Technical recommendations for implementation of Volumetric Modulated Arc Therapy and Helical Tomotherapy Total Body Irradiation.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.

Adjuvant Therapy for Elderly Breast Cancer Patients after Breast-Conserving Surgery: Outcomes in Real World Practice.

We aimed to evaluate the standard of care of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elderly female patients (≥65 years) treated outside of clinical trials and to identify potential factors related to the omission of RT and the interaction with endocrine therapy (ET). All women treated with BCS at two major breast centers between 1998 and 2014 were evaluated. Data were provided by the Tumor Registry Munich. Survival analyses were conducted using the Kaplan-Meier method. Prognostic factors were identified using multivariate Cox regression analysis. The median follow-up was 88.4 months. Adjuvant RT was performed in 82% (2599/3171) of patients. Irradiated patients were younger (70.9 vs. 76.5 years, p < 0.001) and were more likely to receive additional chemotherapy (p < 0.001) and ET (p = 0.014). Non-irradiated patients more often had non-invasive DCIS tumors (pTis: 20.3% vs. 6.8%, p < 0.001) and did not undergo axillary surgery (no axillary surgery: 50.5% vs. 9.5%, p < 0.001). Adjuvant RT was associated with improved locoregional tumor control after BCS in invasive tumors (10-year local recurrence-free survival (LRFS): 94.0% vs. 75.1%, p < 0.001, 10-year lymph node recurrence-free survival (LNRFS): 98.1% vs. 93.1%, p < 0.001). Multivariate analysis confirmed significant benefits for local control with postoperative RT. Furthermore, RT led to increased locoregional control even in patients who received ET (10-year LRFS 94.8% with ET + RT vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.2% vs. 95.0%, p = 0.003). Similarly, RT alone had significantly better locoregional control rates compared to ET alone (10-year LRFS 92.6% with RT alone vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.0% vs. 95.0%, p = 0.014). The present work confirms the efficacy of postoperative RT for breast carcinoma in elderly patients (≥65 years) treated in a modern clinical setting outside of clinical trials, even in patients who receive ET.

Positron Emission Tomography/Computed Tomography (PET/CT)-Based, Local Consolidative Radiotherapy after Chemoimmunotherapy in Metastatic, Non-Oncogene-Addicted Non-Small-Cell Lung Cancer (NSCLC).

The optimal sequence of chemo/immuno- and radiotherapy (RT) in metastatic non-small-cell lung cancer (NSCLC) remains challenging. Here, we describe the case of a 58-year-old female patient with an initially metastasized NSCLC obtaining local and distance durable response after chemo-immunotherapy and local RT associated with immunotherapy maintenance. Our experience offers a valuable perspective in choosing how to combine therapies to ensure the longest possible response in patients with estimated poor prognosis.

ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children.

BACKGROUND AND PURPOSE: Myeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high-risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children. MATERIAL AND METHODS: The European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established. RESULTS: Myeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3-4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III-IV evidence. Preferential TBI dose in children is 12-14.4 Gy in 1.6-2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to ≤10 Gy, and for the lenses to <12 Gy, for dose rates ≥6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies. CONCLUSIONS: These ESTRO ACROP SIOPE recommendations provide expert consensus for conventional and highly conformal myeloablative TBI in children, as well as a supporting literature overview of TBI techniques and toxicities.

Timing of tumor-induced atelectasis resolution and pulmonary function restoration in the course of image-guided moderate hypofractionated thoracic irradiation: a case report and mini-review of literature.

This case report describes a patient with squamous cell carcinoma of the lung (cT4 (Infiltration of left pulmonary artery) cN2 cM0, TNM eighth edition) and subsequent tumor-induced atelectasis of the left upper lobe. Despite initially presenting himself with a poor performance status (ECOG-PS III) and diminished lung function, the patient was treated with image-guided thoracic irradiation to a total dose of 45.0 Gy (to the whole planning target volume) / 52.5 Gy (as simultaneous integrated boost to the Primary Tumor) applied in 15 daily fractions. Through the radiation treatment, the upper lobe could be reaerated, and the patient's lung function and performance were improved.

Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma-an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial.

PURPOSE: In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. PATIENTS AND METHODS: A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. RESULTS: Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. CONCLUSION: In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed.

Novel Multimodal Management of Post-Partum Synchronous Metastatic Pulmonary EBV-Associated Lymphoepithelioma-Like Carcinoma (LELC)-A Case Report.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.

Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

INTRODUCTION: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). METHODS: Four treatment plans were created (3D-CRT and IMRT -/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. RESULTS: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. CONCLUSION: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Towards homogenization of total body irradiation practices in pediatric patients across SIOPE affiliated centers. A survey by the SIOPE radiation oncology working group.

BACKGROUND AND PURPOSE: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers. METHODS: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously. RESULTS: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated ≤10 pediatric patients annually (range: 1-2 to >25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques. CONCLUSION: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI.

Pretreatment central quality control for craniospinal irradiation in non-metastatic medulloblastoma : First experiences of the German radiotherapy quality control panel in the SIOP PNET5 MB trial.

PURPOSE: Several studies have demonstrated the negative impact of radiotherapy protocol deviations on tumor control in medulloblastoma. In the SIOP PNET5 MB trial, a pretreatment radiotherapy quality control (RT-QC) program was introduced. A first analysis for patients enrolled in Germany, Switzerland and Austria with focus on types of deviations in the initial plan proposals and review criteria for modern radiation technologies was performed. METHODS AND PATIENTS: Sixty-nine craniospinal irradiation (CSI) plans were available for detailed analyses. RT-QC was performed according to protocol definitions on dose uniformity. Because of the lack of definitions for high-precision 3D conformal radiotherapy within the protocol, additional criteria for RT-QC on delineation and coverage of clinical target volume (CTV) and planning target volume (PTV) were defined and evaluated. RESULTS: Target volume (CTV/PTV) deviations occurred in 49.3% of initial CSI plan proposals (33.3% minor, 15.9% major). Dose uniformity deviations were less frequent (43.5%). Modification of the RT plan was recommended in 43.5% of CSI plans. Unacceptable RT plans were predominantly related to incorrect target delineation rather than dose uniformity. Unacceptable plans were negatively correlated to the number of enrolled patients per institution with a cutoff of 5 patients (p = 0.001). CONCLUSION: This prospective pretreatment individual case review study revealed a high rate of deviations and emphasizes the strong need of pretreatment RT-QC in clinical trials for medulloblastoma. Furthermore, the experiences point out the necessity of new RT-QC criteria for high-precision CSI techniques.

Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.

Heart sparing radiotherapy in breast cancer: the importance of baseline cardiac risks.

BACKGROUND: Patients with left-sided breast cancer have an increased risk of cardiovascular disease (CVD) after radiotherapy (RT). While the awareness of cardiac toxicity has increased enormously over the last decade, the role of individual baseline cardiac risks has not yet been systematically investigated. Aim of the present study was to evaluate the impact of baseline CVD risks on radiation-induced cardiac toxicity. METHODS: Two hundred ten patients with left-sided breast cancer treated in the prospective Save-Heart Study using a deep inspiration breath-hold (DIBH) technique were analysed regarding baseline risk factors for CVD. Three frequently used prediction tools (Procam, Framingham and Reynolds score) were applied to evaluate the individual CVD risk profiles. Moreover, 10-year CVD excess absolute risks (EAR) were estimated using the individual mean heart dose (MHD) of treatment plans in free breathing (FB) and DIBH. RESULTS: The individual baseline CVD risk factors had a strong impact on the 10-year cumulative CVD risk. The mean baseline risks of the non-diabetic cohort (n = 200) ranged from 3.11 to 3.58%, depending on the risk estimation tool. A large number of the non-diabetic patients had a very low 10-year CVD baseline risk of ≤1%; nevertheless, 8-9% of patients reached ≥10% baseline 10-year CVD risk. In contrast, diabetic patients (n = 10) had significantly higher baseline CVD risks (range: 11.76-24.23%). The mean 10-year cumulative risk (Framingham score) following RT was 3.73% using the DIBH-technique (MHD:1.42Gy) and 3.94% in FB (MHD:2.33Gy), after adding a 10-year-EAR of + 0.34%(DIBH) and + 0.55%(FB) to the baseline risks, respectively. Smoking status was one of the most important and modifiable baseline risk factors. After DIBH-RT, the 182 non-smoking patients had a mean 10-year cumulative risk of 3.55% (3.20% baseline risk, 0.35% EAR) as compared to 6.07% (5.60% baseline risk, 0.47% EAR) for the 28 smokers. CONCLUSION: In the present study, all CVD prediction tools showed comparable results and could easily be integrated into daily clinical practice. A systematic evaluation and screening helps to identify high-risk patients who may benefit from primary prevention. This could result in an even higher benefit than from heart-sparing irradiation techniques alone.

Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.

Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results: Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.

Three-dimensional surface imaging in breast cancer: a new tool for clinical studies?

BACKGROUND: Three-dimensional Surface Imaging (3DSI) is a well-established method to objectively monitor morphological changes in the female breast in the field of plastic surgery. In contrast, in radiation oncology we are still missing effective tools, which can objectively and reproducibly assess and document adverse events in breast cancer radiotherapy within the framework of clinical studies. The aim of the present study was to apply structured-light technology as a non-invasive and objective approach for the documentation of cosmetic outcome and early effects of breast radiotherapy as a proof of principle. METHODS: Weekly 3DSI images of patients receiving either conventionally fractionated radiation treatment (CF-RT) or hypofractionated radiation treatment (HF-RT) were acquired during the radiotherapy treatment and clinical follow-up. The portable Artec Eva scanner (Artec 3D Inc., Luxembourg) recorded 3D surface images for the analysis of breast volumes and changes in skin appearance. Statistical analysis compared the impact of the two different fractionation regimens and the differences between the treated and the contralateral healthy breast. RESULTS: Overall, 38 patients and a total of 214 breast imaging sessions were analysed. Patients receiving CF-RT showed a significantly higher frequency of breast erythema compared to HF-RT (93.3% versus 34.8%, p = 0.003) during all observed imaging sessions. Moreover, we found a statistically significant (p < 0.05) volumetric increase of the treated breast of the entire cohort between baseline (379 ± 196 mL) and follow-up imaging at 3 months (437 ± 224 mL), as well as from week 3 of radiotherapy (391 ± 198 mL) to follow-up imaging. In both subgroups of patients undergoing either CF-RT or HF-RT, there was a statistically significant increase (p < 0.05) in breast volumes between baseline and 3 months follow-up. There were no statistically significant skin or volumetric changes of the untreated healthy breasts. CONCLUSIONS: This is the first study utilizing 3D structured-light technology as a non-invasive and objective approach for the documentation of patients receiving breast radiotherapy. 3DSI offers potential as a non-invasive tool to objectively and precisely monitor the female breast in a radiooncological setting, allowing clinicians to objectively distinguish outcomes of different therapy modalities.

Preoperative radiotherapy: A paradigm shift in the treatment of breast cancer? A review of literature.

The standard of care for early-stage breast cancer (BC) consists of breast-conserving surgery followed by postoperative irradiation. Recently, the concept of changing the usual sequence of treatment components in BC RT has been investigated. Potential advantages of preoperative RT in BC include a possible tumor downstaging with improved surgical cosmetic outcomes, accurate tumor site identification and better target volume delineation. Furthermore, preoperative RT could serve as a tool for treatment stratification for de-escalation of treatments in the event of pathological complete response. The present literature review analyzed the available clinical data regarding the potential impact of preoperative RT. Overall, available clinical evidence of preoperative RT in BC remains limited, deriving mostly from retrospective case series. Nevertheless, the experiences prove the feasibility of the preoperative RT approach and confirm the efficacy in almost all analyzed studies, including experiences using higher prescription RT doses or RT in combination with systemic therapy.

Impact of surface-guided positioning on the use of portal imaging and initial set-up duration in breast cancer patients.

OBJECTIVE: The impact of optical surface guidance on the use of portal imaging and the initial set-up duration in patients receiving postoperative radiotherapy of the breast or chest wall was investigated. MATERIAL AND METHODS: A retrospective analysis was performed including breast cancer patients who received postoperative radiotherapy between January 2016 and December 2016. One group of patients received treatment before the optical surface scanner was installed (no-OSS) and the other group was positioned using the additional information derived by the optical surface scanner (OSS). The duration of the initial set-up was recorded for each patient and a comparison of both groups was performed. Accordingly, the differences between planned and actually acquired portal images during the course of radiotherapy were compared between both groups. RESULTS: A total of 180 breast cancer patients were included (90 no-OSS, 90 OSS) in this analysis. Of these, 30 patients with left-sided breast cancer received radiotherapy in deep inspiration breath hold (DIBH). The mean set-up time was 10 min and 18 s and no significant difference between the two groups of patients was found (p = 0.931). The mean set-up time in patients treated without DIBH was 9 min and 45 s compared to 13 min with DIBH (p < 0.001), as portal imaging was performed in DIBH. No significant difference was found in the number of acquired to the planned number of portal images during the entire radiotherapy treatment for both groups (p = 0.287). CONCLUSION: Optical surface imaging is a valuable addition for primary patient set-up. The findings confirm that the addition of surface-based imaging did not prolong the clinical workflow and had no significant impact on the number of portal verification images carried out during the course of radiotherapy.

