Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial.

Purpose: Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI. Methods and Materials: This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL). Results: Thirty-eight evaluable patients enrolled between 2/2013-11/2016. Median age was 67 years (range 50-79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12-62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively. Conclusion: At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.

Multi-institutional registry study evaluating the feasibility and toxicity of accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy.

PURPOSE: The noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings. METHODS AND MATERIALS: Institutions using the NIBB technique were invited to participate. Data for acute/late toxicity, cosmetic outcome, and tumor recurrence were collected. Toxicity and cosmetic outcome were graded based on the Common Terminology Criteria for Adverse Events version 3.0 and NRG/Radiation Therapy Oncology Group scale, respectively. Treatment variables were analyzed for association with outcomes. RESULTS: A total of 252 patients from eight institutions were analyzed. The median age was 69 years. The mean tumor size was 1.1 cm (0.1-4.0 cm). Treatment was delivered 10 fractions (34-36 Gy) in 75% and five fractions (28.5 Gy) in 22%. B.i.d. fractionation was used in 9%. Acute radiation dermatitis was Grade 0-1, 2, and 3 in 77%, 19%, and 4%, respectively. One hundred ninety-one patients with a median followup of 18 months (4-72 months) were evaluable for late outcomes. Late toxicity Grades 2 and 3 were observed in 8.8% and 1%, respectively. Cosmetic outcome was excellent, good, and fair/poor in 62%, 36%, and 2%, respectively. B.i.d. fractionation was associated with higher acute and late toxicity. Second-generation applicators were associated with lower late toxicity and better cosmetic outcome. Actuarial freedom from ipsilateral breast tumor recurrence and true recurrence were 98.3% and 98.3% at 2 years and 90.9% and 95.4% at 5 years, respectively. CONCLUSIONS: Accelerated partial breast irradiation using NIBB was well tolerated with a low rate of acute and late toxicity across various practice settings. Ipsilateral breast tumor recurrence and cosmetic outcomes were favorable. b.i.d. fractionation was associated with higher toxicity. Longer followup is needed to confirm late endpoints.

The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis.

PURPOSE: To determine if heterogeneity correction significantly affects commonly measured dosimetric parameters predicting pulmonary toxicity in patients receiving radiation for lung cancer. METHODS AND MATERIALS: Sixty-eight patients treated for lung cancer were evaluated. The conformal treatment technique mostly employed anteroposterior/posterior-anterior fields and off-cord obliques. The percent total lung volume receiving 20 Gy or higher (V20) and mean lung dose (MLD) were correlated with the incidence of radiation pneumonitis. Parameters from both heterogeneity-corrected and heterogeneity-uncorrected plans were used to assess this risk. RESULTS: Univariate analysis revealed a significant correlation between the development of radiation pneumonitis and both V20 and MLD. A best-fit line to a plot of V20 from the homogeneous plan against the corresponding V20 heterogeneous value produced a slope of 1.00 and zero offset, indicating no difference between the two parameters. For MLD, a similarly significant correlation is seen between the heterogeneous and homogeneous parameters, indicating a 4% difference when correcting for heterogeneity. A significant correlation was also observed between the MLD and V20 parameters (p < 0.0001). CONCLUSIONS: A high degree of correlation exists between heterogeneity-corrected and heterogeneity-uncorrected dosimetric parameters for lung and the risk of developing pneumonitis. Either V20 or MLD predicts the pneumonitis risk with similar effect.

Palliative Radiation Therapy for Symptomatic Control of Inoperable Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is traditionally considered to be resistant to conventional low dose radiation therapy (RT). The emergence of image-guided stereotactic body radiation therapy (SBRT) made it possible to deliver much higher doses of radiation. Recent clinical trials of SBRT for RCC showed improvement in local control rates and acceptable toxicity. Here we report a case of inoperable symptomatic RCC that was managed with SBRT. Strikingly, the presenting symptoms of gross hematuria and severe anemia were completely resolved following a course of SBRT. Thus, our case report highlights the potential benefit of this technique for patients with inoperable RCC.

US radiation oncology practice patterns for posttreatment survivor care.

