A Prospective Cohort Study of Proton and Photon Therapy for Left-sided Breast Cancer.

A Prospective Cohort Study Comparing Proton and Photon Hypofractionated Radiotherapy for Left-sided Breast Cancer.

The goal of this study is to investigate the differences in toxicity and efficacy between proton and photon hypofractionated radiotherapy following lumpectomy or mastectomy for breast cancer. The main questions it aims to answer are:

1. What is the difference in the incidence of radiation-related grade 2 or higher adverse events within two years following proton versus photon therapy after breast-conserving surgery?
2. What is the difference in the incidence of radiation-related grade 2 or higher adverse events within two years following proton versus photon therapy after mastectomy?

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Proton radiotherapy; Radiation: Photon radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 780
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ping Li, M.D.; Phone Number: 021-38296666; Email: ping.li@sphic.org.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Proton and Heavy Ion Center
    • Contact: Ping Li, M.D.; Phone Number: 021-38296538; Email: ping.li@sphic.org.cn
    • Contact: Jin Meng, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed invasive breast cancer.

2. Indications for adjuvant radiotherapy following lumpectomy or mastectomy for left breast cancer:

   1. Post lumpectomy: Patients who have undergone lumpectomy with postoperative pathology staged as pT1-3 N1-3, excluding N3c.
   2. Post mastectomy: Patients who have undergone mastectomy, with postoperative pathology staged as pT1-3 N1-3, excluding N3c, and who have had an implant (prosthesis or tissue expander) placed.
3. Neoadjuvant therapy patients: Patients who have received neoadjuvant chemotherapy or endocrine/targeted therapy and have a postoperative stage of ypT1-3 N0-3, excluding N3c, requiring radiotherapy to the chest wall/breast and regional lymphatic drainage areas.
4. No distant metastasis.
5. Age range: 18-80 years.
6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0-2.
7. Non-pregnant and non-lactating women.
8. Informed consent: Patients must provide written informed consent prior to receiving radiotherapy.

Exclusion Criteria:

1. Presence of Ductal Carcinoma In Situ (DCIS).
2. Tumor staging: Patients presenting with T4, N0, or N3c disease.
3. History of prior radiotherapy to the ipsilateral chest or breast.

4. Surgical margin status: Margins are either positive or close, defined as:

   Invasive carcinoma within 1 mm of the surgical margin.

5. Bilateral breast cancer: Patients with synchronous or previous contralateral breast cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proton therapy; Proton radiotherapy will be offered to patients who require adjuvant radiotherapy after lumpectomy or mastectomy for breast cancer.	Radiation: Proton radiotherapy; Lumpectomy group: The total dose was 40.05Gy (RBE) , 2.67Gy (RBE) per fraction with 15 fractions. Once a day, five times a week. The tumor bed SIB to 48Gy (RBE). Mastectomy group: The total dose was 42.56Gy (RBE) , 2.66Gy (RBE) per fraction with 16 fractions. Once a day, five times a week.
Active Comparator: photon therapy; Photon radiotherapy will be offered to patients who require adjuvant radiotherapy after lumpectomy or mastectomy for breast cancer.	Radiation: Photon radiotherapy; Lumpectomy group: The total dose was 40.05Gy, 2.67Gy per fraction with 15 fractions. Once a day, five times a week. The tumor bed SIB to 48Gy (RBE). Mastectomy group: The total dose was 42.56Gy, 2.66Gy per fraction with 16 fractions. Once a day, five times a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of patients who develop radiation-associated toxicity (≥ 2 degree) in 2 years	We will record the incidence of ≥ 2 degree radiation-associated toxicity, such as breast or chest wall oedema, dermatitis, breast pain, esophagitis, rib fracture, radiation pneumonia and hypothyroidism and so on. The incidence of all the above is the primary outcome.	Until 2 years after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late toxicities after 2 years of radiotherapy	Evaluation of long-term adverse effects (greater than 2 years) after radiotherapy (including radiation pulmonary fibrosis, radiation skin fibrosis, rib fracture, brachial plexus injury, upper limb lymphedema, heart injury, hypothyroidism, etc.)	Until 5 years after radiotherapy
Locoregional recurrence (LRR)	To estimate and compare the rate of local recurrence between the proton and photon arms	Until 5 years after treatment.
Disease-free survival (DFS)	Disease-free survival, defined as number of days from surgery until the first occurrence of local recurrence, distant metastases, tumor-related death, death without prior progression, or end of follow-up.	Until 5 years after treatment.
Overall survival (OS)	Overall survival time, defined as number of days from date of initial diagnosis until death or end of follow-up.	Until 5 years after treatment.
Cosmetic outcome	photographic cosmetic scores by BCCT.core	Until 5 years after treatment.
uality of life, as measured by EORTC Quality of Life Questionnaires-B23	Impact on quality of life will be assessed by EORTC Quality of Life Questionnaires-B23；Which include functional domains, global health status and symptom scales.	During last week of radiotherapy, at 3 months post radiotherapy and 1,3 and 5 years post radiotherapy

Collaborators and Investigators

• Sponsor: Shanghai Proton and Heavy Ion Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 24, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; proton therapy; photon therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Unilateral Breast Neoplasms; Breast Neoplasms
• Other Study ID Numbers: SPHIC-TR-BCa2024-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No