Do responses to news matter? Evidence from interventional cardiology.

We examine physician responses to a global information shock and how these impact their patients. We exploit international news over the safety of an innovation in healthcare, the drug-eluting stent. We use data on interventional cardiologists' use of stents to define and measure cardiologists' responsiveness to the initial positive news and link this to their patients' outcomes. We find substantial heterogeneity in responsiveness to news. Patients treated by cardiologists who respond slowly to the initial positive news have fewer adverse outcomes. This is not due to patient-physician sorting. Instead, our results suggest that the differences are partially driven by slow responders being better at deciding when (not) to use the new technology, which in turn affects their patient outcomes.

Locoregional breast radiotherapy including IMN: optimizing the dose distribution using an automated non-coplanar VMAT-technique.

BACKGROUND: Volumetric Modulated Arc Therapy (VMAT) offers better conformity, homogeneity and sparing of the heart and ipsilateral lung for locoregional radiotherapy in left-sided breast cancer compared to three-dimensional conformal radiotherapy (3D-CRT). However, conventional coplanar VMAT (cVMAT) can result in higher doses to the normal tissue on the contralateral side. This study investigates a non-coplanar VMAT-technique (ncVMAT) to mitigate this issue. MATERIAL AND METHODS: CT series of 20 left sided breast cancer patients were included for planning of locoregional breast radiotherapy including internal mammary nodes (IMN). Three treatment plans; 3D-CRT, cVMAT and ncVMAT, were generated for each patient with a prescription dose of 40.05 Gy in 15 fractions. Both VMAT-techniques consisted of a single arc in the axial plane, while ncVMAT included an additional arc in the sagittal plane. All plans were optimized to cover the clinical target volume (CTV) by 38.05 Gy for the breast and 36.05 Gy for lymph nodes, with as low as possible dose to organs at risk. RESULTS: Full CTV coverage was achieved for all plans. Both cVMAT and ncVMAT delivered more conformal and homogeneous target doses than 3D-CRT. Doses to the heart and ipsilateral lung were significantly lower with ncVMAT compared to both cVMAT and 3D-CRT. ncVMAT reduced doses to both the contralateral breast and lung compared to cVMAT and achieved levels similar to 3D-CRT for the contralateral breast and moderately higher doses for the contralateral lung. Delivery of high doses (>30 Gy) to the contralateral side was completely avoided with ncVMAT, contrary to the results for cVMAT and 3D-CRT. CONCLUSION: ncVMAT reduced doses to the heart and ipsilateral lung as compared to both cVMAT and 3D-CRT. All contralateral dose metrics were reduced with the novel ncVMAT technique compared to cVMAT, and the mean contralateral breast doses were similar to 3D-CRT.

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.

INTRODUCTION: Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence. METHODS AND ANALYSIS: In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included. ETHICS AND DISSEMINATION: The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05634889.

Selection criteria for early breast cancer patients in the DBCG proton trial - The randomised phase III trial strategy.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial. MATERIALS AND METHODS: 179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose-response relationships for heart and lung. RESULTS: Median mean heart dose was 3.0 Gy (range, 1.1-8.2 Gy) for left-sided and 1.4 Gy (0.4-11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9-57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial. CONCLUSION: The patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%.

Double Trouble: The Burden of Child-rearing and Working on Maternal Mortality.

We document increased old-age mortality rates among Swedish mothers of twins compared with mothers of singletons, using administrative data on mortality for 1990-2010. We argue that twins are an unplanned shock to fertility in the cohorts of older women considered. Deaths due to lung cancer, chronic obstructive pulmonary disease, and heart attacks-all of which are associated with stress during the life course-are significantly increased. Stratifying the sample by education and pension income shows the highest increase in mortality rates among highly educated mothers and those with above-median pension income. These results are consistent with the existence of a double burden on mothers' health resulting from simultaneously child-rearing and working.

Estimating returns to hospital volume: Evidence from advanced cancer surgery.

