chest pain accompanied by acute LBBB confirmed by ECG. We suspected gemcitabine-induced coronary vasospasm exacerbated by the preexisting coronary artery disease as the cause of the acute coronary syndrome. The patient was subsequently treated with antianginal therapy and percutaneous coronary intervention. Her chest pain resolved and LBBB disappeared. She was discharged 2 days later without any further cardiac events. No additional cancer therapy was given and she died 5 months later, due to disease progression. CONCLUSION: This case showed that chemotherapeutic agents must be administered with intensive cardiac monitoring especially in patients with cardiac disease and well-known risk factors to prevent the development of cardiac complications, despite an agent not being known to be 'cardiotoxic'.

Coexistence of gastrointestinal stromal tumor (GIST) of the rectum and adenocarcinoma of the prostate in a patient with familial GIST.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal system. The rectum is a rare location for GIST. Prostate adenocarcinoma is the most common malignancy in geriatric men. Rarely, rectal GIST mimics prostate pathologies. CASE REPORT: We describe a 58-year-old male patient who was admitted with signs and symptoms of prostatism. A presumptive diagnosis of primary prostate sarcoma was made based on imaging studies and a trucut biopsy. Removal of the mass compressing both the prostate and the rectum revealed the final diagnosis of synchronous prostate adenocarcinoma and high-grade GIST originating from the rectum. The patient also had a family history of GIST. CONCLUSION: According to our knowledge, there are 5 more reported cases of rectal GIST, which were misdiagnosed as prostate malignancy. Rectal GIST may simulate prostate carcinoma clinically, and should always be kept in mind in the differential diagnosis of prostate pathologies.

Temozolomide in newly diagnosed malignant gliomas: administered concomitantly with radiotherapy, and thereafter as consolidation treatment.

BACKGROUND: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment. PATIENTS AND METHODS: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles. RESULTS: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. CONCLUSION: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

Single agent gemcitabine in the second-line treatment of advanced non-small cell lung cancer after treatment with taxane + platinum regimens.

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m2 on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.

The results of three different treatment modalities in patients with locally advanced nasopharyngeal carcinoma.

The aim of the study was to evaluate the toxicity and efficacy of 62 patients with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB) treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients. Patients were classified into following three groups: The patients in the group 1 (n=23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2 (n=15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was administered. In the group 3 (n=24), adjuvant chemotherapy, consisting of cisplatin on day 1 and 5-fluorouracil on day 1 to 5 every 3 weeks was used after CCRT. Three arms were treated with the same RT technique and dose. There was no difference for age, sex, and stage among the groups. Radiotherapy was administered in planned dose for all patients. A total of 82% patients completed planned chemotherapy concurrent with RT. The treatment related adverse effects were mild or moderate in intensity. There was no statistical difference between the groups regarding the treatment responses. Complete response rate of RT was 73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1, 2, 3, respectively. No difference was observed in median OS and PFS among three groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant chemotherapy with CCRT and CCRT alone were found similar.

Histiocytic sarcoma: PET-CT evaluation of a rare entity.

Histiocytic sarcoma is a rare malignancy of hematopoietic origin. Lymph nodes, skin, and extranodal sites, especially gastrointestinal tract, are commonly involved. Some cases reported in the past as non-Hodgkin's lymphoma are now classified as histiocytic sarcoma by detailed immunohistochemical studies. Patients with clinically localized disease have a good prognosis whereas those with lymphatic involvement have an aggressive course. In our case, histiocytic sarcoma was detected, originating from the skin over the left shoulder associated with disseminated lymphadenopathy. A positron emission tomography/computed tomography examination was done for evaluating the extent of the disease which showed pathologic increased 18F-fluorodeoxyglucose uptake in the lymph nodes, indicating widespread disease. The pertinent literature is reviewed.

Carboplatin and oral cyclophosphamide combination after temozolomide failure in malignant gliomas.

BACKGROUND: Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients. METHODS: We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks. RESULTS: All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent. CONCLUSIONS: Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.

Acute erythema and edematous skin reaction and ectropion following docetaxel in a patient with non-small cell lung cancer.

Docetaxel can cause skin reactions such as hypersensitivity, edema, and erythrodysesthesia syndrome as well as side effects involving the skin, including alopecia, nail onycholysis, nail pigmentation, photosensitivity, scleroderma, and paresthesia. In this case report, a patient was admitted to the hospital with widespread erythematous and edematous eruption in the head, neck, trunk, and lower and upper extremities, erythema around the eyes, and drooping of the lower eyelids that developed about 2 hours after receiving chemotherapy consisting of docetaxel. Use of the Naranjo Adverse Drug Reaction Probability Scale--a method for estimating the probability of adverse drug reactions--indicated a probable relationship between the skin reaction and docetaxel therapy in this patient. Docetaxel-associated skin reactions that are so extensive and severe as to lead to eye madarosis and ectropion are reported rarely in the literature.

Metachronous Synovial Sarcoma After Treatment of Mixed Germ Cell Tumor in a Child with Complete Gonadal Dysgenesis.

Patients with complete XY gonadal dysgenesis (GD) show a high predisposition to germ cell tumors (GCT). Patients with coexistence of GCT and GD have been reported previously. Here we present a 15-year-old girl with mixed GCT and GD who also developed an intra-abdominal synovial sarcoma one year after the treatment. This is the first report, to our knowledge, of synovial sarcoma associated with XY GD.

Solitary iris metastasis from breast cancer with dramatic course: case report.

Intraocular metastases are the most common malignancy of eye. Breast cancer is more frequently a cause of intraocular metastases. As a first metastatic site, iris and ciliary body are relatively rare. We report a case of a 52-year-old woman, operated for breast cancer 16 months ago and diagnosed multiple brain metastases 1 month ago. After first course of chemotherapy she was admitted to hospital with the complaints of eye pain and she recognized a solid mass on iris. Iris and ciliary metastases were diagnosed by ophthalmological examination. Because of the patient's poor general condition, diagnostic aspiration from eye metastasis could not be performed. Intramedullary mass was determined 1 month later and she died 2 months later. Ciliary body and iris metastases of breast cancer must be considered as a manifestation of aggressive clinical course and poor prognosis. The eye metastases of breast cancer are a part of systemic illness and must be treated by systemic chemotherapy.

Capecitabine plus oxaliplatin (xelox) in the treatment of chemotherapy-naive patients with metastatic colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. PATIENTS AND METHODS: We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m2 on day 1 in combination with capecitabine 1500 mg/m2/day on days 1-14 every 3 weeks. RESULTS: Seventy-six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2-32). Median time to disease progression (TTP) was 11 months (range 2-27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3-4 adverse effects. CONCLUSION: XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.

Malignant epitheloid angiomyolipoma of the kidney in a child treated with sunitinib, everolimus and axitinib.

The malignant variant of epithelioid angiomyolipoma (EAML) of the kidney is uncommon, extremely aggressive and behaves like a renal cell carcinoma. We present a case of a 12-year-old male with malignant EAML who was treated according to adult treatment protocols. To our knowledge, axitinib has not been used before in children. We conclude that adult protocols, in this rare case, could be safely used in rare childhood malignancies.