F. Yumuk

Extrapulmonary small cell carcinoma: multimodality treatment results.

Aims and Background Extrapulmonary small cell carcinoma is a distinct entity that can occur in many sites, and it is pathologically similar to small-cell lung cancer. We report the results of a retrospective study of a multimodality treatment of 16 consecutive patients with a diagnosis of extrapulmonary small-cell carcinoma. Methods Primary tumor site was prostate in 2, gallbladder in 2, uterine cervix in 2, liver in 2, endometrium in 1, epididymis in 1, colon in 1, larynx in 1, breast in 1, and unknown primary tumor in 3 patients. Patients’ ages ranged from 19 to 79 years (median, 62). Nine patients had limited and 7 had extensive disease. Histologically, 14 were pure extrapulmonary small-cell carcinoma and 2 were mixed with squamous-cell carcinoma. Results Curative surgery was attempted in 8 patients. Seven patients received local-regional adjuvant radiotherapy. All patients, except the one with a breast primary, were treated with chemotherapy (mostly platinum-based regimens). Overall survival for all patients was 41% and 11% at 2 and 5 years, respectively (median survival, 14 months). Median survival for patients with limited disease was 25 months compared to 12 months for patients with extensive disease (P = 0.05). Conclusions Treatment results for extrapulmonary small-cell carcinoma are comparable to those of small-cell carcinomas of the lung. Extent of disease is a significant prognostic factor for survival.

Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in patients with non small cell lung cancer

Context: TK1 found to be elevated biomarker in many solid cancers. Objectives: The study aimed to assess the prognostic significance of a serum TK1 in patients with metastatic NSCLC. Methods: The study included 48 consecutive patients, newly diagnosed with metastatic NSCLC, and 10 healthy volunteers. Serum TK1 activity determined by ELISA method. Results: Patients with a bTK1 level >156 Du L–1 had significantly shorter survival. TK1 level showed a strong correlation with primary tumor SUVmax. Discussion and conclusion: The magnitude of maximum fluorodeoxyglucose uptake in primary tumors and the serum TK1 level in patients with metastatic NSCLC were found to be independent prognostic predictors of overall survival.

The efficacy and toxicity of irinotecan with leucovorin and bolus and continuous infusional 5-fluorouracil (FOLFIRI) as salvage therapy for patients with advanced gastric cancer previously treated with platinum and taxane-based chemotherapy regimens

Abstract There is no established standard salvage chemotherapy in the second-line setting for patients with advanced gastric cancer (AGC) pre-treated with platinum and taxane-based chemotherapy. Our study aims to evaluate the safety and efficacy of FOLFIRI regimen (irinotecan with leucovorin and bolus and continuous infusion with 5-fluorouracil) as a salvage chemotherapy regimen in patients with AGC. Medical records of 97 patients with AGC who received second-line FOLFIRI regimen between March 2006 and February 2011 were examined. Complete and partial responses were observed in 3 (3·1%) and 23 (23·7%) patients, respectively. The median time to progression (TTP) was 3·5 months (95% CI: 2·4–4·6) and the median overall survival (OS) was 10·5 months (95% CI: 8·8–12·2). The most common observed grade 3/4 toxicities were neutropenia (23·7%), diarrhea (6·2%), and stomatitis (5·2%). FOLFIRI regimen is safe and effective in the second-line treatment of AGC patients pre-treated with cisplatin and taxanes.

Newly diagnosed breast cancer in a patient receiving imatinib mesylate.

Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML). Despite imatinib is being used in the treatment of other malignancies as well, its potential role on de novo tumor growth is not known. Secondary malignancies are rarely seen in patients with CML and particularly in those receiving imatinib. Here, we present a CML patient taking imatinib therapy that was diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with imatinib. We tried to explain co-occurrence of these rare events by probable pathogenetic mechanisms.