PURPOSE: Increasing numbers of cancer survivors have driven a greater focus on care of cancer patients after treatment. Radiation oncologists have long considered follow-up of patients an integral part of practice. We sought to document current survivor-focused care patterns and identify barriers to meeting new regulatory commission guidelines for survivorship care plans (SCPs) and provide guidance for survivorship care. METHODS AND MATERIALS: A 23-question electronic survey was e-mailed to all practicing US physician American Society of Radiation Oncology members. Responses were collected for 25 days in March 2014. Survey data were descriptively analyzed. RESULTS: A total of 574 eligible providers responded, for a response percentage of 14.7%. Almost all providers follow their patients after treatment (97%). Length of follow-up was frequently extensive: 17% followed up to 2 years, 40% for 3-5 years, 12% for 6-10 years, and 31% indefinitely. Ancillary services, particularly social work and nutrition services, are commonly available onsite to patients in follow-up. Fewer than half of respondents (40%) indicated that they currently use SCPs for curative intent patients and those who do generally use internally developed templates. SCPs typically go to patients (91%), but infrequently to primary care providers (22%). The top 3 barriers to implementation of SCPs were cost (57%), duplicative survivorship care plans provided by other physicians (43%), and lack of consensus or professional guidelines (40%). Eighty-seven percent indicated that SCPs built into an electronic medical record system would be useful. CONCLUSIONS: A significant part of radiation oncology practice includes the care of those in the surveillance of follow-up phase of care. SCPs may be beneficial in improving communication with the patient and other care but are not widely used within our field. This survey identified key barriers to use of SCPs and provides specialty guidance for important information to be included in a radiation oncology oriented SCP.

Development of a standard survivorship care plan template for radiation oncologists.

PURPOSE: In response to a need expressed by members of the American Society for Radiation Oncology (ASTRO), the ASTRO Board of Directors approved an initiative to create a radiation oncology-specific survivorship care plan (SCP) template. METHODS AND MATERIALS: Members of the ASTRO Health Services Research Committee (which was subsequently renamed the Clinical, Translational, and Basic Science Advisory Committee) were charged with this task. Creation of the ASTRO SCP template was informed by existing SCP templates published by other organizations and modified to add radiation treatment details felt to be important by committee members. An emphasis was placed on describing diagnostic and treatment details in ways that patients and referring physicians can understand. The resulting template subsequently underwent ASTRO committee review, public comment, and was ultimately approved by the ASTRO Board of Directors. RESULTS: The standardized template includes 2 components: the first 2 pages represent an SCP that is to be given to the patient and referring physicians, whereas page 3 includes additional technical radiation therapy details which are usually included in a traditional radiation treatment summary. That is, the template serves two purposes - obviating the need for radiation oncologists to create an SCP for patients and a separate treatment completion note. CONCLUSIONS: The standardized ASTRO SCP template serves an immediate need of practicing radiation oncologists to have a template that is radiation-specific and meets current requirements for SCP and radiation treatment summary. Potential future work may include development of disease-specific templates that will include more granular details regarding expected toxicities and follow-up care recommendations and working with electronic medical record system vendors to facilitate autocreation of SCP documents to reduce the burden on physicians and other staff. These future developments can make this intervention more helpful to patients, and further reduce the burden of creating SCPs.

Updated feasibility and reproducibility results of multi-institutional study of noninvasive breast tumor bed boost.

PURPOSE: To report updated feasibility and reproducibility results for high-dose-rate noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT) in the setting of expanded patient and treatment facility number. METHODS AND MATERIALS: Fifteen independent community-based and academic centers reported 518 early-stage breast cancer patients from July 2007 to February 2015 on a privacy-encrypted online data registry. All patients' treatment included lumpectomy followed by combination of WBRT and NIBB. NIBB was completed with commercially available (AccuBoost, Billerica, MA) mammography-based system using high-dose-rate 192Ir emissions along orthogonal axes. Harvard scale was used to grade cosmesis. RESULTS: Total patient cohort had median followup of 12 months (1-75 months) with subset of 268 having available cosmesis. Greater than 2- and 3-year followup was 29% and 14%, respectively. Entire cohort had 97.4% excellent/good (E/G) breast cosmesis and freedom from recurrence of 97.6% at the final followup. WBRT timing with respect to NIBB delivery demonstrated no statistically significant difference in E/G cosmesis. Achieved E/G cosmesis rate was also not statistically significant (χ2p-value = 0.86) between academic and community institutions with 97.8% vs. 96.6%. CONCLUSIONS: NIBB represents an alternative method for delivery of breast tumor cavity boost that has shown feasibility in a diverse group of both academic and community-based practices with reproducible early cosmesis and tumor control results. Recommendations are updated noting ideal timing of boost delivery likely to be before or early during WBRT given equal cosmesis and less documented treatment discomfort.

Postmastectomy radiotherapy: patterns of recurrence and long-term disease control using electrons.

