Evaluation of Radiation Dose Effect on Lung Function Using Iodine Maps Derived From Dual-Energy Computed Tomography.

PURPOSE: There is interest in using dual-energy computed tomography (DECT) to evaluate organ function before and after radiation therapy (RT). The purpose of this study (trial identifier: NCT04863027) is to assess longitudinal changes in lung perfusion using iodine maps derived from DECT in patients with lung cancer treated with conventional or stereotactic RT. METHODS AND MATERIALS: For 48 prospectively enrolled patients with lung cancer, a contrast-enhanced DECT using a dual-source CT simulator was acquired pretreatment and at 6 and 12 months posttreatment. Pulmonary functions tests (PFT) were obtained at baseline and at 6 and 12 months posttreatment. Iodine maps were extracted from the DECT images using a previously described 2-material decomposition framework. Longitudinal iodine maps were normalized using a reference region defined as all voxels with perfusion in the top 10% outside of the 5 Gy isodose volume. Normalized functional responses (NFR) were calculated for 3 dose ranges: <5, 5 to 20, and >20 Gy. Mixed model analysis was used to assess the correlation between dose metrics and NFR. Pearson correlation was used to assess if NFRs were correlated with PFT changes. RESULTS: Out of the 48 patients, 21 (44%) were treated with stereotactic body RT and 27 (56%) were treated with conventionally fractionated intensity-modulated RT. Thirty-one out of these 48 patients were ultimately included in data analysis. It was found that NFR is linearly correlated with dose (P < .001) for both groups. The number of months elapsed post-RT was also found to correlate with NFR (P = .029), although this correlation was not observed for the stereotactic body RT subgroup. The NFR was not found to correlate with PFT changes. CONCLUSIONS: DECT-derived iodine maps are a promising method for detailed anatomic evaluation of radiation effect on lung function, including potentially subclinical changes.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

PURPOSE: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology. METHODS AND MATERIALS: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible. The maximally tolerated dose was defined as the dose of radiation therapy associated with a ≤30% rate of grade (G) 3 to 5 prespecified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume; tumors with endobronchial invasion were excluded. This primary analysis occurred 2 years after completion of accrual. RESULTS: Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range, 65-87) and 17 (57%) were female. Planning tumor volume was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%), and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range, 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia. The latter had computed tomography findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% CI, 52.3%-85.3%), progression-free survival 66.1% (95% CI, 46.1%-80.2%), local control 89.6% (95% CI, 71.2%-96.5%), regional control 96.4% (95% CI, 77.2%-99.5%), and distant control 85.9% (95% CI, 66.7%-94.5%). Quality-of-life scores declined numerically over time, but the decreases were not clinically or statistically significant. CONCLUSIONS: Sixty Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the prespecified acceptability criteria and results in excellent control for ultracentral tumors.

Stereotactic Radiation Therapy in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease: A Nonrandomized Clinical Trial.

Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.

An exploratory cross-sectional study of the effects of ongoing relationships with accompanying patients on cancer care experience, self-efficacy, and psychological distress.

BACKGROUND: Centre hospitalier de l'Université de Montréal in Canada introduced accompanying patients (APs) into the breast cancer care trajectory. APs are patients who have been treated for breast cancer and have been integrated into the clinical team to expand the services offered to people affected by cancer. This study describes the profiles of the people who received the support and explores whether one-offs vs ongoing encounters with APs influence their experience of care, on self-efficacy in coping with cancer, and on their level of psychological distress. METHODS: An exploratory cross-sectional study was carried out among patients to compare patients who had one encounter with an AP (G1) with those who had had several encounters (G2). Five questionnaires were administered on socio-demographic characteristics, care pathway, evaluation of the support experience, self-efficacy in coping with cancer, and level of psychological distress. Logbooks, completed by the APs, determined the number of encounters. Linear regression models were used to evaluate the associations between the number of encounters, patient characteristics, care pathway, number of topics discussed, self-efficacy measures in coping with cancer, and level of psychological distress. RESULTS: Between April 2020 and December 2021, 60% of 535 patients who were offered support from an AP accepted. Of these, one hundred and twenty-four patients participated in the study. The study aimed to recruit a minimum of 70 patients with the expectation of obtaining at least 50 participants, assuming a response rate of 70%. There were no differences between G1 and G2 in terms of sociodemographic data and care pathways. Statistical differences were found between G1 and G2 for impacts on and the return to daily life (p = 0.000), the return to the work and impacts on professional life (p = 0.044), announcement of a diagnosis to family and friends (p = 0.033), and strategies for living with treatment under the best conditions (p = 0.000). Significant differences were found on the topics of cancer (p = 0.000), genetic testing (p = 0.023), therapeutic options (p = 0.000), fatigue following treatment (p = 0.005), pain and discomfort after treatment or surgery (p = 0.000), potential emotions and their management (p = 0.000) and the decision-making processes (p = 0.011). A significant relationship was found between the two groups for patients' ability to cope with cancer (p = 0.038), and their level of psychological distress at different stages of the care pathway (p = 0.024). CONCLUSIONS: This study shows differences between one-time and ongoing support for cancer patients. It highlights the potential for APs to help patients develop self-efficacy and cope with the challenges of cancer treatment.