CECOG experts’ recommendations on the use of denosumab in the prevention of skeletal-related events in bone metastases of lung cancer

PurposeSkeletal-related events represent a substantial burden for patients with advanced cancer. Randomized, controlled studies suggested superiority of denosumab over zoledronic acid in the prevention of skeletal-related events in metastatic cancer patients, with a favorable safety profile. Experts gathered at the 2012 Skeletal Care Academy in Istanbul to bring forward practical recommendations, based on current evidence, for the use of denosumab in patients with bone metastases of lung cancer.RecommendationsBased on current evidence, use of denosumab in lung cancer patients with confirmed bone metastases is recommended. It is important to note that clinical judgment should take into consideration the patient’s general performance status, overall prognosis, and live expectancy. Currently, the adverse event profile reported for denosumab includes hypocalcemia and infrequent occurrence of osteonecrosis of the jaw. Therefore, routine calcium and vitamin D supplementation, along with dental examination prior to denosumab initiation are recommended. There is no evidence for renal function impairment due to denosumab administration. At present, there is no rationale to discourage concomitant use of denosumab and surgery or radiotherapy.

Correlation of high FDG uptake in PET/CT with poor prognosis in metastatic gastric adenocarcinoma.

e14668 Background: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. 18F-FDG PET may have a role in predicting patient prognosis on the basis of the metabolic activity of primary tumors (PT). We retrospectively evaluated prognostic value of FDG-PET/CT in metastatic gastric cancer. METHODS This was a retrospective analysis of 75 patients with metastatic G who attended chemotherapy units of the participating centers from January 2007 to June 2010 and underwent FDG PET/CT imaging before the first line chemotherapy. RESULTS Median age in our study group was 62 and 25 of them were women. Median follow-up was 10 months. The patients received either ECF (n=16) or TCF (n=47) or cisplatin and capesitabine (n=12). Both PFS and OS were significantly higher in the ECOG PS 0 and 1 group of patients (n=58) compared to ECOG PS 2 (n=17; 6 vs 4 months, p= 0.032) and 13 vs 8 months, p= 0.002 respectively). 57 patients were adenocarcinoma while signet ring cell type were diagnosed in 18 patients. Median PFS and OS were 5 and 11 months respectively. Median SUV max value (>8.6) for the PT was significantly associated with both PFS (6 vs 4 months, , p= 0.04, HR: 0.45 (0.21-0.98) and OS (16 vs 8 ay, HR: 0.40 [0.17-0.90] p= 0.03). Median highest SUV max value (>7) for distant metastasis (DM) was not correlated with PFS (p= 0.7) and OS (p= 0.1). When the correlation between median SUV max for each metastatic site with PFS and OS were assessed, only liver metastasis had a significant association with OS; (15 vs 7.5 months, HR: 0.18 [0.07-0.46] p= 0.0003). In multivariate analysis ECOG PS (p=0.0015), SUV max of the primary tumor sites (p=0.02) and metastatic liver lesions (p= 0.00001) remained as significant predictors for poor OS. CONCLUSIONS In metastatic gastric cancer PET CT is a useful instrument for predicting poor prognosis. High FDG uptake of primary tumor site and metastatic liver lesions are significantly associated with shorter OS.

A malign mesenchymal tumor (sarcoma) of the pulmonary artery presenting as a form of acute thromboembolism: educational case.

