Cost-Effectiveness of Surveillance after Metastasectomy of Stage IV Colorectal Cancer.

Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. METHODS: Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. RESULTS: Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08-0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33-0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33-0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38-1.02, p = 0.06). CONCLUSIONS: In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Patient and family financial burden associated with cancer treatment in Canada: a national study.

GOAL: To determine patient-reported financial and family burden associated with treatment of cancer in the previous 28 days across Canada. METHODS: A self-administered questionnaire (P-SAFE v7.2.4) was completed by 901 patients with cancer from twenty cancer centres nationally (344 breast, 183 colorectal, 158 lung, 216 prostate) measuring direct and indirect costs related to cancer treatment and foregone care. Monthly self-reported out-of-pocket-costs (OOPCs) included drugs, homecare, homemaking, complementary/ alternative medicines, vitamins/supplements, family care, accommodations, devices, and "other" costs. Travel and parking costs were captured separately. Patients indicated if OOPC, travel, parking, and lost income were a financial burden. RESULTS: Mean 28-day OOPCs were CA$518 (US Purchase Price Parity [PPP] $416), plus CA$179 (US PPP $144) for travel and CA$84 (US PPP $67) for parking. Patients self-reporting high financial burden had total OOPCs (33%), of CA$961 (US PPP $772), while low-burden participants (66%) had OOPCs of CA$300 (US PPP $241). "Worst burden" respondents spent a mean of 50.7% of their monthly income on OOPCs (median 20.8%). Among the 29.4% who took time off work, patients averaged 18.0 days off. Among the 26.0% of patients whose caregivers took time off work, caregivers averaged 11.5 days off. Lastly, 41% of all patients had to reduce spending. Fifty-two per cent of those who reduced spending were families earning < CA$50,000/year. CONCLUSIONS: In our Canadian sample, high levels of financial burden exist for 33% of patients, and the severity of burden is higher for those with lower household incomes.

Effect of sorafenib starting dose and dose intensity on survival in patients with hepatocellular carcinoma: Results from a Canadian Multicenter Database.

BACKGROUND: Sorafenib has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC), however, full dose can be difficult to tolerate. The aim of this study was to determine whether sorafenib starting dose and mean dose intensity affect survival. METHODS: Patients treated with sorafenib for HCC from January 2008 to July 2016 in several Canadian provinces were included and retrospectively analyzed. The primary end point was overall survival (OS) of patients starting on sorafenib full dose compared to reduced dose. Secondary analysis compared OS with different mean dose-intensity groups. Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. A propensity score analysis was performed to account for treatment bias and confounding. RESULTS: Of 681 patients included, sorafenib was started at full dose in 289 patients (42%). Median survival for starting full and reduced dose was 9.4 months and 8.9 months (P = .15) respectively. After propensity score matching and adjusting for potential confounders there was still no difference in survival (HR 0.8, 95% CI, 0.61-1.06, P = .12). Almost half of the patients (45%) received a dose intensity < 50%. Median survival for mean dose intensity > 75%, 50%-75%, and < 50% were 9.5 months, 12.9 months, and 7.1 months (P = .005) respectively. In multivariable models, starting dose(HR 1.16, 95% CI 0.93-1.44, P = .180) and mean dose intensity were not associated with survival. CONCLUSIONS: Starting HCC patients on a reduced dose of sorafenib compared to full dose may not compromise survival. Mean dose-intensity of sorafenib may also not affect survival.

Second-line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real-world eligibility for cabozantinib, regorafenib, and ramucirumab.

BACKGROUND: The CELESTIAL, RESORCE, and REACH-2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0-1) and liver function (Child-Pugh-A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child-Pugh-B7). METHODS: HCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH-2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan-Meier method. RESULTS: A total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial-specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH-2. CONCLUSIONS: A small proportion of real-world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.

Real-World Adherence to Guideline-Recommended Treatment for Small Cell Lung Cancer.

