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2.
Front Immunol ; 15: 1336798, 2024.
Article in English | MEDLINE | ID: mdl-38779667

ABSTRACT

Background: Neoadjuvant chemotherapy plus immunotherapy (nCT + ICIs) and neoadjuvant chemoradiotherapy plus immunotherapy (nCRT + ICIs) both induced favorable pathological response and tolerant toxicities for locally resectable esophageal squamous cell carcinoma (ESCC). However, few studies compared safety and efficacy between the two treatment strategies. Methods: This retrospective study collected clinical data of locally resectable ESCC patients who underwent nCT + ICIs or nCRT + ICIs followed by esophagectomy from November 2019 to December 2022. The incidence of adverse events, surgical outcomes, short and long-term efficacy, and treatment costs were compared. Results: A total of 206 patients were included, with a ratio of 158:48 between nCT + ICIs group and nCRT + ICIs group. The two groups exhibited well-balanced baseline characteristics. Most adverse events were grade 1-2 in both groups. The nCT + ICIs group had a longer operative time (334.00 ± 170.2 min vs 279.60 ± 88.31 min, P=0.020) than nCRT + ICIs group, but there were no differences in surgical complications. Although nCT + ICIs group had a lower pCR rate (32.3% vs 52.1%, P=0.004), the 2-year overall survival (84.42% vs 81.70%, P=0.860), 2-year disease-free survival (83.21% vs 80.47%, P=0.839), and recurrence patterns were similar to nCRT + ICIs group. In addition, nCT + ICIs group had significantly lower expenses (188796.00 ± 107704.00 RMB vs 231808.00 ± 48067.00 RMB, P=0.045). Conclusion: Overall, nCT + ICIs have comparable safety and efficacy compared to nCRT + ICIs for locally resectable ESCC, but with lower hospitalization costs.


Subject(s)
Chemoradiotherapy , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagectomy , Immunotherapy , Neoadjuvant Therapy , Humans , Male , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/mortality , Female , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Middle Aged , Esophageal Neoplasms/therapy , Esophageal Neoplasms/mortality , Retrospective Studies , Chemoradiotherapy/methods , Chemoradiotherapy/adverse effects , Aged , Esophagectomy/adverse effects , Immunotherapy/methods , Immunotherapy/adverse effects , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
3.
Front Immunol ; 15: 1366271, 2024.
Article in English | MEDLINE | ID: mdl-38779675

ABSTRACT

A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (Streptococcus pneumoniae). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.


Subject(s)
Hemangiosarcoma , Liver Neoplasms , Splenectomy , Splenic Neoplasms , Humans , Splenectomy/adverse effects , Male , Hemangiosarcoma/therapy , Splenic Neoplasms/secondary , Splenic Neoplasms/therapy , Fatal Outcome , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Immunotherapy/methods , Adult , Pneumococcal Infections/etiology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors
5.
Medicine (Baltimore) ; 103(18): e38037, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701263

