Impact of new cancer therapies on outpatient treatment delivery for colorectal cancer: A population-based study.

We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase. Mean, total and adjusted total duration for CVs increased for P1-5. CVs increased in P1-5, and in P1-4 when adjusted by treatment length. Adjusted and unadjusted OIs decreased in P1 coinciding with the introduction of an oral treatment option, but increased in P2-5. Mean OI duration increased in P1-5, while total and adjusted total decreased in P1 and increased in P2-5. OPs increased in P2-4, but were unchanged in P1 and P5. Multi-fold increases in resources and time required per patient were also observed, which have significant implications for demand projections in cancer care planning and delivery. In conclusion, patients required more visits in almost all treatment phases, visits on average took longer and patients were in treatment for longer periods of time.

Prognostic Factors for Locoregional Recurrence in Neuroendocrine Tumors of the Rectum.

BACKGROUND: Optimal management of rectal neuroendocrine tumors is not yet well defined. Various pathologic factors, particularly tumor size, have been proposed as prognostic markers. OBJECTIVE: We characterized sequential patients diagnosed with rectal neuroendocrine tumors in a population-based setting to determine whether tumor size and other pathologic markers could be useful in guiding locoregional management. DESIGN: This study is a retrospective analysis of data from the British Columbia provincial cancer registry. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: Sequential patients diagnosed with rectal neuroendocrine tumors between 1999 and 2011 were identified. Neuroendocrine tumors were classified as G1 and G2 tumors with a Ki-67 ≤20% and/or mitotic count ≤20 per high-power field. MAIN OUTCOME MEASURES: Baseline clinicopathologic data including TNM staging, depth of invasion, tumor size, treatment modalities, and outcomes including survival data were measured. RESULTS: Of 91 rectal neuroendocrine tumors, the median patient age was 58 years, and 35 were men. Median tumor size was 6 mm. Median length of follow-up was 58.1 months, with 3 patients presenting with stage IV disease. Treatment included local ablation (n = 5), local excision (n = 79), surgical resection (n = 4), and pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17 cases. Local relapse occurred in 8 cases and 1 relapse to bone 13 months after T3N1 tumor resection. Univariate analysis demonstrated an association between local relapse and Ki-67, mitotic count, grade, and lymphovascular invasion (p < 0.01). Larger tumor size was associated with decreased disease-free survival. LIMITATIONS: Sample size was 91 patients in the whole provincial population over a 13-year time period because of the low incidence of rectal neuroendocrine tumors. CONCLUSIONS: In this population-based cohort, rectal neuroendocrine tumors generally presented with small, early tumors and were treated with local excision or surgical resection without pelvic radiation. Pathologic markers play a role in risk stratification and prognostication. See Video Abstract at http://links.lww.com/DCR/A514.

The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used in clinical settings. Prior research suggests that PROs collected at baseline may be associated with cancer survival, but most of those studies were conducted in patients with breast or lung cancer. The objective of this study was to determine the correlation between prospectively collected PROs and cancer-specific outcomes in patients with early stage colorectal cancer. METHODS: Patients who had newly diagnosed stage II or III colorectal cancer from 2009 to 2010 and had a consultation at the British Columbia Cancer Agency completed the brief Psychosocial Screen for Cancer (PSSCAN) questionnaire, which collects data on patients' perceived social supports, quality of life (QOL), anxiety and depression, and general health. PROs from the PSSCAN were linked with the Gastrointestinal Cancers Outcomes Database, which contains information on patient and tumor characteristics, treatment details, and cancer outcomes. Cox regression models were constructed for overall survival (OS), and Fine and Gray regression models were developed for disease-specific survival (DSS). RESULTS: In total, 692 patients were included. The median patient age was 67 years (range, 26-95 years), and the majority had colon cancer (61%), were diagnosed with stage III disease (54%), and received chemotherapy (58%). In general, patients felt well supported and reported good overall health and QOL. On multivariate analysis, increased fatigue was associated with worse OS (hazard ratio [HR], 1.99; P = .00007) and DSS (HR, 1.63; P = .03), as was lack of emotional support (OS: HR, 4.36; P = .0003; DSS: HR, 1.92; P = .02). CONCLUSIONS: Although most patients described good overall health and QOL and indicated that they were generally well supported, patients who experienced more pronounced fatigue or lacked emotional support had a higher likelihood of worse OS and DSS. These findings suggest that abbreviated PROs can inform and assist clinicians to identify patients who have a worse prognosis and may need more vigilant follow-up. Cancer 2017;123:1839-1847. © 2017 American Cancer Society.

Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.

PURPOSE: We hypothesized different Overall Survival (OS) in metastatic breast cancer (MBC) after relapse vs de novo presentation. METHODS: We identified women in British Columbia with MBC diagnosed between 01/2001 and 12/2009. OS from MBC was calculated for relapsed vs de novo cohorts in 3 subgroups, based on hormone receptors (HR) and HER2 status. Age at MBC, disease-free interval (DFI), de novo vs relapsed, year of MBC diagnosis, and systemic treatment were entered into univariable and multivariable analyses. RESULTS: We identified 3645 pts with known HR of which 2796 had known HER2. Median follow-up was 91 months. Median OS was longer for de novo vs relapsed MBC: HR+/HER2- 34 versus 23 months (mos) (p < 0.0001), HR-/HER2- (TN) 11 versus 8 mos (p = 0.02), HER2+ 29 versus 15 mos (p < 0.0001). For TN disease, no variable independently discriminated a group with increased risk of death. For both the HR +/HER2- and the HER2 + groups, relapsed vs de novo status (HzR 1.4 [95% CI 1.2-1.5; p < 0.0001], and HzR 1.6 [95% CI 1.4-1.9; p < 0.0001], respectively) and age >50 (HzR 1.2 [95% CI 1.1-1.4; p = 0.001] and HzR 1.3 [95% CI 1.1-1.5; p = 0.01], respectively) were associated with increased risk of death on multivariable analysis. CONCLUSION: These data provide information that may guide discussions about prognosis between physicians and patients with MBC. In addition, it highlights the importance of stratifying for initial stage at diagnosis in future MBC therapeutic trials.

Micrometastatic node-positive breast cancer: long-term outcomes and identification of high-risk subsets in a large population-based series.

PURPOSE: The prognostic implication of breast cancer with nodal micrometastases measuring >0.2 mm but < or =2 mm (pNmic) is unclear. This study evaluates survival in pNmic relative to node-negative (N0) and macroscopic node-positive (pNmac) disease in a large population-based series. METHODS: Subjects were 9,637 women diagnosed between 1989 and 1999, referred to the British Columbia Cancer Agency with pT1-2, node-negative and node-positive, M0 breast cancer. Kaplan-Meier breast-cancer-specific survival (BCSS) and overall survival (OS) were compared between patients with pN0 (n = 7,988), pNmic (n = 491), and pNmac disease (n = 1,158), according to the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes. Cox regression and recursive partitioning analyses were performed to identify significant factors associated with survival. RESULTS: Median follow-up was 8.2 years. Patients with pNmic disease had significantly poorer outcomes compared with pN0 cancers, with progressively lower BCSS and OS with increasing number of positive nodes and with LNR > 0.25. On multivariable analysis, histologic subtype, T stage, number of positive nodes, LNR, grade, lymphovascular invasion, estrogen receptor status, and systemic therapy use were factors significantly associated with BCSS and OS. Recursive partitioning trees for BCSS and OS both selected the pN/LNR variable at the first split, indicating that this variable provided the strongest prognostic separation. CONCLUSION: Patients with nodal micrometastases are a heterogeneous population with varying breast cancer mortality risks. The number of positive nodes and the LNR should be considered in conjunction with tumor factors in risk estimates and treatment decisions for patients with nodal micrometastatic breast cancer.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada's single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study.