High-volume hospitals typically perform better than low-volume hospitals. In this paper, we study whether such patterns reflect a causal effect of case volume on patient outcomes. To this end, we exploit closures and openings of entire cancer clinics in Swedish hospitals which provides sharp and arguably exogenous variation in case volumes. Using detailed register data on more than 100,000 treatment episodes of advanced cancer surgery, our results suggest substantial positive effects of operation volume on survival. Complementary analyses point to learning-by-doing as an important explanation.

A comparison of conventional and dynamic radiotherapy planning techniques for early-stage breast cancer utilizing deep inspiration breath-hold.

BACKGROUND: For breast cancer patients, radiotherapy increases the risk of cardiac disease. Conventional three-dimensional conformal radiotherapy (3D-CRT) in deep inspiration breath-hold (DIBH) has demonstrated substantial reduction in cardiac doses as compared to treatment in free breathing. The purpose of this treatment planning study is to investigate if dynamic techniques in combination with DIBH could improve the quality of the treatment plans and further reduce the doses to the heart and other organs at risk for early-stage breast cancer patients. MATERIAL AND METHODS: CT series in DIBH of 16 patients from a previous study were used. For each patient, treatment plans were generated with the following three techniques: 3D-CRT, tangential intensity-modulated radiotherapy (tIMRT) and volumetric modulated arc therapy with partial arcs (pVMAT). The treatment planning was performed focusing on planning target volume (PTV) coverage, V95% >95%. Dose-volume histograms were calculated and compared. Doses to the heart, left anterior descending (LAD) coronary artery, ipsilateral and contralateral lung as well as the contralateral breast (CB) were assessed. RESULTS: All plans fulfilled the criterion on PTV coverage. Compared to 3D-CRT, the dynamic plans obtained better dose homogeneity and conformity. The mean heart dose was similar for 3D-CRT and tIMRT, 1.3 and 1.1 Gy, respectively, but significantly higher for pVMAT, 1.6 Gy. The median V25 Gy to the heart was 0% for all techniques. The LAD doses were generally lower with the dynamic techniques. The mean doses to the ipsi- and contralateral lung and CB were similar with tIMRT and 3D-CRT but significantly higher with pVMAT. V20 Gy to the ipsilateral lung was significantly lower with tIMRT compared to 3D-CRT. CONCLUSION: tIMRT and 3D-CRT with DIBH are better techniques for sparing heart tissue and other organs at risk without compromising target coverage in early-stage breast cancer irradiation compared to VMAT.

Pulmonary function tests - an easy selection method for respiratory-gated radiotherapy in patients with left-sided breast cancer.

PURPOSE: The purpose of this study was to establish a feasible and convenient method for selection of the subset of patients with left-sided breast cancer for whom respiratory-gated radiotherapy (RT) would be necessary to meet the national recommendation regarding radiation dose to the heart. MATERIAL AND METHODS: The volume of heart receiving a dose equal to or higher than 25 Gy (V25Gy), the mean heart dose (Dmean) and total lung volume (TLV-CT) were obtained from treatment plans based on computer tomography (CT) series recorded during free breathing (FB), and the correlation between dose to the heart and TLV-CT was studied. Second, the correlation between TLV-CT and TLV defined from three pulmonary function tests (PFTs); spirometry, gas diffusion and plethysmograhy, was evaluated. RESULTS: Dose to the heart (V25Gy and Dmean) decreased with increasing TLV-CT. Pearson's correlation coefficient (r) for TLV-CT versus V25Gy and Dmean was equal (r = -0.809, p < 0.01) for patients planned for tangential breast RT only, and r = -0.853 and -0.861 (p < 0.01) for patients planned for loco-regional RT. Regression analysis showed good correlation between TLV-CT and TLV calculated from pulmonary function tests (R(2) ≥ 0.717, p < 0.01). CONCLUSION: TLV defined by routine pulmonary function tests can be used to identify the subset of left-sided breast cancer patients who require respiratory-gated RT.

Radiation during deep inspiration allows loco-regional treatment of left breast and axillary-, supraclavicular- and internal mammary lymph nodes without compromising target coverage or dose restrictions to organs at risk.