PURPOSE: To determine the patterns of failure and prognostic factors for locoregional recurrence after postmastectomy radiotherapy (RT), using a specific electron beam technique. METHODS AND MATERIALS: A uniform electron beam was used in 323 patients with invasive breast cancer at the University of Florida Health Science Center. The patterns of disease recurrence, prognostic factors, and overall outcome were studied. RESULTS: At 10 years, the freedom from locoregional recurrence, disease-free survival, and absolute survival rate was 90%, 62%, and 55%, respectively. The 10-year disease-free survival rate for patients with 0, 1-3, and >3 positive lymph nodes was 73%, 75%, and 47%, respectively. On multivariate analysis, the three factors significantly associated with locoregional recurrence were T stage, number of involved nodes, and RT fields. Full axillary fields appeared to be beneficial (p = 0.02). Patients with positive surgical margins appeared to benefit from a mastectomy incision boost to >/=65 Gy. Finally, patients with T2N0 disease had a substantial risk of chest wall recurrence without chest wall RT. CONCLUSION: Findings include a low rate of clinically detectable locoregional recurrence. The data suggest benefits for the addition of full axillary RT in node-positive patients and chest wall RT in patients with T2N0 disease.

Complete response of endemic Kaposi sarcoma lesions with high-dose-rate brachytherapy: treatment method, results, and toxicity using skin surface applicators.

PURPOSE: To analyze the clinical outcome of Kaposi sarcoma skin lesions treated with high-dose-rate (HDR) brachytherapy in patients with a minimum of 2 years of followup. METHODS AND MATERIALS: Between February 2006 and July 2008, all patients with Kaposi sarcoma who received (192)Ir HDR brachytherapy using a skin surface applicator were evaluated for clinical response. Responses to treatment and toxicity were scored using standard criteria. RESULTS: Sixteen cases were collected. Treatment was delivered in four to six fractions, over a period of approximately 12 days. The specified dose ranged from 24 to 35Gy. Median followup the lesion was 41.4 months. No lesion was greater than 2cm. All patients had a complete response to treatment, with no evidence of local recurrence or tumor progression. Thirteen lesions developed Grade 1 and two lesions had Grade 2 acute skin reactions. One patient developed late skin changes with telangiectasias and hypopigmentation. CONCLUSIONS: HDR brachytherapy treatment seems to be an effective noninvasive option for patients with small cutaneous Kaposi sarcoma lesions, delivering excellent cosmesis and local control in our small series. Fewer fractions over a shorter period used in our group offer patients more convenience compared with other common regimens. Although HDR is being used more frequently for many surface applications, additional clinical studies with larger numbers of patients and longer followup are needed to confirm the general impression that it is an excellent option for many patients.

A multi-institutional study of feasibility, implementation, and early clinical results with noninvasive breast brachytherapy for tumor bed boost.

PURPOSE: To evaluate the feasibility, implementation, and early results of noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT). METHODS AND MATERIALS: NIBB is a commercially available (AccuBoost, Billerica, MA) mammography-based, brachytherapy system in which the treatment applicators are centered on the planning target volume (PTV) to direct (192)Ir emissions along orthogonal axes. A privacy-encrypted online data registry collected information from 8 independent academic and community-based institutions. Data were from 146 consecutive women with early-stage breast cancer after lumpectomy and WBRT receiving boost with NIBB between July 2007 and March 2010. Toxicity and cosmesis were graded according to the Common Toxicity Criteria (v. 3.0) and the Harvard scale. Median follow-up was 6 months (1-39 months). RESULTS: Grade 1-2 skin toxicity was observed in 64%, 48%, and 21% during the acute (1-3 weeks), intermediate (4-26 weeks), and late-intermediate (>26 weeks) periods. There was no Grade 4 toxicity. At 6 months, for the entire cohort, cosmesis was excellent/good in 62%/38%. The subset receiving NIBB before WBRT had cosmetic scores of 32% and 63%, whereas during WBRT, 58% and 37% were rated as excellent and good, respectively. Breast compression was scored as "uncomfortable" in 12%, 29%, and 59% when NIBB was delivered before, during, or after WBRT. For each patient, the fraction-to-fraction variability in PTV was low. Skin flash was associated with a higher proportion of excellent cosmesis (58% vs. 42%) relative to having the applicator all within breast tissue. CONCLUSIONS: These data indicate that NIBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIBB is associated with acceptably mild normal tissue toxicity and favorable early cosmesis. The application of NIBB before WBRT may be associated with better patient tolerance at the expense of less favorable cosmetic outcome.