Faculty Bibliography

PURPOSE/OBJECTIVE:To investigate cardiac toxicity associated with breast radiation therapy (RT) at 10-year follow-up in BCIRG-001, a phase 3 trial comparing adjuvant anthracycline chemotherapy (fluorouracil, doxorubicin, and cyclophosphamide) with anthracycline-taxane chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) in women with lymph node-positive early breast cancer. METHODS AND MATERIALS/METHODS:Prospective data from all 746 patients in the control arm (fluorouracil, doxorubicin, and cyclophosphamide) of BCIRG-001 at 10-year follow-up were obtained from Project Data Sphere. Cardiac toxicities examined included myocardial infarction (MI), heart failure (HF), arrhythmias, and relative and absolute left ventricular ejection fraction decrease of >20% from baseline. Toxicities were compared between patients who received RT versus no RT, left-sided RT versus no RT, and internal mammary nodal RT versus no RT. RESULTS:Of the 746 patients, 559 (75%) received RT to a median dose of 50 Gy. Myocardial infarction occurred in 3 RT patients (0.5%) versus 6 no-RT patients (3%) (P=.01). Heart failure was seen in 15 RT patients (2.7%) versus 3 no-RT patients (1.6%) (P=.6). Among these, 35 RT patients (18%) had a left ventricular ejection fraction relative decrease of >20% baseline versus 7 (10%) who did not receive RT (P=.1). Arrhythmias were more common in RT patients (3.2%) versus no-RT patients (0%) (P=.01). On univariable and multivariable analysis HF was not significantly associated with RT, and MI was negatively associated with RT. CONCLUSIONS:In this retrospective analysis of prospective toxicity outcomes, there is an increased risk of arrhythmias but no clear evidence of significantly increased risk of MI or HF at 10 years in lymph node-positive women treated with breast RT and uniform adjuvant doxorubicin-based chemotherapy. Given the low incidence of these outcomes, studies with larger numbers are needed to confirm our findings.

Purpose/UNASSIGNED:Brain metastases are common in patients with limited-stage small cell lung cancer (LS-SCLC) due to the inability of most chemotherapeutics to penetrate the blood-brain barrier. Prophylactic cranial irradiation (PCI) is therefore recommended for use in patients with a good response to concurrent chemoradiotherapy. However, PCI is not always delivered; therefore, we investigated the reasons for PCI omission in patients who underwent therapy with curative intent. Methods and materials/UNASSIGNED:We retrospectively reviewed all patients with LS-SCLC who were treated with curative intent at our institution. Overall survival and cumulative incidence of brain metastasis were estimated by the Kaplan-Meier method. The Pearson χ2 test and Mann-Whitney U test were used to examine factors associated with PCI use, and prognostic factors were analyzed with Cox proportional hazards modeling. Results/UNASSIGNED:We examined 208 patients who were treated for LS-SCLC at our institution. A total of 115 patients (55%) received PCI. The most common documented reason for PCI omission was patient refusal due to neurotoxicity concerns (38%). Physician assessment of being medically unfit (33%) and of advanced age (8%) were the second and third most common reasons, respectively. Karnofsky performance status and clinical American Joint Committee on Cancer stage but not PCI were significantly associated with overall survival. Only clinical stage remained an independent factor on multivariate analysis. Conclusions/UNASSIGNED:Approximately half of patients with LS-SCLC ultimately receive PCI, generally for guideline-recommended reasons. The most common reason for PCI omission was patient concerns regarding neurotoxicity. Efforts to decrease PCI neurotoxicity, including hippocampal-sparing radiation and memantine use, may increase the use of this survival-improving intervention in eligible patients with LS-SCLC.

BACKGROUND: Patients undergoing implant-based reconstruction in the setting of postmastectomy radiation therapy suffer from increased complications and inferior outcomes compared with those not irradiated, but advances in radiation delivery have allowed for more nuanced therapy. The authors investigated whether these advances impact patient outcomes in implant-based breast reconstruction. METHODS: Retrospective chart review identified all implant-based reconstructions performed at a single institution from November of 2010 to November of 2013. These data were cross-referenced with a registry of patients undergoing breast irradiation. Patient demographics, treatment characteristics, and outcomes were analyzed. RESULTS: Three hundred twenty-six patients (533 reconstructions) were not irradiated, whereas 83 patients (125 reconstructions) received radiation therapy; mean follow-up was 24.7 months versus 26.0 months (p = 0.49). Overall complication rates were higher in the irradiated group (35.2 percent versus 14.4 percent; p < 0.01). Increased maximum radiation doses to the skin were associated with complications (maximum dose to skin, p = 0.05; maximum dose to 1 cc of skin, p = 0.01). Different treatment modalities (e.g., three-dimensional conformal, intensity-modulated, field-in-field, and hybrid techniques) did not impact complication rates. Prone versus supine positioning significantly decreased the maximum skin dose (58.5 Gy versus 61.7 Gy; p = 0.05), although this did not translate to significantly decreased complication rates in analysis of prone versus supine positioning. CONCLUSIONS: As radiation techniques evolve, the maximum dose to skin should be given consideration similar to that for heart and lung dosing, to optimize reconstructive outcomes. Prone positioning significantly decreases the maximum skin dose and trends toward significance in reducing reconstructive complications. With continued study, this may become clinically important. Interdepartmental studies such as this one ensure quality of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PURPOSE/OBJECTIVE:Ir-192 is the predominant source for high-dose-rate (HDR) brachytherapy in United States markets. Co-60, with longer half-life and fewer source exchanges, has piloted abroad with comparable clinical dosimetry but increased shielding requirements. We sought to identify practitioner knowledge of Co-60 and establish acceptable willingness-to-pay (WTP) thresholds for additional shielding requirements for use in future cost-benefit analysis. METHODS AND MATERIALS/METHODS:A nationwide survey of U.S. radiation oncologists was conducted from June to July 2015, assessing knowledge of HDR sources, brachytherapy unit shielding, and factors that may influence source-selection decision-making. Self-identified decision makers in radiotherapy equipment purchase and acquisition were asked their WTP on shielding should a more cost-effective source become available. RESULTS:Four hundred forty surveys were completed and included. Forty-four percent were ABS members. Twenty percent of respondents identified Co-60 as an HDR source. Respondents who identified Co-60 were significantly more likely to be ABS members, have attended a national brachytherapy conference, and be involved in brachytherapy selection. Sixty-six percent of self-identified decision makers stated that their facility would switch to a more cost-effective source than Ir-192, if available. Cost and experience were the most common reasons provided for not switching. The most common WTP value selected by respondents was <$25,000. CONCLUSIONS:A majority of respondents were unaware of Co-60 as a commercially available HDR source. This investigation was novel in directly assessing decision makers to establish WTP for shielding costs that source change to Co-60 may require. These results will be used to establish WTP threshold for future cost-benefit analysis.

BACKGROUND AND PURPOSE: We evaluated the effect of post-mastectomy radiation (PMRT) in 1-3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. MATERIALS AND METHODS: Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000-2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. RESULTS: A total of 523 women with 1-3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% (p=0.001) but had no effect on overall survival (OS) (84% vs. 86%, p=0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03-0.62; p=0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04-0.50; p=0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55-1.51; p=0.7). Results remained consistent with the use of propensity score analysis. CONCLUSIONS: In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.