BACKGROUND AND PURPOSE: Loco-regional radiotherapy of left-sided breast cancer represents a treatment planning challenge when the internal mammary chain (IMC) lymph nodes are included in the target volume. This treatment planning study evaluates the reduction in cardiopulmonary doses when radiation is given during deep inspiration breath-hold (DIBH). This was achieved without compromising dose coverage to the planning target volume (PTV). PATIENTS AND METHODS: Seventeen patients with early breast cancer, referred for adjuvant radiotherapy, were included. For each patient two computed tomography (CT)-scans were acquired; the first during free breathing (FB) and the second during DIBH. The scans were monitored by the Varian RPM respiratory gating system. Audio-visual guidance was used. The treatment planning of the two CT studies was performed focusing on good coverage (V95% > 98%) of the PTV. Doses to the heart, left anterior descending (LAD) coronary artery, lungs and contralateral breast were assessed. RESULTS: With equal PTV coverage, average mean heart dose was reduced from 6.2 Gy to 3.1 Gy in DIBH plans as compared to FB. Average volume receiving 25 Gy or more (V25Gy) was reduced from 6.7% to 1.2%, and the number of patients with V25Gy > 5% was reduced from 8 to 1 utilizing DIBH. The average mean dose to the LAD coronary artery was reduced from 25.0 Gy to 10.9 Gy. The average ipsilateral lung volume receiving 20 Gy or more (V20Gy) was reduced from 44.5% to 32.7% with DIBH. In 11 of the DIBH plans V20Gy was lower than 35%, in accordance with national guidelines, while none of the FB plans fulfilled this recommendation. CONCLUSION: Respiratory gated radiotherapy during DIBH is a suitable technique for loco-regional breast irradiation even when IMC lymph nodes are included in the PTV. Cardiopulmonary doses are considerably decreased for all dose levels without compromising the dose coverage to PTV.

Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing.

PURPOSE: To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast. MATERIAL AND METHODS: Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated. RESULTS: Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans. CONCLUSION: No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models.

Cardiac and pulmonary dose reduction for tangentially irradiated breast cancer, utilizing deep inspiration breath-hold with audio-visual guidance, without compromising target coverage.

BACKGROUND AND PURPOSE: cardiac disease and pulmonary complications are documented risk factors in tangential breast irradiation. Respiratory gating radiotherapy provides a possibility to substantially reduce cardiopulmonary doses. This CT planning study quantifies the reduction of radiation doses to the heart and lung, using deep inspiration breath-hold (DIBH). PATIENTS AND METHODS: seventeen patients with early breast cancer, referred for adjuvant radiotherapy, were included. For each patient two CT scans were acquired; the first during free breathing (FB) and the second during DIBH. The scans were monitored by the Varian RPM respiratory gating system. Audio coaching and visual feedback (audio-visual guidance) were used. The treatment planning of the two CT studies was performed with conformal tangential fields, focusing on good coverage (V(95)>98%) of the planning target volume (PTV). Dose-volume histograms were calculated and compared. Doses to the heart, left anterior descending (LAD) coronary artery, ipsilateral lung and the contralateral breast were assessed. RESULTS: compared to FB, the DIBH-plans obtained lower cardiac and pulmonary doses, with equal coverage of PTV. The average mean heart dose was reduced from 3.7 to 1.7 Gy and the number of patients with >5% heart volume receiving 25 Gy or more was reduced from four to one of the 17 patients. With DIBH the heart was completely out of the beam portals for ten patients, with FB this could not be achieved for any of the 17 patients. The average mean dose to the LAD coronary artery was reduced from 18.1 to 6.4 Gy. The average ipsilateral lung volume receiving more than 20 Gy was reduced from 12.2 to 10.0%. CONCLUSION: respiratory gating with DIBH, utilizing audio-visual guidance, reduces cardiac and pulmonary doses for tangentially treated left sided breast cancer patients without compromising the target coverage.