INTRODUCTION: Primary breast cancer involving four or more axillary lymph nodes carries a poor prognosis. We hypothesized that use of an immunohistochemical biomarker scoring system could allow for identification of variable risk subgroups. METHODS: Patients with four or more positive axillary nodes were identified from a clinically annotated tissue microarray of formalin-fixed paraffin-embedded primary breast cancers and randomized into a 'test set' and a 'validation set'. A prospectively defined prognostic scoring model was developed in the test set and was further assessed in the validation set combining expression for eight biomarkers by immunohistochemistry, including estrogen receptor, human epidermal growth factor receptors 1 and 2, carbonic anhydrase IX, cytokeratin 5/6, progesterone receptor, p53 and Ki-67. Survival outcomes were analyzed by the Kaplan-Meier method, log rank tests and Cox proportional-hazards models. RESULTS: A total of 313 eligible patients were identified in the test set for whom 10-year relapse-free survival was 38.3% (SEM 2.9%), with complete immunohistochemical data available for 227. Tumor size, percentage of positive axillary nodes and expression status for the progesterone receptor, Ki-67 and carbonic anhydrase IX demonstrated independent prognostic significance with respect to relapse-free survival. Our combined biomarker scoring system defined three subgroups in the test set with mean 10-year relapse-free survivals of 75.4% (SEM 7.0%), 35.3% (SEM 4.1%) and 19.3% (SEM 7.0%). In the validation set, differences in relapse-free survival for these subgroups remained statistically significant but less marked. CONCLUSION: Biomarkers assessed here carry independent prognostic value for breast cancer with four or more positive axillary nodes and identified clinically relevant prognostic subgroups. This approach requires refinement and validation of methodology.

Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study.

BACKGROUND: Women have been shown to experience longer overall survival after colorectal cancer (CRC) diagnosis than men even after adjusting for disease stage and management. However, the etiology of this observation is not well understood, and the impact of non-CRC health conditions on survival has not been described. We aimed to evaluate the prognostic role of sex on CRC-specific outcomes. PATIENTS AND METHODS: All patients who underwent primary resection of stage I to III CRC from 2001 to 2005, and who were referred to cancer centers in a large, representative Canadian province were reviewed. Baseline patient characteristics, including common comorbidities, were compared between men and women. Multivariable analysis was used to evaluate the associations between sex and survival outcomes. RESULTS: We identified 1837 patients. Median age was 69 (interquartile range 60-76) years, and there were 867 women (47%) and 970 men (53%). Men were more likely to report ischemic heart disease, diabetes, dyslipidemia, and obesity (all P < .001). On multivariable analysis, men had worse overall and recurrence-free survival compared to women (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.15-1.64; and HR = 1.40, 95% CI, 1.18-1.67, respectively). However, CRC-specific outcomes, including CRC-specific survival and time to recurrence, did not differ significantly between men and women (HR = 1.15, 95% CI, 0.91-1.45; and HR = 1.12, 95% CI, 0.90-1.40, respectively). CONCLUSION: Women diagnosed with early stage CRC lived longer and had better general health than men. When noncancer causes of death were excluded, however, the trajectory of CRC appeared similar irrespective of sex. Early identification and better management of comorbidities may narrow the survival gap between men and women.

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.

Real-World Effect of Maintenance and Intermittent Chemotherapy on Survival in Metastatic Colorectal Cancer.

