scholarly journals Diagnostic utility of CT for suspected immune checkpoint inhibitor enterocolitis

2020 ◽  
Vol 8 (2) ◽  
pp. e001329
Author(s):  
Sienna M Durbin ◽  
Meghan J Mooradian ◽  
Florian Johannes Fintelmann ◽  
Leyre Zubiri ◽  
Donald F Chute ◽  
...  
Keyword(s):  
Ct Scan ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Primary Objective ◽  
Institutional Review ◽  
Grade 3 ◽  
Sensitivity Specificity ◽  
Tumor Types

Background and aimsImmune checkpoint inhibitor (ICI) enterocolitis is a common immune-related adverse event and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, but CT scan is a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of ICI enterocolitis.MethodsWith institutional review board approval, we conducted a retrospective cohort study of patients who received ICI therapy between 2015 and 2019 across a healthcare system. Patients were included if they underwent both abdominal CT and endoscopy with biopsy within 3 days. The radiological and pathological diagnoses, as well as clinical characteristics, were extracted from the electronic medical record. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT for diagnosing ICI enterocolitis when compared with tissue diagnosis.ResultsOf the 4474 patients screened, 138 met inclusion criteria. Most common tumor types were melanoma (37%) and lung cancer (19%). Seventy-four per cent were treated with antiprogrammed cell death (PD-1)/PD-L1 therapy. Thirty-nine per cent had signs of enterocolitis on CT scan and 58% had biopsy-proven ICI enterocolitis. Sensitivity and specificity of CT were 50% and 74%, respectively. PPV was 73% and NPV was 52%. Of those with confirmed ICI enterocolitis, 70% had grade 3 or higher symptoms, 91% received steroids and 40% received infliximab.ConclusionThe performance of CT scan for diagnosis of ICI enterocolitis is moderate to poor and does not replace endoscopy with biopsy.

Diagnostic evaluation of immune checkpoint inhibitor (CPI) colitis: The role of CT scan.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 821-821
Author(s):  
Sienna Durbin ◽  
Meghan Mooradian ◽  
Leyre Zubiri ◽  
Ian Matthew Allen ◽  
Florian Fintelmann ◽  
...  
Keyword(s):  
Ct Scan ◽  
Predictive Value ◽  
Gold Standard ◽  
Invasive Procedure ◽  
Primary Objective ◽  
Lower Endoscopy ◽  
Grade 3 ◽  
Sensitivity Specificity ◽  
Tumor Types

821 Background: CPI therapy has expanded rapidly in recent years and represents a major advancement in the treatment of many cancers, including hepatocellular carcinoma, gastric cancer, and colon cancer. However, these therapies are associated with significant toxicities. CPI colitis is one of the most common toxicities and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, an invasive procedure that is resource- and time-intensive. CT has emerged as a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of CPI colitis. Methods: With IRB approval, we conducted a retrospective cohort study of patients who received CPI therapy between 2009-2019 across a single healthcare system. Patients were included if they underwent both abdominal CT and upper/lower endoscopy with biopsy within 72 hours of each other. We reviewed the electronic medical record to identify possible cases of colitis based on either CT or pathology. All cases were labeled as either true positive or false positive based on pathology. We examined clinical characteristics, including CTCAE grade and treatment received. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for diagnosing CPI colitis when compared to the gold standard of tissue diagnosis. Results: Of the 4,474 patients screened, 141 met inclusion criteria. Average age was 63 years (23 – 91); 43% were male. Most common tumor types were melanoma (36%) and NSCLC (20%). Seventy-four percent of patients were treated with anti-PD-1/PD-L1 monotherapy. Forty percent had signs of colitis on CT scan and 59% had biopsy-proven CPI colitis. Sensitivity and specificity of CT were 51% and 74%, respectively. PPV of CT was 74% and NPV was 51%. Of those with confirmed CPI colitis, 78% had symptoms that were classified as grade 3 or above. Seventy-three percent received IV steroids and 38% received infliximab. Conclusions: CT demonstrates moderate specificity and PPV and remains an important diagnostic test but does not replace endoscopy/biopsy in the evaluation of CPI colitis.

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

scholarly journals Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianyang Fu ◽  
Wang-Zhong Li ◽  
Nicole A. McGrath ◽  
Chunwei Walter Lai ◽  
Gagandeep Brar ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
High Grade ◽  
Liver Cancers ◽  
Grade 3

BackgroundOverall risks of hepatotoxicity with immune checkpoint inhibitors (ICIs) have yet to be compared in primary liver cancers to other solid tumors.MethodsWe reviewed data from the PubMed, Embase, and Scopus databases, and assessed the risk of hepatotoxicity associated with ICIs.ResultsA total of 117 trials were eligible for the meta‐analysis, including 7 trials with primary liver cancers. The most common hepatotoxicity was ALT elevation (incidence of all grade 5.29%, 95% CI 4.52-6.20) and AST elevation (incidence of all grade 5.88%, 95% CI 4.96-6.97). The incidence of all grade ALT and AST elevation was 6.01% and 6.84% for anti-PD‐1 (95% CI 5.04-7.18/5.69-8.25) and 3.60% and 3.72% for anti-PD-L1 (95% CI 2.72-4.76/2.82-4.94; p< 0.001/p<0.001). The incidence of ≥ grade 3 ALT and AST elevation was 1.54% and 1.48% for anti-PD‐1 (95% CI 1.19-1.58/1.07-2.04) and 1.03% and 1.08% for anti-PD-L1 (95% CI 0.71-1.51/0.80-1.45; p= 0.002/p<0.001). The incidence of all grade ALT and AST elevation was 13.3% and 14.2% in primary liver cancers (95% CI 11.1-16.0 and 9.93-20.36) vs. 4.92% and 5.38% in other solid tumors (95% CI 4.21-5.76 and 4.52-5.76 in other solid tumors; p <0.001/p<0.001).ConclusionOur study indicates that anti-PD-1 is associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to anti-PD-L1, and primary liver cancers are associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to other solid tumors.