OBJECTIVES: The authors sought to quantify the treatment patterns and outcomes for limited-stage (LS) and extensive-stage (ES) small cell lung cancer (SCLC) in a real-world setting. METHODS: A review was conducted using the Glans-Look Research Database of patients with SCLC managed at a tertiary cancer center in Canada from 2010 to 2016. Adherence was defined as the commencement of planned SCLC treatment. Rate of compliance with the Alberta Health Services, American Society of Clinical Oncology, and National Comprehensive Cancer Network SCLC treatment guidelines was evaluated. Outcomes were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of 404 patients met our inclusion criteria, 31% were LS. The median age at first treatment receipt was 67 years. LS treatment consisted mostly of chemoradiation (62%). Chemoradiation and surgery±adjuvant predicted better survival (median, 32 and 40 mo, respectively) compared with no treatment. ES treatment consisted mostly of chemotherapy (90%). Chemotherapy and thoracic radiotherapy correlated with longer overall survival (13 vs. 9 mo, respectively) compared with chemotherapy alone. Prophylactic cranial irradiation receipt in LS (50%) and ES (20%) predicted favorable survivals than none (LS: hazard ratio, 0.48; 95% CI, 0.29-0.79; ES: hazard ratio, 0.48; 95% CI, 0.33-0.70). Approximately a quarter of relapsed LS and ES had second-line chemotherapy; improved survival with second line was observed only in ES (P<0.01). CONCLUSIONS: This study highlights high rates of guideline-recommended first treatment among the real-world LS and ES patients but it also revealed important outcome differences in relapsed LS and ES patients treated with second-line chemotherapy.

Population-based assessment of the National Comprehensive Cancer Network recommendations for baseline imaging of rectal cancer.

Aim: To examine the performance characteristics of alternative criteria for baseline staging, in a cohort of contemporary rectal cancer patients from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The SEER database (2010-2015) was accessed and patients with rectal cancer plus complete information on clinical T and N stages as well as metastatic sites were evaluated. We examined various performance characteristics of baseline imaging, including specificity, sensitivity, number needed to investigate (NNI), positive predictive value (PPV), negative predictive value and accuracy. Results: A total of 15,836 rectal cancer patients were included. Based on current guidelines that suggest cross-sectional chest and abdominal imaging for all cases of invasive rectal cancer, these recommendations would yield a PPV of 11.9% for the detection of liver metastases and 6.2% for the detection of lung metastases. This would translate to an NNI of 8.4 for liver metastases and an NNI of 16.1 for lung metastases. When patients with T1N0 were excluded from routine imaging, this resulted in a PPV of 6.4% and an NNI of 15.6 to identify one case of lung metastasis. Likewise, this resulted in a PPV of 12.3% and an NNI of 8.0 to detect one case of liver metastasis. Similarly, when patients with either T1N0 or T2N0 were excluded from routine imaging, the PPV and NNI for lung metastases improved to 6.6% and 15.1, respectively, and the PPV and NNI for liver metastases improved to 12.6 and 7.9%, respectively. Conclusion: Our study suggests that the specificity of the current imaging approach for rectal cancer staging is limited and that the omission of chest and abdominal imaging among selected early stage asymptomatic cases may be reasonable to consider.

Association Between Adjuvant Chemotherapy Duration and Survival Among Patients With Stage II and III Colon Cancer: A Systematic Review and Meta-analysis.

