IMPORTANCE The most appropriate dose-fractionation for whole breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and six-month toxicity and quality of life (QoL) with conventionally fractionated WBI (CF-WBI) versus hypofractionated WBI (HF-WBI). DESIGN Unblinded randomized trial of CF-WBI (n=149; 50 Gy/25 fractions + boost [10–14 Gy/5–7 fractions]) versus HF-WBI (n=138; 42.56 Gy/16 fractions + boost [10–12.5 Gy/4–5 fractions]). SETTING Community-based and academic cancer centers. PARTICIPANTS 287 women age ≥ 40 years with stage 0–II breast cancer treated with breast-conserving surgery for whom whole breast irradiation without addition of a third field was recommended. 76% (n=217) were overweight or obese. Patients were enrolled from February 2011 through February 2014. INTERVENTION(S) FOR CLINICAL TRIALS CF-WBI versus HF-WBI. MAIN OUTCOME MEASURES Physician-reported acute and six-month toxicities using NCICTCv4.0 and patient-reported QoL using the FACT-B version 4. All analyses were intention-to-treat, with outcomes compared using chi-square, Cochran-Armitage test, and ordinal logistic regression. Patients were followed for a minimum of 6 months. RESULTS Treatment arms were well-matched for baseline characteristics including FACT-B total score (P=0.46) and individual QoL items such as lack of energy (P=0.86) and trouble meeting family needs (P=0.54). Maximal physician-reported acute dermatitis (P<0.001), pruritus (P<0.001), breast pain (P=0.001), hyperpigmentation (P=0.002), and fatigue (P=0.02) during radiation were lower in patients randomized to HF-WBI. Overall grade ≥2 acute toxicity was less with HF-WBI vs. CF-WBI (47% vs. 78%; P<0.001). Six months after radiation, physicians reported less fatigue in patients randomized to HF-WBI (P=0.01), and patients randomized to HF-WBI reported less lack of energy (P<0.001) and less trouble meeting family needs (P=0.01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (OR 0.39, 95% CI 0.24–0.63) and trouble meeting family needs (OR 0.34, 95% CI 0.16–0.75). CONCLUSIONS AND RELEVANCE HF-WBI appears to yield less acute toxicity than CF-WBI, as well as less fatigue and trouble meeting family needs six months after completing radiation. These findings should be communicated to patients as part of shared decision-making. TRIAL REGISTRATION NCT01266642 (https://clinicaltrials.gov/ct2/show/NCT01266642)

Purpose Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP per the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ2 test and logistic multivariate regression. Results Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grade 1–3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V20 >30%, V15 >35%, V10 >40% and V5>55%. The likelihood ratio (LR) χ2 value was highest for V5< 55% (LR χ2=19.37). Conclusions In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.

PurposeHigh cure rates for Hodgkin’s lymphoma must be balanced with long-term treatment-related toxicity. Here we report an intensity-modulated radiation therapy (IMRT) technique that achieves adequate target coverage for mediastinal disease while minimizing high- and low-dose exposure of critical organs.Methods and materialsTreatment plans for IMRT and conventional anteroposterior-posteroanterior (AP-PA) techniques, with comparable coverage of the planning target volume (PTV), were generated for 9 female patients with mediastinal Hodgkin’s lymphoma assuming use of inclined positioning, daily breath-hold, and CT-on-rails verification. Our “butterfly” IMRT beam arrangement involved anterior beams of 300°−30° and posterior beams of 160°−210°. Percentages of normal structures receiving 30 Gy (V30), 20 Gy (V20), and 5 Gy (V5) were tabulated for the right and left breasts, total lung, heart, left and right ventricles, left anterior descending coronary artery (LAD), and spinal cord. Differences in each variable, conformity index, homogeneity index, and V107% between the two techniques were calculated (IMRT minus conventional).ResultsUse of IMRT generally reduced the V30 and V20 to critical structures: −1.4% and +0.1% to the right breast, −1.7% and −0.9% to the left breast, −14.6% and −7.7% to the total lung, −12.2% and −10.5% to the heart, −2.4% and −14.2% to the left ventricle, −16.4% and −8.4% to the right ventricle, −7.0% and −14.2% to the LAD, and −52.2% and −13.4% to the spinal cord. Differences in V5 were +6.2% for right breast, +2.8% for left breast, +12.9% for total lung, −3.5% for heart, −8.2% for left ventricle, −1.5% for right ventricle, +0.1% for LAD, and −0.1% for spinal cord. Use of IMRT significantly reduced the volume of tissue receiving 107% of the dose (mean 754 cm3 reduction).ConclusionsThis butterfly technique for IMRT avoids excess exposure of heart, breast, lung, and spinal cord to doses of 30 or 20 Gy; mildly increases V5 to the breasts; and decreases the V107%.

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Immediate breast reconstruction may impose limitations on the treatment planning of postmastectomy radiotherapy, particularly in regard to providing broad coverage of the chest wall and IMC region while avoiding excess exposure of the heart and lung.