Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Plans in Internal Mammary Irradiation (RADIANT)

Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Radiotherapy Plans for Internal Mammary Irradiation in Postoperative Breast Cancer

This study is an investigator-initiated, single-arm, single-center, prospective, observational study. The hypothesis is that during the implementation of deep inspiration breath-hold (DIBH) radiotherapy plans in postoperative breast cancer patients receiving internal mammary irradiation, the actual target dose coverage and organ-at-risk (OARs) dose parameters remain within clinically acceptable ranges.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: DIBH with 3mm Gating Window; Radiation: DIBH with 2 mm Gating Window; Radiation: DIBH with 1.5 mm Gating Window

Detailed Description

For patients with left-sided breast cancer, postoperative radiotherapy can expose the heart to excessive radiation, increasing the risk of cardiac toxicity. DIBH displaces the heart away from the chest wall by expanding the thoracic cavity during breath-holding to reduce cardiac radiation doses. Although DIBH has demonstrated efficacy in reducing cardiac exposure in left-sided breast cancer, its application in internal mammary and regional lymph node irradiation remains uncertain due to potential issues related to dose robustness associated with larger target volumes near the heart.

The success of DIBH depends on maintaining a stable respiratory gating window; however, individual variations in breath-holding capacity and fatigue may lead to intrafractional and interfractional positional errors, which can compromise target coverage and increase doses to OARs. Surface-guided systems monitor respiratory motion but may not accurately represent the positions of deep-seated targets and OARs, raising concerns about dose coverage, particularly for the internal mammary target.

State-of-the art radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) provide improved dose conformality and reduce high-dose cardiac exposure. However, the integration of these techniques with DIBH and the impact of positional errors on dose robustness remain inadequately studied. Proton therapy, due to its steep dose fall-off, minimizes cardiac and pulmonary exposure but is highly sensitive to positional changes. This sensitivity may amplify uncertainties during DIBH, particularly in the context of internal mammary irradiation.

This study aims to evaluate the dose robustness of DIBH in left-sided breast cancer patients undergoing internal mammary irradiation, with a specific focus on the impact of respiratory motion amplitude during breath-holding on dose distribution, as well as intrafractional and interfractional positional errors. Using offline CT and Cone-Beam CT (CBCT) data, it will assess positional deviations and compare the performance of IMRT, VMAT, and Intensity-Modulated Proton Therapy (IMPT) during DIBH. The findings will provide critical evidence to optimize DIBH for internal mammary and regional lymph node irradiation, improving clinical outcomes while minimizing cardiac toxicity.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Lu Cao, PhD; Phone Number: +86-021-64370045; Email: cl11879@rjh.com.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Lu Cao, PhD; Phone Number: 602400 86-021-64370045; Email: cl11879@rjh.com.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Female patients aged ≥18 years with left-sided postoperative invasive breast cancer scheduled for DIBH radiotherapy targeting the internal mammary and regional lymph nodes at Ruijin Hospital, Shanghai JiaoTong University School of Medicine.

The study will recruit a total of 25 participants, divided into three cohorts based on different respiratory gating tolerances (3 mm, 2 mm, and 1.5 mm).

Description

Inclusion Criteria:

1. Provide a signed and dated informed consent form (ICF) before the initiation of any trial-specific procedures.
2. Female patients aged ≥ 18 years.
3. Histologically confirmed invasive breast cancer.
4. Have received breast-conserving surgery or mastectomy with axillary staging, including sentinel lymph node biopsy and/or axillary lymph node dissection.
5. Able to hold breath for more than 30 seconds after deep inspiration.
6. Planned to receive postoperative radiotherapy targeting regional lymph nodes, including the internal mammary nodes, under DIBH conditions.
7. Planned to undergo moderate hypofractionated radiotherapy.
8. Karnofsky Performance Status (KPS) score ≥ 80.
9. The estimated life expectancy of greater than 5 years .
10. Sufficient wound healing from surgery, with no signs of active infection at the intended radiation site.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. Presence of any severe, uncontrolled comorbidity or medical condition that, in the investigator's judgment, would render the participant unsuitable for the study, compromise protocol compliance, or confound the interpretation of study results.
3. Unable to understand or comply with breath-hold training instructions.
4. Right-sided breast cancer.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm1: 3 mm Gating Window Group; Participants will receive regional nodal and internal mammary irradiation using a hypofractionated regimen and the DIBH technique, with a respiratory gating tolerance of ±1.5 mm (a total of 3 mm).	Radiation: DIBH with 3mm Gating Window; The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ±1.5 mm (3 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the center of the gating window. CT2: Breath-hold at the upper edge, simulating maximum thoracic expansion. CT3: Breath-hold at the lower edge, simulating minimum thoracic expansion. Setup errors (intrafraction and interfraction) and respiratory waveforms monitored via Surface Guided Radiation Therapy（SGRT）systems will be recorded for analysis.
Arm2: 2 mm Gating Window Group; Participants will receive regional nodal and internal mammary irradiation using a hypofractionated regimen and the DIBH technique, with a respiratory gating tolerance of ±1.0 mm (a total of 2 mm).	Radiation: DIBH with 2 mm Gating Window; The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ±1 mm (2 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the center of the gating window. CT2: Breath-hold at the upper edge, simulating maximum thoracic expansion. CT3: Breath-hold at the lower edge, simulating minimum thoracic expansion. Setup errors (intrafraction and interfraction) and respiratory waveforms monitored via SGRT systems will be recorded for analysis.
Arm3: 1.5 mm Gating Window Group; Participants will receive regional nodal and internal mammary irradiation using a hypofractionated regimen and the DIBH technique, with a respiratory gating tolerance of ± 0.75 mm (a total of 1.5 mm).	Radiation: DIBH with 1.5 mm Gating Window; The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ± 0.75 mm (1.5 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the center of the gating window. CT2: Breath-hold at the upper edge, simulating maximum thoracic expansion. CT3: Breath-hold at the lower edge, simulating minimum thoracic expansion. Setup errors (intrafraction and interfraction) and respiratory waveforms monitored via SGRT systems will be recorded for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target coverage of the Planning treatment volume (PTV)	Target coverage of the PTV, defined by V95% (the percentage of the PTV volume receiving at least 95% of the prescribed dose).	Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional dose-volume parameters of the PTV	PTV coverage as measured by V90%, and high-dose volume as measured by V105% and V110%.	Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.
Dose-volume parameters of the organs at risk (OARs)	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 and V5-V25 for the left lung, and V2 and V4 for the right lung. Serial Organs: Maximum dose for the spinal cord (Dmax), D0.1cc for the left brachial plexus, and D1cc for the esophagus. Other Structures: Mean dose for the left humeral head, contralateral right breast, and thyroid gland.	Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.
Conformity Index (CI) of the PTV	Calculated as V95% / PTV volume. A value closer to 1 indicates better conformity.	Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.
Homogeneity Index (HI) of the PTV	Calculated as (D2% - D98%)/D50%. A lower value indicates better homogeneity.	Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.