Importance: The results from the recent International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration have led some clinicians to adopt shorter durations of adjuvant chemotherapy for patients with stage III colon cancer. The extent to which these findings are supported by other data is unknown. Objective: To conduct a systematic review and meta-analysis of randomized and observational studies investigating the association between the duration of adjuvant chemotherapy and survival among individuals diagnosed as having stage II and III colon cancer (PROSPERO protocol CRD42018108711]). Data Sources: Abstracts published in English between 2003 and 2018 within the MEDLINE, Embase, CENTRAL, and CINAHL databases were reviewed by 2 authors. Also searched were conference proceedings and the indexes of high-impact oncology journals. Study Selection: Studies were excluded if they did not present original data; focused on animal populations, on cancers in sites other than the colon, or on patients with stage 0, I, or IV disease; did not examine a 5-flourouracil-based monotherapy or combination therapy; or did not evaluate the association between treatment duration and survival. The search identified 2341 articles, from which 2 randomized trials and 20 observational studies were included in the meta-analysis. Data Extraction and Synthesis: This study followed the PRISMA and MOOSE reporting guidelines. The risk of bias was assessed by 2 authors using the Cochrane and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tools. The results were synthesized using a random-effects model. Main Outcomes and Measures: The primary and secondary outcomes were overall survival and disease-free survival, respectively. It was hypothesized a priori that 3 months of chemotherapy would be as effective as 6 months of chemotherapy. Results: Twenty-two studies were included in the meta-analysis, representing 43 671 patients. The inclusion of patients with stage II disease or with rectal cancer was identified as a source of heterogeneity. After restricting the analysis to patients with stage III colon cancer, there was no association between the duration of chemotherapy and overall survival among studies involving FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) regimens (hazard ratio [HR], 0.80; 95% CI, 0.58-1.09). Among studies focused exclusively on monotherapy, the standard 6-month regimen relative to a 3-month regimen was associated with improved survival (HR, 0.59; 95% CI, 0.52-0.68). Conclusions and Relevance: Shortened durations of chemotherapy may reduce survival among patients with stage III colon cancer prescribed monotherapy but not a combination regimen.

Population-based assessment of the national comprehensive cancer network recommendations for baseline imaging of hepatocellular carcinoma.

This analysis aims to evaluate the performance characteristics of alternative baseline imaging thresholds in a cohort of hepatocellular carcinoma (HCC) patients from the Surveillance, Epidemiology, and End Results (SEER) database. HCC patients within the SEER database (2010-2015) who had complete information on clinical T and N stages as well as complete information on metastatic sites were eligible for the current study. Various performance characteristics associated with baseline imaging were investigated, including specificity, sensitivity, positive likelihood ratio (LR), negative LR, number needed to investigate (NNI), negative predictive value (NPV), positive predictive value (PPV), and accuracy. A total of 27,201 HCC patients were included. Based on current recommendations that advocate for the use of cross-sectional chest imaging in all newly diagnosed cases of HCC, these recommendations would yield a PPV of 5.0% for the detection of lung metastases. This would translate to an NNI of 20.0. When T1N0 patients were excluded from routine chest or bone imaging, this resulted in a PPV of 6.8% for the identification of lung metastases and an NNI of 14.7. Likewise, this translated to a PPV of 4.6% for the identification of bone metastases and an NNI of 21.7. Similarly, when patients with T1N0 disease and normal alpha-fetoprotein (AFP) were excluded from routine imaging, this resulted in a PPV of 5.6% for the identification of lung metastases and an NNI of 17.8. Also, this translated to a PPV of 3.8% for the identification of bone metastases and an NNI of 26.3. The current study suggests that the omission of routine baseline chest imaging may be considered in selected patients with asymptomatic early-stage HCC and normal AFP.

The Expanding Role of Systemic Therapy in the Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents a global health problem, with the majority of patients presenting at an advanced or incurable stage. The development of effective systemic therapy options for this disease has been challenging because many HCC patients suffer from underlying liver cirrhosis that precludes the safe delivery of systemic therapy. The current review seeks to provide an overview of the current systemic therapeutic approaches for advanced HCC as well as some of the novel management strategies that are currently being evaluated.

Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer.

BACKGROUND: Capecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort. PATIENTS AND METHODS: We identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen. RDI was defined as the total dose received divided by the intended total dose if all cycles were received. RESULTS: FOLFOX was associated with increased mucositis (6.2% vs. 0.7%, P = .0069) and neutropenia (25.9% vs. 8.6%, P < .0001), while CAPOX was associated with increased dose-limiting toxicities (DLTs) (90.7% vs. 80.2%, P = .0055), diarrhea (31.8% vs. 9.0%, P < .0001), and hand-foot syndrome (19.9% vs. 2.1%, P < .0001). Higher median RDI of fluoropyrimidine (93.7% vs. 80.0%, P < .0001) and oxaliplatin (87.2% vs. 76.3%, P < .0001) was noted for patients receiving FOLFOX. Reducing the duration from 6 to 3 months would have prevented 28.7% of FOLFOX and 20.5% of CAPOX patients from ever experiencing a DLT (P = .0008). Overall survival did not differ by regimen (hazard ratio = 0.73; 95% confidence interval 0.45-1.22; P = .24). However, CAPOX was associated with improved disease-free survival (3-year disease-free survival 83.8% vs. 73.4%, P = .022), which remained significant in high-risk (T4 or N2) (P = .039) but not low-risk patients (P = .19). CONCLUSION: CAPOX may be associated with improved disease-free survival despite greater toxicities and lower RDI. Reducing adjuvant chemotherapy duration to 3 months would prevent 26% of patients from ever experiencing a DLT.

