Kelly Brennan

Association Between Prognosis and Tumor Laterality in Early-Stage Colon Cancer

Importance Recent data have suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumors. However, the literature on the prognostic value of tumor laterality is conflicting. Objective To explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer. Design, Setting, and Participants This investigation was a population-based retrospective cohort study of patients with early-stage colon cancer from the province of Ontario, Canada. Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer who underwent resection between January 1, 2002, and December 31, 2008. The date of the final analysis was October 20, 2016. The study population included a 25% random sample of all patients with resected stage I to III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure, or transverse colon. Left-sided colon cancer was defined as any tumor arising in the splenic flexure, descending colon, sigmoid colon, or rectosigmoid colon. Main Outcomes and Measures Overall survival (OS) and cancer-specific survival (CSS) measured from the time of resection. Results This study identified 6365 patients with early-stage colon cancer (48.7% [3098 of 6365] female). Their median age was 72 years, and 51.7% (3291 of 6365) had right-sided disease. Stage distribution was 18.3% (1163 of 6365) stage I, 38.4% (2446 of 6365) stage II, and 43.3% (2756 of 6365) stage III. Patients with right-sided colon cancer were more likely to be older (median age, 73 vs 70 years; P < .001) and female (54.4% [1790 of 3291] vs 42.6% [1308 of 3074], P < .001) and have greater comorbidity. Right-sided cancers were more likely to be T4 (19.2% [631 of 3291] vs 15.9% [490 of 3074], P < .001) and poorly differentiated (21.1% [695 of 3291] vs 9.6% [295 of 3074], P < .001) but less likely to be node positive (42.0% [1383 of 3291] vs 44.7% [1373 of 3074], P = .03) compared with left-sided disease. In adjusted analyses, there was no difference in long-term survival for right-sided compared with left-sided colon cancer: the hazard ratios were 1.00 (95% CI, 0.92-1.08) for OS and 1.00 (95% CI, 0.91-1.10) for CSS. These results were consistent when the survival analyses were restricted to stage III disease: the hazard ratios were 1.03 (95% CI, 0.93-1.14) for OS and 1.10 (95% CI, 0.97-1.24) for CSS. Conclusions and Relevance In this population-based cohort of early-stage resected colon cancer, disease laterality was not associated with long-term OS or CSS.

Radical Treatment of the Primary Tumor in Metastatic Bladder Cancer: Potentially Dangerous Findings From Observational Data

Population-based observational studies allow investigators to evaluate the adoption of new therapies and to determine whether benefits seen in clinical trials are realized in the real world. These studies also provide rich insights into factors that affect access and quality of cancer care in the general population. However, except in a few specific circumstances, real-world data are much less useful in establishing treatment efficacy. Studies that compare outcomes between nonrandomized groups of patients are fundamentally problematic because the patients may also differ with respect to other prognostic factors. This is just as true for modern population-based studies of electronic records as it was for the traditional nonrandomized institution-based reviews of paper charts that were popular 50 years ago before the widespread adoption of hierarchies of evidence raised awareness of the relative weakness of observational study designs. Population-based studies may have greater external validity than institution-based studies, but there is no reason to believe they have any greater internal validity; both are therefore classified as level-3 evidence in Sackett’s original hierarchy.

Management of stage III colon cancer in the elderly: Practice patterns and outcomes in the general population

Clinical trials have established surgical resection and adjuvant chemotherapy (ACT) as the standard management for stage III colon cancer; however, the extent to which these results apply to elderly patients in routine practice is unclear. This article describes the management and outcomes of elderly patients with stage III colon cancer.

Perioperative chemotherapy for bladder cancer in the general population: Are practice patterns finally changing?

