Kamal Haider

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).

Should noncurative resection of the primary tumour be performed in patients with stage IV colorectal cancer? A systematic review and meta-analysis

PURPOSE Surgical resection of the primary tumour in patients with advanced colorectal cancer (crc) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (qol). METHODS Reports in the central, medline, and embase databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle-Ottawa Scale. Data were collected and synthesized per protocol. RESULTS From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10-30.7 months) in the resection group and 11.4 months (range: 3-22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (ci): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% ci: 0% to 9.7%) and 25.9% (95%ci: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% ci: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 ci: 15.4% to 39.9%). No study provided qol data. CONCLUSIONS Although this review supports primary tumour resection in advanced crc, the results have significant biases. Randomized trials are warranted to confirm the findings.

Survival impact of surgical resection of primary tumor in patients with stage IV colorectal cancer: Results from a large population‐based cohort study

Currently, there is very low‐quality evidence available regarding benefit of surgical resection of the primary tumor (SRPT), in patients with stage IV colorectal cancer (CRC). In the absence of randomization, the reported benefit may reflect selection of younger and healthier patients with good performance status. A large population‐based cohort study was undertaken to determine the survival benefit of SRPT in advanced CRC by eliminating various biases reported in the literature.

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.

Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience

BACKGROUND Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between ≥ 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease.

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

Background: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies. We previously have shown that SRPT, independent of chemotherapy and performance status, improves survival of stage IV CRC patients. The current study aims to validate our findings in patients with stage IV CRC who were diagnosed during the period of modern chemotherapy. Methods: A cohort of 569 patients with stage IV CRC diagnosed during 2006-2010 in the province of Saskatchewan was evaluated. Cox regression model was used for the adjustment of prognostic variables. Results: Median age was 69 years (59-95) and M: F was 1.4:1. Fifty-seven percent received chemotherapy, 91.4% received FOLFIRI or FOLFOX & 67% received a biologic agent. Median overall survival (OS) of patients who underwent SRPT and received chemotherapy was 27 months compared with 14 months of the non-resection group (p<0.0001). Median OS of patients who received all active agents and had SRPT was 39 months (95%CI: 25.1-52.9). On multivariate analysis, SRPT, hazard ratio (HR):0.44 (95%CI: 0.35-0.56), use of chemotherapy, HR: 0.33 (95%CI: 0.26-0.43), metastasectomy, HR: 0.43 (95%CI: 0.31-0.58), second line therapy, HR: 0.50 (95%CI: 0.35-0.70), and third line therapy, HR: 0.58 (95%CI: 0.41-0.83) were correlated with superior survival. Conclusions: This study confirms our findings and supports a favorable association between SRPT and survival in patients with stage IV CRC who are treated with modern therapy.

Red blood cell transfusion and outcome in cancer

Oncology services utilize about 15% of the blood transfusion resources in the USA. Red blood cell transfusion is performed immediately before, during or after major surgery to compensate for blood loss and hemodilution. However, a lack of evidence-based guidelines leads to variable transfusion practices among clinicians. The benefits of transfusing blood products are obvious in life-threatening low blood cell counts or bleeding, but it is becoming apparent that deliberate blood transfusion in some cancer patients can trigger negative clinical impacts. This review attempts to provide an overview of the impact of red blood cell transfusion in patients suffering from various types of oncologic pathologies.

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.

The Management of the Primary Tumor in Patients with Metastatic Colorectal Cancer

Over the past decade, the role of surgery in stage IV colorectal cancer (CRC) has evolved, yet the optimal surgical management of the primary tumor in patients with metastatic CRC that is not amenable to curative resection is unknown. A high rate of surgical resection of the primary tumor has been reported in patients with unresectable metastatic disease. Resection of the primary tumor in patients with metastatic CRC is often performed to deal with presenting primary tumor symptoms and or to prevent future primary tumor complications. Nevertheless, with access to novel agents and their efficacy in the primary tumor as well as lack of major complications related to an intact primary tumor, surgery is less commonly performed today. Although the data regarding survival advantages of resection of the primary tumor are inconsistent, overall the evidence suggests potential survival benefit of removal of the primary tumor in patients with both symptomatic and asymptomatic primary tumors even with access to more effective combination chemotherapy. However, the published literature favoring surgery mostly comprises retrospective observational studies. Consequently, the survival benefit related to surgery has been attributed to selection bias, and in the absence of randomized controlled trial no definite conclusion can be drawn. Current‐ ly, two randomized controlled trials are enrolling patients to answer this important question in the management of metastatic CRC.

Prognostic significance of regional lymph nodes status in stage IV colorectal cancer.

721 Background: Lymph node involvement is one of the most important prognostic variables in early stage CRC and an indication for adjuvant therapy. However, the prognostic significance of regional nodal metastases and the ratio of metastatic to examined lymph nodes (LNR), in stage IV CRC remain unknown. The current study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC who undergo primary tumor resection (PTR). Methods: Retrospective cohort study involving patients with synchronous metastatic CRC diagnosed in Saskatchewan, during 1992-2010 and underwent PTR. Cox Proportional multivariate analyses were performed to determine prognostic significance of nodal status and LNR. Results: 2,294 patients were diagnosed with synchronous metastatic CRC during the study period. Of those 1257 underwent PTR, 148 patients did not have information about nodal status and were excluded. Median age of 1109 eligible patients was 70 yrs (22-98) and M:F was 1.2:1. 26% patients had r...