S. Yadav

Extrapulmonary small cell cancer: a Canadian province's experience.

The objective of this study was to determine variables that correlate with the survival of patients with extrapulmonary small cell carcinoma (EPSCC).

Early Discontinuation but Not the Timing of Adjuvant Therapy Affects Survival of Patients With High-Risk Colorectal Cancer: A Population-Based Study

BACKGROUND: Adjuvant therapy results in significant improvement in survival of patients with high-risk colorectal cancer. Little is known about the significance of timing and early discontinuation of adjuvant treatment in such patients. Our study aims to determine the prognostic impact of timing and completion of adjuvant therapy in patients with high-risk colorectal cancer. METHODS: Medical records of patients with stage III colon and stage II/III rectal cancer diagnosed between 1993 and 2000 in the province of Saskatchewan were reviewed. Cox proportional hazards models were used to analyze the impact of timing and completion of adjuvant therapy on survival. RESULTS: Six hundred sixty-three eligible patients with a median age of 66 years were identified. Sixty-five percent patients received adjuvant <56 days after surgery and 79% patients completed planned treatment. Median follow-up was 54.6 months. Five-year disease-free survival and overall survival of patients who received adjuvant therapy <56 days after surgery was 54.6% and 59.5%, respectively, compared with 51.9% and 57.1%, respectively, of patients who received therapy ≥56 days after surgery (P = NS). The five-year disease disease-free survival and overall survival of patients who completed planned treatment was 56.7% and 62.3%, respectively, compared with 42.1% and 45%, respectively, of patients who required early treatment discontinuation (P < .0001). On multivariate analysis, age ≥65 years, T4 tumor, grade 3 cancer, node-positive disease, rectal tumor, and early treatment discontinuation were identified as poor prognostic factors. CONCLUSIONS: Although time to adjuvant therapy following surgical resection did not impact the outcomes, failure to complete planned therapy was associated with adverse prognosis.

Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

Background RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and methods Patients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored. Results At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1–26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0–29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9–1.6]. Median OS was 22.4 months (95% CI 18.6–33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8–33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9–1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences. Conclusions Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals. Clinical Trials number ClinicalTrials.gov identifier, NCT00903175

Largest series of extrapulmonary small cell carcinoma (ESCC): The Saskatchewan Experience

9681 Background: : Although ESCC has been recognized as a rare and distinct clinicopathologic entity, limited data is available about its clinical behavior and outcome. Our experience with ESCC over the past 3 decades is presented here. METHODS Patients with ESCC were identified using Saskatchewan Cancer Registry - Canada, from 1971-2002. Diagnosis was based on immunohistochemistry and/or morphology. Patients with abnormal chest radiology at diagnosis or with well-differentiated neuroendocrine tumor or Merkel cell carcinoma were excluded. Survival was calculated using the Kaplan-Meier method. RESULTS A total of 101 eligible patients with ESCC were identified. Median age was 72 yrs (24-100) and M:F was 1.4:1. Median duration of symptoms prior to definitive diagnosis was 2 months [m] (0.25-40). 51 patients had localized disease and 50 had extensive disease.No significant difference was noted in age, gender distribution, comorbid illness, and incidence of of secondary cancer, however 96% of patients with limited disease (LD) had ECOG performance status of ≤2 compared with 52% in extensive disease (ED) [p=<0.0001]. The primary disease sites were as follows: Breast n=9; gastrointestinal n=20, genitourinary n=18, gynecologic n=11, head & neck n=10, thymus n=2, and unknown primary n=31 . Ninety percent of patients with LD received treatment and 98% of them had an objective response (OR). In contrast, 54% patients with ED received therapy and 44% of them had OR(p<0.0001). Median progression/relapse free survival in responding patients with LD was 20+ m (2-276) compared with 12+ m (2-68) in ED (p<0.0001). All the patients with LD had median OS of 34+ m (0.2-276) compared with 2+ m (0.1-108) in patients with ED (p<0.0001). 5 year survival in patients with LD was 31% compared with 2% in patients with ED. CONCLUSIONS Our results reveal that natural history of ESCC seems comparable to small cell carcinoma of lung and that extent of disease is an important factor predicting survival. No significant financial relationships to disclose.