BACKGROUND: With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear. PATIENTS AND METHODS: Using a population-based cohort of mCRC patients who received combination chemotherapy, we aimed to describe the use of IC/MC and their effect on overall survival (OS). RESULTS: Among 617 patients, 120 (19%) had periods of IC, 67 (11%) had periods of MC, and 53 (9%) had periods of both. Most (85.5%) modifications occurred in the first-line setting. The receipt of IC (median OS [mOS], 37 vs. 21 months; P < .0001) or MC (mOS, 36 vs. 24 months; P = .0015) was associated with improved mOS compared with continuous combination therapy. In multivariate analysis adjusting for age, sex, and regimen used at the time of treatment modification, IC (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.42-0.65; P < .0001), MC (HR, 0.71; 95% CI, 0.58-0.88; P = .002), and the combination (HR, 0.45; 95% CI, 0.33-0.63; P < .0001) were all associated with improved mOS. Among patients receiving MC, individuals with (HR, 0.69; 95% CI, 0.53-0.90; P = .005) and without (HR, 0.74; 95% CI, 0.55-1.00; P = .048) re-escalation to their original cytotoxic regimen had improved mOS compared with continuous therapy. The use of IC was associated with an improved OS compared with MC (HR, 0.65; 95% CI, 0.47-0.90; P = .009). CONCLUSION: In patients with mCRC, IC and MC are reasonable options to maintain quality of life and do not appear to negatively affect OS in carefully selected patients.

Population-Based Patterns and Factors Associated With Underuse of Palliative Systemic Therapy in Elderly Patients With Metastatic Colon Cancer.

BACKGROUND: We compared the patterns and factors associated with chemotherapy and bevacizumab use in elderly versus young patients with metastatic colon cancer (mCC) and determined the effect of systemic therapy on overall survival (OS) according to age. MATERIALS AND METHODS: Patients diagnosed with mCC from 2009 to 2010 in British Columbia, Canada were reviewed and categorized as elderly patients (age ≥ 70 years) and young patients (age < 70 years). Cox regression models adjusted for age and confounders were used to determine the effect of systemic therapy on OS. RESULTS: We identified 1013 patients with a median age of 67 years. Of the 1013 patients, 42% were elderly and 58% were young; 57% were men; and 66% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Fewer elderly patients were offered systemic therapy compared with young patients (48% vs. 77%; P < .001). Among those treated, elderly patients were less likely than young patients to receive combination chemotherapy (47% vs. 81%; P < .0001) and bevacizumab (19% vs. 47%; P < .0001). The most common reasons for no treatment were similar for the elderly and young patients: patient choice, poor ECOG PS, and significant comorbidities. Advanced age alone was also cited as a reason for elderly but not for young patients (7% vs. 0%). When treated, the risk of adverse events and treatment interruptions was comparable between age groups. The receipt of systemic therapy was associated with improved OS in both elderly (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.37-0.56; P < .0001) and young (HR, 0.43; 95% CI, 0.35-0.53; P < .0001) patients, regardless of age (interaction P > .05). CONCLUSION: In carefully selected elderly patients, the outcomes from systemic therapy were comparable to those for young patients. Thus, age alone should not be a barrier to treatment of mCC.

Impact of Travel Distance and Urban-Rural Status on the Multidisciplinary Management of Rectal Cancer.

OBJECTIVES: Optimal treatment of rectal cancer (RC) requires multidisciplinary care. We examined whether distance to treatment center or community size impacts access to multimodality care and population-based outcomes in RC. METHODS: Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6 regional cancer centers in British Columbia were reviewed. Distance to treatment center was determined for each patient. Communities were classified as rural, small, medium, and large population centers. Logistic and Cox regression models assessed associations of distance and community size with treatment received as well as cancer-specific (CSS) and overall survival (OS). RESULTS: Of 3,158 patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic consultation was longer for those >100 km from a treatment center or residing in medium/rural communities. Logistic regression demonstrated no correlation between distance or community size and receipt of treatment modality. Univariate analysis showed similar CSS (P = .18, .88) and OS (P = .36, .47) based on community size and distance, respectively. In multivariate analysis, distance >100 km had inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no consistent trend between decreasing community size and outcomes; however, living in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). CONCLUSIONS: In this population-based study, there were no urban-rural differences in access to multidisciplinary care, but increased distance may be associated with worse cancer-specific outcomes.

