Dosimetric and Hematologic Implications of Prostate-Only Versus Whole Pelvic Radiotherapy: Results of the Multicentric Phase 3 PROPER Study.

Objectives: The aim is to evaluate the incidental dose to the lymphatic regions in prostate-only radiotherapy (PORT) and to compare hematological outcome between PORT and whole pelvic radiotherapy (WPRT) in node-positive prostate cancer (pN1 PCa), in the era of modern radiotherapy techniques. Methods: We performed a prospective phase 3 trial in which a total of 64 pN1 PCa patients were randomized between PORT (ARM A) and WPRT (ARM B) delivered with volumetric-modulated arc therapy (VMAT). The lymph node (LN) regions were delineated separately and differences between groups were calculated using Welch t-tests. Hematological toxicity was scored according to common terminology criteria for adverse events (CTCAE) version 4.03. To evaluate differences in the evolution of red blood cell (RBC), white blood cell (WBC), and platelet count over time between PORT and WPRT, 3 linear mixed models with a random intercept for the patient was fit with model terms randomization group, study time point, and the interaction between both categorical predictors. Results: Except for dose to the obturator region, the incidental dose to the surrounding LN areas was low in ARM A. None of the patients developed severe hematological toxicity. The change in RBC from time point pre-external beam radiotherapy (EBRT) to month 3 and for WBC from time point pre-EBRT to months 3 and 12 was significantly different with ARM B showing a larger decrease. Conclusion: The incidental dose to the lymphatic areas becomes neglectable when PORT is delivered with VMAT. Hematological toxicity is very low after WPRT with VMAT and when bone marrow constraints are used for planning, although WPRT causes a decrease in RBC and WBC count over time.

Quality assurance and safety of hippocampal avoidance prophylactic cranial irradiation in the multicenter randomized phase III trial (NCT01780675).

Objective: NCT01780675, a multicenter randomized phase III trial of prophylactic cranial irradiation (PCI) versus PCI with hippocampal sparing in small cell lung cancer (SCLC) investigated neurocognitive decline and safety. As part of quality assurance, we evaluated if hippocampal avoidance (HA)-PCI was performed according to the NCT01780675 trial protocol instructions, and performed a safety analysis to study the incidence and location of brain metastases for patients treated with HA-PCI. Methods: This retrospective analysis evaluated the quality of the irradiation given in the randomized controlled trial (RCT) comparing SCLC patients receiving PCI with or without hippocampal avoidance, using intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). The dose distribution for each patient receiving HA-PCI was retrieved and analyzed to evaluate if the treatment dose constraints were met. A questionnaire was sent out to all participating sites, and data on radiotherapy technique, pre-treatment dummy runs, phantom measurements and treatment electronic portal imaging device (EPID) dosimetry were collected and analyzed. As part of the safety analysis, the follow-up magnetic resonance imaging (MRI) or computerized tomography (CT) scans on which cranial disease progression was first diagnosed were collected and matched to the radiotherapy planning dose distribution. The matched scans were reviewed to analyze the location of the brain metastases in relation to the prescribed dose. Results: A total of 168 patients were randomized in the NCT01780675 trial in 10 centers in the Netherlands and Belgium from April 2013 until March 2018. Eighty two patients receiving HA-PCI without evidence of brain metastases were analyzed. All patients were treated with 25 Gy in 10 fractions. Dummy runs and phantom measurements were performed in all institutions prior to enrolling patients into the study. The radiotherapy (RT) plans showed a median mean bilateral hippocampal dose of 8.0 Gy, range 5.4-11.4 (constraint ≤ 8.5 Gy). In six patients (7.3%) there was a protocol violation of the mean dose in one or both hippocampi. In four of these six patients (4.9%) the mean dose to both hippocampi exceeded the constraint, in 1 patient (1.2%) only the left and in 1 patient (1.2%) only the right hippocampal mean dose was violated (average median dose left and right 8.9 Gy). All patients met the trial dose constraint of V 115% PTV ≤ 1%; however the D max PTV constraint of ≤ 28.75 Gy was violated in 22.0% of the patients. The safety analysis showed that 14 patients (17.1%) developed cranial progression. No solitary brain metastases in the underdosed region were found. Two out of 11 patients with multiple brain metastasis developed metastasis in the underdosed region(s). Conclusions: The radiotherapy quality within the HA-PCI trial is performed according to the protocol guidelines. The dose constraints to the hippocampi are met in the vast majority of cases. In all patients, the volume of the brain for which a higher dose was accepted, is according to the trial. However, within this volume there are small areas with higher doses than advised.

Four irradiation and three positioning techniques for whole-breast radiotherapy: Is sophisticated always better?