ABSTRACT

BACKGROUND AND OBJECTIVE: The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma (HCC) has gained increasing attention. However, there are variations in the efficacy and safety outcomes between TACE-T-I versus TACE combined with targeted drugs (TACE-T). This study aims to systematically evaluate the efficacy and safety of TACE-T-I versus TACE-T in unresectable HCC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 21, 2023, for comparative studies on TACE-T-I versus TACE-T for unresectable HCC. Outcome measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (TRAEs). OS was the primary outcome of this study. Weighted mean difference (WMD) or hazard ratio (HR) was used as the pooled statistic for OS and PFS. Relative risk (RR) was employed as the pooled statistic for ORR, DCR and the incidence of TRAEs. And 95% confidence intervals (CIs) were calculated for all effect measures. Data analysis was conducted using Stata 14.0 software. RESULTS: The meta-analysis included 14 studies with 2144 patients. The pooled results showed that compared with patients in the TACE-T group, patients in the TACE-T-I group had higher ORR (RR = 1.61; 95%CI: 1.38-1.89) and DCR (RR = 1.17; 95%CI: 1.09-1.26). Patients in the TACE-T-I group experienced prolonged PFS (WMD = 3.08; 95%CI: 2.63-3.53) and OS (WMD = 5.76; 95%CI: 4.68-6.84). And the risk of disease progression (HR = 0.45; 95%CI: 0.37-0.55) and death (HR = 0.43; 95%CI: 0.38-0.49) was lower in the TACE-T-I group. Common TRAEs included fever, pain, abdominal pain, nausea, vomiting, elevated ALT, elevated AST, hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence and severity of TRAEs in the TACE-T-I group were similar to those in the TACE-T group, with no significant differences (P > .05). CONCLUSION: Current evidence suggests that, on the basis of TACE combined with targeted therapy, the addition of immunotherapy provides better clinical efficacy and survival benefits for unresectable HCC patients, with good tolerability.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Immunotherapy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/methods , Chemoembolization, Therapeutic/adverse effects , Liver Neoplasms/therapy , Liver Neoplasms/mortality , Immunotherapy/methods , Immunotherapy/adverse effects , Combined Modality Therapy , Treatment Outcome , Molecular Targeted Therapy/methods
6.
Front Immunol ; 15: 1351739, 2024.
Article in English | MEDLINE | ID: mdl-38690281

ABSTRACT

Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI. Methods: Using two-sided Fisher exact and Cochran-Armitage tests, we determined the relative timing of initial efficacy assessment and irAE occurrence in a cohort of 155 ICI-treated patients (median age 68 years, 40% women). Results: Initial efficacy assessment was performed a median of 50 days [interquartile range (IQR) 39-59 days] after ICI initiation; median time to any irAE was 77 days (IQR 28-145 days) after ICI initiation. Median time to first irAE was 42 days (IQR 20-88 days). Overall, 58% of any irAE and 47% of first irAE occurred after initial efficacy assessment. For clinically significant (grade ≥2) irAE, 60% of any and 53% of first occurred after initial efficacy assessment. The likelihood of any future irAE did not differ according to response (45% for complete or partial response vs. 47% for other cases; P=1). In landmark analyses controlling for clinical and toxicity follow-up, patients demonstrating greater tumor shrinkage at initial efficacy assessment were more likely to develop future grade ≥2 (P=0.05) and multi-organ (P=0.02) irAE. Conclusions: In contrast to that seen with chemotherapy and molecularly targeted therapies, the temporal relationship between ICI efficacy and toxicity is complex and bidirectional. In practice, neither parameter can be routinely relied on as a clinical biomarker to predict the other.


Subject(s)
Biomarkers , Immune Checkpoint Inhibitors , Neoplasms , Humans , Female , Male , Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/therapy , Immunotherapy/adverse effects , Immunotherapy/methods , Treatment Outcome , Time Factors
8.
Cancer Treat Rev ; 127: 102751, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729086

ABSTRACT

Chemotherapy associated with Immune Checkpoint Inhibitors is currently the standard of care in several tumor indications. This combination approach improves progression free survival (PFS), overall survival (OS) and complete pathological response (pCR) in several cancer types both in the early and metastatic approaches. However, the distinct spectrum of toxicities between cytotoxic side effects and immune related adverse events (irAEs) with similar clinical presentations and different management strategies remains a challenge in daily practice for healthcare professionals. This review summarizes the most common toxicities reported in the randomized clinical trials that led to the subsequent FDA approval of these combinations, across tumor indications. We cite in particular: non-small cell lung cancer, small cell lung cancer, triple negative breast cancer, squamous cell carcinoma of the head and neck, gastric carcinoma, esophageal carcinoma, cervical carcinoma and biliary tract carcinoma. We found that the combination of chemotherapy and immunotherapy was associated with an increased incidence of all grade adverse events (RR 1.11 [1.09; 1.12]) without an excess in treatment related mortality when compared to chemotherapy alone. We report also an increase in the incidence of serious adverse events (grade ≥ 3) (RR 1.16 [1.10;1.24]); in particular: high grade diarrhea, dyspnea, fatigue, rash and elevated liver enzymes. Together with the collaboration of our institutional network of organ specialists with expertise in irAEs, we propose practical recommendations for physicians to enhance clinical care and management of patients undergoing treatment with combined ICI immunotherapy and chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Immune Checkpoint Inhibitors , Neoplasms , Humans , Neoplasms/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Immunotherapy/methods , Immunotherapy/adverse effects , Randomized Controlled Trials as Topic
9.
Drugs Aging ; 41(5): 431-441, 2024 May.
Article in English | MEDLINE | ID: mdl-38727992