Impact of Duration of Neoadjuvant Radiation on Rectal Cancer Survival: A Real World Multi-center Retrospective Cohort Study.

BACKGROUND: The utility of neoadjuvant radiotherapy (nRT) for the treatment of stage II and III rectal cancer is well-established. However, the optimal duration of nRT in this setting remains controversial. Using a population-based cohort of patients with stage II and III rectal cancer (RC) treated with curative intent, our aims were to (1) examine the patterns of nRT use and (2) explore the relationship between different nRT schedules and survival in the real-world setting. METHODS: This is a multi-center retrospective cohort study based on population-based data from 5 regional comprehensive cancer centers in British Columbia, Canada. We analyzed patients diagnosed with clinical stage II or III RC from 2006 to 2010 and treated with either short-course (SC) or long-course (LC) nRT prior to curative intent surgery. Logistic regression models were constructed to determine the factors associated with the course of nRT delivered to patients. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between nRT schedule and overall (OS), disease-free (DFS), local recurrence-free (LRFS), and distant recurrence-free survival (DRFS). RESULTS: We identified 427 patients: the median age was 65 years (range, 31 to 94 years), 67% were men, 87% had T3 or T4 tumors, and 74% had N1 or N2 disease. Among them, 241 (56%) received SC and 186 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to undergo LC (odds ratio [OR], 5.08; 95% confidence interval [CI], 2.51-11.22; P < .0001 and OR, 8.35; 95% CI, 3.35-22.39; P < .0001, respectively), whereas older age patients were less likely to receive LC (OR, 0.95; 95% CI, 0.94-0.98; P < .0001). In Kaplan-Meier analysis, there were no significant differences observed in OS, DFS, LRFS, and DRFS between SC and LC. Likewise, multivariate analyses demonstrated that OS (hazard ratio [HR], 0.91; 95% CI, 0.61-1.37; P = .66), DFS (HR, 1.06; 95% CI, 0.68-1.64; P = .80), LRFS (HR, 0.79; 95% CI, 0.39-1.57; P = .50) and DRFS (HR, 0.99; 95% CI, 0.60-1.61; P = .95) were similar regardless of nRT schedules. Additional baseline clinical and tumor characteristics did not influence outcomes (all P > .05). CONCLUSION: Appropriate preoperative selection of SC versus LC nRT for locally advanced RC based on patient and tumor characteristics was not associated with differences in survival outcomes in the real-world setting.

Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.

Population-Based Cost-Minimization Analysis of CAPOX Versus Modified FOLFOX6 in the Adjuvant Treatment of Stage III Colon Cancer.

BACKGROUND: Evidence suggests that CAPOX (capecitabine and oxaliplatin) has efficacy similar to 5-fluorouracil and oxaliplatin (mFOLFOX6) in the adjuvant treatment of colon cancer. CAPOX is partly administered orally and associated with a 3-week rather than a 2-week treatment cycle. A population-based cost-minimization analysis was conducted from the health care payer and societal perspectives to evaluate the potential cost savings of replacing mFOLFOX6 with CAPOX. METHODS: We applied treatment and toxicity data from phase III trials of CAPOX and FOLFOX-based regimens to the adjuvant colon cancer population in British Columbia, Canada. In this cost-minimization analysis we compared the total costs associated with chemotherapy medications, drug administration and delivery, hospital and clinic visits, treatment-related toxicities, and central venous access devices. Costs to patients in terms of lost time and travel were also considered. It was assumed that patients would receive either 8 cycles of CAPOX or 12 cycles of mFOLFOX6. RESULTS: From the payer perspective, the use of CAPOX resulted in cost savings of $5339 CAD per patient compared with the use of mFOLFOX6. From a societal perspective, CAPOX was also associated with savings of $6080 CAD per patient. The greatest cost savings with CAPOX were attributed to fewer visits for chemotherapy treatment and decreased central venous access device usage. CAPOX was also associated with reduced loss of time and decreased travel for patients because of the requirement of fewer clinic visits. CONCLUSIONS: Replacement of mFOLFOX6 with CAPOX in the adjuvant treatment of colon cancer might be associated with potential cost savings from the payer and societal perspectives.