PURPOSE: We report on a dosimetrical study of three patient positions (supine, prone dive, and prone crawl) and four irradiation techniques for whole-breast irradiation (WBI): wedged-tangential fields (W-TF), tangential-field intensity-modulated radiotherapy (TF-IMRT), multi-beam IMRT (MB-IMRT), and intensity-modulated arc therapy (IMAT). This is the first study to evaluate prone crawl positioning in WBI and the first study to quantify dosimetrical and anatomical differences with prone dive positioning. METHODS: We analyzed five datasets with left- and right-sided patients (n = 51). One dataset also included deep-inspiration breath hold (DIBH) data. A total of 252 new treatment plans were composed. Dose-volume parameters and indices of conformity were calculated for the planning target volume (PTV) and organs-at-risk (OARs). Furthermore, anatomical differences among patient positions were quantified to explain dosimetrical differences. RESULTS: Target coverage was inferior for W-TF and supine position. W-TF proved overall inferior, and IMAT proved foremost effective in supine position. TF-IMRT proved competitive to the more demanding MB-IMRT and IMAT in prone dive, but not in prone crawl position. The lung-sparing effect was overall confirmed for both prone dive and prone crawl positioning and was largest for prone crawl. For the heart, no differences were found between prone dive and supine positioning, whereas prone crawl showed cardiac advantages, although minor compared to the established heart-sparing effect of DIBH. Dose differences for contralateral breast were minor among the patient positions. In prone crawl position, the ipsilateral breast sags deeper and the PTV is further away from the OARs than in prone dive position. CONCLUSIONS: The prone dive and prone crawl position are valid alternatives to the supine position in WBI, with largest advantages for lung structures. For the heart, differences are small, which establishes the role of DIBH in different patient positions. These results may be of particular interest to radiotherapy centers with limited technical resources.

International Consensus Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy: Update From an IBIS Workgroup.

PURPOSE: In 2016, international consensus clinical target volume (CTV) guidelines for adjuvant radiation treatment after radical cystectomy in patients with muscle-invasive bladder cancer with high risk for locoregional failure (LRF) were published. A subsequent external validation study recommended several CTV optimizations (CTV-OPT). This study aimed to update international consensus guidelines based on new clinical experiences. METHODS AND MATERIALS: Phase 1 (delineation interobserver variability): Four observers delineated the CTV of 9 patients post radical cystectomy, as in clinical practice. Interobserver agreement in contouring was evaluated using volume- and κ-statistics. Phase 2 (pattern of failure analysis): Among a prospective cohort of 72 patients treated with adjuvant radiation treatment, 11 developed LRF (10 available for review). LRFs were mapped in predefined pelvic subsites (ie, common, external and internal iliac, obturator and presacral node regions, and cystectomy bed), and their distance to CTV-OPT was measured. The actual delivered dose at each relapse site was calculated. Phase 3 (review CTV): Based on the results of phase 1 and 2, 5 senior radiation-oncologists (International Bladder Investigator Society) reviewed the published CTV borders and provided an update when indicated. RESULTS: Phase 1: The mean overall κ-value was 0.66 (range, 0.60-0.70), indicating substantial overall agreement per Landis-Koch criteria. Specific κ-values per area indicated for the common iliac and obturator node regions only slight and moderate variability, respectively. Phase 2: Thirteen out of 16 LRFs centers were not included in the CTV-OPT. Ten LRF sites received a median dose <45 Gy, of which 6 were located in the cystectomy bed that was not included in the CTV because of negative radical cystectomy margins. Phase 3: Key recommendations by the panel were to include the entire common iliac node region and the cystectomy bed regardless of surgical margin status and a reaffirmation to not crop the CTV out of bowel. CONCLUSIONS: International consensus guidelines were updated.

Prone Breast and Lymph Node Irradiation in 5 or 15 Fractions: A Randomized 2 × 2 Design Comparing Dosimetry, Acute Toxicity, and Set-Up Errors.

PURPOSE: Prone whole breast irradiation results in lower dose to organs at risk compared with supine position, especially lung dose. However, the adoption of prone position for whole breast irradiation + lymph node irradiation remains limited and data on lymph node irradiation in 5 fractions are lacking. Although the study was ended prematurely for the primary endpoint (breast retraction at 2 years), we decided to report acute toxicity for prone and supine positions and 5 and 15 fractions. Additionally, dosimetry and set-up accuracy between prone and supine positions were evaluated. METHODS AND MATERIALS: A randomized open-label factorial 2 × 2 design was used for an acute toxicity comparison between prone and supine positions and 5 and 15 fractions. The primary endpoint of the trial was breast retraction 2 years after treatment. In total, 57 patients were evaluated. Dosimetry and set-up errors were compared between prone and supine positions. All patients were positioned on either our in -house developed prone crawl breast couch or a Posirest-2 (Civco). RESULTS: No difference in acute toxicity between prone and supine positions was found, but 5 fractions did result in a lower risk of desquamation (15% vs 41%; P = .04). Prone positioning resulted in lower mean ipsilateral lung dose (2.89 vs 4.89 Gy; P < .001), mean thyroid dose (3.42 vs 6.61 Gy; P = .004), and mean contralateral breast dose (0.41 vs 0.54 Gy; P = .007). No significant difference in mean heart dose (0.90 vs 1.07 Gy; P = .22) was found. Set-up accuracy was similar between both positions. CONCLUSIONS: Unfortunately, the primary endpoint of the trial was not met due to premature closure of the trial. Acceleration in 5 fractions resulted in a lower risk of desquamation. Prone positioning did not influence acute toxicity or set-up accuracy, but did result in lower ipsilateral mean lung dose, thyroid dose, and contralateral breast dose.