BACKGROUND Uptake of perioperative chemotherapy for muscle-invasive bladder cancer (MIBC) has been historically poor. We describe contemporary use of neoadjuvant (NACT) and adjuvant chemotherapy (ACT) as well as medical oncology (MO) referral patterns in routine practice. METHODS Electronic treatment records were linked to the population-based Ontario Cancer Registry to identify all MIBC patients treated with cystectomy in Ontario 1994 to 2013. Physician billing records were used to identify consultation with MO. Practice patterns in the contemporary era (2009-2013) are compared with data from 1994 to 2008. RESULTS A total of 5,582 patients had cystectomy for MIBC. Use of NACT increased from 4% in 1994 to 2008 to 19% in 2009 to 2013 (P<0.001); rates continued to rise in the most recent era from 12% in 2009 to 27% in 2013 (P<0.001). ACT was delivered to 20% of patients in 2009 to 2013 (19% in 1994-2008, P = 0.875). Use of any chemotherapy (NACT or ACT) in 2009 to 2013 was 35% compared to 23% in 1994 to 2008 (P<0.001). Preoperative referral rates during 2009 to 2013 to MO were greater than 1994 to 2008 (32% vs. 11%, P<0.001); referral rates continued to increase in recent years from 21% in 2009 to 44% in 2013 (P<0.001). The proportion of referred patients ultimately treated with NACT increased substantially; from 32% in 1994 to 1998 to 54% in 2009 to 2013 (P<0.001). CONCLUSIONS After many years of practice lagging behind evidence, use of NACT in the general population has increased substantially. Our results suggest that increased uptake has been driven by greater preoperative referral to MO as well as greater propensity of MOs to treat referred patients.

Peri-operative blood transfusion for resected colon cancer: Practice patterns and outcomes in a population-based study

BACKGROUND & OBJECTIVES Literature suggests that peri-operative blood transfusion among patients with resected colon cancer may be associated with inferior long-term survival. The study objective was to characterize this association in our population. METHODS This is a retrospective cohort study using the population-based Ontario Cancer Registry (2002-2008). Pathology reports were obtained for a 25% random sample of all cases and constituted the study population. Log binomial regression was used to identify factors associated with transfusion. Cox proportional hazards model explored the association between transfusion and cancer specific survival (CSS) and overall survival (OS). RESULTS The study population included 7198 patients: 18% stage I, 36% stage II, 40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused. Factors independently associated with transfusion included advanced age (p<0.001), female sex (p<0.001), greater comorbidity (p<0.001), more advanced disease (p<0.001) and open surgical resection (p<0.001). Transfusion was associated with inferior CSS (HR 1.51, 95% CI 1.38-1.65) and OS (HR 1.52, 95% CI 1.41-1.63), after adjusting for important confounders. CONCLUSIONS Peri-operative transfusion rates among patients with colon cancer have decreased over time. Transfusion is associated with inferior long-term CSS and OS.

Concurrent chemoradiotherapy for bladder cancer: Practice patterns and outcomes in the general population

BACKGROUND Clinical trials have shown that chemoradiotherapy (CRT) improves survival compared to radiation therapy (RT) alone in muscle-invasive bladder cancer. We describe uptake of CRT and comparative effectiveness in routine practice. METHODS Electronic treatment records were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with curative-intent RT in 1999-2013. Modified Poisson regression was used to analyze factors associated with use of CRT. Cox model and propensity score analyses were used to explore factors associated with cancer-specific (CSS) and overall survival (OS). RESULTS 1192 patients underwent RT during 1999-2013; median age was 79. Use of CRT increased over time: 36% (124/341) in 1999-2003, 38% (153/399) in 2004-2008, 48% (217/452) in 2009-2013 (p = 0.001). Drug details were available for 82% (402/493) of CRT cases; the most common regimens were single-agent Cisplatin (57%, 230/402), single-agent Carboplatin (31%, 125/402) and 5-FU/Mitomycin (4%, 17/402). Factors associated with CRT include younger age (p < 0.001), lower comorbidity (p = 0.001), and geographic region (range 14-89%, p < 0.001). Five year CSS and OS among CRT cases were 45% (95%CI 39-51%) and 35% (95%CI 30-40%). On adjusted analyses CRT was associated with superior survival compared to RT (CSS HR 0.70, 95%CI 0.59-0.84; OS HR 0.74, 95%CI 0.64-0.85); results were consistent on propensity score analysis. There was significant improvement in survival of all RT-treated cases (irrespective or chemotherapy delivery) in 2009-2013 compared to 1999-2003 (CSS HR 0.77, 95%CI 0.61-0.97; OS HR 0.82, 95%CI 0.69-0.98). CONCLUSION CRT is associated with superior survival compared to RT alone and its uptake corresponded to improved survival among all RT-treated cases in the general population. Uptake of CRT varies widely by geographic region.

