Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast.

BACKGROUND: In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allred's subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level. PATIENTS AND METHODS: From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras. RESULTS: Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P < 0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P < 0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET. CONCLUSIONS: ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

Treatment Outcomes of Low-grade Lymphoma of the Orbit.

AIMS: Radiation therapy can be used with curative intent in patients with low-grade orbital non-Hodgkin's lymphoma (NHL) stages IE and IVE (limited to the bilateral orbits). This study evaluated local control and survival outcomes of patients with unilateral or bilateral orbital lymphoma treated in a provincial population. MATERIALS AND METHODS: The study subjects were 176 patients with low-grade orbital or conjunctival lymphoma referred for management from 1980 to 2016. Demographic, tumour and treatment characteristics were abstracted by chart review. Recurrence-free survival (RFS) and overall survival were assessed with competing risks analysis and Gray's test. RESULTS: The median follow-up was 8.5 years (range 0.4-29.5 years). The median age at diagnosis was 65 years (range 20-97 years). The most common histological subtype was mucosa-associated lymphoid tissue (MALT) (73%). Stage IVE accounted for 20.5% of the cohort. Orbital radiation therapy was used in 122 patients with stage IE (87%) and 12 patients with stage IVE (28%). The median dose was 25 Gy (range 2-35 Gy). Other treatments were antibiotics (seven patients), chemotherapy (10 patients), radioimmunotherapy (six patients), surgery (three patients) and observation (16 patients). Within the group treated with orbital external beam radiation therapy (EBRT) there were no local recurrences. Among those with stage IE NHL, EBRT was associated with improved local RFS (P ≤ 0.001) but did not have an impact on contralateral or distant RFS. In patients with stage IVE NHL limited to the bilateral orbit, bilateral EBRT was associated with improved RFS (P = 0.012) but did not affect distant recurrences or overall survival. CONCLUSION: There were no local recurrences after EBRT for stage IE and IVE orbital low-grade NHL. The treatments offered over the study period varied, but only EBRT for stage IVE disease improved RFS. This supports EBRT as the preferred primary treatment for patients with localised orbital low-grade lymphoma, including those with bilateral disease.

Survival Outcomes Following Discontinuation of Ipilimumab and Nivolumab for Advanced Melanoma in a Population-based Cohort.

AIMS: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. MATERIALS AND METHODS: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan-Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. RESULTS: Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan-Meier method. Any grade and grade 3-4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15-0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17-0.81, P = 0.01). Grade 3-4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20-1.01, P = 0.05). CONCLUSION: In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.

Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab.

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. Methods: All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Results: Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). Conclusions: In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments.

Phyllodes tumors of the breast: The British Columbia Cancer Agency experience.

PURPOSE: Phyllodes tumors of the breast are uncommon fibroepithelial lesions for which optimal management remains unclear. This retrospective population-based study reports treatment and outcomes for patients with phyllodes tumors and evaluates characteristics that influence outcome. MATERIALS AND METHODS: Data were analysed on 183 patients with newly diagnosed phyllodes tumors from 1999 to 2014. Five-year Kaplan-Meier local recurrence and survival were compared between cohorts with benign (n=83), borderline (n=50) and malignant phyllodes tumor (n=49) histology. RESULTS: Median (range) follow-up was 65 (0.5-197) months. Local excision was performed in 163 and mastectomy in 19 patients. Eleven patients with malignant phyllodes tumors received radiation therapy. Overall, local recurrence occurred in 8.7%, distant metastases in 4.4%, and cause specific deaths in 3.8%. Five-year Kaplan-Meier outcomes among women with benign, borderline, and malignant phyllodes tumors were: local recurrence 6% vs 9% vs 21%, P=0.131; overall survival 96% vs 100% vs 82%, P=0.002; and disease-free survival 94% vs 91% vs 67%, P<0.001. Five-year Kaplan-Meier local recurrence among women with negative vs close vs positive margins were 8% vs 6% vs 37%, P<0.001. Corresponding rates for intermediate vs pushing vs infiltrative borders were 6% vs 6% vs 33%, P=0.006. Positive margins and infiltrative tumor borders were associated with increased local recurrence (all P≤0.006), and the latter remained significant in exploratory analyses after adjusting for margin status and phyllodes tumor classification. CONCLUSIONS: Five-year outcomes among women with phyllodes tumors were comparable to those reported in the literature. Exploratory analysis has suggested that infiltrative tumor borders may be used in conjunction with margin status to assess local recurrence risk.

Inoperable early stage non-small cell lung cancer: comorbidity, patterns of care and survival.

