Breast Induration Research Articles

Pembrolizumab Induced Recall Dermatitis Occurring 5 Years After Radiotherapy

Background and Clinical Significance: Radiation recall dermatitis (RRD) following immune checkpoint inhibitor (ICI) therapy has been infrequently reported. Case Presentation: We present a 47-year-old female patient who developed RRD of the breast following three doses of pembrolizumab administered as an adjuvant treatment post-nephrectomy for Stage III renal cell carcinoma (RCC). Notably, the affected breast had previously undergone external beam radiotherapy 247 weeks earlier for Stage IA invasive ductal carcinoma. She had received no prior chemotherapy at any point. RRD manifested as breast induration, erythema, and peau d’orange, and contraction of breast volume was noted following three cycles of pembrolizumab on week 17 (400 mg dose every 6 weeks). The dermatitis responded rapidly to systemic corticosteroids and no treatment interruption was needed. Conclusion: To date, this is the longest reported interval from completion of radiotherapy to RRD. A literature search underscores the variability in presentation and management of ICI-associated RRD.

Breast induration and irradiated volume in the DBCG HYPO trial: The impact of age, smoking, and boost

PurposeTo investigate the association between irradiated breast volume and grade 2–3 breast induration three years after radiotherapy in the phase III Danish Breast Cancer Group HYPO trial randomizing patients ≥ 41 years to whole breast irradiation (WBI) with 40 Gy/15fr versus 50 Gy/25fr. MethodsTreatment plans were available for all Danish patients. Associations between frequency of induration and irradiated volume, age, smoking status, and boost were assessed by logistic regression. A sequential boost was given to patients < 50 years or in case of a narrow (<2 mm) resection margin. ResultsRT plans from 1,333 patients were analyzed with 178 (13 %) having grade 2–3 induration. 1135 patients had only WBI. For this group, induration was correlated with irradiated breast volume for patients ≥ 65 years (n = 343, 10 %/22 % for small/large irradiated volumes, p = 0.005) but not for patients aged 50–64 years (n = 792, 11 % for both small and large volumes, p = 0.82). Smoking doubled the frequency irrespective of irradiated volume and age. All patients < 50 years (n = 156) had a boost. A volume effect was found for this group (5 %/21 % induration for small/large volume, p = 0.002). 42 patients ≥ 50 years had a boost and 14 (33 %) had grade 2–3 induration, however, with a p-value > 0.05 due to the few numbers of patients. ConclusionA relationship between irradiated breast volume and 3-year frequency of breast induration was found for patients ≥ 65 years, whilst not for patients aged 50–64 years. Smoking doubled the risk of induration irrespective of volume and age. A dose-induration relationship was seen for boost patients < 50 years.

Uptake of ultra-hypofractionated radiation therapy following breast-conserving surgery among patients with early-stage breast cancer: a multi-institutional questionnaire survey.

In patients with early-stage breast cancer following breast surgery, ultra-hypofractionated (UHF) breast/chest wall radiation therapy (RT) has been shown to be non-inferior to a moderate-hypofractionated (MHF) regimen, with a minimal risk of breast induration, in the FAST-Forward trial, and UHF is now becoming the standard regimen in Europe. Herein, we aimed to investigate Japanese patients' attitudes toward the UHF regimen. A questionnaire-based survey was conducted at 13 RT centers in nine prefectures across Japan. All patients underwent breast-conserving surgery, followed by either conventional fractionation (2Gy/fr) or MHF (2.66Gy/fr) whole-breast irradiation (WBI) with or without a tumor bed boost. The questionnaire consisted of 13 questions mainly addressing quality-of-life during RT. Key questions included an 11-point scale (0-10) for rating the patients' enthusiasm for the UHF regimen and prioritization of the following treatment-related effects: treatment efficacy, acute/late adverse effects, physical/emotional/financial burden, and breast cosmesis. The patient and treatment characteristics were assessed by a physician. In total, 247 questionnaires were administered between November 2022 and June 2023. The age distribution was as follows: < 50:50s:60s: ≥ 70 = 59 (24%):76 (30%):63 (26%):49 (20%). Sixty-nine percent of patients rated their enthusiasm for the UHF regimen at ≥ 6 out of 10 points (45% rated 10/10). Treatment efficacy was the highest priority for most patients (89%), whereas breast cosmesis the lowest priority (53%). Patients' enthusiasm for UHF-WBI was observed across the cohort. These results could motivate researchers and clinicians to introduce UHF regimens in clinical practice.