Delivery of Pediatric Cancer Care in Mexico: A National Survey

Purpose Limited data describe the delivery of pediatric cancer care in Mexico. We report a nationwide survey of pediatric cancer units. Methods An electronic survey was distributed to 74 pediatric cancer units in Mexico to describe case volumes; organization of care; and availability of medical/surgical specialists, supportive care, complex therapies, and diagnostic services. Centers were classified as low (< 30 new patients/year), medium (30 to 59/year) and high (≥ 60/year). Results Sixty-two centers completed the survey (response rate, 84%). The median annual new case volume per center was 50 (interquartile range [IQR], 23 to 81). Thirty-four percent (n = 21), 26% (n = 16), and 40% (n = 25) of units were low-, medium-, and high-volume centers, respectively. Treatment units reported a median of two pediatric oncologists (IQR, 2) and one pediatric hematologist (IQR, 1 to 2). Availability of medical and surgical subspecialists varied by center size, with substantially more specialist support at higher-volume centers (P < .01). Multidisciplinary tumor boards are available at 29% (six of 21), 56% (nine of 16), and 76% (19 of 25) of low- to high-volume centers, respectively (P = .005). Radiation and palliative care services are available at 42% (n = 26) and 63% (n = 36) of all centers, which did not vary by center volume. Educational support for hospitalized children and school reintegration programs are available at 56% (n = 36) and 58% (n = 36) of centers, respectively. One third (38% [n = 23]) of centers reported that at least one half of patients were lost to follow-up during the transition from pediatric to adult programs. Conclusion A large variation exists in annual case volumes across Mexican pediatric cancer centers. Additional efforts to increase access to multidisciplinary, supportive, and palliative care across all pediatric cancer units in Mexico are required.

Disease Characteristics, Clinical Management, and Outcomes of Young Patients With Colon Cancer: A Population-based Study

Micro‐Abstract The present population‐based study explored the disease characteristics, treatment, and outcomes of young patients (age < 40 years) with resected colon cancer. Younger patients were more likely than were older patients to have advanced‐stage disease. They were also more likely to receive adjuvant chemotherapy. Despite the more aggressive biology, the survival of young patients was superior to that of older patients with colon cancer. Introduction The incidence of colorectal cancer in young patients has been increasing. We evaluated whether the disease characteristics, management, and outcomes of patients with colon cancer differ among patients aged ≤ 40 years compared with those of older patients. Materials and Methods Using the Ontario Cancer Registry, all cases of colon cancer (stage I, II, III) treated with surgery in Ontario from 2002 to 2008 were identified. The electronic medical records of treatment were used to identify the use of surgery and adjuvant chemotherapy (ACT). The pathology reports were obtained for a random 25% sample of all cases. A Cox model was used to identify the factors associated with overall (OS) and cancer‐specific survival (CSS). Results The study population included 6775 patients. The age distribution was 2%, 5%, 14%, and 79% for patients aged ≤ 40, 41 to 50, 51 to 60, and > 60 years, respectively. Compared with patients aged > 60 years, younger patients (age ≤ 40 years) were more likely to have lymphovascular invasion (35% vs. 27%; P = .005), T3/T4 tumors (88% vs. 79%; P = .005) and lymph node–positive disease (58% vs. 41%; P < .001). The stage distribution varied by age: stage I, 8% versus 19%; stage II, 34% versus 40%; and stage III, 58% versus 41% for those aged ≤ 40 years versus those aged > 60 years, respectively (P < .001). ACT was delivered more often to patients aged ≤ 40 years than to those aged > 60 years for stage II (50% vs. 13%; P < .001) and stage III (≥ 92% vs. 57%; P < .001) disease. The adjusted OS (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.21‐0.49) and CSS (HR, 0.41; 95% CI, 0.26‐0.64) were superior for patients aged ≤ 40 years compared with the OS and CSS for those aged > 60 years. Conclusion Young patients with colon cancer have more aggressive and advanced disease but improved outcomes compared with older patients.

Temporal trends in management and outcomes of testicular cancer: A population-based study: Testicular Cancer in Routine Practice

Treatment guidelines for early‐stage testicular cancer have increasingly recommended de‐escalation of therapy with surveillance strategies. This study was designed to describe temporal trends in routine clinical practice and to determine whether de‐escalation of therapy is associated with inferior survival in the general population.