PURPOSE: To evaluate comorbidities, patterns of care and outcomes for patients with inoperable stage I and II non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients diagnosed with stage I or II NSCLC in British Columbia between 1996 and 2005 who did not undergo primary surgery and were referred for oncology assessment were identified in a retrospective analysis. Baseline comorbidity and pulmonary function data for patients treated with curative radiotherapy (CurRT; biologically effective dose [BED]>58 Gy(10)) were abstracted by chart review. Kaplan-Meier and Cox regression were used to determine factors associated with overall survival (OS) and cause-specific survival (CSS) based on treatment group [no radiotherapy (NoRT), palliative radiotherapy (PallRT), or CurRT]. RESULTS: Of 1043 patients identified, approximately 1/3 received CurRT, and these patients had better performance status and lower stage disease than the other groups. There was a high prevalence of comorbid conditions in the CurRT group; 90% of CurRT patients had an age-adjusted Charlson comorbidity index (CCI) score ≥5. CurRT patients had a median survival 1-year longer than patients treated with PallRT or NoRT (p < 0.0001). In CurRT patients, CCI was predictive of OS (HR 1.1 per point CCI increase; p = 0.044), but not CSS. Patients receiving PallRT with a BED > 50 Gy(10) had significantly longer OS than those receiving PallRT of ≤50 Gy(10) (p < 0.0001). CONCLUSIONS: Treatment of medically inoperable early stage NSCLC patients with CurRT is associated with a significantly longer survival, and for these patients CCI is a significant predictor of OS. For patients treated with PallRT, higher doses of palliative thoracic RT is associated with improved OS.

Caring for survivors of breast cancer: perspective of the primary care physician.

BACKGROUND AND OBJECTIVES: Increasing numbers of women are surviving breast cancer, and survivorship care is becoming more complex. Primary care physicians provide care for most survivors of breast cancer in the Canadian province of British Columbia. The present study offers insight into the confidence of primary care physicians in their abilities to provide such care. It also explores potential ways to assist those providers in enhancing this aspect of their practice. METHODS: A questionnaire was mailed to 1000 primary care physicians caring for survivors of breast cancer. The questionnaire explored the perspectives of the responding physicians on their ability to manage various aspects of survivorship care for breast cancer patients, identified preferences for the content and format of communication from oncologists at the time of transition from active oncology treatment to survivorship, and determined the means most commonly used to obtain knowledge about breast cancer. This 1-page, 31-item checkbox and open-answer questionnaire assessed the perceptions of primary care physicians about the care of breast cancer survivors after completion of active treatment and their personal preferences for resources providing information about breast cancer. RESULTS: The questionnaire response rate was 59%. Primary care physicians reported being most confident in screening for recurrence and managing patient anxiety; they were least confident in managing lymphedema and providing psychosocial counselling. Compared with physicians following fewer survivors of breast cancer, those who followed more breast cancer survivors had higher confidence in managing the biomedical aspects of follow-up and in providing counselling about nutrition and exercise. Most physicians found discharge letters from oncologists to be useful. Point-form discharge information was preferred by 43%; detailed description, by 19%; and both formats, by 38%. The most useful information items identified for inclusion in a discharge letter were a diagnosis and treatment summary and the recommended surveillance and endocrine therapy. Continuing medical education events and online resources were the means most commonly used to obtain knowledge about breast cancer. CONCLUSIONS: Primary care physicians who provide follow-up for survivors of breast cancer report that they are confident in managing care and satisfied with discharge letters containing a diagnosis and treatment summary, and recommendations for surveillance and endocrine treatment. At the time of patient discharge, additional information about common medical and psychosocial issues in this patient population would be useful to primary care physicians. Preferred means to access current breast cancer information include continuing medical education events and online resources.

Comparison of 1- and 2-year screening intervals for women undergoing screening mammography.

We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50-74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial mammography). Survival was estimated for both periods using a prognostic model and the expected rate of interval and screen-detected cancers. The likelihood of a screen-detected cancer with annual screening was 2.32 per thousand screens and with biennial screening was 3.32 per thousand screens. The prognostic profile of screen-detected cancers was better than that of interval cancers. Among both screen-detected and interval cancers, the prognostic profiles with annual and biennial screening were similar. The estimated breast cancer-specific survival rates for women undergoing annual and biennial screening mammography were 95.2 and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual compared to biennial mammography was associated with a 1.2% increase in the estimated 10-year breast cancer-specific survival for women aged 50-74 years, diagnosed with invasive breast cancer after screening programme attendance.

Health system costs of metastatic breast cancer.

To assess the costs of treating patients with incurable breast cancer, all health system costs during the interval from diagnosis of first recurrence or metastasis until death for 75 female subjects randomly selected from those known to have died of breast cancer in British Columbia, Canada between July 1, 1995 and December 31, 1996, were identified. Costs were determined from several databases within the British Columbia (BC) Ministry of Health, as well as from BC Cancer Agency patient charts. The mean total cost to the health system was CDN $36,474.33 (95% confidence interval $29,752-$43,196) per subject. The mean costs were highest for the youngest age group and lowest for the middle age group, but these only differed by $2,300. Inpatient costs accounted for the greatest proportion of the total, over 50% in all age groups. This data may be valuable in assessing the cost-effectiveness of interventions that are known to affect mortality due to breast cancer.