The diagnostic and therapeutic evaluation of Idiopathic granulomatous mastitis. A case series

Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory condition of the breast that is commonly found in young women of childbearing age with a history of recent breastfeeding. In our study, we aimed to present the detailed clinical and morphological features of IGM cases, diagnostic clues, and treatment. The most common clinical presentation is a unilateral, breast induration, nipple retraction, and even a multiple sinus formation often associated with an inflammation of the overlying skin. It usually mimics with breast abscess, rarely inflammatory breast cancer. Although etiology is still unknown. Many factors, including autoimmunity, infection, chemical agent, lactation, and hormonal imbalance, are supposed to play a role for etiology. Therefore, thorough history taking, examination, imaging, and histopathology make a proper diagnosis that determines the optimal management to be administered. We are presenting three cases of granulomatous mastitis from our clinical practice with varying clinical features. After the necessary investigation, we diagnose it as IGM. There is no definitive treatment guideline still now. In literature, many therapeutic operations, including conservative treatment, surgery, steroid, and immunotherapy, have been shown. However, we successfully treated this patient by conservative treatment, by incision and drainage, surgical debridement, or by in a combination of both, followed by regular dressing, antibiotics, and other supportive measures with no use of the steroid.

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial

A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. Cancer Research UK.

OC-0768 Breast induration and irradiated volume in the DBCG HYPO trial: The importance of age and smoking

OC-0768 Breast induration and irradiated volume in the DBCG HYPO trial: The importance of age and smoking

Radiation-Induced Undifferentiated Pleomorphic Sarcoma after Breast Conserving Therapy: Case Report

Introduction: Breast sarcoma is a rare form of malignancy that arises from connective tissue, comprising less than 5% of all sarcomas. Undifferentiated pleomorphic sarcoma (UPS) of the breast is a rare and aggressive subtype of radiation-induced sarcoma that can occur in treated breast cancer patients. The diagnosis is challenging and often missed due to the low incidence, long latency period, unspecific imaging finding, and difficulties in clinical and histological detection. Case report: A 56-year-old woman was diagnosed with early-stage triple-negative breast cancer in 2013 and underwent breast-conserving therapy (BCT). After five years follow-up, she developed mastalgia and breast induration, and after mammography and ultrasound without suspicious lesions, a magnetic resonance imaging (MRI) was performed and showed a highly suggestive malignancy mass measuring 8.0 cm and invading the chest wall. The core biopsy revealed a spindle cells malignant tumor, negative for pan cytokeratin and most of immuno-histochemical markers, suggesting sarcoma, but requiring investigation of surgical specimen to exclude metaplastic carcinoma. She underwent Halsted radical mastectomy, full-thickness left anterior chest wall resection contemplating segments of the 4th and 5th ribs and reconstruction with synthetic mesh. The surgical specimen evidenced a UPS with clear margins. The patient had good postoperative recovery and remains in follow-up with the mastology team. Conclusion: This report shows that radiation-induced sarcomas of the breast can be difficult to diagnose, and how later treatment can demand a major surgery with higher morbidity. Prognosis may improve if detected early.

Abstract PD3-03: Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894)

