Bulky Tumor, Solid Tumor, Unresectable Malignant Neoplasm
Conditions
Keywords
partial stereotactic ablative boost radiotherapy, P-SABR, proton therapy, proton-photon hybrid radiotherapy, bulky tumor, large tumor, stereotactic ablative radiotherapy, spatially fractionated radiotherapy, biologically effective dose, conventionally fractionated radiotherapy
Brief summary
This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable larege tumors (longest diameter \> 5 cm) who receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons. The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0). Secondary objectives are dosimetric and the 1-year local control rate (RECIST 1.1, in-field). Participants are followed for up to 5 years.
Detailed description
BACKGROUND Large tumors (longest diameter \> 5 cm) are often unresectable and respond poorly to conventionally fractionated radiotherapy (CFRT) because of their size and hypoxic core, while normal-tissue tolerance prevents delivering stereotactic ablative radiotherapy (SABR) to the whole tumor. Partial stereotactic ablative boost radiotherapy (P-SABR) delivers a SABR boost only to the central part of a large tumor, followed by CFRT to the whole target. Proton beams, with their Bragg-peak dose fall-off, may sharpen this "onion-skin" dose distribution and further increase the biologically effective dose (BED) within the tumor core. DESIGN This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable bulky tumors (longest diameter \> 5 cm) who, as part of routine care, receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons (IMRT/VMAT) either at the same center or at Peking University First Hospital or one of six photon sub-centers, after central review of the composite plan. Cohort membership follows the patient's own choice and care pathway; the study does not assign treatment or intervene in clinical decisions, and no formal between-cohort hypothesis testing is planned. OUTCOMES The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0). Secondary objectives are dosimetric (percentage of the GTV receiving BED10 ≥ 100 Gy, PTV V95% and V100%, organ-at-risk doses) and the 1-year local control rate (RECIST 1.1, in-field). Participants are followed for up to 5 years.
Interventions
RADIATIONProton P-SABR
Course 1 (proton partial-SABR boost, IMPT): CTV 1.8-3 Gy per fraction with a simultaneous boost to the boost volume within the GTV (GTVb) of 8 Gy × 3 fractions; in larger tumors the inner GTVb (GTVb shrunk by 1 cm) is further boosted to 12 Gy × 3 fractions; critical organs at risk \< 3 Gy per fraction; robust optimization on the CTV. Course 2 (proton CFRT): CTV 1.8-3 Gy per fraction with robust optimization, to a cumulative PTV dose of 60-70 Gy on the summed plan, with GTVb BED10 ≥ 100 Gy. Proton dose is expressed with a constant RBE of 1.1. Both courses are delivered at Hebei Yizhou Cancer Hospital.
RADIATIONProton-Photon Hybrid P-SABR
Course 1 identical to Cohort A: proton partial-SABR boost (IMPT) with GTVb 8 Gy × 3 fractions and inner GTVb 12 Gy × 3 fractions, delivered at Hebei Yizhou Cancer Hospital. Course 2 (photon CFRT): IMRT/VMAT with daily CBCT recommended, PTV 1.8-3 Gy per fraction to a cumulative PTV dose of 60-70 Gy on the summed plan, with GTVb BED10 ≥ 100 Gy, delivered at Hebei Yizhou Cancer Hospital (same-center) or at Peking University First Hospital or a photon sub-center (cross-center). For cross-center participants, DICOM-RT structure, plan and dose files of both courses are reviewed by the central radiotherapy QA committee, which performs deformable registration and dose summation (MIM; proton RBE = 1.1) before course 2 starts. Target interval between courses ≤ 3 working days (maximum 7 working days).
Sponsors
Peking University First Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed malignancy * At least one tumor with a longest diameter \> 5 cm * Not amenable to curative surgical resection, or patient declines surgery, or surgery contraindicated because of medical comorbidities * Age ≥ 18 years * ECOG performance status 0-2 * Life expectancy \> 3 months * Written informed consent
Exclusion criteria
* Prior radiotherapy to the same site * Severe cardiopulmonary insufficiency precluding radiotherapy * Concurrent other active malignancy * Uncontrolled acute infection or bowel obstruction * Pregnancy or breastfeeding * Intracranial lesion * Tumor directly invading the full thickness of the esophageal, gastric or intestinal wall with active ulceration, fistula or uncontrolled risk of perforation (tumors that only abut or displace a hollow organ without full-thickness invasion are not excluded) * Uncontrolled active tumor bleeding, or impending pathological fracture requiring orthopedic intervention * Any other condition that, in the investigator's judgment, makes the patient unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-related adverse events of grade ≥ 3 (CTCAE v5.0) | From the first fraction of radiotherapy to the end of the study | Up to 5 years after completion of radiotherapy (acute events: from the first fraction of radiotherapy through 90 days after completion; late events: from day 91 after completion through 5 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the gross tumor volume (GTV) receiving a biologically effective dose (BED10) ≥ 100 Gy | Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized) | Volume fraction (%) of the GTV receiving BED10 ≥ 100 Gy on the composite (summed) plan, extracted from the treatment planning system (proton dose converted with RBE = 1.1; dose summation in MIM ). |
| Planning target volume (PTV) coverage: V95% and V100% | Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized) | Percentage of the PTV receiving ≥ 95% (V95%) and ≥ 100% (V100%) of the prescribed cumulative dose on the composite plan, reported per cohort as mean ± SD. |
| Doses to organs at risk (OARs) | Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized) | Dose metrics of organs at risk (e.g., spinal cord maximum dose, esophagus, lung, bowel, brachial plexus) on the composite plan, and the proportion of participants meeting each OAR dose constraint, reported per OAR and per cohort with 95% CI. |
| 1-year local control (LC) rate | 12 months after the first fraction of radiotherapy | Local control is defined as the absence of progressive disease (RECIST 1.1) in in-field lesions; the in-field region is defined by the GTV/CTV/PTV projections exported from the treatment planning system (DICOM-RT) and confirmed by blinded central imaging review. Time to local progression is measured from the first fraction of radiotherapy. The 1-year LC rate and its Greenwood 95% CI are estimated per cohort with the Kaplan-Meier method; no between-cohort test is performed. |
Contacts
CONTACTXianshu Gao, MD, PhD
Outcome results
None listed