Reasons for Underuse of Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer.

BACKGROUND: Undertreatment has been frequently reported in the elderly cancer patient population. For this reason, we aimed to characterize adjuvant chemotherapy (AC) use among elderly patients (EPs) with stage III colon cancer (CC) and to identify potential reasons for undertreatment. PATIENTS AND METHODS: Patients diagnosed with stage III CC between 2008 and 2010 were included in this review. Multivariate Cox regression models were constructed to evaluate the associations between AC and cancer-specific, disease-free, and overall survival and to determine whether these were modified by age. RESULTS: We identified 810 patients: 423 (52%) men, 423 (52%) young patients (YPs), and 603 (74%) received AC. Compared with YPs, EPs were less likely to receive AC (57% vs. 91%; P < .01), particularly 5-fluorouracil and oxaliplatin (FOLFOX) (32% vs. 74%, P < .01). Frequent reasons for nontreatment included age, comorbidities, and perceived minimal benefit from AC. When AC was given, EPs had similar rates of treatment discontinuations (34% vs. 26%; P > .05) and dose reductions (63% vs. 61%; P > .05) as YPs. Reasons for treatment interruptions included side effects, progressive disease, and patient choice. Receipt of either FOLFOX or capecitabine was correlated with improved cancer-specific survival, disease-free survival, and overall survival compared with surgery alone; this effect was not modified by age. CONCLUSION: Elderly patients with stage III CC frequently received either no AC or capecitabine monotherapy because of advanced age and comorbidities. The effect of AC on survival was similar across age groups, with comparable side effects and rates of treatment modifications. AC should not be withheld because of advanced age alone.

Effect of Adjuvant FOLFOX Chemotherapy Duration on Outcomes of Patients With Stage III Colon Cancer.

BACKGROUND: Studies have demonstrated that patients with stage III colon cancer who receive adjuvant FOLFOX (5-fluorouracil and oxaliplatin) chemotherapy experience an improved disease-free (DFS) and overall survival (OS). However, the magnitude of benefit among patients who discontinue FOLFOX early is not well known. We sought to examine the rate of FOLFOX treatment completion, determine the factors associated with adherence, and explore the relationship between duration of FOLFOX treatment and survival. PATIENTS AND METHODS: We analyzed patients diagnosed with stage III colon cancer from 2006 to 2010 and initiated at least 1 cycle of adjuvant FOLFOX at any 1 of 5 regional cancer centers in British Columbia. Logistic regression models were constructed to determine the clinical factors associated with treatment completion, which was defined as receipt of ≥ 10 cycles of FOLFOX. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between early FOLFOX discontinuation and DFS and OS. RESULTS: We identified 616 patients: median age of 62 years (range, 26-80), 321 (52%) men, 536 (87%) with T3/4 tumors, and 245 (40%) with N2 disease. Among them, 183 (30%) received < 10 and 433 (70%) received ≥ 10 cycles. Adjusting for covariates, female sex and the absence of obstruction or perforation were each associated with receiving ≥ 10 cycles of FOLFOX (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.12-2.32; P = .01 and OR, 1.82; 95% CI, 1.08-3.05; P = .02, respectively). In multivariate analyses, early discontinuation of FOLFOX did not affect DFS or OS (hazard ratio [HR], 1.16; 95% CI, 0.82-1.63; P = .40 and HR, 1.07; 95% CI, 0.70-1.61; P = .76, respectively). CONCLUSION: Early discontinuation of FOLFOX was not associated with differences in survival outcomes, lending support to clinical trials that are under way to evaluate the efficacy of shorter durations of therapy.