Abstract Introduction. Breast-conserving surgery (BCS) followed by postoperative radiotherapy (RT) still represents the standard of care for early breast cancer (BC) patients. Hypofractionated schedules in maximum 15 fractions are currently accepted as the gold standard for external beam whole and partial breast irradiation (PBI). PBI for selected early BC patients allowed a shorter overall treatment duration and an improved patient compliance as compared to old-fashioned RT schedules. Preoperative PBI, due to the advantage of treating a well-defined volume, has been gaining attention in this multidisciplinary scenario. It avoids local treatment delay and might allow tumour downstaging with increased rates of BCS and improved cosmetic outcomes. Since local recurrence might be driven by biological mechanisms of radioresistance rather than geographical miss, higher dose per fraction may overcome repair mechanisms allowing tumoral cells to escape from conventional RT damage. We report the results of the phase II ROCK trial (NCT03520894), enrolling early BC patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods. The study recruited between August 2018 and September 2021 at the Radiation Oncology Unit of the University of Florence (Florence, Italy). Eligible patients were women aged 50+ years, with histologically proven invasive early BC, HR+/HER2- disease, without lymph vascular invasion, tumour size up to 25 mm suitable for BCS. Exclusion criteria were clinical node positive disease, multiple foci tumours, and patients with breast lesion limiting within 5 mm from the skin surface. The study aimed to prospectively assess the safety and feasibility of a single Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) 21Gy-fraction prRS in preoperative setting, and to identify predictive factors for outcomes based on biologic and clinical features. The primary endpoint was the acute skin toxicity (from the end of prRS to surgery) according to the RTOG and the EORTC scales. Secondary endpoints were the rate of early late skin and non-skin toxicity as measured 90 days from the end of prRS, the rate of pathological complete response (pCR) according to Chevalier score. Cosmetic outcomes were prospectively scored every 6-month using the BCCT.core software. Results. From August 2018 to September 2021, a total of 70 patients were recruited and enrolled. Of those, 41 were excluded due to tumour biology exclusion criteria and 7 due to multiple foci breast disease evidenced at basal MRI. Therefore, 22 patients were successfully treated with pRS. Median age at diagnosis was 68 years (range 50-86), median tumour size was 14 mm (range 7.5-25). Required target dosimetric parameters were met in all patients, as well as normal tissue constraints. Patients received surgery after a median time of 29 days from biopsy, without any delay or postoperative complication. Overall, three G1 adverse events (13.6%) were recorded within 7 days from prRS (1 erythema, 2 breast pain). Three events (13.6%) were recorded between 7 and 30 days from prRS, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity (1 breast pain, 4 breast induration). One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Overall, pCR after surgery was reported in 2 patients (9%). Two patients received postoperative whole breast irradiation, according to histopathological results. Conclusions. ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing a good safety profile and a promising effectiveness. Citation Format: Icro Meattini, Giulio Francolini, Vanessa Di Cataldo, Luca Visani, Carlotta Becherini, Erika Scoccimarro, Monica Mangoni, Viola Salvestrini, Laura Masi, Chiara Bellini, Raffaela Doro, Federica Di Naro, Marco Bernini, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Lorenzo Livi. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-03.

Volume matters: Breast induration is associated with irradiated breast volume in the Danish Breast Cancer Group phase III randomized Partial Breast Irradiation trial

PurposeThe relation between breast induration grade 2–3 at 3 years after radiation therapy and irradiated breast volume was investigated for patients in the Danish Breast Cancer Group (DBCG) Partial Breast Irradiation (PBI) trial. METHODS Treatment plan data was obtained from the Danish radiotherapy plan database. Dosimetric parameters for breast and organs at risk were determined. Breast induration data was obtained from the DBCG database. The volume of the whole breast (CTVp_breast) treated to various dose levels was determined for treatment plans in both arms. Logistic regression was used to assess the frequency of induration on breast volume irradiated to ≥40 Gy. RESULTS PBI and WBI was given to 433 and 432 patients, respectively. Median and interquartile ranges (IQR) for CTVp_breast were 710 mL (467–963 mL; PBI) and 666 mL (443–1012 mL; WBI) (p = 0.98). Median and IQR for CTVp_breast treated to ≥40 Gy was 24.9% (18.6–32.6%; PBI) and 59.8% (53.6–68.5%; WBI). Grade 2–3 induration was observed in 5% (PBI) and 10% (WBI) of the patients. A dose–response relationship was established between irradiated breast volume and frequency of breast induration. From the model, 5% and 10% risks of breast induration were observed for ≥40 Gy delivered to CTVp_breast volumes of 177 mL (95%CI, 94–260 mL) and 426 mL (95%CI, 286–567 mL), respectively. CONCLUSION The frequency of breast induration increased significantly with increasing irradiated breast volume, strongly favouring small volumes and PBI. Thus, treated breast volume – not the breast size itself - is the risk factor for induration. This is the first report directly linking the 40 Gy irradiated breast volume to breast induration.

Preoperative robotic radiosurgery for early breast cancer: Results of the phase II ROCK trial (NCT03520894)

Background and purposePreoperative partial breast irradiation (PBI) has got the advantage of treating a well-defined target. We report the results of the phase II ROCK trial (NCT03520894), enrolling early breast cancer (BC) patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methodsThe study recruited between 2018 and 2021 at our Radiation Oncology Unit. Eligible patients were 50 + years old BC, hormonal receptors positive/human epidermal growth factor receptor 2 negative (HR+/HER2-), sized up to 25 mm. The study aimed to prospectively assess the toxicity and feasibility of a robotic single 21 Gy-fraction prRS in preoperative setting. ResultsA total of 70 patients were recruited and 22 patients were successfully treated with pRS. Overall, three G1 adverse events (13.6 %) were recorded within 7 days from prRS. Three events (13.6 %) were recorded between 7 and 30 days, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity. One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6–29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. ConclusionsROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing an acceptable preliminary toxicity profile.