A case of pulmonary artery mesenchymal tumour (sarcoma) presented as an acute pulmonary embolism (APE) with features of a prothrombotic state. A 54-year-old man presented with a sudden onset of progressive dyspnea, haemoptysis and fever. The patient had had 4 h of airplane travel and immobilization. The prothrombotic state of the patient was a significant indicator of a risk of pulmonary thromboembolism. Radiologically, a thrombus formation was found to occlude the proximal part of the right pulmonary artery. Laboratory and radiological investigation showed an elevation of the erythrocyte sedimentation rate (ESR) at 106 mm/h and a progression of the pulmonary arterial thrombus under appropriate anticoagulation treatment. Tumour identification was achieved after pulmonary thromboendarterectomy, which was indicated by the persistence of the patient’s symptoms with the progression of the pulmonary arterial thrombus throughout the vascular bed and a persistent elevation of the ESR (Fig. 1). As far as the present authors know, this is the first case report of malign mesenchymal tumour of pulmonary artery and its coexistence with a prothrombotic state which was positive for both prothrombin-II and the methylene tetrahydrofolate reductase mutation, and also showed an elevated homocystein level, presenting clinically like an APE and progression to the features of chronic thromboembolic disease. Significantly, the survival of our case has been greater than 3.5 years which has not been reported before. It is difficult to differentiate a pulmonary artery sarcoma from a pulmonary embolism especially in the acute stage. Laboratory clues for the diagnosis of pulmonary artery sarcomas in a patient who has the clinical features of acute pulmonary embolism include a highly elevated erythrocyte sedimentation rate and unexplained anaemia (1, 2). Radiological key points for the diagnosis are nodular parenchymal infiltrates on computed tomography, perfusion defects that remain unchanged after treatments such as fibrinolysis (3). Weight loss and fever are symptoms and signs that help to indicate pulmonary artery sarcoma in a patient with a clinical picture of pulmonary embolism. Also, clinical unresponsiveness or partial clinical responsiveness to appropriate anticoagulant therapy should force consideration of a process other than pulmonary embolism (4, 5). However, none of these clues are either totally decisive or specific to differentiate a tumour from a thrombus. Nevertheless, a sensitive method for differentiating a tumour from a thrombus has been suggested. This is known as enhancement of an intraluminal filling defect with gadoliniumdiethylenetriamine pentaacetic acid on magnetic resonance imaging and may be a persistent defect in ventilation perfusion imaging despite adequate anticoagulation therapy (6–11). Pulmonary sarcoma is usually fatal and the longest survival time reported has been 3.5 years in one series (12). To increase the survival time, surgical resection is the best treatment (13, 14). Effects of chemotherapy and radiotherapy are unknown (15, 16). Clues for the correct diagnosis of pulmonary artery sarcoma are difficult to detect but it is important to suspect this possibility and to undertake a proper diagnostic and therapeutic workup, including surgical resection either with or without chemo/radiotherapy to increase survival.

Prognostic value of thymidylate synthase and cox-2 expression in colorectal cancer patients' tumors

3731 Background: Colorectal cancer (CRC) is a major health problem in the world for both men and women due to its high incidence and limited benefit with chemotherapy when the disease recurs. There is a need for progress in assessment of the prognosis of patients and predict who would benefit from treatment. In this study, the value of molecular markers thymidylate synthase (TS) and cox-2 were evaluated as prognostic predictors in patients with stage II and III CRC. PATIENTS AND METHODS We retrospectively analyzed the prognostic value of TS and cox-2 in 49 patients with stage II (n=23) and III (n=26) CRC. They were treated with either surgery alone or surgery followed by adjuvant fluorouracil and leucovorin chemotherapy in Marmara University Hospital, Medical Oncology Department between April 1997 and 2003. A specialized pathologist evaluated these markers using immunohistochemical techniques. Samples were scored as high and low TS and Cox-2 intensity according to their staining properties.Low intensity: No staining or less than 10% of tumoral cells are stained. High intensity: More than 10% of tumoral cells are stained. RESULTS High TS intensity was found in 20.4% of tumor samples with mucinous component and in 64.1% without mucinous component (p=0.01). In patients whose tumor samples had low or high TS intensity 5 year overall survival was 61.5% and 37.5% respectively (p=0.86). Also with low or high cox-2 intensity, overall 5-year survival did not improved (40% vs 70.6%) statistically (p=0.72). More patients with high TS staining tumors relapsed compared to those with low TS staining (p=0.01). CONCLUSIONS Although we did not find a significant relationship between TS, cox-2 and overall survival, statistically significant RFS rates are suggestive of a correlation if these markers are studied in a greater sample size. No significant financial relationships to disclose.