ABSTRACT

BACKGROUND: Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. OBJECTIVE: This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. METHODS: Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3-5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. RESULTS: Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41-13.02); OR 1.33 (95% CI 0.45-4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61-8.31); OR 2.18 (95% CI 0.7-6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39-35.4); OR 1.31 (95% CI 0.35-4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1-2 toxicity as well. CONCLUSIONS: Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1-2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.


Subject(s)
Immunotherapy , Neoplasms , Humans , Aged , Neoplasms/drug therapy , Neoplasms/therapy , Neoplasms/immunology , Male , Female , Immunotherapy/adverse effects , Aged, 80 and over , Frailty , Immune Checkpoint Inhibitors/adverse effects , Hospitalization/statistics & numerical data
10.
J Immunother Cancer ; 12(5)2024 May 30.
Article in English | MEDLINE | ID: mdl-38816231

ABSTRACT

BACKGROUND: Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined. METHODS: We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared. RESULTS: Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p<0.01) and completeness (3.83 vs 3.46, p<0.01). Scores of 1-2 (completely or mostly inaccurate or incomplete) were particularly rare for ChatGPT (6/800 answer-ratings, 0.75%). Of the 50 questions, all eight physician raters gave ChatGPT a rating of 4 (fully accurate or complete) for 22 questions (for accuracy) and 16 questions (for completeness). In the 20 patient scenarios, the average accuracy score was 3.725 (median 4) and the average completeness was 3.61 (median 4). CONCLUSIONS: AI chatbots provided largely accurate and complete information regarding irAEs, and wildly inaccurate information ("hallucinations") was uncommon. However, until accuracy and completeness increases further, appropriate guidelines remain the gold standard to follow.


Subject(s)
Artificial Intelligence , Humans , Immunotherapy/methods , Immunotherapy/adverse effects , Neoplasms/drug therapy , Neoplasms/immunology , Drug-Related Side Effects and Adverse Reactions
11.
Dermatologie (Heidelb) ; 75(6): 440-450, 2024 Jun.
Article in German | MEDLINE | ID: mdl-38772932

ABSTRACT

BACKGROUND: Oncological therapies can cause a variety of mucocutaneous adverse events. Exanthematous adverse events can be challenging in the context of the urgent need for cancer treatment due to their spread, sometimes rapid progression, and mucous membrane or organ involvement. MATERIALS AND METHODS: This article provides an overview of the most important exanthematic dermatoses as side effects of modern drug-based tumor therapies with diagnostic and therapeutic information for clinicians, taking into account the current literature and guidelines. RESULTS: Exanthematous adverse events of immune checkpoint inhibitors, EGFR antagonists, kinase inhibitors, bispecific T­cell engagers, and the CCR4 inhibitor mogamulizumab are reviewed in detail. CONCLUSIONS: Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.