Partial Breast Irradiation Versus Whole Breast Irradiation for Early Breast Cancer Patients in a Randomized Phase III Trial: The Danish Breast Cancer Group Partial Breast Irradiation Trial.

On the basis of low risk of local recurrence in elderly patients with breast cancer after conservative surgery followed by whole breast irradiation (WBI), the Danish Breast Cancer Group initiated the noninferiority external-beam partial breast irradiation (PBI) trial (ClinicalTrials.gov identifier: NCT00892814). We hypothesized that PBI was noninferior to WBI regarding breast induration. Patients operated with breast conservation for relatively low-risk breast cancer were randomly assigned to WBI versus PBI, and all had 40 Gy/15 fractions. The primary end point was 3-year grade 2-3 breast induration. In total, 865 evaluable patients (434 WBI and 431 PBI) were enrolled between 2009 and 2016. Median follow-up was 5.0 years (morbidity) and 7.6 years (locoregional recurrence). The 3-year rate of induration was 9.7% for WBI and 5.1% for PBI (P = .014). Large breast size was significantly associated with induration with a 3-year incidence of 13% (WBI) and 6% (PBI) for large-breasted patients versus 6% (WBI) and 5% (PBI) for small-breasted patients. PBI showed no increased risk of dyspigmentation, telangiectasia, edema, or pain, and patient satisfaction was high. Letrozole and smoking did not increase the risk of radiation-associated morbidity. Sixteen patients had a locoregional recurrence (six WBI and 10 PBI; P = .28), 20 patients had a contralateral breast cancer, and eight patients had distant failure (five WBI and three PBI). A nonbreast second cancer was detected in 73 patients (8.4%), and there was no difference between groups. External-beam PBI for patients with low-risk breast cancer was noninferior to WBI in terms of breast induration. Large breast size was a risk factor for radiation-associated induration. Few recurrences were detected and unrelated to PBI.

Accelerated hypofractionated breast radiotherapy with simultaneous integrated boost: a feasibility study.

PurposeTo assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer.Materials and MethodsA total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves.ResultsThe mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively.ConclusionWith this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

OC-0930 Breast induration versus irradiated breast volume in the randomized phase III DBCG PBI trial

OC-0930 Breast induration versus irradiated breast volume in the randomized phase III DBCG PBI trial

Effectiveness and safety of intraoperative radiotherapy (IORT) with low-energy X-rays (INTRABEAM®) for accelerated partial breast irradiation (APBI).

To evaluate treatment outcomes in patients with early-stage breast cancer (ESBC) treated with targeted intraoperative radiation therapy (IORT) administered as accelerated partial breast irradiation (APBI). Between December 2014 and May 2019, 50 patients diagnosed with ESBC were treated with a 50 kilovoltage (kV) X-ray source with a single dose of 20Gy using the Intrabeam® radiotherapy delivery system. All patients were followed prospectively to assess local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), radiation-induced toxicity, and cosmetic outcomes. We also evaluated the prognostic implications of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Median follow-up was 53months. Mean patient age was 70years. The mean duration of radiation delivery was 22.25min. Two patients developed a recurrence. One death was recorded. Elevated pretreatment NLR levels were a significant risk factor for mortality (p = 0.0026). The most common treatment-related toxicities were breast induration (30%) and seroma (18%). Five-year LC, DFS, CSS, and OS rates were 97.1%, 93.9%, 100%, and 94.4%, respectively. Cosmesis was excellent or good in most cases (94%). These findings confirm the effectiveness of a single dose of 20Gy of IORT with the Intrabeam device as APBI. The toxicity profile was good with excellent cosmesis. These results provide further support for the clinical use of APBI in well-selected patients.