Effect of delay in adjuvant oxaliplatin-based chemotherapy for stage III colon cancer.

BACKGROUND: Less than 8 weeks has been recommended as the optimal time to initiate AC based on 2 meta-analyses that suggested worse survival with delayed AC. However, neither study included patients treated with an oxaliplatin-based chemotherapy. We aimed to investigate the effect of delay in initiating oxaliplatin-based chemotherapy on RFS and CSS for stage III colon cancer. PATIENTS AND METHODS: Records of patients who initiated oxaliplatin-based AC for stage III colon cancer between 2006 and 2011 at the British Columbia Cancer Agency were retrospectively reviewed. Cox proportional models were used to analyze the effect of time to AC (TTAC) on RFS and CSS. TTAC was categorized into ≤ 8 weeks (G1) and > 8 weeks (G2). RESULTS: Six hundred thirty-five patients were included (G1, n = 291; G2, n = 344). Median time from surgery to initiation of AC was 8.3 weeks. At a median follow-up of 57.9 months, 176 patients (27.7%) had disease recurrence and 118 (18.6%) had died. Five-year RFS was 70.9% (95% confidence interval [CI], 65.2-76.5) for G1 and 72.1% (95% CI, 67.2-77) for G2. Five-year CSS was 82% for G1 (95% CI, 87.09-76.91) and 82.8% for G2 (95% CI, 78.30-87.30). On multivariate analysis, delayed TTAC did not have prognostic significance on either RFS (hazard ratio [HR], 1.08; P = .609) or CSS (HR, 1.02; P = .893). CONCLUSION: In our population-based study, TTAC after stage III colon cancer resection did not have an effect on RFS or CSS. Contrary to most of the existing data, which are primarily based on 5-fluorouracil-based AC, delay of oxaliplatin-based AC beyond 8 weeks did not appear to be associated with inferior outcomes.

The predictive and prognostic value of sex in early-stage colon cancer: a pooled analysis of 33,345 patients from the ACCENT database.

PURPOSE: To compare long-term outcomes between men and women in a large cohort of clinical trial participants with early-stage colon cancer, specifically by examining whether the prognostic effect of sex varies based on age, stage of disease, and type of adjuvant therapy received. METHODS: A pooled analysis of individual patient data from 33,345 patients with colon cancer enrolled in 24 phase III studies of various adjuvant systemic therapies was conducted. Chemotherapy consisted of (1) fluorouracil (5-FU), (2) 5-FU variations, (3) 5-FU plus oxaliplatin, (4) 5-FU plus irinotecan, or (5) oral fluoropyrimidine-based regimens. The primary endpoint was disease-free survival; secondary endpoints included overall survival and time to recurrence. Stratified Cox models were used to assess the effect of sex on outcomes. Multivariate models were used to assess adjusted effects and to explore the interaction among sex and other factors. RESULTS: A total of 18,244 (55%) men and 15,101 (45%) women were included. In the entire cohort, the median age was 61 years; 91% (24,868) were white; 31% (10,347) and 69% (22,964) had stage I/II and III disease, respectively. Overall, men had inferior prognoses when compared with women for time to recurrence (hazard ratio [HR] 1.05 [95% CI, 1.01-1.09]) and other endpoints after adjusting for age, stage, and treatment. Sex was not a predictive factor of treatment efficacy (P for interaction between sex and treatment when adjusting for age and stage were .40, .67, and .77 for disease-free survival, overall survival, and time to recurrence, respectively). In exploratory analyses, worse outcomes in men were more prominent in the older patients when adjusting for stage and treatment (HR 1.08 in age ≤ 65 years vs. HR 1.18 in age > 65 years; interaction P = .016 for disease-free survival). The stage of disease and type of adjuvant regimen did not modify the prognostic value of sex. CONCLUSIONS: Sex is a modest independent prognostic marker for patients with early-stage colon cancer, particularly in older patients.