Intra-fractional Error-PTV	Intra-fractional error is defined as any patient movement occurring during a single radiotherapy fraction, measured by surface-guided or image-guided systems. This outcome evaluates the impact of intra-fractional motion on target coverage using DVH-based metrics. PTV Metrics include: V95%: percentage of PTV receiving ≥95% of prescribed dose, V90%: percentage of PTV receiving ≥90% of prescribed dose, High-dose volume: V105% and V110%, percentage of PTV receiving ≥105% or ≥110% of prescribed dose, HI: (D2% - D98%) / D50%, where D2%, D98%, D50% are doses covering 2%, 98%, and 50% of PTV, CI: (PTV volume covered by prescription dose)² / (PTV volume × prescription isodose volume).	During each treatment fraction (daily, approximately 3-4 weeks per patient)
Intra-fractional Error-OARs	Intra-fractional error is defined as any patient movement occurring during a single radiotherapy fraction, measured by surface-guided or image-guided systems. This outcome evaluates the impact of intra-fractional motion on OAR doses using DVH-based metrics. OAR Dose Metrics: Heart and LV: mean dose, D1cc, V2-V30, LAD : D0.1cc, Lungs: mean dose and V5-V25 for left lung, V2 and V4 for right lung, Spinal cord: Dmax, Left brachial plexus: D0.1cc, Esophagus: D1cc, Other relevant structures: mean dose for left humeral head, contralateral breast, thyroid gland, Unit of measurement: Gy for absolute doses; % for volume-based metrics.	During each treatment fraction (daily, approximately 3-4 weeks per patient)
Inter-fractional Error- PTV	Inter-fractional error is defined as positional variation occurring between different treatment days, measured using daily CBCT image registration and dose recalculation. This outcome evaluates the impact of inter-fractional motion on PTV coverage using DVH metrics. PTV Metrics include: V95%: percentage of PTV receiving ≥95% of prescribed dose, V90%: percentage of PTV receiving ≥90% of prescribed dose, High-dose volume: V105% and V110%, percentage of PTV receiving ≥105% or ≥110% of prescribed dose, HI: (D2% - D98%) / D50%, where D2%, D98%, D50% are doses covering 2%, 98%, and 50% of PTV, CI: (PTV volume covered by prescription dose)² / (PTV volume × prescription isodose volume).	Across all treatment fractions (approximately 3-4 weeks per patient)
Inter-fractional Error- OAR	Inter-fractional error is defined as positional variation occurring between different treatment days, measured using daily CBCT image registration and dose recalculation. This outcome evaluates the impact of inter-fractional motion on OAR doses using DVH metrics. OAR Dose Metrics: Heart and LV: mean dose, D1cc, V2-V30, LAD : D0.1cc, Lungs: mean dose and V5-V25 for left lung, V2 and V4 for right lung, Spinal cord: Dmax, Left brachial plexus: D0.1cc, Esophagus: D1cc, Other relevant structures: mean dose for left humeral head, contralateral breast, thyroid gland, Unit of measurement: Gy for absolute doses; % for volume-based metrics.	Across all treatment fractions (approximately 3-4 weeks per patient)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Dose to PTV	Cumulative dose is calculated using DVH-based metrics derived from all treatment fractions. Quantitative metrics include:V95%: percentage of PTV receiving ≥95% of prescribed dose, V90%: percentage of PTV receiving ≥90% of prescribed dose, HI: (D2% - D98%) / D50%, where D2%, D98%, D50% are doses covering 2%, 98%, and 50% of PTV, CI: (PTV volume covered by prescription dose)² / (PTV volume × prescription isodose volume).Unit of measurement: % for volumetric coverage; Gy for absolute doses	Across all treatment fractions (approximately 3-4 weeks per patient)
Cumulative Dose to OARs	Cumulative OAR dose is assessed using DVH -derived metrics across all treatment fractions. Quantitative metrics include: Heart and LV: mean dose, D1cc, V2-V30, LAD : D0.1cc, Lungs: mean dose and V5-V25 for left lung, V2 and V4 for right lung, Spinal cord: Dmax, Left brachial plexus: D0.1cc, Esophagus: D1cc, Other relevant structures: mean dose for left humeral head, contralateral breast, thyroid gland, Unit of measurement: Gy for absolute doses; % for volume-based metrics.	Across all treatment fractions (approximately 3-4 weeks per patient)

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: DIBH; regional nodal irradiation; Internal Mammary Irradiation; Robustness Evaluation; Postoperative breast cancer radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: RJBC-DIBH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. All imaging and dosimetric data are stored in an anonymized, password-protected database at Ruijin Hospital and will be used solely by the study investigators in accordance with institutional data protection policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No