A Five-step Systematic Therapy for Treating Plugged Ducts and Mastitis in Breastfeeding Women: A Case–Control Study

This study aimed to describe the clinical response to five-step systematic therapy (FSST) in the management of plugged ducts and mastitis. FSST was a comprehensive milk stasis dredging treatment, which contained five steps to make the milk out of the plugged duct. This retrospective study included 922 breastfeeding women, 714 with plugged ducts, and 208 with mastitis who received FSST from June to September 2017. The breast pain score, swelling degree, and range of breast induration were recorded pre-FSST and post-FSST. After a single FSST, pain score and swelling degree were significantly improved (bothp<.001) in all cases. After FSST, the mean breast pain relief score was 1.69±0.70, whereas the mean swelling fade away degree was 1.61±0.62. In the subgroup analysis, pain score and swelling degree were significantly improved (bothp<.001) in the plugged ducts group and the mastitis group. The score of pain relief in the plugged ducts group was less than that in the mastitis group (1.63±0.68 vs. 1.91±0.70, t=5.30; p<.001), whereas improvement of swelling fade away was greater in the plugged ducts group than the mastitis group (1.65±0.64 vs. 1.48±0.56, t=3.49; p=.001). The composition ratio of changes in induration range between the two groups was statistically different (Pearson χ2=137.87, p<.001), of which more obvious improvement in the plugged ducts group than the mastitis group (χ2=25.65, p<.001). FSST can relieve pain, reduce breast swelling and range of induration, and for plugged ducts or mastitis varied degree differently.

Abstract GS4-03: RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT)

Abstract Background Whole breast irradiation (WBI) after lumpectomy reduces the risk of local recurrence, thereby avoiding subsequent mastectomy. It is a key component of breast conserving therapy. WBI is usually given in daily fractions over 3-6 weeks. With accelerated partial breast irradiation (APBI), radiation is delivered over a week or less to the surgical cavity with a margin of normal tissue. It was introduced to provide treatment in a shorter more convenient form. 3D-CRT is an attractive approach as it is non-invasive and uses standard techniques for external beam RT that are widely available. The objective of the RAPID trial was to determine if APBI using 3D-CRT was not inferior to WBI following breast conserving surgery (BCS). Methods Women ≥40 years of age with axillary node-negative invasive ductal carcinoma, or ductal carcinoma in situ (DCIS) ≤3cm treated by BCS with clear margins of excision were eligible. Randomization was stratified for age (&amp;lt; or ≥50y), histology (DCIS alone or invasive breast cancer), tumor size (&amp;lt; or ≥1.5cm), ER status (+/-) if invasive disease, and treatment center. Patients were allocated to APBI using 3D-CRT (38.5Gy in 10 fractions delivered twice daily) or WBI (42.5Gy in 16 daily fractions or 50Gy in 25 daily fractions; boost radiation was permitted). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Important secondary outcomes included radiation toxicity and nurse assessed adverse cosmesis (fair or poor on global assessment). The trial was designed to show that the 5-year IBTR rate in the APBI arm was not inferior to the WBI arm by more than 1.5% (hazard ratio [HR] ≤ 2.02) with 85% power and a one-sided alpha of 5%. Results From February 2006 to July 2011, 2135 patients from sites in Canada, Australia, and New Zealand were randomly assigned: 1070 to APBI and 1065 to WBI. The median follow-up was 8.6 years. The mean age of the study population was 61 years; 82% of patients had invasive breast cancer and 18% had DCIS only. For invasive cancers: 60% were &amp;lt; 1.5cm and 90% were ER positive. For DCIS tumors: 68% were &amp;lt; 1.5cm. A total of 65 IBTRs were observed. For the APBI patients, the 5-year and 8-year cumulative rates of IBTR were 2.3% and 3.0%, respectively. The corresponding data for the WBI patients were 1.7% and 2.8%. The HR for APBI versus WBI was 1.27, 90% confidence interval, 0.84 to 1.91. Acute radiation toxicity (occurring within 3 months of treatment start) e.g. radiation dermatitis and breast swelling was less in patients treated with APBI compared with WBI (≥ Grade 2, 28% vs 45%, p&amp;lt;0.001). Late radiation toxicity (beyond 3 months) e.g. breast induration and telangiectasia was greater in patients treated with APBI (≥ Grade 2, 32% vs 13%, p&amp;lt;0.001 and Grade 3, 4.5% vs 1.0%, p&amp;lt;0.001). Adverse cosmesis was higher in patients treated with APBI compared with WBI at 3 years (29% vs 17%, p&amp;lt;0.001) and at 5 years (32% vs 16%, p&amp;lt;0.001). Conclusions The APBI regimen used in our trial was non-inferior to WBI in preventing local recurrence. Although it was associated with less acute toxicity, an increase in late normal tissue toxicity and adverse cosmesis was observed with APBI. Citation Format: Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS, Germain I, Nichol A, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera F, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham W, Chua B, Olivotto I. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-03.

