External partial breast irradiation in prone position: how to improve accuracy?

INTRODUCTION: In view of the limited incremental benefit between whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) and omission of radiotherapy in favorable early-stage breast cancer (ESBC), APBI can only be justified if it combines adequate target coverage with the lowest achievable toxicity. Interobserver exercises demonstrated the difficulty of precise target delineation, especially in prone position; information on accuracy is even scarcer. We tested the impact of inserting an additional indicator clip, marking the depth of the tumor in the breast, and the added value of a preoperative CT in treatment position on precision and accuracy. MATERIAL AND METHODS: In 12 patients, tumor bed delineation was performed by four radiation oncologists, with CTVstandard (clinical target volume) based on standard delineation guidelines, CTVclip resulting from a 1-2-cm symmetrical expansion with the indicator clip as center and CTVclip_CT expanding from the midpoint between the indicator clip and preoperative gross tumor volume (GTV) as center. Precision was measured as the mean pairwise Jaccard index (JIpairs) between observers, accuracy as the mean overlap between GTV and respective CTVs. RESULTS: JIpairs was 0.38 for CTVstandard, 0.75 for CTVclip and 0.59 for CTVclip_CT. Overlap rate of GTV with CTVs was respectively 0.48, 0.67 and improved further to 0.88 for CTVclip_CT. High-dose coverage of GTV (D95 and D90) improved with an indicator clip, but the most optimal result was reached when preoperative CT was added. CONCLUSIONS: If EB-APBI in prone position is aimed for, an indicator clip intended to mark the depth of the tumor increases the probability of accurate target coverage, but cannot entirely replace the added value of a preoperative CT in treatment position. Avoiding the cost and effort of such CT implies a risk of missing the target, especially when small volumes are aimed for. Increasing target volumes to reduces this risk, questions the concept of APBI.

A new approach for modeling patient overall radiosensitivity and predicting multiple toxicity endpoints for breast cancer patients.

INTRODUCTION: Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. METHODS AND MATERIALS: In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. RESULTS: With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB2 rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with radiosensitivity, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. DISCUSSION: The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall radiosensitivity. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient characteristics that are associated with radiosensitivity were identified without explicitly quantifying radiosensitivity.

Dutch Translation of the Yost Self-Report Lower Extremity Lymphedema Screening Questionnaire in Women.

BACKGROUND: Validated questionnaires of self-reported LEL are important in the assessment and diagnosis of LEL. The aim of this study was to validate and translate a Dutch version of the screening questionnaire, the LELSQ developed and validated by Yost et al. Methods: We tested the questionnaire on a group of healthy women and a group of patients diagnosed with LEL. The translation was carried out using the forward and backward method from English to Dutch. STATISTICAL ANALYSES: SPSS (IBM corp, Armonk, New York, NY, USA) version 28.0.1.0 (001) was used for statistical analysis in the process of validation. The internal consistency was assessed by determining Cronbach's alpha. The reliability was tested by test-retest reliability. The validity was determined by ROC analysis, and content and face validity were evaluated. RESULTS: The internal consistency score in both groups had a strong value (0.83 to 0.90). The test-retest reliability was also strong in both groups. Face and content validity showed the LELSQ is an easy, understandable questionnaire that is not too time-consuming in the early detection of LEL. The ROC analysis showed an AUC value of 0.93, indicating strong validity. CONCLUSIONS: The validated Dutch translation showed high values for internal consistency, test-retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment.

Reply to Bourgeois, P. Comment on "Devoogdt et al. The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial. Cancers 2023, 15, 1545".

We appreciate the commentary by Pierre Bourgeois [...].

Incidence and radiotherapy treatment patterns of complicated bone metastases.

Background: Despite the encouraging results of the SCORAD trial, single fraction radiotherapy (SFRT) remains underused for patients with complicated bone metastases with rates as low as 18-39%. We aimed to evaluate the incidence and treatment patterns of these metastases in patients being referred to a tertiary centre for palliative radiotherapy. Materials and methods: We performed a retrospective review of all bone metastases treated at our centre from January 2013 until December 2017. Lesions were classified as uncomplicated or complicated. Complicated was defined as associated with (impending) fracture, existing spinal cord or cauda equina compression. Our protocol suggests using SFRT for all patients with complicated bone metastases, except for those with symptomatic neuraxial compression and a life expectancy of ≥28 weeks. Results: Overall, 37 % of all bone metastases were classified as complicated. Most often as a result of an (impending) fracture (56 %) or spinal cord compression (44 %). In 93 % of cases, complicated lesions were located in the spine, most commonly originating from prostate, breast and lung cancer (60 %). Median survival of patients with complicated bone metastases was 4 months. The use of SFRT for complicated bone metastases increased from 51 % to 85 % over the study period, reaching 100 % for patients with the poorest prognosis. Conclusions: Approximately 37 % of bone metastases are classified as complicated with the majority related to (impending) fracture. Patients with complicated bone metastases have a median survival of 4 months and were mostly treated with SFRT.

SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.

INTRODUCTION: Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema. METHODS AND ANALYSIS: A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased. ETHICS AND DISSEMINATION: The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT05064176.

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma.

BACKGROUND: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs and analyze the PD-L1 expression levels in pILC. METHODS: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. The PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections using SP142 and 22C3 antibodies. RESULTS: A total of 82% of the sixty-six patients were hormone receptor positive and 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs (≥1%) were present in 64% of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of ≥1%, and using the 22C3 antibody, 28% had a positive PD-L1 score of ≥1. There was no correlation between sTILs or PD-L1 expression and tumor size, tumor grade, nodal status, expression of estrogen receptor (ER), or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. CONCLUSION: This study shows that pILCs show some degree of sTILs and PD-L1 expression; however, this was not associated with a survival improvement. Additional large trials are needed to understand immune infiltration in lobular cancer, especially in the pleomorphic subtype.

The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial.

The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL.

Accelerated radiotherapy in patients over sixty years old after mastectomy: Acute and one-year physician-assessed toxicity and health-related quality of life.

INTRODUCTION: Postmastectomy radiotherapy reduces the risk of locoregional recurrence in breast cancer patients. The first results on accelerated radiotherapy in five fractions after breast conserving surgery are promising. The data on postmastectomy radiotherapy in five or six fractions is limited. We now present the data on acute and one-year toxicity and health related quality of life (HRQoL) after postmastectomy radiotherapy in patients of sixty years or older. METHODOLOGY: 119 patients received five fractions of 5.7 Gy to the chest wall and five fractions of 5.4 Gy to the lymph nodes over ten to twelve days. Physician-assessed toxicity were scored using the Common Terminology Criteria for Adverse Events version 4.03 toxicity scoring system and the LENT-SOMA scale. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI-206). HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire the breast cancer specific module and the BREAST-Q questionnaire. RESULTS: Fatigue and edema were the most frequently observed physician-assessed toxicities. One year after radiotherapy only 12.9% experienced a clinically important deterioration in chest wall symptoms and in 22.9% of the patients were improved. Future perspective at one year after radiotherapy was improved in 40.0% of the patients. Patient-reported fatigue showed the greatest improvement. CONCLUSION: Accelerated radiotherapy should be considered to minimize the burden of breast cancer treatment, especially in older patients.

Reproducibility of repeated breathhold and impact of breathhold failure in whole breast and regional nodal irradiation in prone crawl position.

In whole breast and regional nodal irradiation (WB + RNI), breathhold increases organ at risk (OAR) sparing. WB + RNI is usually performed in supine position, because positioning materials obstruct beam paths in prone position. Recent advancements allow prone WB + RNI (pWB + RNI) with increased sparing of OARs compared to supine WB + RNI. We evaluate positional and dosimetrical impact of repeated breathhold (RBH) and failure to breathhold (FTBH) in pWB + RNI. Twenty left-sided breast cancer patients were scanned twice in breathhold (baseline and RBH) and once free breathing (i.e. FTBH). Positional impact was evaluated using overlap index (OI) and Dice similarity coefficient (DSC). Dosimetrical impact was assessed by beam transposition from the baseline plan. Mean OI and DSC ranges were 0.01-0.98 and 0.01-0.92 for FTBH, and 0.73-1 and 0.69-1 for RBH. Dosimetric impact of RBH was negligible. FTBH significantly decreased minimal dose to CTV WBI, level II and the internal mammary nodes, with adequate mean doses. FTBH significantly increased heart, LAD, left lung and esophagus dose. OI and DSC for RBH and FTBH show reproducible large ROI positions. Small ROIs show poor overlap. FTBH maintained adequate target coverage but increased heart, LAD, ipsilateral lung and esophagus dose. RBH is a robust technique in pWB + RNI. (Clinicaltrials.gov: NCT05179161, registered 05/01/2022).

Manual lymphatic drainage with or without fluoroscopy guidance did not substantially improve the effect of decongestive lymphatic therapy in people with breast cancer-related lymphoedema (EFforT-BCRL trial): a multicentre randomised trial.