Prospective evaluation of severe skin toxicity and pain during postmastectomy radiation therapy.

PURPOSE: To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects. METHODS AND MATERIALS: Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain. RESULTS: Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grade 3 moist desquamation was significantly associated with severe pain (P<.001). On multivariate analysis, smoking, high-energy photons, and skin bolus were significantly associated with severe moist desquamation. Skin toxicity doubled for smokers, with 40% severe pain, 48% grade 3 moist desquamation, and 64% grade 3 skin toxicity. Without skin bolus 4.2% had severe pain, none moist desquamation, and 2.1% grade 3 skin toxicity. When skin bolus was used on alternate days, the frequency increased to 15% for pain, 22% for moist desquamation, and 26% for grade 3 skin toxicity. When bolus was used daily, 32% had pain, 41% moist desquamation, and 47% grade 3 skin toxicity. Symptoms peaked 1 to 2 weeks after the end of PMRT. CONCLUSIONS: The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus.

A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis.

PURPOSE: Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution. PATIENTS AND METHODS: A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy. RESULTS: A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003). CONCLUSION: Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.

The impact of the number of excised axillary nodes and of the percentage of involved nodes on regional nodal failure in patients treated by breast-conserving surgery with or without regional irradiation.

PURPOSE: After breast-conserving surgery, recommendations for regional nodal radiotherapy are usually based on the number of positive nodes. This number is dependent on the number of nodes removed during the axillary dissection. This study examines whether the percentage of positive nodes may help to select patients for regional radiotherapy. METHODS AND MATERIALS: A retrospective study was conducted on 1,372 T1-T2 node-positive breast cancer patients treated at L'Hôtel-Dieu de Québec Hospital between 1972 and 1997. RESULTS: Among the patients who did not receive regional radiotherapy, the percentage of involved nodes was significantly associated with axillary failure. Ten-year axillary control rates were 97% and 91% when the percentage of involved nodes was <50% and > or =50%, respectively (p = 0.007). In addition, regional radiotherapy is always significantly associated with a decrease in overall regional failure (axillary and/or supraclavicular), regardless of the percentage of involved nodes. However, regional radiotherapy reduced the axillary failure rate (2% vs. 9%, p = 0.007) only when more than a specific percentage of nodes was involved (> or =40% if N1-3 and > or =50% if N>3 nodes). CONCLUSIONS: The percentage of involved nodes should be taken into consideration in selecting patients for regional radiotherapy. Irradiation of the axilla should be reserved for patients with a specific ratio: >40% involved nodes if N1-3 and > or =50% involved nodes if N>3 nodes.

Impact of locoregional radiotherapy in node-positive patients treated by breast-conservative treatment.

PURPOSE: The aim of this study is to evaluate the impact of locoregional radiation in node-positive patients treated by tumorectomy and radiation therapy. METHODS: A retrospective study including all our 1368 T1-2 node-positive patients was conducted. Conservative surgery was followed by breast irradiation. Axillary and supraclavicular irradiation was left to the discretion of the treating radiation oncologist. RESULTS: In the group receiving locoregional radiation (472 patients), the 10-year regional control was 97% vs. 91% for the group receiving radiation to the breast only (896 patients) (p = 0.004). In a Cox model analysis, locoregional radiation is associated with a better regional control rate (hazard ratio: 0.27; 95% confidence interval: 0.13-0.54, p = 0.0001). Locoregional radiotherapy is associated with a better rate of locoregional control (hazard ratio: 0.56; 95% confidence interval: 0.38-0.8, p = 0.002). In particular, for the N>3 group, the substantial 10-year locoregional failure rate (26% with breast irradiation only) is cut by 50%. Locoregional radiotherapy, however, is not associated with a lower rate of distant metastases. CONCLUSION: Locoregional radiation decreases the rate of locoregional failure by nearly 50%. Locoregional radiotherapy should be considered for node-positive patients, especially if they have more than 3 positive nodes.