Abstract GS4-05: Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003)

Abstract Background IMPORT HIGH is a randomised, multi-centre phase III trial testing dose escalated simultaneous integrated boost (SIB) against sequential boost each delivered by intensity modulated radiotherapy (IMRT) for early stage breast cancer with higher risk of local relapse. The primary endpoint was initially breast induration at 3 years, requiring 840 patients; accrual was extended (target 2568) with the new primary endpoint of local relapse. We report adverse effects (AE) at 3 years. Methods Women age ≥18 after breast conservation surgery for pT1-3 pN0-pN3a M0 invasive carcinoma were eligible. Randomisation was 1:1:1 between 40Gy/15F to whole breast (WB) + 16Gy/8F sequential photon boost to tumour bed (40+16Gy), 36Gy/15F to WB, 40Gy to partial breast + 48Gy (48Gy) or + 53Gy (53Gy) in 15F SIB to tumour bed. AEs were assessed annually by clinicians in all patients and in a planned sub-set (840) of patients by photographs at 3 years and by patients at 6 months, 1 and 3 years. AE scores were dichotomised as none/mild vs marked for photographs and none/mild vs moderate/marked for patients and clinicians. Fisher's exact tests compared groups; principal comparison (protocol-specified) between 53Gy and 48Gy (p&amp;lt;0.01 defined as statistical significance). Results 2617 women consented between 03/2009 and 09/2015 from 39 UK radiotherapy centres. Median follow-up was 49.1 (IQR 36.8-63.2) months. Median age was 49 (IQR 44-56); 9%, 38% &amp; 53% were tumour grade 1, 2 &amp; 3 respectively; 30% were node positive. 66% received chemotherapy and 73% endocrine therapy. 3-year AE data were available for 2017 clinician assessments, 641 photographs and 842 patient assessments. Proportions of patients with marked AEs were low overall. Rates of moderate/marked AEs at 3 years were broadly similar between the randomised groups; with a suggestion of a slightly increased risk for breast induration in 53Gy compared with control (borderline significance). AE at 3 years 40+16Gy n(%)48Gy n(%)53Gy n(%)ClinicianBreast induration;N656668654None451 (69)483 (72)445 (68)Mild167 (25)141 (21)146 (22)Moderate32 (5)42 (6)56 (9)Marked6 (1)2 (1)7 (1)P-value 0.57010.0102 0.0443Breast shrinkage;N655669654None442 (68)472 (71)448 (69)Mild167 (26)161 (24)166 (25)Moderate40 (6)33 (5)35 (5)Marked6 (1)3 (1)5 (1)P-value 0.25410.5772 0.6373Breast distortion;N656669654None451 (69)464 (69)442 (68)Mild169 (26)170 (25)170 (26)Moderate33 (5)32 (5)38 (6)Marked3 (1)3 (1)4 (1)P-value 0.90310.4862 0.4113PatientChange in breast appearance;N287264285None38 (13)50 (19)58 (20)Mild164 (57)151 (57)142 (50)Moderate57 (20)45 (17)54 (19)Marked28 (10)18 (7)31 (11)P-value 0.14910.9992 0.1243PhotographChange in breast appearance;N218210213None183 (84)185 (88)177 (83)Mild25 (11)23 (11)32 (15)Marked10 (5)2 (1)4 (2)P-value 0.03610.1732 0.6853148Gy v 40+16Gy; 253Gy v 40+16Gy; 353Gy v 48Gy Conclusions These results represent the largest and most mature reported AE outcomes of breast SIB within a clinical trial. At 3 years, rates of moderate/marked AEs were similar between SIB IMRT and WB + sequential boost IMRT delivered over 3 and 4.5 weeks respectively. Citation Format: Coles CE, Griffin CL, Kirby AM, Haviland JS, Titley JC, Benstead K, Brunt AM, Chan C, Ciurlionis L, Din OS, Donovan EM, Eaton DJ, Harnett AN, Hopwood P, Jefford ML, Jenkins PJ, Lee CE, McCormack M, Sherwin L, Syndikus I, Tsang Y, Twyman NI, Ventikaraman R, Wickers S, Wilcox MH, Bliss JM, Yarnold JR. Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-05.

