Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation.

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Outcomes of HER2-positive non-metastatic breast cancer patients treated with anti-HER2 therapy without chemotherapy.

PURPOSE: Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy. METHODS: The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups. RESULTS: Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1-42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68-1.15) or after propensity score matching (HR 0.80 95% CI 0.57-1.11). CONCLUSIONS: There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

Ductal Carcinoma in Situ in Young Women: Increasing Rates of Mastectomy and Variability in Endocrine Therapy Use.

BACKGROUND: Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS). METHODS: Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models. RESULTS: A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11-27%; p < 0.001). In women < 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p < 0.001). CONCLUSION: The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women < 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

The Clinical Utility of DCISionRT® on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery.

BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT®) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT. METHODS: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. CONCLUSIONS: DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

Automatic treatment planning for VMAT-based total body irradiation using Eclipse scripting.

The purpose of this work is to establish an automated approach for a multiple isocenter volumetric arc therapy (VMAT)-based TBI treatment planning approach. Five anonymized full-body CT imaging sets were used. A script was developed to automate and standardize the treatment planning process using the Varian Eclipse v15.6 Scripting API. The script generates two treatment plans: a head-first VMAT-based plan for upper body coverage using four isocenters and a total of eight full arcs; and a feet-first AP/PA plan with three isocenters that covers the lower extremities of the patient. PTV was the entire body cropped 5 mm from the patient surface and extended 3 mm into the lungs and kidneys. Two plans were generated for each case: one to a total dose of 1200 cGy in 8 fractions and a second one to a total dose of 1320 cGy in 8 fractions. Plans were calculated using the AAA algorithm and 6 MV photon energy. One plan was created and delivered to an anthropomorphic phantom containing 12 OSLDs for in-vivo dose verification. For the plans prescribed to 1200 cGy total dose the following dosimetric results were achieved: median PTV V100% = 94.5%; median PTV D98% = 89.9%; median lungs Dmean = 763 cGy; median left kidney Dmean = 1058 cGy; and median right kidney Dmean = 1051 cGy. For the plans prescribed to 1320 cGy total dose the following dosimetric results were achieved: median PTV V100% = 95.0%; median PTV D98% = 88.7%; median lungs Dmean = 798 cGy; median left kidney Dmean = 1059 cGy; and median right kidney Dmean = 1064 cGy. Maximum dose objective was met for all cases. The dose deviation between the treatment planning dose and the dose measured by the OSLDs was within ±4%. In summary, we have demonstrated that scripting can produce high-quality plans based on predefined dose objectives and can decrease planning time by automatic target and optimization contours generation, plan creation, field and isocenter placement, and optimization objectives setup.

Radiation effect on late cardiopulmonary toxicity: An analysis comparing supine DIBH versus prone techniques for breast treatment.

Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left-sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S-DIBH) with prone free breathing (P-FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S-DIBH and P-FB plans was compared using paired two-tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%-0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%-0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%-15.4%) for S-DIBH and 1.0% (range 0.4%-9.8%) for P-FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%-6.0%) with S-DIBH and 0.0% (range 0.0%-0.4%) with P-FB (P = .008). Both S-DIBH and P-FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S-DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI.

Post-mastectomy Radiation Therapy in Breast Cancer Patients with Nodal Micrometastases.

BACKGROUND: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS: The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS: From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION: In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

Ductal carcinoma in situ on core needle biopsy only with no residual disease at surgery.

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) remains controversial and may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core needle biopsy (CNB), who have no residual disease in the lumpectomy specimen. The purpose of this study was to explore the frequency of this presentation and short-term outcomes in these patients. METHODS: Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010 to 2016 and treated with lumpectomy. Variables included patient and tumor characteristics, adjuvant treatment, and ipsilateral breast tumor recurrence (IBTR). Statistical analyses included Pearson's chi-square, Fisher's exact tests, and Kaplan-Meier analysis. RESULTS: Of 547 patients with pure DCIS, 50 (14%) had DCIS on CNB only. Of the patients with DCIS on CNB only, 15 were treated with lumpectomy and radiation therapy (RT), while 35 underwent lumpectomy without RT. At a median follow-up of 4 years, there were 3 (6%) IBTR all within the same quadrant as the original lumpectomy site. None of the patients who recurred received adjuvant RT or hormonal therapy. CONCLUSIONS: Despite the minimal extent of disease exhibited in these cases, 6% of patients with DCIS on CNB only had IBTR at a median follow-up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Size and margins are not sufficient criteria to stratify risk and guide decisions for adjuvant therapies.