scholarly journals Phase Ib/II trial of ibrutinib and nivolumab in patients with advanced refractory renal cell carcinoma1

Kidney Cancer ◽  
2021 ◽  
pp. 1-7
Author(s):  
Mamta Parikh ◽  
Matthew E. Tenold ◽  
Lihong Qi ◽  
Frances Lara ◽  
Daniel Robles ◽  
...  
Keyword(s):  
Dose Level ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Once Daily ◽  
Checkpoint Inhibitor Therapy ◽  
Level 1 ◽  
Grade 3 ◽  
Expansion Cohort

Background: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. Methods: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). Results: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). Conclusions: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.

Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14525-e14525
Author(s):  
Abdul Miah ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
Madison Grogan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Grade 3

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

Abstract B79: PET CT might be better than CT scan when evaluating immune checkpoint inhibitor response

2020 ◽  
Author(s):  
JuWhan Choi ◽  
Hyun Seock Shin ◽  
Jee Youn Oh ◽  
Young Seok Lee ◽  
Kyung Hoon Min ◽  
...  
Keyword(s):  
Ct Scan ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Pet Ct ◽  
Better Than

scholarly journals Case Report: Good responsiveness of metastatic sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation to immune checkpoint inhibitor after radical surgery and adjuvant chemotherapy

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1458
Author(s):  
Hyung Ho Lee ◽  
Hye Ju Kang ◽  
Weon Seo Park ◽  
Wonyoung Choi ◽  
Ho Kyung Seo ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Radical Surgery ◽  
Checkpoint Inhibitor ◽  
Final Diagnosis ◽  
Histological Variant ◽  
Grade 3 ◽  
The Right

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation (SUCCD) in the ureter has a poor prognosis and is a rare histological variant of ureteral cancer. The majority of ureteral cancers are urothelial carcinomas. Clinical case: We present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor after radical surgery and failed adjuvant chemotherapy. The patient was a 68-year-old male with previous cure history of cT1 staged esophageal squamous cell carcinoma referred to the urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass. After ureteroscopic biopsy and intraureteral urine cytology, atypical pleomorphic cell nests and chondroid tissue consistent with sarcomatoid urothelial carcinoma were observed. The patient underwent a successful radical right nephroureterectomy with bladder cuffing. The final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma (heterologous component: chondrosarcoma > 95%) located at the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. On the postoperative one-month follow-up computed tomography scan, multiple enlarged lymph nodes and metastatic lung nodules were detected. The initiated adjuvant three cycles of gemcitabine-carboplatin therapy was marked by disease progression; thus, second-line therapy with atezolizumab was used for treatment. After five cycles of atezolizumab, the tumors showed a partial response without any grade 3 complications. Conclusion: The recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after unsuccessful therapy with radical surgery and first line chemotherapy despite the unfavorable outcome of the pathology.

Programmed death (PD)-ligand 1 (L1) expression and mismatch repair (MMR) deficiency across tumor types: Candidates for checkpoint inhibitor based immunotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14622-e14622
Author(s):  
Seung Tae Kim ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
Young Suk Park ◽  
Ho Yeong Lim ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
The Status ◽  
Mmr Deficiency ◽  
Tumor Types

e14622 Background: The identification of biomarkers associated with response to therapeutic agents has changed the paradigm of cancer treatment into the precision medicine by identification of right targets across cancer types. PD-L1 expression and mutational or neoatigen burden (Mismatch repair (MMR) deficiency) have been actively studied as the predictive biomarkers for the response to immune checkpoint inhibitors. Methods: We have conducted the PD-L1 and hMLH1/MSH2 expression (MMR deficiency) as part of a clinical practice for 430 patients with advanced gastrointestinal (GI) cancer, genitourinary (GU) cancer or rare cancers between June 2012 and March 2016. Herein, we evaluated potential candidates who could be targeted to further immune checkpoint inhibitors. Results: In 430 patients, 414 (96.2%) patients were available to evaluate the status of PD-L1 expression by immunohistochemistry (IHC). Irrespective of tumor-types, overall 26.8% (111 of 414) exhibited expression of PD-L1 in tumor tissues. The PD-L1 expression was examined as follows; 33.5% in HCC, 31.0% in CRC, 27.3% in GC, 25.5% in melanoma, 18.8% in BTC, 16.7% in pancreatic cancer, 15.8% in sarcoma and 13.0% in GU cancer. Among the 394 patients available for MLH1/MSH2 expression, only 18 patients (4.5%) had the MMR-deficient tumors with complete loss of MLH1/MSH2 expression. The MMR-deficiency was observed as follows; 7.9% in GC, 6.7% in HCC, 4.0% in CRC, and 2.7% in sarcoma. On 382 patients evaluable for the status of both PD-L1 and MLH1/MSH2 expression, there was no the significant association between the PD-L1 expression and MLH1/MSH2 loss (p = 0.267) Conclusions: These data may provide useful information and background for future research for immune checkpoint inhibitor across tumor-types. As a single selection biomarker for immune checkpoint inhibitor in various tumor-types, neither the PD-L1 expression nor the MMR deficiency is optimal application in clinical trials.

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