Résumé
Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Place™ and Analytics Dose module. Characteristics of the patients and tumors (including TNM, histology, HER2, estrogen and progesterone receptor) were recorded at baseline. Characteristics of the treatments, skin, lung, cardiovascular, neurological, musculoskeletal toxicities (CTCAE v4.0), QOL (BR23, QLQC30), cosmetic, and oncological outcomes were assessed at diagnosis (baseline), 3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months after completion of primary surgery, chemotherapy or radiotherapy whichever came last together, with blood, plasma and serum tests. Results: CANTO-RT enrolled 3875 BC patients between June 2012 and February 2017 with a median follow-up of 64 months :1947 (50.2%) left side, 1850 (47.8%) right side and 78 (2%) bilateral BC. The vast majority of patients had hormone receptor-positive tumors 3321 (85.7%) and 553 (14.3%) had human epidermal growth factor 2 (HER2) positive tumors; 2586 (66.7%) had stage pT1 and 2525 (65.2%) pN0 disease; 2087 (53.8%) neoadjuvant or adjuvant chemotherapy, 477 (12.3%) adjuvant trastuzumab and 3138 (81%) adjuvant endocrine therapy. Among 3797 patients with unilateral RT, 3065 (80.4%) had breast conserving surgery, 747 (19.6%) total mastectomy; 2712 (71.5%) sentinel node and 1080 (28.5%) axillary dissection. 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 and 184 (4.7%) with intensity-modulated RT. Normofractionated RT (2Gy/fraction) was mostly used (69.9%). Clinical target (breast, chest wall, lymph nodes) and contoured organs at risk (heart, left anterior descending coronary, lung, spinal cord, esophagus, thyroid, brachial plexus, contralateral breast, humeral head) contours and dose/volume histograms were automatically extracted after quality control procedure excluding corrupted files and inconsistencies 36 (1%) (Table 1). Conclusion: CANTO-RT is the largest early breast cancer prospective cohort with full individual clinical and DICOM RT data available. CANTO-RT is a valuable resource, open for collaborative projects, for identification and validation of clinical and dosimetric predictive factors of RT related toxicities. Further long term follow up is ongoing. Table 1.Baseline characteristics of the CANTO RT breast cancer patients.CharacteristicsBreast Cancer Patients [N(%) or Mean (range)]Age at enrolmentMean (range), years56.5 (23.3-85.8)Tumour size (pT)T037 (1)T12586 (66.7)T21058 (27.3)T3177 (4.6)Missing17 (0.4)Nodal status (pN)02525 (65.2)11035 (26.7)2223 (5.8)379 (2)Missing13 (0.3)Tumour histologyInfiltrating Ductal3011 (77.7)Lobular473 (12.2)Others (including mixed)381 (9.8)Missing10 (0.3)Hormone Receptors positiveNegative541 (14)Positive3321 (85.7)Missing13 (0.3)HER2Negative3305 (85.3)Positive553 (14.3)Missing17 (0.4)Type of chemotherapyNo chemotherapy1788 (46.1)Neoadjuvant chemotherapy450 (11.6)Adjuvant chemotherapy1629 (42)Peri-adjuvant chemotherapy (neo + adjuvant)8 (0.2)Hormonal therapyNo730 (18.8)Yes3138 (81)Missing7 (0.2)Herceptin treatmentNo or Not applicable3378 (87.2)Yes477 (12.3)Missing20 (0.5)Type of breast surgerylumpectomy3113 (80.3)Mastectomy734 (18.9)Right lumpectomy and Left mastectomy13 (0.3)Right mastectomy and Left lumpectomy9 (0.2)None6 (0.2)Type of lymph node surgerySentinel node2746 (70.9)Axillary dissection1086 (28)Right sentinel node, Left axillary dissection20 (0.5)Right axillary dissection, left sentinel node12 (0.3)None11 (0.3)Radiation therapyRight Side1850 (47.8)Left Side1947 (50.2)Bilateral78 (2.0)Patients with boostNo or Not applicable1217 (31.4)Yes2658 (68.6)Lymph node levels treatedNone2519 (65)Yes1356 (35)Level 1284 (20.9)Level 2340 (25.1)Level 31072 (79.1)Level 41348 (99.4)Internal mammary chain844 (62.2)Irradiation techniques3D3691 (95.3)IMRT184 (4.7)Fractionation regimensNormofractionation 25-fractions2707 (69.9)Hypofractionation 15-16 fractions166 (4.3)Hypofractionation and Partial breast irradiation51 (1.3)Unspecified fractionation - CTV breast or chest wall not delineated951 (24.5) Citation Format: Thomas Sarrade, Rodrigue Allodji, Youssef Ghannam, Guillaume Auzac, Sibille Everhard, Ophélie Querel, Youlia Kirova, Karine Peignaux, Philippe Guilbert, Claire Charra-Brunaud, Julien Blanchecotte, Rezart Belshi, David Pasquier, Séverine Racadot, Céline Bourgier, Sandrine Ducornet, David Gibon, Fabrice André, Florent De Vathaire, Sofia Rivera. CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-01.