Mastectomy or Breast-Conserving Therapy for Early Breast Cancer in Real-Life Clinical Practice: Outcome Comparison of 7565 Cases.

Although the organ preservation strategy by breast-conserving surgery (BCS) followed by radiation therapy (BCT) has revolutionized the treatment approach of early stage breast cancer (BC), the choice between treatment options in this setting can still vary according to patient preferences. The aim of the present study was to compare the oncological outcome of mastectomy versus breast-conserving therapy in patients treated in a modern clinical setting outside of clinical trials. 7565 women diagnosed with early invasive BC (pT1/2pN0/1) between 1998 and 2014 were included in this study (median follow-up: 95.2 months). In order to reduce selection bias and confounding, a subgroup analysis of a matched 1:1 case-control cohort consisting of 1802 patients was performed (median follow-up 109.4 months). After adjusting for age, tumor characteristics and therapies, multivariable analysis for local recurrence-free survival identified BCT as an independent predictor for improved local control (hazard ratio [HR]:1.517; 95%confidence interval:1.092⁻2.108, p = 0.013) as compared to mastectomy alone in the matched cohort. Ten-year cumulative incidence (CI) of lymph node recurrences was 2.0% following BCT, compared to 5.8% in patients receiving mastectomy (p < 0.001). Similarly, 10-year distant-metastasis-free survival (89.4% vs. 85.5%, p = 0.013) was impaired in patients undergoing mastectomy alone. This translated into improved survival in patients treated with BCT (10-year overall survival (OS) estimates 85.3% vs. 79.3%, p < 0.001), which was also significant on multivariable analysis (p = 0.011). In conclusion, the present study showed that patients treated with BCS followed by radiotherapy had an improved outcome compared to radical mastectomy alone. Specifically, local control, distant control, and overall survival were significantly better using the conservative approach. Thus, as a result of the present study, physicians should encourage patients to receive BCS with radiotherapy rather than mastectomy, whenever it is medically feasible and appropriate.

Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: an observational study.

BACKGROUND AND PURPOSE: Due to the rarity of male breast cancer (male BC), no consensus has been reached regarding the most appropriate curative treatment strategy. The objective of the present observational study was to identify patient and tumor characteristics and assess the role of radiotherapy (RT) in clinical practice. METHODS: Between 1998 and 2014, data of male BC patients treated at two breast centers were consecutively collected and retrospectively analyzed. Patients were stratified based on the addition of adjuvant RT. Data on overall survival (OS) and local recurrence-free survival (LRFS) were estimated with the Kaplan-Meier method and compared by the log-rank test. RESULTS: A consecutive cohort of 58 male BC patients was evaluated. Median follow-up was 56 months. Twenty-one patients (36.2%) received adjuvant RT. Overall, patients undergoing postoperative RT were characterized by more high-risk features. Patients receiving postoperative RT had significantly more frequently a high UICC stage (50 vs. 9.7% UICC III, p = 0.018) and positive lymph nodes as compared to patients undergoing surgery alone (65 vs. 34.4% pN+, p = 0.046). Accordingly, there was a higher proportion of patients receiving axillary lymph node dissection in the RT group (71.4 vs. 35.6%). Mastectomy was performed in 31/37 (86.1%) in the surgery group as compared to 14/21 (66.7%) in patients receiving postoperative RT. In addition, RT patients were more likely to receive endocrine therapy (78.9 vs. 39.3%, p = 0.016). Outcome was not significantly different between the groups (5-year LRFS: 89.8 vs. 80.0%, p = 0.471 and 5­year OS 88.4 vs. 88.9%, p = 0.819). CONCLUSION: The present observational study evaluated the pattern of care in male BC patients treated in clinical practice. Due to its rarity, randomized clinical trials are unlikely and male BC remains an entity with a poor evidence base. Nevertheless, RT remains a crucial component of the multidisciplinary treatment strategy in male BC.