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).

Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes.

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.

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.

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.

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.

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.

Longitudinal radiomics of cone-beam CT images from non-small cell lung cancer patients: Evaluation of the added prognostic value for overall survival and locoregional recurrence.

BACKGROUND AND PURPOSE: The prognostic value of radiomics for non-small cell lung cancer (NSCLC) patients has been investigated for images acquired prior to treatment, but no prognostic model has been developed that includes the change of radiomic features during treatment. Therefore, the aim of this study was to investigate the potential added prognostic value of a longitudinal radiomics approach using cone-beam computed tomography (CBCT) for NSCLC patients. MATERIALS AND METHODS: This retrospective study includes a training dataset of 141 stage I-IV NSCLC patients and three external validation datasets of 94, 61 and 41 patients, all treated with curative intended (chemo)radiotherapy. The change of radiomic features extracted from CBCT images was summarized as the slope of a linear regression. The CBCT slope-features and CT-extracted features were used as input for a Cox proportional hazards model. Moreover, prognostic performance of clinical parameters was investigated for overall survival and locoregional recurrence. Model performances were assessed using the Kaplan-Meier curves and c-index. RESULTS: The radiomics model contained only CT-derived features and reached a c-index of 0.63 for overall survival and could be validated on the first validation dataset. No model for locoregional recurrence could be developed that validated on the validation datasets. The clinical parameters model could not be validated for either overall survival or locoregional recurrence. CONCLUSION: In this study we could not confirm our hypothesis that longitudinal CBCT-extracted radiomic features contribute to improved prognostic information. Moreover, performance of baseline radiomic features or clinical parameters was poor, probably affected by heterogeneity within and between datasets.

Comparison of supine or prone crawl photon or proton breast and regional lymph node radiation therapy including the internal mammary chain.

We report on a dosimetrical study comparing supine (S) and prone-crawl (P) position for radiotherapy of whole breast (WB) and loco-regional lymph node regions, including the internal mammary chain (LN_IM). Six left sided breast cancer patients were CT-simulated in S and P positions and four patients only in P position. Treatment plans were made using non-coplanar volumetric modulated arc photon therapy (VMAT) or pencil beam scanning intensity modulated proton therapy (IMPT). Dose prescription was 15*2.67 Gy(GyRBE). The average mean heart doses for S or P VMAT were 5.6 or 4.3 Gy, respectively (p = 0.16) and 1.02 or 1.08 GyRBE, respectively for IMPT (p = 0.8; p < 0.001 for IMPT versus VMAT). The average mean lung doses for S or P VMAT were 5.91 or 2.90 Gy, respectively (p = 0.002) and 1.56 or 1.09 GyRBE, respectively for IMPT (p = 0.016). In high-risk patients, average (range) thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 6.8(5.4-9.4)% or 3.8(2.8-5.1)% for S or P VMAT (p < 0.001), respectively, and 1.6(1.1-2.0)% or 1.2(0.8-1.6)% for S or P IMPT (p = 0.25), respectively. Radiation-related mortality risk could outweigh the ~8% disease-specific survival benefit of WB + LN_IM radiotherapy for S VMAT but not P VMAT. IMPT carries the lowest radiation-related mortality risks.

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.

Potential benefits of crawl position for prone radiation therapy in breast cancer.

PURPOSE: To investigate crawl position with the arm at the treated side alongside the body and at the opposite side above the head for prone treatment in patients requiring breast and regional lymph node irradiation. METHODS: Patient support devices for crawl position were built for CT simulation and treatment. An asymmetric fork design resulted from an iterative process of prototype construction and testing. The fork's large horn supports the hemi-thorax, shoulder, and elevated arm at the nontreated side and the head. The short, narrow horn supports the arm at the treated side. Between both horns, the treated breast and its regional lymph nodes are exposed. Endpoints were pain, comfort, set-up precision, beam access to the breast and lymph nodes, and plan dose metrics. Pain and comfort were tested by volunteers (n = 9); set-up precision, beam access, and plan dose metrics were tested by means of a patient study (n = 10). The AIO™ (Orfit, Wijnegem, Belgium) prone breastboard (AIO™) was used as a reference regarding comfort and set-up precision. RESULTS: Pain at the sternum, the ipsilateral shoulder, upper arm, and neck was lower in crawl position than with bilateral arm elevation on AIO™. Comfort and set-up precision were better on the crawl prototype than on AIO™. In crawl position, beam directions in the coronal and near-sagittal planes have access to the breast or regional lymph nodes without traversing device components. Plan comparison between supine and crawl positions showed better dose homogeneity for the breast and lymph node targets and dose reductions to all organs at risk for crawl position. CONCLUSIONS: Radiation therapy for breast and regional lymph nodes in crawl position is feasible. Good comfort and set-up precision were demonstrated. Planning results support the hypothesis that breast and regional lymph nodes can be treated in crawl position with less dose to organs at risk and equal or better dose distribution in the target volumes than in supine position. The crawl technique is a candidate methodology for further investigation for patients requiring breast and regional lymph node irradiation.