Biologically Effective Dose and Rectal Bleeding in Definitive Proton Therapy for Prostate Cancer.

Purpose and Objectives: With increasing use of hypofractionation and extreme hypofractionation for prostate cancer, rectal dose-volume histogram (DVH) parameters that apply across dose fractionations may be helpful for treatment planning in clinical practice. We present an exploratory analysis of biologically effective rectal dose (BED) and equivalent rectal dose in 2 Gy fractions (EQD2) for rectal bleeding in patients treated with proton therapy across dose fractionations. Materials and Methods: From 2016 to 2018, 243 patients with prostate cancer were treated with definitive proton therapy. Rectal DVH parameters were obtained from treatment plans, and rectal bleeding events were recorded. The BED and EQD2 transformations were applied to each rectal DVH parameter. Univariate analysis using logistic regression was used to determine DVH parameters that were significant predictors of grade ≥ 2 rectal bleeding. Youden index was used to determine optimum cutoffs for clinically meaningful DVH constraints. Stepwise model-selection criteria were then applied to fit a "best" multivariate logistic model for predicting Common Terminology Criteria for Adverse Events grade ≥ 2 rectal bleeding. Results: Conventional fractionation, hypofractionation, and extreme hypofractionation were prescribed to 117 (48%), 84 (34%), and 42 (17.3%) patients, respectively. With a median follow-up of 20 (2.5-40) months, 10 (4.1%) patients experienced rectal bleeding. On univariate analysis, multiple rectal DVH parameters were significantly associated with rectal bleeding across BED, EQD2, and nominal doses. The BED volume receiving 55 Gy > 13.91% was found to be statistically and clinically significant. The BED volume receiving 55 Gy remained statistically significant for an association with rectal bleeding in the multivariate model (odds ratio, 9.81; 95% confidence interval, 2.4-40.5; P = .002). Conclusion: In patients undergoing definitive proton therapy for prostate cancer, dose to the rectum and volume of the rectum receiving the dose were significantly associated with rectal bleeding across conventional fractionation, hypofractionation, and extreme hypofractionation when using BED and EQD2 transformations.

Breast density measurements with ultrasound tomography: a comparison with film and digital mammography.

PURPOSE: To investigate the use of the whole-breast sound speed measurement as a marker of breast density (BD), a known risk factor for breast cancer. METHODS: As part of an ongoing study of breast cancer detection, 249 patients were scanned with a clinical prototype that operates on the principles of ultrasound tomography. Typically, 40-100 sound speed tomograms were reconstructed from the scan data, corresponding to the entire volume of the breast of each patient. The data were used to estimate the volume averaged sound speed (VASS) of the breast for each patient. The corresponding mammograms were used to calculate mammographic percent density (MPD) using CUMULUS software. Film mammograms were available for 164 patients while 85 digital mammograms were available for the remaining patients. Standard statistical techniques were used to determine associations of breast sound speed with a variety of mammographic measures such as percent density, area of dense tissue, and area of nondense tissue. Furthermore, associations of breast sound speed with continuous variables such as age and weight and dichotomous variables such as parity and menopausal status were also assessed. RESULTS: VASS was found to be significantly associated with MPD. The Spearman correlation coefficient (r(s)) between VASS and MPD was found to be 0.77 and 0.71 for film and digital mammography, respectively. VASS was positively correlated with dense areas by mammography, both digital (r(s) = 0.46) and film (r(s) = 0.56). VASS was negatively associated with nondense area by mammography, both digital (r(s) = -0.58) and film (r(s) = -0.63). BD by all methods was less in postmenopausal than in premenopausal women. The MPD was lower in the postmenopausal group (by 6.6%, p < 0.08, for the digital group and 7.73%, p < 0.007, for the film group). The VASS was also lower in the postmenopausal group (by 15 m∕s, p < 0.001 for the digital group and 8 m∕s, p < 0.08, for the film group). The association of MPD with age was characterized with r(s) = -0.06 (p < 0.6) for digital mammography and r(s) = -0.53 (p < 0.002) for film mammography. For weight, the MPD associations were characterized by r(s) = -0.53 (p < 0.0001) for digital mammography and -0.38 (p < 0.0001) for film mammography. The association of VASS with age was r(s) = -0.33 (p < 0.002) for the digital group and -0.17 (p < 0.03) for the film group. For weight, the relationship was characterized with r(s) = -0.45 (p < 0.001) for the digital group and -0.37 (p < 0.0001) for the film group. CONCLUSIONS: The association between VASS and MPD is strong for both film and digital mammography, suggesting that VASS is a viable measure of breast density. This result sets the stage for future work that will focus on directly testing the association of VASS with breast cancer risk.

Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

BACKGROUND: Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. METHODS: We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. RESULTS: Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. CONCLUSIONS: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.