Ipilimumab and whole brain radiation therapy for melanoma brain metastases.

Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3-4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity.

Comparative patient-centered outcomes (health state and adverse sexual symptoms) between adjuvant brachytherapy versus no adjuvant brachytherapy in early stage endometrial cancer.

PURPOSE: To determine a relationship between sexual functioning and health state among survivors of stage I endometrial cancer, and to examine whether adjuvant intravaginal radiotherapy (IVRT) affects these measures compared to hysterectomy alone. METHODS: Two hundred five survivors (>1 year from surgery) completed questionnaires containing the EuroQol (EQ5D) and the Female Sexual Function Index (FSFI). A total of 136 (66.3 %) underwent surgery alone, and 69 (33.7 %) received IVRT. Pearson correlation was used to correlate FSFI and EQ5D-Health State scores. Multivariable regression was performed to measure the impact of IVRT on sexual functioning and health state. RESULTS: A majority of patients (80 %) met criteria for sexual dysfunction by FSFI < 26.5. A significant correlation was detected between FSFI and EQ5D scores (Pearson correlation = 0.21, p = 0.003). Compared to the IVRT group, the surgery group was younger (p = 0.001) and trended toward more frequent use of minimally invasive surgery versus laparotomy (p = 0.08). Otherwise, the two groups were well balanced with respect to demographics, comorbidities, and baseline sexual activity. Controlling for age and surgery type, IVRT was not associated with poorer health state or sexual function. Receipt of laparotomy was associated with both poorer health state and sexual function (p = 0.0156 and p = 0.0247, respectively). CONCLUSIONS: Sexual functioning was generally poor among endometrial cancer survivors; however, those with improved FSFI scores tended to have superior health states. IVRT was not a significant risk factor; however, receipt of laparotomy appeared to be associated with poorer sexual functioning and health state.

Whole-lung irradiation in the treatment of metastatic synovial sarcoma.

Whole-lung irradiation (WLI) is standard of care in the treatment of patients with rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor and pulmonary metastases. However, it is not routinely utilized in the treatment of pulmonary metastases arising from other soft tissue sarcoma histologies. A patient presented with synovial sarcoma of his groin and punctate pulmonary metastases. After completion of multimodality treatment to his primary lesion, he received WLI. The patient is without evidence of disease at 3.8 years. This case demonstrates the need for further study of WLI in synovial sarcoma as it may improve outcomes in patients with this disease.

Harnessing the cGAS-STING pathway to potentiate radiation therapy: current approaches and future directions.

In this review, we cover the current understanding of how radiation therapy, which uses ionizing radiation to kill cancer cells, mediates an anti-tumor immune response through the cGAS-STING pathway, and how STING agonists might potentiate this. We examine how cGAS-STING signaling mediates the release of inflammatory cytokines in response to nuclear and mitochondrial DNA entering the cytoplasm. The significance of this in the context of cancer is explored, such as in response to cell-damaging therapies and genomic instability. The contribution of the immune and non-immune cells in the tumor microenvironment is considered. This review also discusses the burgeoning understanding of STING signaling that is independent of inflammatory cytokine release and the various mechanisms by which cancer cells can evade STING signaling. We review the available data on how ionizing radiation stimulates cGAS-STING signaling as well as how STING agonists may potentiate the anti-tumor immune response induced by ionizing radiation. There is also discussion of how novel radiation modalities may affect cGAS-STING signaling. We conclude with a discussion of ongoing and planned clinical trials combining radiation therapy with STING agonists, and provide insights to consider when planning future clinical trials combining these treatments.

A Radiation Therapy Contouring Atlas for Delineation of the Level I and II Axillae in the Prone Position: A Single-Institution Experience.

PURPOSE: With transition from supine to prone position, tenting of the pectoralis major occurs, displacing the muscle from the chest wall and shifting the level I and II axillary spaces. For patients for whom we aim to treat the level I and II axillae using the prone technique, accurate delineation of these nodal regions is necessary. Although different consensus guidelines exist for delineation of nodal anatomy in supine position, to our knowledge, there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I and II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by 2 radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I and II axillae on noncontrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I and II axillae in prone position using bone, muscle, and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior borders of level II and the anterior, posterior, medial, and lateral borders of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I and II axillae when the axillae are targets in addition to the breast.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.