Subject(s)
Drug Eruptions , Exanthema , Immune Checkpoint Inhibitors , Immunotherapy , Humans , Exanthema/chemically induced , Exanthema/therapy , Drug Eruptions/therapy , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Drug Eruptions/immunology , Immunotherapy/adverse effects , Immunotherapy/methods , Immune Checkpoint Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Neoplasms/drug therapy , Neoplasms/immunology , Molecular Targeted Therapy/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use
12.
World J Gastroenterol ; 30(17): 2321-2331, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38813052

ABSTRACT

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Hepatocellular , Fluorouracil , Hepatic Artery , Infusions, Intra-Arterial , Leucovorin , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Male , Female , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Middle Aged , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/therapeutic use , Aged , Adult , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Treatment Outcome , Molecular Targeted Therapy/methods , Progression-Free Survival , Retrospective Studies , Immunotherapy/methods , Immunotherapy/adverse effects , Combined Modality Therapy/methods
13.
Clin Chest Med ; 45(2): 325-337, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38816091

ABSTRACT

Drug-induced lung disease is commonly encountered, especially in the oncology setting. Diagnosis is challenging because clinical and radiologic findings are nonspecific, often overlapping with other lung pathologies in these patients due to underlying neoplasia, infection, or other treatment effects such as radiotherapy. Furthermore, oncology patients often receive multiple antineoplastic agents concurrently, and virtually every agent has an association with lung injury. In this article, we will review a variety of antineoplastic agents that are associated with drug-induced injury and discuss incidence, their typical timing of onset, and imaging features.


Subject(s)
Antineoplastic Agents , Immunotherapy , Humans , Antineoplastic Agents/adverse effects , Immunotherapy/adverse effects , Lung Diseases/chemically induced , Lung Diseases/etiology , Neoplasms/drug therapy , Neoplasms/complications
14.
Front Immunol ; 15: 1369531, 2024.
Article in English | MEDLINE | ID: mdl-38799429

ABSTRACT

Background: Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by high immunogenicity which makes it particularly suitable for immune checkpoint inhibitors (ICIs) treatment. Case presentation: We report the case of a 53-year-old man with metastatic DM successfully treated with the combination of anti-CTLA-4 and anti-PD-1 antibodies, who developed serious immune-related adverse events (irAEs). The primary tumor was characterized by absent PD-L1 expression and no-brisk lymphocytes infiltration. NGS showed absence of BRAF mutation, a high tumor mutational burden, and an UV-induced DNA damage signature. Metastatic lesions regressed rapidly after few cycles of ICIs until complete response, however the patient developed serious irAEs including hypothyroidism, adrenal deficiency, and acute interstitial nephritis which led to the definitive suspension of treatment. Currently, the patient has normal renal functionality and no disease relapse after 26 months from starting immunotherapy, and after 9 months from its definitive suspension. Conclusion: Efficacy and toxicity are two sides of the same coin of high sensitivity to ICIs in DM. For this reason, these patients should be closely monitored during ICIs therapy to promptly identify serious side effects and to correctly manage them.


Subject(s)
Immune Checkpoint Inhibitors , Melanoma , Humans , Male , Melanoma/drug therapy , Melanoma/immunology , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Immunotherapy/methods , Skin Neoplasms/drug therapy , Skin Neoplasms/immunology , CTLA-4 Antigen/antagonists & inhibitors , Treatment Outcome , Programmed Cell Death 1 Receptor/antagonists & inhibitors
15.
Front Immunol ; 15: 1376590, 2024.
Article in English | MEDLINE | ID: mdl-38799431

ABSTRACT

Background: Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments. Methods: The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn. Results: Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS. Conclusion: In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Immunotherapy , Humans , Cholangiocarcinoma/therapy , Cholangiocarcinoma/immunology , Cholangiocarcinoma/mortality , Male , Female , Middle Aged , Bile Duct Neoplasms/therapy , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/immunology , Aged , Prognosis , Immunotherapy/adverse effects , Immunotherapy/methods , Retrospective Studies , Adult , Fibrosis , Aged, 80 and over , Risk Factors
16.
Front Immunol ; 15: 1292325, 2024.
Article in English | MEDLINE | ID: mdl-38585276

ABSTRACT

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.


