Elaine S. Wai

Effect of radiotherapy boost and hypofractionation on outcomes in ductal carcinoma in situ.

Boost radiotherapy (RT) improves outcomes for patients with invasive breast cancer, but whether this is applicable to patients with pure ductal carcinoma in situ (DCIS) is unclear. This study examined outcomes from whole breast RT, with or without a boost, and the impact of different dose‐fractionation schedules in a population‐based cohort of women with pure DCIS treated with breast‐conserving surgery (BCS).

Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

PURPOSE To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). METHODS AND MATERIALS Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. RESULTS Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). CONCLUSIONS This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management.

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

PURPOSE The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. METHODS AND MATERIALS Between 1990 and 1998, 5334 women ≤ 80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. RESULTS The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). CONCLUSIONS There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.

Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer

BACKGROUND AND PURPOSE Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. MATERIALS AND METHODS Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded baseline patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hospital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. RESULTS For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p=0.74), even after propensity-score adjustment (p=0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no difference in mortality for the three causes of death. CONCLUSIONS At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI.

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non–Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis

Introduction: The programmed death 1 antibodies (PD‐1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non–small‐cell lung cancer (NSCLC). We evaluated the correlation between immune‐related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD‐1 Ab in advanced NSCLC. Patients and Methods: Advanced NSCLC patients treated with PD‐1 Ab between June 2015 to November 2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Common Terminology Criteria for Adverse Events, version 4.0) of irAE were abstracted from chart review. Kaplan‐Meier curves of OS from initiation of PD‐1 Ab were generated. Multivariable analysis with 6‐ and 12‐week landmark analysis was performed by Cox proportional hazard regression models. Results: In a cohort of 271 patients, irAEs were observed in 116 patients (42.8%). Nivolumab recipients developing colitis had lower OS compared to those who did not at the 6‐week landmark (P = .010) and 12‐week landmark (P = .072). For the entire cohort, 56 patients (20.7%) needed treatment interruption because of an irAE. Treatment interruption correlated with lower OS at the 6‐week landmark (P = .005) and 12‐week landmark (P = .008). Six‐week landmark multivariable analysis identified Charlson Comorbidity Index score of 3 or higher, Eastern Cooperative Oncology Group Performance Status of 2 or higher, presence of liver metastases, and irAE greater than grade 2 versus no irAE to be associated with decreased OS (each P < .05). Conclusion: Treatment interruption due to irAE was associated with a lower median OS compared to continuous PD‐1 Ab therapy. Shorter OS seen with severe irAE might reflect the need for improved physician education in irAE treatment algorithms.