QUESTIONS: When added to decongestive lymphatic therapy (DLT), what is the effect of fluoroscopy-guided manual lymphatic drainage (MLD) versus traditional MLD or placebo MLD for the treatment of breast cancer-related lymphoedema (BCRL)? DESIGN: Multicentre, three-arm, randomised controlled trial with concealed allocation, intention-to-treat analysis and blinding of assessors and participants. PARTICIPANTS: At five hospitals in Belgium, 194 participants with unilateral chronic BCRL were recruited. INTERVENTION: All participants received standard DLT (education, skin care, compression therapy and exercises). Participants were randomised to also receive fluoroscopy-guided MLD (n = 65), traditional MLD (n = 64) or placebo MLD (n = 65). Participants received 14 sessions of physiotherapy during the 3-week intensive phase and 17 sessions during the 6-month maintenance phase. Participants performed self-management on the other days. OUTCOME MEASURES: All outcomes were measured: at baseline; after the intensive phase; after 1, 3 and 6 months of maintenance phase; and after 6 months of follow-up. The primary outcomes were reduction in excess volume of the arm/hand and accumulation of excess volume at the shoulder/trunk, with the end of the intensive phase as the primary endpoint. Secondary outcomes included daily functioning, quality of life, erysipelas and satisfaction. RESULTS: Excess lymphoedema volume decreased after 3 weeks of intensive treatment in each group: 5.3 percentage points of percent excessive volume (representing a relative reduction of 23.3%) in the fluoroscopy-guided MLD group, 5.2% (relative reduction 20.9%) in the traditional MLD group and 5.4% (relative reduction 24.8%) in the placebo MLD group. The effect of fluoroscopy-guided MLD was very similar to traditional MLD (between-group difference 0.0 percentage points, 95% CI -2.0 to 2.1) and placebo MLD (-0.2 percentage points, 95% CI -2.1 to 1.8). Fluid accumulated at the shoulder/trunk in all groups. The average accumulation with fluoroscopy-guided MLD was negligibly less than with traditional MLD (-3.6 percentage points, 95% CI -6.4 to -0.8) and placebo MLD (-2.4 percentage points, 95% CI -5.2 to 0.4). The secondary outcomes also showed no clinically important between-group differences. CONCLUSION: In patients with chronic BCRL, MLD did not provide clinically important additional benefit when added to other components of DLT. REGISTRATION: NCT02609724.

Does Manual Lymphatic Drainage Add Value in Reducing Suprafascial Fluid Accumulation and Skin Elasticity in Patients With Breast Cancer-Related Lymphedema?

OBJECTIVE: The purpose of this study was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD) versus that of traditional and placebo MLD, when added to decongestive lymphatic therapy (DLT) for the treatment of breast cancer-related lymphedema (BCRL) (EFforT-BCRL trial), on the suprafascial accumulation of lymphatic fluid and skin elasticity. METHODS: In this multicenter, 3-arm, double-blind, randomized controlled trial (EFforT-BCRL trial), 194 participants (mean age = 61 [SD = 10] years) with unilateral BCRL were recruited. All participants received standardized DLT (education, skin care, compression therapy, exercises) and were randomized to fluoroscopy-guided, traditional, or placebo MLD. Participants received 60 min/d of treatment during the 3-week intensive phase and 18 sessions of 30 minutes during the 6-month maintenance phase. During this phase, participants were instructed to wear a compression garment, to perform exercises, and to perform a self-MLD procedure once daily. This study comprises secondary analyses of the EFforT-BCRL trial. Outcomes were the amount of fluid accumulation in the suprafascial tissues (local tissue water, extracellular fluid, and thickness of the skin and subcutaneous tissue) and skin elasticity at the level of the arm and trunk. Measurements were performed at baseline; after intensive treatment; after 1, 3, and 6 months of maintenance treatment; and after 6 months of follow-up. RESULTS: At the level of the arm, there was a significant improvement over time in the 3 groups for most of the outcomes. At the level of the trunk, no remarkable improvement was noted within the individual groups. No significant interaction effects (between-group differences) were present. Only skin elasticity at the level of the arm, evaluated through palpation, showed a significant interaction effect. CONCLUSION: All 3 groups showed similar improvements in response to DLT regardless of the type of MLD that was added. The effect of the addition of MLD to other components of DLT for reducing local tissue water and extracellular fluid or skin thickness and for improving skin elasticity and fibrosis in participants with chronic BCRL was limited. IMPACT: Although MLD has been applied all over the world for many years, evidence regarding its added value in reducing arm volume in patients with BCRL is lacking. These results show that adding MLD to other components of DLT has limited value in reducing local tissue water and extracellular fluid or skin thickness and in improving skin elasticity and fibrosis in patients with chronic BCRL. To date, there is no clinical indication to continue including time-consuming MLD in physical therapist sessions for patients with chronic BCRL.

Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost.

INTRODUCTION: Acceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10-12 days. MATERIAL AND METHODS: Acute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15- or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 15∗2.67 Gy (40.05 Gy) or 5∗5.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (15∗3.12 Gy) or 31 Gy (5∗6.2 Gy). RESULTS: Physician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical well-being (p = 0.002). CONCLUSION: In this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10-12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective.

Adoption of single fraction radiotherapy for uncomplicated bone metastases in a tertiary centre.

BACKGROUND: Single-fraction radiotherapy (SFRT) offers equal pain relief for uncomplicated painful bone metastases as compared to multiple-fraction radiotherapy (MFRT). Despite this evidence, the adoption of SFRT has been poor with published rates of SFRT for uncomplicated bone metastases ranging from <10% to 70%. We aimed to evaluate the adoption of SFRT and its evolution over time following the more formal endorsement of the international guidelines in our centre starting from 2013. MATERIALS AND METHODS: We performed a retrospective review of fractionation schedules at our centre for painful uncomplicated bone metastases from January 2013 until December 2017. Only patients treated with 1 × 8 Gy (SFRT-group) or 10 × 3 Gy (MFRT-group) were included. We excluded other fractionation schedules, primary cancer of the bone and post-operative radiotherapy. Uncomplicated was defined as painful but not associated with impending fracture, existing fracture or existing neurological compression. Temporal trends in SFRT/MFRT usage and overall survival were investigated. We performed a lesion-based patterns of care analysis and a patient-based survival analysis. Mann-Whitney U and Chi-square test were used to assess differences between fractionation schedules and temporal trends in prescription, with Kaplan-Meier estimates used for survival analysis (p-value <0.05 considered significant). RESULTS: Overall, 352 patients and 594 uncomplicated bone metastases met inclusion criteria. Patient characteristics were comparable between SFRT and MFRT, except for age. Overall, SFRT was used in 92% of all metastases compared to 8% for MFRT. SFRT rates increased throughout the study period from 85% in 2013 to 95% in 2017 (p = 0.06). Re-irradiation rates were higher in patients treated with SFRT (14%) as compared to MFRT (4%) (p = 0.046). Four-week mortality and median overall survival did not differ significantly between SFRT and MFRT (17% vs 18%, p = 0.8 and 25 weeks vs 38 weeks, p = 0.97, respectively). CONCLUSIONS: Adherence to the international guidelines for SFRT for uncomplicated bone metastasis was high and increased over time to 95%, which is the highest reported rate in literature.

5-Year Outcomes of a Randomized Trial Comparing Prone and Supine Whole Breast Irradiation in Large-Breasted Women.

PURPOSE: Prone position for whole breast irradiation (WBI) results in lower rates of toxicity and reduced ipsilateral mean lung and heart doses. No randomized trials comparing toxicity and cosmesis at 5 years with prone and supine positioning are available. METHODS AND MATERIALS: In this phase 2 open-label trial, 100 patients with large breast size requiring WBI were randomized between prone and supine positioning. Physician-assessed toxicity (retraction, fibrosis, edema, telangiectasia, pigmentation changes) was scored yearly for a total of 5 years, and photographs were taken at 5 years to assess cosmesis. The data were analyzed longitudinally and cross-sectionally. RESULTS: Longitudinal analysis shows lower grade 2 late toxicity with prone positioning. The results for at least grade 1 physician-assessed toxicity at 5 years are similar between supine and prone position, respectively, for retraction (56% vs 54%), fibrosis outside the tumor bed (33% vs 24%), tumor bed fibrosis (49% vs 46%), edema (11% vs 8%), telangiectasia (8% vs 3%), and breast pain (6% vs 8%) using cross-sectional analysis. However, the risk of pigmentation changes in prone position (0% vs 19%) 5 years after radiation therapy was significantly lower. Cosmesis was good or excellent in 92% and 75% of patients who used prone and supine positioning, respectively. The 5-year overall survival is 96% in both groups. CONCLUSION: Prone positioning results in reduced rates of late toxicity.

