Proton vs Photon IMRT Toxicity in Breast Cancer

Definition: The composite toxicity endpoint is a binary outcome (yes/no), defined as the occurrence of at least one of the following events from the start of radiotherapy up to 1 year post-treatment:

Event A (Lymphedema): Development of ≥ Grade 2 upper limb lymphedema;Event B (Lymphopenia): Development of ≥ Grade 2 lymphopenia within 3 months after completion of treatment;Event C (Cardiotoxicity): Development of ≥ Grade 1 cardiotoxicity within 1 year post-treatment. All assessed according to CTCAE v5.0.This primary outcome measure will report the proportion (%) of subjects who experience at least one composite toxicity event.

The incidence and grade of acute radiation-induced cardiac morbidities (e.g., EKG changes or pericardial abnormalities) will be assessed using the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Acute Radiation Morbidity Scoring Criteria. Assessments will be conducted weekly during treatment, and at 4 weeks and 3 months post-treatment.

The incidence and severity of other acute toxicities will be graded using CTCAE v5.0, including fatigue , malaise, radiation dermatitis, and esophageal pain，Esophagitis，Breast infection，pneumonia，Cough and blood system disorder. Assessments will follow the same schedule as above.

The incidence and grade of chronic radiation-induced Other skin and cardiac toxicities will be assessed at 6 and 12 months post-treatment using the RTOG/EORTC Late Radiation Morbidity Scoring Criteria. Specific assessments include: Chronic radiation dermatitis (Late skin toxicity) and Chronic cardiac injury (e.g., pericardial effusion, constrictive pericarditis, cardiomyopathy)

The incidence and severity of chronic radiation-induced toxicities will be assessed at 6 and 12 months post-treatment completion. Evaluations will employ the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, assessing the following specific adverse events: chest wall necrosis (soft tissue necrosis)；hyperpigmentation ；hypopigmentation；radiation pneumonitis (lung toxicity)；breast atrophy；nipple deformity；breast infection；hyperparathyroidism；hyperthyroidism；lib fracture, brachial plexopathy and joint range of motion decreased.

The incidence and severity of late radiation-induced breast toxicities will be assessed at 6 and 12 months post-treatment using the Late Effects of Normal Tissue-Subjective, Objective, Management, Analytic (LENT-SOMA) scoring system. Specific assessments include: Telangiectasia;Fibrosis; breast/chest edema; ulceration and arm lymphedema.

Assessed via patient self-assessment and physician photographic review using the Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. This scale rates cosmetic outcome on a 4-point scale: Excellent, Good, Fair, or Poor, where higher grades indicate worse cosmetic outcomes.

Assessed using the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). This is a patient-reported outcome measurement system developed by the National Cancer Institute to evaluate symptomatic adverse events in cancer clinical trials. Each symptom is rated on a 5-point scale ranging from 0 to 4, where higher scores indicate worse symptoms (0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Very severe).

Assessed using the breast cancer specific EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) questionnaires. This is a 30-item questionnaire assessing functional scales (physical, role, emotional, cognitive, social functioning) and symptom scales. Scores range from 0 to 100. For functional scales, higher scores indicate better quality of life; for symptom scales, higher scores indicate worse symptoms.

Target coverage of the PTV, defined by V95% (the percentage of the PTV receiving at least 95% of the prescribed dose).PTV coverage as measured by V90%, and high-dose volume as measured by V105% and V110%.

The dose-volume histograms (DVHs) of OARs will be analyzed. The evaluation will cover:Cardiac Structures: Mean dose, D1cc, and V2-V30 for the heart and left ventricle (LV), along with D0.1cc for the left anterior descending artery (LAD).Lungs: Mean dose, D0.1cc, and V5-V25 for the ipsilateral lung, and V2 and V4 for the contralateral lung.Serial Organs: Maximum dose for the spinal cord (Dmax), D0.1cc for the ipsilateral brachial plexus, and D1cc for the esophagus.

Other Structures: Contralateral breast, and thyroid gland.

Assessed using the breast cancer specific EORTC QLQ-BR 23 questionnaire. This is a 23-item breast cancer specific module assessing functional scales(body image, sexual functioning, sexual enjoyment, future perspective) and symptom scales (systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss). Scores range from 0 to 100. For functional scales, higher scores indicate better functioning; for symptom scales, higher scores indicate worse symptoms.