Evolving treatment strategies for inflammatory breast cancer: a population-based survival analysis.

PURPOSE: To determine if mastectomy (Mx) use, chemotherapy (CT) intensity, or treatment sequence of CT, radiation therapy (RT), and Mx have improved outcome for inflammatory breast cancer (IBC). PATIENTS AND METHODS: A retrospective analysis of 485 patients with IBC diagnosed in British Columbia between 1980 and 2000 analyzed locoregional relapse-free survival (LRFS) and breast cancer-specific survival (BCSS) by treatment intent and treatment received. Curative intent was defined as delivery of more than four cycles of anthracycline-based CT plus locoregional RT in patients without distant metastases. RESULTS: Median follow-up among survivors was 6.5 years. Median BCSS was 1.0 and 3.2 years for patients with distant metastases at diagnosis or those who were curatively treated, respectively. Among patients treated curatively (n = 308), there were no significant differences in LRFS or BCSS with timing of Mx before or after CT/RT, time between diagnosis and RT, or the sequence of RT and CT. Patients receiving more intensive CT had improved 10-year BCSS compared with standard CT (43.7% v 26.3%; P = .04). Ten-year LRFS for patients having Mx after CT, Mx before CT, and without Mx was 62.8%, 58.6%, and 34.4%, respectively (P = .0001); the corresponding 10-year BCSS was 36.9%, 19.9%, and 22.5%, respectively (P = .005). On multivariate analysis, Mx was associated with improved LRFS (P = .04). Independent prognostic factors for BCSS were menopausal status (P = .02), estrogen receptor status (P = .02), and CT type (P = .05). CONCLUSION: This retrospective analysis suggested that mastectomy, in conjunction with CT and RT, seemed to enhance locoregional control, whereas modern CT regimens seemed to improve BCSS.

Population-based validation of the prognostic model ADJUVANT! for early breast cancer.

PURPOSE: Adjuvant! (www.adjuvantonline.com) is a web-based tool that predicts 10-year breast cancer outcomes with and without adjuvant systemic therapy, but it has not been independently validated. METHODS: Using the British Columbia Breast Cancer Outcomes Unit (BCOU) database, demographic, pathologic, staging, and treatment data on 4,083 women diagnosed between 1989 and 1993 in British Columbia with T1-2, N0-1, M0 breast cancer were abstracted and entered into Adjuvant! to calculate predicted 10-year overall survival (OS), breast cancer-specific survival (BCSS), and event-free survival (EFS) for each patient. Individual BCOU observed outcomes at 10 years were independently determined. Predicted and observed outcomes were compared. RESULTS: Across all 4,083 patients, 10-year predicted and observed outcomes were within 1% for OS, BCSS, and EFS (all P > .05). Predicted and observed outcomes were within 2% for most demographic, pathologic, and treatment-defined subgroups. Adjuvant! overestimated OS, BCSS, and EFS in women younger than age 35 years (predicted-observed = 8.6%, 9.6%, and 13.6%, respectively; all P < .001) or with lymphatic or vascular invasion (LVI; predicted-observed = 3.6%, 3.8%, and 4.2%, respectively; all P < .05); these two prognostic factors were not automatically incorporated within the Adjuvant! algorithm. After adjusting for the distribution of LVI, using the prognostic factor impact calculator in Adjuvant!, 10-year predicted and observed outcomes were no longer significantly different. CONCLUSION: Adjuvant! performed reliably. Patients younger than age 35 or with known additional adverse prognostic factors such as LVI require adjustment of risks to derive reliable predictions of prognosis without adjuvant systemic therapy and the absolute benefits of adjuvant systemic therapy.

Management and outcomes of isolated axillary node recurrence in breast cancer.