Delineation guidelines for the lymphatic target volumes in 'prone crawl' radiotherapy treatment position for breast cancer patients.

Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP. Nine volunteers were MRI scanned in both SP and PCP. Lymph node regions were delineated in SP using the existing ESTRO and PROCAB guidelines and were then translated to PCP, based on the observed changes in reference structure position. Nine PCP patient CT scans were used to verify if the new reference structures were consistently identified and easily applicable on different patient CT scans. Based on these data, a team of specialists in anatomy, CT- and MRI radiology and radiation oncology postulated the final guidelines. By taking the ESTRO and PROCAB guidelines for SP into account and by using a relatively big number of datasets, these new PCP specific guidelines incorporate anatomical variability between patients. The guidelines are easily and consistently applicable, even for people with limited previous experience with delineations in PCP.

Two-year toxicity of simultaneous integrated boost in hypofractionated prone breast cancer irradiation: Comparison with sequential boost in a randomized trial.

INTRODUCTION: A simultaneous integrated boost (SIB) leads to less acute toxicity. Less is known for late toxicity due to SIB. In this first and only randomized trial, two-years toxicity is analysed. MATERIALS AND METHODS: Physician-assessed toxicity, using the LENT SOMA scale, and photographs, analysed with the BCCT.core software, was examined for 150 patients, randomized between SIB and sequential boost (SEB). RESULTS: Differences in physician-assessed two-years toxicity and photographic analysis between SIB and SEB are very small and not significant. CONCLUSION: There is no indication that a SIB leads to an excess in toxicity or worse cosmetic outcome at 2 years.

Prolonging deep inspiration breath-hold time to 3 min during radiotherapy, a simple solution.

BACKGROUND AND PURPOSE: Deep inspiration breath-hold is an established technique to reduce heart dose during breast cancer radiotherapy. However, modern breast cancer radiotherapy techniques with lymph node irradiation often require long beam-on times of up to 5 min. Therefore, the combination with deep inspiration breath-hold (DIBH) becomes challenging. A simple support technique for longer duration deep inspiration breath-hold (L-DIBH), feasible for daily use at the radiotherapy department, is required to maximize heart sparing. MATERIALS AND METHODS: At our department, a new protocol for multiple L-DIBH of at least 2 min and 30 s was developed on 32 healthy volunteers and validated on 8 breast cancer patients during radiotherapy treatment, using a pragmatic process of iterative development, including all major stakeholders. Each participant performed 12 L-DIBHs, on 4 different days. Different methods of pre-oxygenation and voluntary hyperventilation were tested, and scored on L-DIBH duration, ease of use, and comfort. RESULTS: Based on 384 L-DIBHs from 32 healthy volunteers, voluntary hyperventilation for 3 min whilst receiving high-flow nasal oxygen at 40 L/min was the most promising technique. During validation, the median L-DIBH duration in prone position of 8 breast cancer patients improved from 59 s without support to 3 min and 9 s using the technique (p < 0.001). CONCLUSION: A new and simple L-DIBH protocol was developed feasible for daily use at the radiotherapy center.

Crawl positioning improves set-up precision and patient comfort in prone whole breast irradiation.

Prone positioning for whole-breast irradiation (WBI) reduces dose to organs at risk, but reduces set-up speed, precision, and comfort. We aimed to improve these problems by placing patients in prone crawl position on a newly developed crawl couch (CrC). A group of 10 right-sided breast cancer patients requiring WBI were randomized in this cross-over trial, comparing the CrC to a standard prone breastboard (BB). Laterolateral (LL), craniocaudal (CC) and anterioposterior (AP) set-up errors were evaluated with cone beam CT. Comfort, preference and set-up time (SUT) were assessed. Forty left and right-sided breast cancer patients served as a validation group. For BB versus CrC, AP, LL and CC mean patient shifts were - 0.8 ± 2.8, 0.2 ± 11.7 and - 0.6 ± 4.4 versus - 0.2 ± 3.3, - 0.8 ± 2.5 and - 1.9 ± 5.7 mm. LL shift spread was reduced significantly. Nine out of 10 patients preferred the CrC. SUT did not differ significantly. The validation group had mean patient shifts of 1.7 ± 2.9 (AP), 0.2 ± 3.6 (LL) and - 0.2 ± 3.3 (CC) mm. Mean SUT in the validation group was 1 min longer (P < 0.05) than the comparative group. Median SUT was 3 min in all groups. The CrC improved precision and comfort compared to BB. Set-up errors compare favourably to other prone-WBI trials and rival supine positioning.