Extra-Pulmonary Small Cell Cancer: Diagnosis, Treatment, and Prognosis

Small cell carcinoma (SCC) is a high grade epithelial cancer of neuroendocrine origin, which is considered to be a distinct cinicopathological entity. It has been reported in the literature by using various terminologies including oat cell carcinoma, anaplastic carcinoma, small cell undifferentiated carcinoma, undifferentiated carcinoma, microcytoma, reserve cell carcinoma, small cell neuroendocrine carcinoma, Kulchitsky cell carcinoma, and carcinoma with amineprecursor uptake and decarboxylase (APUD) cell differentiation. Small cell carcinoma is, however, the recommended pathological term (Beasley et al., 2005). It is most commonly of bronchogenic origin and accounts for about 20–25% of all pulmonary malignancies (Hoffman et al., 2006). Small cell carcinoma of lung is well recognized for its aggressive clinical behavior and an increased propensity for early metastases. Uncommonly, SCCs can originate in non-pulmonary organs and are collectively known as “extrapulmonary small cell carcinoma” (Remick et al., 1987; Remick and Ruckdeschel, 1992). Extrapulmonary small cell carcinoma (EPSCC) often represents a diagnostic and therapeutic challenge. In 1930, it was first reported in the mediastinal glands without pathologic evidence of primary pulmonary involvement (Duguid and Kennedy, 1930). Since its first description, EPSCC has been reported in virtually all anatomical sites. The primary sites most frequently involved are gynecologic organs, especially the cervix; genitourinary organs, especially the urinary bladder and the prostate gland; the gastrointestinal tract, especially the esophagus, and head and neck region. In addition, SCC has been reported in the breast, thyroid, skin, and thymus gland. If the primary site remains undetected, these tumors are known as small cell carcinoma of unknown primary. Limited data are available regarding its clinical behavior and outcome. The available literature is predominantly based on reviews of published cases or analysis of institutional data (Remick and Ruckdeschel, 1992; Vrouvas and Ash, 1995). In general, EPSCCs resemble their pulmonary counterparts with respect to purported histogenesis, morphology, and behavior. The clinico-pathological features, diagnosis, and general management of EPSCC are reviewed here, followed by a brief description of

A phase II trial of alternating cycles of carboplatin/paclitaxel and carboplatin/gemcitabine for stage IIIB/IV non-small cell lung cancer

19113 Background: Combination chemotherapies have demonstrated response rate (RR) of 30–50% with median survival of only approx 10 months for patients with stage IIIB/ IV NSCLC. Therefore it is important to search for new agents or new combinations of existing regimens. Goldie and Codman model proposed that alternating non-cross resistant combinations would prevent the overgrowth of resistant cancer cells and improve the probability of tumor control. We conducted a phase II study at Saskatoon Cancer Ctr, (Canada) to determine clinical response of Carboplatin/Paclitaxel (C/P) alternating with Carboplatin/Gemcitabine (C/G) for advanced NSCLC. Methods: Patients with chemotherapy naive Stage IIIB or IV NSCLC, ECOG PS ≤2, with measurable or evaluable disease and no known CNS metastases were eligible. Chemotherapy consisted of Paclitaxel (175 mg/m2) and Carboplatin (AUC=5) day 1 alternating with Carboplatin (AUC=5) day 1 and Gemcitabine 1000 mg/m2 days 1 and 8 every three weeks for a total of six cycles. Primar...

Long term outcomes in malignant hemangiopericytoma

9072 Background: Malignant hemangiopericytoma (MH) is a rare entity, arising from the capillary pericyte. Limited data is available regarding its clinical behavior and outcome. We present a series of patients with long term follow up period. Methods: Clinical characteristics, pathologic data and treatment of 14 patients diagnosed with MH between 1972 and 1992, at our centre, were reviewed retrospectively. All cases were biopsy proven. Survival was determined by using Kaplan-Meier curve. Results: The median age was 49 yrs. (range 34 - 74) and male: female ratio was 1:6. The primary disease sites were as follows: intracranial meningeal 5 (35.7%), extremities 3 (21.4%), uterus 3 (21.4%), metastatic 2 (14.3%), sinonasal 1 (7.1%). Thirteen patients had complete surgical resection of tumor at initial presentation. Two patients got post operative RT. No patient got adjuvant chemotherapy. Two patients got chemotherapy on disease recurrence. Median survival was 14 years. Out of 12 patients with localized disease, ...