Hypofractionated Partial Breast Irradiation after Breast-conserving Surgery for Patients with Low-risk Breast Cancer: Preliminary Safety Results in initial 50 Cases

To report preliminary safety results of initial 50 cases with early-stage hormone receptor (HR)-positive breast cancer treated with hypofractionated partial breast irradiation using simplified intensity-modulated radiation therapy (sIMRT) technique after breast conservation surgery. From Dec of 2014 to Oct of 2016, fifty women patients aged more than 50 years affected by early-stage hormone receptor (HR)-positive breast cancer, with a maximum pathological size of 25 mm and negative axillary nodes, were enrolled to receive a total dose of 40Gy to the tumor bed in 15 fractions using sIMRT technique at our institute. The primary endpoint was occurrence of ipsilateral breast tumor recurrence (IBTR); the secondary endpoint was radiation-associated toxicity graded according to the common terminology of criteria for adverse events version 4.0 (CTCAE v4.0) issued by the National Cancer Institute; and the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov (registration No. NCT03411174). The median age was 64 (range: 57-74) years old. The median size of the primary tumor was 15 (range: 2-25) mm. At a median follow-up of 23 (range: 13-37) months, no IBTRs were found to develop. The most frequently observed acute adverse event was skin erythema. Grade 1 radiation dermatitis was found to occur in 9 cases (18.0%). No grade 2 or higher radiation dermatitis was observed. 7 patients (14.0%) experienced grade 1 breast pain. Only 1 patient was noted to develop grade 1 breast induration. None were observed to have skin telangiectasis or fatty necrosis. This preliminary analysis demonstrated that hypofractionated partial breast irradiation delivered with IMRT technique was clinically safe in patients with early-stage HR-positive breast cancer after breast-conserving surgery. Further study with greater number of patients and longer follow-up is warranted.

Electronic Brachytherapy at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer: Early Follow-Up Results of a Nonrandomized, Multicenter Trial

To describe early follow-up results of a trial of single-fraction, intra-operative radiation therapy (IORT) delivered with an electronic brachytherapy system immediately following surgical resection for treatment of early-stage breast cancer. To date, 1,028 participants have been enrolled in this open label, single-arm, prospective, non-randomized trial at 28 hospitals in the USA (27) and Portugal (1). 1,023 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by IORT to the lumpectomy cavity. A presterilized lead shield was placed on the chest wall and a balloon applicator suitable to the surgical bed was placed in the lumpectomy cavity and inflated with saline (30-75 cc). Balloon surface-to-skin distance of ≥ 1.0 cm was confirmed by ultrasound. Single-fraction IORT (20 Gy) was delivered at the balloon applicator surface with a mean radiation treatment time of 11.3 minutes. Following IORT, balloon was deflated and removed along with lead shielding, and surgical site was sutured. The prespecified primary outcome of this 10-year follow-up study is ipsilateral breast tumor recurrence at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Median follow-up time was 1.2 years with 320, 102, and 10 participants completing 2-, 3-, and 4-year follow-up, respectively. Mean age at enrollment was 66 years (range 41-93). 246 participants had DCIS and 777 had invasive ductal carcinoma. DCIS nuclear grades were high (82), intermediate (119), or low (45) with three identified as bilateral. Invasive cancers were Grade 1 (318) including two bilateral cases, Grade 2 (340) with one bilateral case, Grade 3 (105) with two bilateral cases, or no Grade (14). Mean tumor size was 12.01 ± 10.8 mm. Cosmesis was excellent in 100% of participants at 4-year follow-up and excellent to good in 94% and 91% of participants at 2- and 3-year follow-up, respectively. The number of reported adverse events (AEs) that were Grade 2 or higher was 169 (9%). Seroma, breast induration, erythema, breast fibrosis, and breast pain were the most frequent AEs. There were ten deaths, none of which were breast cancer related. There were six ipsilateral breast recurrences and three new contralateral breast cancers. Single-fraction IORT using an electronic brachytherapy system following breast conservation surgery may be a promising treatment option for select early-stage breast cancer patients. Early findings from this multicenter trial suggest that the short and convenient course of radiation therapy has low morbidity, excellent to good cosmetic results, and a low rate of high-grade adverse events and recurrences.

Abstract P1-10-19: Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.