Radiation-induced lung injury after breast cancer treatment: incidence in the CANTO-RT cohort and associated clinical and dosimetric risk factors.

Purpose: Radiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence. Material and methods: Data from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging. Results: RILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p<0.01) and high V30 Gy (OR=1.06, p=0.04) remained statistically significant risk factors for RILI occurrence. V30 Gy >15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03). Conclusion: Our study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

CANTO-RT: One of the Largest Prospective Multicenter Cohort of Early Breast Cancer Patients Treated with Radiotherapy including Full DICOM RT Data.

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities.

Educative Impact of Automatic Delineation Applied to Head and Neck Cancer Patients on Radiation Oncology Residents.

To evaluate the educational impact on radiation oncology residents in training when introducing an automatic segmentation software in head and neck cancer patients regarding organs at risk (OARs) and prophylactic cervical lymph node level (LNL) volumes. Two cases treated by exclusive intensity-modulated radiotherapy were delineated by an expert radiation oncologist and were considered as reference. Then, these cases were delineated by residents divided into two groups: group 1 (control group), experienced residents delineating manually, group 2 (experimental group), young residents on their first rotation trained with automatic delineation, delineating manually first (M -) and then after using the automatic system (M +). The delineation accuracy was assessed using the Overlap Volume (OV). Regarding the OARs, mean OV was 0.62 (SD = 0.05) for group 1, 0.56 (SD = 0.04) for group 2 M - , and 0.61 (SD = 0.03) for group 2 M + . Mean OV was higher in group 1 compared to group 2 M - (p = 0.01). There was no OV difference between group 1 and group 2 M + (p = 0.67). Mean OV was higher in the group 2 M + compared to group 2 M - (p < 0.003). Regarding LNL, mean OV was 0.53 (SD = 0.06) in group 1, 0.54 (SD = 0.03) in group 2 M - , and 0.58 (SD = 0.04) in group 2 M + . Mean OV was higher in group 2 M + for 11 of the 12 analysed structures compared to group 2 M - (p = 0.016). Prior use of the automatic delineation software reduced the average contouring time per case by 34 to 40%. Prior use of atlas-based automatic segmentation reduces the delineation duration, and provides reliable OARs and LNL delineations.

Impact of radiation therapy on fatigue at 1 year in breast cancer survivors in the prospective multicentre CANcer TOxicity cohort.

BACKGROUND: Fatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. METHODS: We used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I-III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. RESULTS: The final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03-2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06-3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04-3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. CONCLUSION: We found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.

CANTO-RT: Skin toxicities evaluation of a multicentre large prospective cohort of irradiated patients for early-stage breast cancer.

Skin damage is the most common and most important toxicity during and after radiation therapy (RT). Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients irradiated for an early breast cancer. CANTO is a prospective clinical cohort study of 10 150 patients with stage I-III BC treated from 2012 to 2017 in 26 cancer centres. In our study, we used CANTO-RT, a subcohort of CANTO, including 3480 patients who received RT. We are focus on specific skin toxicities: erythema, fibrosis, telangiectasia and cutaneous pigmentation. The prevalence of toxicities of interest varied over time, so at baseline for early toxicity Month (M) 0-3-6, 41.1% of patients had erythema while 24.8% of patients had fibrosis. At M12 and M36, the prevalence of erythema decreased, respectively, while fibrosis remains stable. The prevalence of telangiectasia increases from 1% to 7.1% from M0-3-6 to M36. After adjustments, we showed an association between the occurrence of skin erythema and obesity; the type of surgery; the presence of axillary dissection; the use of taxane-based CT and the 3D vs IMRT irradiation technique. Regarding fibrosis, an association is found, at M0-3-6, with age at diagnosis, obesity, tobacco and the use of boost. Only obesity and the type of surgery received by the patient remained statistically significant at M12 and M36. In our study we identified several risk factors for acute and late skin reactions. The use of a boost was mainly related to the occurrence of fibrosis while the use of IMRT-type technique decreased the occurrence of skin erythema.