ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 69 papers, 5 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 5 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Heating the Cold: Overcoming Immunotherapy Resistance in Microsatellite-Stable Colorectal Cancer: A Systematic Review.Molecules (Basel, Switzerland) · 2026Pooled it
- Optimal early endpoint for second-line or subsequent immune checkpoint inhibitors in previously treated advanced solid cancers: a systematic review.BMC cancer · 2025Pooled it
- The Efficacy and Safety of Durvalumab and Tremelimumab with Concomitant Treatment for MSS/pMMR Metastatic Colorectal Cancer: A Single Arm Meta-Analysis.Journal of gastrointestinal cancer · 2025Pooled it
- The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.The oncologist · 2024Pooled it
- Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of advanced colorectal cancer: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort.Journal for immunotherapy of cancer · 2025Trial
- Metronomic chemotherapy plus anti-PD-1 in metastatic breast cancer: a Bayesian adaptive randomized phase 2 trial.Nature medicine · 2024Trial
- Multicenter, single-arm, phase II study (CAP) of radiotherapy plus liposomal irinotecan followed by camrelizumab and anti-angiogenic treatment in advanced solid tumors.Frontiers in immunology · 2023Trial
- Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial.The Lancet. Oncology · 2022Trial
- Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.Oncoimmunology · 2026Review
- Review
- Combining radiotherapy with CAR-T cell therapy for solid tumors: Challenges, mechanisms, and future directions.Precision radiation oncology · 2026Review
- Low-dose radiotherapy synergizes with PD-1 blockade to achieve durable survival in advanced NSCLC through antitumor neutrophil programming.Signal transduction and targeted therapy · 2026Article
- The Proteo-Transcriptome of Extracellular Vesicles and Particles Is Largely Preserved After Cryopreservation.Journal of extracellular biology · 2026Article
- TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how.Journal for immunotherapy of cancer · 2026Review
- Harnessing the abscopal effect: mechanistic insights and therapeutic strategies for systemic cancer immunotherapy.Frontiers in immunology · 2026Review
- Towards a personalized utilization of stereotactic body radiotherapy for the management of liver metastases in solid tumors.Cancer metastasis reviews · 2025Review
- Low Radiation Doses to Gross Tumor Volume in Metabolism Guided Lattice Irradiation Based on Lattice-01 Study: Dosimetric Evaluation and Potential Clinical Research Implication.Journal of personalized medicine · 2025Article
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
34 authors at 11 institutions in 2 countries.
Funding
Abstract
purposeProspective human data are lacking regarding safety, efficacy, and immunologic impacts of different radiation doses administered with combined PD-L1/CTLA-4 blockade. PATIENTS AND
methodsWe performed a multicenter phase II study randomly assigning patients with metastatic microsatellite stable colorectal cancer to repeated low-dose fractionated radiation (LDFRT) or hypofractionated radiation (HFRT) with PD-L1/CTLA-4 inhibition. The primary endpoint was response outside the radiation field. Correlative samples were analyzed using multiplex immunofluorescence (IF), IHC, RNA/T-cell receptor (TCR) sequencing, cytometry by time-of-flight (CyTOF), and Olink.
resultsEighteen patients were evaluable for response. Median lines of prior therapy were four (range, 1-7). Sixteen patients demonstrated toxicity potentially related to treatment (84%), and 8 patients had grade 3-4 toxicity (42%). Best response was stable disease in 1 patient with out-of-field tumor shrinkage. Median overall survival was 3.8 months (90% confidence interval, 2.3-5.7 months). Correlative IF and RNA sequencing (RNA-seq) revealed increased infiltration of CD8
conclusionsWe demonstrate the feasibility and safety of adding LDFRT and HFRT to PD-L1/CTLA-4 blockade. Although the best response of stable disease does not support the use of concurrent PD-L1/CTLA-4 inhibition with HFRT or LDFRT in this population, biomarkers provide support that both LDFRT and HFRT impact the local immune microenvironment and systemic immunogenicity that can help guide future studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.