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Purpose To quantify the multi-institutional and multi-observer variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT), and its dosimetric impacts, as the first step of a RTOG effort to establish a breast cancer atlas. Methods and Materials Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, and chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative patients with breast cancer. Inter-observer differences in structure delineation were quantified with regard to volume, distance between centers of mass, percent overlap, and average surface distance. The mean, median and standard deviation for these quantities were calculated for all possible combinations. To asses the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. Results The variability in contouring the targets and OARs between the institutions/observers was substantial. The structure overlaps were as low as 10% and the volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries as well as approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These inter-observer differences result in substantial variations in dosimetric planning for breast RT. Conclusions The differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of IMRT/IGRT.

A B S T R A C T PurposeWe describe the health-related quality of life (HRQoL) of a cohort of children with brain tumors treated with proton radiotherapy. Patients and MethodsWe recruited 142 pediatric patients with brain tumors (age 2 to 18 years) and parents of such patients treated with proton radiation at Massachusetts General Hospital from 2004 to 2010. HRQoL was assessed using the PedsQL core, brain tumor, and cancer modules (range, 0 to 100). Assessments took place during radiation and annually thereafter. We examined correlations of HRQoL with disease, treatment, and cognitive and behavioral data. ResultsOverall reports of HRQoL during treatment were 74.8 and 78.1 for child self-report (CSR) and 67.0 and 74.8 for parent proxy report (PPR) for the core and brain tumor modules, respectively. PPR demonstrated lower HRQoL scores than CSR, but the two were highly correlated. Higher HRQoL scores were significantly associated with Wechsler Full Scale Intelligence Quotient scores (administered via the age-appropriate version) and better scores on two behavioral measures. Disease type also correlated with PPR core total HRQoL score at the beginning of treatment: medulloblastoma or primitive neuroectodermal tumors, 57.8; germ cell tumors, 63.5; ependymoma or high-grade glioma, 69.8; low-grade glioma, 71.5; and other low-grade neoplasms, 78.0 (P ϭ .001). Craniospinal irradiation and chemotherapy were negatively correlated with HRQoL. ConclusionThis is the first study to our knowledge of HRQoL in a cohort of children with brain tumors treated with proton radiation. This prospective study demonstrates the effect of disease type and intensity of treatment on HRQoL. It further suggests that where CSR is not possible, PPR is appropriate in most circumstances.

Purpose/Objective Lymphedema following breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiotherapy-related risk factors for lymphedema. Methods and Materials From 2005–2012, we prospectively performed arm volume measurements on 1,476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099/1501 (73%) received radiotherapy. Arm measurements were performed pre- and post-operatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months post-operative. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. Results At a median follow-up of 25.4 months (range 3.4–82.6), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiotherapy type was: 3.0% (no radiotherapy), 3.1% (breast or chest wall alone), 21.9% (supraclavicular (SC)), and 21.1% (SC and posterior axillary boost (PAB)). On multivariate analysis, the hazard ratio for RLNR (SC±PAB) was 1.7 (p = 0.025) compared to breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC+PAB (p=0.96). Other independent risk factors included early post-operative swelling (p <0.0001), higher BMI (p<0.0001), greater number of lymph nodes dissected (p =0.018), and axillary lymph node dissection (p=0.0001). Conclusions In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased risk of lymphedema compared to breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease with the increased risk of lymphedema.

BACKGROUND The leading cause of death for patients with hereditary retinoblastoma is second malignancy. Radiotherapy (RT), despite its high rate of efficacy, is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of non-target tissue. We compared the risk of second malignancy in retinoblastoma patients treated with photon and proton RT. METHODS We performed a retrospective review of patients with retinoblastoma treated with proton RT at the Massachusetts General Hospital or photon RT at Children’s Hospital Boston between 1986 and 2011. RESULTS Eighty-six patients were identified. Fifty-five patients received proton RT, and 31 patients received photon RT. Patients were followed for a median of 6.9 years (range, 1.0 to 24.4) in the proton cohort and 13.1 years (range, 1.4 to 23.9) in the photon cohort. The 10-year cumulative incidence of RT-induced or in-field second malignancies was significantly different between radiation modalities (Proton vs. Photon; 0% vs. 14%; p=0.015). The 10-year cumulative incidence of all second malignancies was also different, though with borderline significance (5% vs. 14%; p=0.120). CONCLUSION Retinoblastoma is highly responsive to radiation. The central objection to the use of radiation--the risk of second malignancy--is founded on studies of patients treated with antiquated, relatively non-conformal techniques. We present the first series of patients treated with the most conformal of currently available external beam therapy modalities. While longer follow up is necessary, our preliminary data suggest that proton RT significantly lowers the risk of RT-induced malignancy.

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Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.

Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.