Christel Monten

Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?

INTRODUCTION A series of health economic evaluations (HEE) has analysed the efficiency of new fractionation schedules and techniques for adjuvant breast radiotherapy. This overview assembles the available evidence and evaluates to what extent HEE-results can be compared. METHODS Based on a systematic literature review of HEEs from 1/1/2000 to 30/10/2016, all cost comparison (CC) and cost-effectiveness analyses (CEA) comparing different adjuvant breast radiotherapy approaches were analysed. Costs were extracted and converted to Euro 2016 and costs per QALY were summarized in cost-effectiveness planes. RESULTS Twenty-four publications are withheld, comparing different fractionation schedules and/or irradiation techniques or evaluating the value of adding radiotherapy. Normofractionation and intensity-modulated, interstitial or intraluminal techniques are important cost-drivers. Highest reimbursements are observed in the US, but may overestimate the real cost. Hypofractionation is cost-effective compared to normofractionation, the results of partial breast irradiation are less unequivocal. Intra-operative and external beam approaches seem the most cost-effective for favourable risk groups, but whole breast irradiation is superior in terms of health effect and omission of radiotherapy in terms of costs. CONCLUSION Hypofractionation may be considered the most relevant comparator for new strategies in adjuvant breast radiotherapy, with omission of radiotherapy as an interesting alternative in the very favourable subcategories, especially for partial breast techniques. Although comparison of CC and CEA is hampered by the variability in clinical and economic settings, HEE-based evidence can guide decision-making to tailor-made strategies, allocating the optimal treatment in terms of effectiveness as well as efficiency to the right indication.

Deep inspiration breath hold in the prone position retracts the heart from the breast and internal mammary lymph node region

Deep inspiration breath hold in the prone position causes a caudal shift of the heart away from the nearly unmodified breast and internal mammary lymph node region, suggesting better heart protection for left-sided whole breast irradiation with or without regional nodal radiotherapy.

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer

BackgroundProne whole breast irradiation (WBI) leads to reduced heart and lung doses in breast cancer patients receiving adjuvant radiotherapy. In this feasibility trial, we investigated the prone position for whole breast + lymph node irradiation (WB + LNI).MethodsA new support device was developed for optimal target coverage, on which patients are positioned in a position resembling a phase from the crawl swimming technique (prone crawl position). Five left sided breast cancer patients were included and simulated in supine and prone position. For each patient, a treatment plan was made in prone and supine position for WB + LNI to the whole axilla and the unoperated part of the axilla. Patients served as their own controls for comparing dosimetry of target volumes and organs at risk (OAR) in prone versus in supine position.ResultsTarget volume coverage differed only slightly between prone and supine position. Doses were significantly reduced (P < 0.05) in prone position for ipsilateral lung (Dmean, D2, V5, V10, V20, V30), contralateral lung (Dmean, D2), contralateral breast (Dmean, D2 and for total axillary WB + LNI also V5), thyroid (Dmean, D2, V5, V10, V20, V30), oesophagus (Dmean and for partial axillary WB + LNI also D2 and V5), skin (D2 and for partial axillary WB + LNI V105 and V107). There were no significant differences for heart and humeral head doses.ConclusionsProne crawl position in WB + LNI allows for good breast and nodal target coverage with better sparing of ipsilateral lung, thyroid, contralateral breast, contralateral lung and oesophagus when compared to supine position. There is no difference in heart and humeral head doses.Trial registrationNo trial registration was performed because there were no therapeutic interventions.

Does an integrated boost increase acute toxicity in prone hypofractionated breast irradiation? A randomized controlled trial

BACKGROUND AND PURPOSE The safety of a simultaneous integrated boost (SIB) in combination with prone hypofractionated whole-breast irradiation (WBI) was investigated. MATERIALS AND METHODS 167 patients were randomized between WBI with a sequential boost (SeB) or SIB. All patients were treated in prone position to 40.05Gy in 15 fractions to the whole breast. In the control arm, a SeB of 10Gy in 4 fractions (negative surgical margins) or 14.88Gy in 6 fractions (transsection) was prescribed. In the experimental arm a SIB of 46.8 or 49.95Gy (negative and positive surgical margins, respectively) was prescribed. RESULTS Patient age was the only significantly different parameter between treatment arms with patients in the SIB arm being slightly older. In both arms, 6/83 patients developed moist desquamation. Grade 2/3 dermatitis was significantly more frequent in the SeB arm (38/83vs 24/83 patients, p=0.037). In the SIB and SeB arm, respectively, 36 patients (43%) and 51 patients (61%) developed pruritus (p=0.015). The incidence of oedema was lower in the SIB arm (59vs 68 patients), but not statistically significant (p=0.071). CONCLUSIONS The primary endpoint, moist desquamation, was not significantly different between treatment arms.

A systematic review of health economic evaluation in adjuvant breast radiotherapy: Quality counted by numbers

BACKGROUND Evolving practice in adjuvant breast radiotherapy inevitably impacts healthcare budgets. This is reflected in a rise of health economic evaluations (HEE) in this domain. The available HEE literature was analysed qualitatively and quantitatively, using available instruments. METHODS HEEs published between 1/1/2000 and 31/10/2016 were retrieved through a systematic search in Medline, Cochrane and Embase. A quality-assessment using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) was translated into a quantitative score and compared with Tufts Medical Centre CEA registry and Quality of Health Economic Studies (QHES) results. RESULTS Twenty cost-effectiveness analyses (CEA) and thirteen cost comparisons (CC) were analysed. In qualitative evaluation, valuation or justification of data sources, population heterogeneity and discussion on generalizability, in addition to declaration on funding, were often absent or incomplete. After quantification, the average CHEERS-scores were 74% (CI 66.9-81.1%) and 75.6% (CI 70.7-80.5%) for CEAs and CCs respectively. CEA-scores did not differ significantly from Tufts and QHES-scores. CONCLUSION Quantitative CHEERS evaluation is feasible and yields comparable results to validated instruments. HEE in adjuvant breast radiotherapy is of acceptable quality, however, further efforts are needed to improve comprehensive reporting of all data, indispensable for assessing relevance, reliability and generalizability of results.

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

Abstract 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 forks 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.

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

Abstract 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.