Subject(s)
Bone Neoplasms , Sarcoma , Soft Tissue Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Prospective Studies , Sarcoma/drug therapy , Immunotherapy/adverse effects
17.
PLoS One ; 19(4): e0300789, 2024.
Article in English | MEDLINE | ID: mdl-38625861

ABSTRACT

PURPOSE: Immunotherapy has been shown to improve cancer survival, but there are no consensus guidelines to inform use in patients with both cancer and autoimmune disease (AD). We sought to examine immunotherapy utilization patterns between cancer patients with and without AD. PATIENTS AND METHODS: This retrospective cohort study utilized data from a de-identified nationwide oncology database. Patients diagnosed with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma were included. Outcomes of interest included first-line immunotherapy, overall immunotherapy, and number of immunotherapy cycles. We used logistic and Poisson regression models to examine associations between AD and immunotherapy utilization patterns. RESULTS: A total of 25,076 patients were included (796 with AD). Patients with AD were more likely to be female, White, receive care at academic centers, and have ECOG ≥ 3. Controlling for demographic and clinical variables, AD was associated with lower odds of receiving first-line (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.56-0.82) and overall (OR = 0.80, 95% CI 0.67-0.94) immunotherapy. Among patients who received at least one cycle of immunotherapy, there was no difference in mean number of cycles received between patients with and without AD (11.3 and 10.5 cycles respectively). The incident rate of immunotherapy cycles received for patients with AD was 1.03 times that of patients without AD (95% CI 1.01-1.06). DISCUSSION: Patients with AD were less likely to receive immunotherapy as first-line and overall therapy for treatment of their advanced cancer. However, among those who did receive at least one cycle of immunotherapy, patients with AD received a similar number of cycles compared to patients without AD. This not only indicates that AD is not an absolute contraindication for immunotherapy in clinical practice but may also demonstrate overall treatment tolerability and net benefit in patients with AD.


Subject(s)
Autoimmune Diseases , Carcinoma, Non-Small-Cell Lung , Kidney Neoplasms , Lung Neoplasms , Humans , Female , Male , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Retrospective Studies , Immunotherapy/adverse effects , Kidney Neoplasms/etiology , Autoimmune Diseases/therapy , Autoimmune Diseases/etiology
18.
BMC Med ; 22(1): 165, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38637772

ABSTRACT

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases. METHODS: In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%). CONCLUSIONS: External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation. TRIAL REGISTRATION: NCT03898895. Registered 2 April 2019.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Drug-Related Side Effects and Adverse Reactions , Humans , Immunotherapy/adverse effects , Drug Therapy, Combination , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/radiotherapy , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/radiotherapy , Bile Ducts, Intrahepatic
19.
World J Gastroenterol ; 30(14): 1941-1948, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38681126

ABSTRACT

Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the cessation of ICIs. Although irAE gastritis is rarely reported, it may lead to serious complications such as gastrorrhagia. Furthermore, irAE gastritis is often difficult to identify early due to its diverse symptoms. Although steroid hormones and immunosuppressants are commonly used to reverse irAEs, the best regimen and dosage for irAE gastritis remains uncertain. In addition, the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered. In this editorial, strategies such as early identification, pathological diagnosis, management interventions, and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.


Subject(s)
Gastritis , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/adverse effects , Gastritis/immunology , Gastritis/chemically induced , Gastritis/diagnosis , Gastritis/drug therapy , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/immunology , Immunotherapy/adverse effects , Immunotherapy/methods
20.
Rheum Dis Clin North Am ; 50(2): 229-239, 2024 May.
Article in English | MEDLINE | ID: mdl-38670722

ABSTRACT

Cancer immunotherapy is revolutionary for survival but has complications due to immunogenicity with unpredictable and potentially long-lasting autoimmune side effects known as immune-related adverse events (irAEs). Currently, treatment beyond corticosteroids can be complicated by the diversity of providers who are needed across a variety of clinical settings to manage irAEs. We outline the role of critical players in the management of irAEs, discuss the current limitations that exist, and propose various methodologies that can be adapted across clinical settings to tackle these needs. We aim to better understand who can be affected by irAEs and tailor diagnostics and therapeutics appropriately.


Subject(s)
Immunotherapy , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Drug-Related Side Effects and Adverse Reactions/diagnosis
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