HYPOTHESIS: Management strategies affect the outcome of axillary recurrence in breast cancer. DESIGN: Population-based analysis. SETTING: Cancer agency breast cancer database. PATIENTS: Two hundred twenty women diagnosed with stage 0 through III breast cancer between 1989 and 2003 who subsequently developed an isolated axillary relapse. MAIN OUTCOME MEASURES: Overall survival rate and disease-free survival rate according to treatment strategy of the axillary recurrence. RESULTS: Among 19 789 women diagnosed with stage 0 through III breast cancer during the study era, 220 had an isolated axillary recurrence (Kaplan-Meier 5-year isolated axillary relapse rate, 1.0%). The median interval between primary breast cancer diagnosis and axillary recurrence was 2.2 years (range,1.8 months to 11.9 years). Median follow-up time after axillary recurrence was 5.4 years. Treatment for the axillary recurrence included lymph node biopsy (47.3%), complete axillary dissection (25.9%), axillary radiation (65.0%), chemotherapy (24.1%), and hormonal therapy (68.2%). The 5-year Kaplan-Meier overall survival rate estimate after axillary recurrence was 49.3% (95% confidence interval, 42.0-56.3). Median survival time from the isolated axillary recurrence was 4.9 years (range, 2.0 months to 15.1 years). Overall (P < .001) and disease-free (P = .006) survival times were highest in those treated with a combination of surgery and radiation. Other factors associated with improved overall survival rate were an interval from diagnosis to relapse greater than 2.5 years (P = .003), no initial axillary radiation (P < .001), asymptomatic presentation of the recurrence (P = .05), and subsequent systemic treatment (P = .02). CONCLUSIONS: The 5-year isolated axillary recurrence rate of women treated for breast cancer was 1.0%. Multimodality management at the time of recurrence, including axillary surgery, radiation, and systemic therapy, significantly improved overall and disease-free survival.

Radiotherapy omission after breast-conserving surgery is associated with reduced breast cancer-specific survival in elderly women with breast cancer.

PURPOSE: To evaluate the effect of radiotherapy (RT) omission on survival in older breast cancer patients treated with breast-conserving surgery. METHODS: Data were analyzed for 4836 women aged 50 to 89 with T1-T2, N0-N1, M0 breast cancer. Tumor and treatment factors, relapse rates, and overall survival (OS) and breast cancer-specific survival (BCSS) were compared between women treated with and without RT in 3 age categories: 50 to 64 (n = 2398), 65 to 74 (n = 1665), and > or = 75 years (n = 773). RESULTS: Median follow-up was 7.5 years. Rates of RT omission significantly increased with advancing age (7%, 9%, and 26% in age 50-64, 65-74, and > or = 75 years respectively, P < .0001). RT omission was associated with significantly reduced local control, BCSS, and OS. Despite similar tumor characteristics and higher rates of systemic therapy use, women aged > or = 75 years were observed to have lower 5-year OS and BCSS when RT was omitted. CONCLUSION: These findings support the hypothesis that inadequate local therapy is associated with reduced survival in elderly women treated with breast-conserving therapy.

Effect of Adjuvant Chemotherapy on Stage II Rectal Cancer Outcomes After Preoperative Short-Course Radiotherapy.

