Phase II Study of Proton-Based Stereotactic Body Radiation Therapy for Liver Metastases: Importance of Tumor Genotype
Bibliographic record
Abstract
Background: We evaluated the efficacy and safety of risk-adapted, proton-based stereotactic body radiation therapy (SBRT) for liver metastases from solid tumors. Methods: This single-arm phase II single institutional study (NCT01239381) included patients with limited extrahepatic disease, 800 mL or greater of uninvolved liver, and no cirrhosis or Child-Pugh A, who had received proton-based SBRT to one to four liver metastases from solid tumors. Treatment comprised 30 to 50 Gray equivalent (GyE) in five fractions based on the effective volume of liver irradiated. Sample size was calculated to determine if local control (LC) at one year was greater than 70%. The cumulative incidence of local failure was used to estimate LC. The association of tumor characteristics, including genetic alterations in common cancer genes such as BRAF, EGFR, HER2, KRAS, NRAS, PIK3CA, and TP53 with local tumor control, was assessed. All statistical tests were two-sided. Results: Eighty-nine patients were evaluable (colorectal, n = 34; pancreatic, n = 13; esophagogastric, n = 12; other, n = 30). Median tumor size was 2.5 cm (range = 0.5-11.9 cm). Median dose was 40 GyE (range = 30-50 GyE), and median follow-up was 30.1 months (range = 14.7-53.8 months). There was no grade 3 to 5 toxicity. Median survival time was 18.1 months. The one- and three-year LC rates were 71.9% (95% confidence limit [CL] = 62.3% to 80.9%) and 61.2% (95% CL = 50.8% to 71.8%), respectively. For large tumors (≥6 cm), one-year LC remained high at 73.9% (95% CL = 54.6% to 89.8%). Mutation in the KRAS oncogene was the strongest predictor of poor LC (P = .02). Tumor with both mutant KRAS and TP53 were particularly radioresistant, with a one-year LC rate of only 20.0%, compared with 69.2% for all others (P = .001). Conclusions: We report the largest prospective evaluation to date of liver SBRT for hepatic metastases, and the first with protons. Protons were remarkably well tolerated and effective even for metastases that were 6 cm or larger. KRAS mutation is a strong predictor of poor LC, stressing the need for tumor genotyping prior to SBRT and treatment intensification in this patient subset.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".