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JAMA·Oncology: Is radiotherapy followed by immunotherapy safe or not?
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JAMA·Oncology: Is radiotherapy followed by immunotherapy safe or not? The largest study to date makes it clear
Radiotherapy, surgery, and drug therapy are the three basic treatments for malignant tumors.
It is estimated that approximately 50 percent of patients with malignancies may require radiation therapy .
In recent years, with the gradual rise of immunotherapy represented by immune checkpoint inhibitors (ICI), more and more patients may receive ICI and radiotherapy simultaneously or sequentially .
ICI has been approved for the treatment of various malignant tumors, and its immune-related adverse reactions have some characteristics different from those of traditional chemotherapy, mainly involving the lung, liver, thyroid, gastrointestinal tract and other organs . Radiation therapy may also cause immune-related adverse reactions in patients.
Therefore, the medical community has long been concerned that patients may experience serious immune-related adverse reactions when they receive combined radiotherapy and ICI therapy .
The U.S. Food and Drug Administration (FDA) has accepted numerous ICI new drug marketing applications, and therefore received a large amount of clinical trial data. In these ICI-related clinical trials, many patients received radiotherapy and ICI treatment simultaneously or sequentially.
Recently, FDA expert Chana Weinstock and her team conducted the largest retrospective analysis to date on the safety of radiotherapy combined with ICI therapy . The findings were published in the journal JAMA Oncology  .
The study found that patients who received ICI within 90 days after radiotherapy had roughly the same rate of adverse effects compared with patients who received ICI alone .
Therefore, the researchers believe that receiving ICI within 90 days after radiotherapy did not increase the incidence of serious adverse reactions, and radiotherapy followed by immunotherapy should be relatively safe .
▲ Screenshot of the homepage of the paper
Next, let’s take a look at how this research is carried out.
After screening and exclusion, a total of 16,835 patients with malignant tumors who had received ICI therapy were included in this study, of which 13,956 (83%) patients received ICI therapy only, and 1773 (11%) patients received radiotherapy followed by sequential ICI therapy within 90 days. 1146 (6%) patients received sequential ICI therapy 90 days after RT.
More than 56% of patients were younger than 65 years, 62% were male, 79% were white, and 40% were from the United States. The main types of cancer are: lung cancer, melanoma, kidney cancer, head and neck cancer, bladder cancer.
▲ Flowchart of patient intake and discharge
If the patients were divided into those who received ICI alone and those who received radiotherapy plus ICI, the researchers found that the spectrum of AEs in the two groups(mainly neutropenia, thrombocytopenia, pneumonia, colitis, endocrinopathy, fatigue, diarrhea, etc.)are similar .
Specifically, the absolute difference in the incidence of fatigue between the two groups was 8%, and the smallest adverse reaction was nervous system adverse reactions, and the incidence of the two groups was almost the same. The mean difference in the incidence of various adverse reactions was 1.2%.
There was little difference in grade 3-4 adverse reactions between the two groups (the absolute value of the incidence of different adverse reactions varied from 0.01% to 2%) .
If all patients are divided into three groups: group 1 is the time from the end of radiotherapy to ICI ≤90 days (defined as RT≤90), group 2 is the time from the end of radiotherapy to ICI >90 days (RT>90), Group 3 consisted of patients who did not receive radiotherapy and only received ICI therapy.
The analysis found that compared with the non-radiotherapy group, the RT≤90 group had a slightly higher incidence of adverse reactions , mainly fatigue (53.1% vs. 45.5%), endocrinopathy (14.8% vs. 13.4%), and pneumonia (6.8% vs. 3.8%). %), the main difference was in grade 1 and 2 adverse reactions.
Compared with the RT>90 group, the incidence of adverse reactions was slightly higher in the RT≤90 group , and the main difference was in low-grade adverse reactions, such as pneumonia (6.8% vs. 3.6%), endocrinopathy (14.8% vs. 9.9%) , fatigue (53.1% vs. 41.4%).
After propensity score matching, RT≤90 had a slightly higher incidence of pneumonia, thrombocytopenia, and fatigue compared with the non-RT population. The incidence of pneumonitis was slightly higher in the RT>90 compared with the non-RT population, with the main difference being in grade 1 and 2 AEs.
In order to reduce potential selection bias, the study carried out propensity score matching according to the basic conditions of patients, such as age and gender.
After propensity score matching, RT≤90 had a slightly higher incidence of pneumonia (6.8% vs 4.6%), thrombocytopenia (3.4% vs 2.1%), and fatigue (53.5% vs 51.1%) compared to the non-RT group.
The incidence of colitis was slightly higher (2.5% vs 1.9%) compared to the non-RT group with RT > 90, with the main difference being grade 1 and 2 adverse events.
▲ The occurrence of adverse reactions in each group of people
The study concluded that although patients received ICI within 90 days of radiotherapy, the incidence of pneumonia, thrombocytopenia, kidney-related adverse reactions, and fatigue increased, and the incidence of pneumonia increased after ICI therapy 90 days after radiotherapy. increased, but the magnitude of the increase was very small, and the adverse reactions that differed were all low-grade.
Therefore, it can be considered that immunotherapy combined with ICI did not significantly increase the occurrence of adverse reactions .
1. Jaffray DA, Gospodarowicz MK. Radiation therapy for cancer. In: Gelband H, Jha P, Sankaranarayanan R, et al (eds): Disease Control Priorities: Cancer. TheWorld Bank; 2015: 239-248.
2. Vaddepally RK, Kharel P, Pandey R, Garje R, Chandra AB. Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence. Cancers (Basel). 2020 Mar 20;12(3):738. doi: 10.3390/cancers12030738. PMID: 32245016; PMCID: PMC7140028.
3. Esfahani K, Elkrief A, Calabrese C, Lapointe R, Hudson M, Routy B, Miller WH Jr, Calabrese L. Moving towards personalized treatments of immune-related adverse events. Nat Rev Clin Oncol. 2020 Aug;17(8):504-515. doi: 10.1038/s41571-020-0352-8. Epub 2020 Apr 3. PMID: 32246128.
4. Anscher MS, Arora S, Weinstock C, Amatya A, Bandaru P, Tang C, Girvin AT, Fiero MH, Tang S, Lubitz R, Amiri-Kordestani L, Theoret MR, Pazdur R, Beaver JA. Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database. JAMA Oncol. 2022 Jan 6. doi: 10.1001/jamaoncol.2021.6439. Epub ahead of print. PMID: 34989781.
JAMA·Oncology: Is radiotherapy followed by immunotherapy safe or not?
(source:internet, reference only)