BACKGROUND: Adjuvant chemotherapy (AC) is offered to patients with stage II rectal cancer, but its use is controversial. We examined population-based outcomes of patients with pathologic stage II rectal cancer treated with AC after preoperative short-course radiotherapy. MATERIALS AND METHODS: We included patients diagnosed with pathologic stage II tumors from 1999 to 2009 in British Columbia. The disease-specific survival (DSS), relapse-free (RFS), and overall survival (OS) were assessed. Multivariate models adjusting for age, gender, Eastern Cooperative Oncology Group, and high-risk features (ie, pT4, poor differentiation, < 12 lymph nodes removed, lymphovascular invasion, perineural invasion, or obstruction or perforation) were constructed. RESULTS: Of 851 patients reviewed, 330 had received preoperative short-course radiotherapy, of whom 123 (37%) subsequently received AC. Patients treated with AC were younger (median age 61 vs. 73 years; P < .0001), reported better Eastern Cooperative Oncology Group status (P < .0001), and had more high-risk features (P < .0001). On univariate analysis, AC was associated with improved DSS (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.36-0.94; P = .028), RFS (HR, 0.62; 95% CI, 0.39-0.98; P = .043), and OS (HR, 0.42; 95% CI, 0.30-0.59; P < .0001). On multivariate analysis, these outcomes were not significant (DSS HR, 0.83; 95% CI, 0.43-1.61; P = .58; RFS HR, 0.82; 95% CI, 0.44-1.50; P = .51; OS HR, 0.62; 95% CI, 0.37-1.03; P = .064). Subgroup analysis suggested AC improved DSS (HR, 0.25; 95% CI, 0.07-0.89; P = .033), RFS (HR, 0.24; 95% CI, 0.07-0.85; P = .027), and OS (HR, 0.22; 95% CI, 0.069-0.70; P = .011) only in patients with ≥ 2-high risk features. CONCLUSION: In the present population-based cohort of patients with stage II rectal cancer, AC did not improve the outcomes in unselected patients. In a small subgroup of patients with ≥ 2 risk factors, we noted improved outcomes with AC use.

Long-term survival of patients with supraclavicular metastases at diagnosis of breast cancer.

BACKGROUND: Patients with supraclavicular metastases at diagnosis of breast cancer were classified between 1987 and 2002 as having stage M(1) breast cancer according to the tumor-node-metastasis (TNM) system. The 2003 edition of the TNM staging guidelines has classified such patients as having stage IIIC disease. To determine relative prognosis, we compared long-term survival in a population-based cohort of patients with isolated supraclavicular metastases (nodal-M(1)) to outcomes of patients with stage IIIB or M(1) (other) disease at presentation. MATERIALS AND METHODS: Among patients with breast cancer and known tumor stage referred to the British Columbia Cancer Agency from 1976 to 1985, 336 IIIB, 233 M(1), and 51 nodal-M(1) patients were identified. Actuarial overall and breast cancer-specific survival rates were determined to 20 years. RESULTS: Overall survival at 20 years was 13.2% for nodal-M(1) cases (95% confidence interval [CI], 5% to 26%), 9.4% for IIIB cases (95% CI, 6% to 14%), and 1.3% for M(1) (other) cases (95% CI, 0.4% to 3.5%; log-rank P <.0005). Overall survival was similar between nodal-M(1) and IIIB cases (P =.27). Breast cancer-specific survival at 20 years was 24.1% for nodal-M(1) cases (95% CI, 13% to 37%), 30.2% for IIIB cases (95% CI, 23% to 38%), and 3.9% for M(1) (other) cases (95% CI, 2% to 8%; log-rank P <.0005). Breast cancer-specific survival was significantly different for nodal-M(1) cases compared with either IIIB or M(1) (other) cases (P =.008 for both). CONCLUSION: Patients with supraclavicular metastases at diagnosis have significantly better outcomes than patients with M(1) (other) disease and overall survival similar to patients with IIIB disease. Reclassification as stage IIIC is appropriate for patients with breast cancer who present with supraclavicular nodal metastases alone.

Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies.

PURPOSE: To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N-) lymphovascular negative (LV-) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy. METHODS: One thousand one hundred eighty-seven cases of pT(1-2)N(0) LV- breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade. RESULTS: The median age of this series was 62 years. Four hundred thirty tumors were < or = 1 cm in diameter (cohort 1), 507 were 1.1-2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT(1)N(0) breast cancers. CONCLUSION: This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV-, N - breast cancer had a > or = 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of > or = 10% if they had either a grade 3 tumor < or = 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.