RESUMO
BACKGROUND AND AIMS: No endoscopic scoring system has been established for immune-mediated colitis (IMC). This study aimed to establish such a system for IMC and explore its utility in guiding future selective immunosuppressive therapy (SIT) use compared to clinical symptoms. METHODS: This retrospective, international, 14-center study included 674 patients who developed IMC after immunotherapy and underwent endoscopic evaluation. Ten endoscopic features were selected by group consensus and assigned 1 point each to calculate an IMC endoscopic score (IMCES). IMCES cutoffs were chosen to maximize specificity for SIT use. This specificity was compared between IMCESs, and clinical symptoms were graded according to a standardized instrument. RESULTS: A total of 309 (45.8%) patients received SIT. IMCES specificity for SIT use was 82.8% with a cutoff of 4. The inclusion of ulceration as a mandatory criterion resulted in higher specificity (85.0% for a cutoff of 4). In comparison, the specificity of a Mayo endoscopic subscore of 3 was 74.6%, and the specificity of clinical symptom grading was much lower at 27.4% and 12.3%, respectively. Early endoscopy was associated with timely SIT use (P < .001; r = 0.4084). CONCLUSIONS: This is the largest multicenter study to devise an endoscopic scoring system to guide IMC management. An IMCES cutoff of 4 has a higher specificity for SIT use than clinical symptoms, supporting early endoscopic evaluation for IMC.
Assuntos
Colite , Colonoscopia , Índice de Gravidade de Doença , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Colite/patologia , Colonoscopia/métodos , Imunossupressores/uso terapêutico , Idoso , Imunoterapia/métodos , Sensibilidade e Especificidade , Úlcera/patologiaRESUMO
INTRODUCTION: Immune checkpoint inhibitor-mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC refractory to steroids plus infliximab and/or vedolizumab. RESULTS: Nineteen patients were treated with UST for IMC refractory to steroids plus infliximab (57.9%) and/or vedolizumab (94.7%). Most of them had grade ≥3 diarrhea (84.2%), and colitis with ulceration was present in 42.1%. Thirteen patients (68.4%) attained clinical remission with UST, and mean fecal calprotectin levels dropped significantly after treatment (629 ± 101.5 mcg/mg to 92.0 ± 21.7 mcg/mg, P = 0.0004). DISCUSSION: UST is a promising therapy for the treatment of refractory IMC.
Assuntos
Colite , Humanos , Infliximab/uso terapêutico , Colite/tratamento farmacológico , Ustekinumab/uso terapêutico , Interleucina-12/uso terapêuticoRESUMO
BACKGROUND AND AIM: The diagnosis and treatment of gastrointestinal (GI) bleeding secondary to malignancy can be challenging. Endoscopy is the gold standard to diagnose and treat gastrointestinal bleeding but clinical characteristics and outcomes of patients with malignancy-related bleeding are not well understood. This study aims to look at clinical characteristics, endoscopic findings, safety and clinical outcomes of endoscopic interventions for GI malignancy-related bleeding. METHODS: We retrospectively reviewed outcomes of patients with confirmed GI malignancies who underwent endoscopy for GI bleeding at MD Anderson Cancer Center between 2010 and 2019. Cox hazard analysis was conducted to identify factors associated with survival. RESULTS: A total of 313 patients were included, with median age of 59 years; 74.8% were male. The stomach (30.0%) was the most common tumor location. Active bleeding was evident endoscopically in 47.3% of patients. Most patients (77.3%) did not receive endoscopic treatment. Of the patients who received endoscopic treatment, 57.7% had hemostasis. No endoscopy-related adverse events were recorded. Endoscopic treatment was associated with hemostasis (P < 0.001), but not decreased recurrent bleeding or mortality. Absence of active bleeding on endoscopy, stable hemodynamic status at presentation, lower cancer stage, and surgical intervention were associated with improved survival. CONCLUSIONS: This study indicates that endoscopy is a safe diagnostic tool in this patient population; while endoscopic treatments may help achieve hemostasis, it may not decrease the risk of recurrent bleeding or improve survival.
Assuntos
Hemostase Endoscópica , Recidiva Local de Neoplasia , Endoscopia Gastrointestinal , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Estudos RetrospectivosRESUMO
Immune checkpoint inhibitors (ICIs) can cause myenteric plexopathy, which could result in delayed gastric emptying (GE) and possibly gastroparesis. We assessed the clinical outcomes of patients who had pre-existing gastroparesis or who developed symptoms of delayed GE following ICI therapy. We retrospectively identified adults with ICD-9 and ICD-10 codes for gastroparesis who received ICI therapy between 1 January 2020 and 31 December 2022 at a tertiary cancer center. Of 76 eligible patients, 37 had pre-existing gastroparesis; 39 (0.2% of the more than 18,000 screened) developed symptoms of delayed GE after ICI therapy, of which 27 (69%) patients had an alternative etiology for delayed GE. Four patients (11%) with pre-existing gastroparesis had a flare-up after ICI, and the median time to flare-up was 10.2 months (IQR, 0.7-28.6 months); for patients with new onset of suspected delayed GE after ICI, the median time to symptom onset was 12.8 months (IQR, 4.4-35.5 months). The clinical symptom duration of patients without an alternative etiology (74.5 days (IQR, 21.5-690 days)) and those with an alternative etiology (290 days (IQR, 147-387 days)) did not differ significantly (p = 1.00). Delayed GE after ICI therapy is a rare presentation but has a late onset and a prolonged symptom duration.
RESUMO
A proportion of patients who undergo intraoperative cholangiogram (IOC) do not have bile duct stones at the time of endoscopic retrograde cholangiopancreatography (ERCP), either due to the spontaneous passage of stones or a false-positive IOC. Glucagon has been utilized as an inexpensive tool to allow the passage of micro-choledocholithiasis to the duodenum and resolve filling defects caused by stones or air bubbles. The purpose of our study is to understand the change in diagnostic accuracy of IOC to detect choledocholithiasis with intraoperative glucagon. We conducted a retrospective study at a tertiary care center on adult patients who underwent laparoscopic cholecystectomy with IOC. The diagnostic accuracy of IOC was assessed before and after the administration of intravenous glucagon. Of 1455 patients, 374 (25.7%) received intraoperative glucagon, and 103 of these 374 patients (27.5%) showed resolution of the filling defect with the passage of contrast to the duodenum. Pre- and post-glucagon administration comparison showed enhancement in specificity from 78% to 83%, an increase in positive predictive value from 67.3% to 72.4%, and an improvement in the diagnostic accuracy of IOC from 81.5% to 84.3%. Our findings suggest that intraoperative glucagon administration carries the potential to reduce the rate of false-positive IOCs, thereby reducing the performance of unnecessary ERCPs.
RESUMO
BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC. METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI. RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies. CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.
RESUMO
PURPOSE: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib. METHODS: We conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characteristics of PI-related gastrointestinal adverse events. RESULTS: Our sample comprised 973 patients with PI exposure and stool studies ordered between January 2017 and December 2022. Of these, 193 patients (20%) had PI-related gastrointestinal toxicity based on clinical symptoms and stool study results. The most common symptom was diarrhea, present in 169 (88% of those with gastrointestinal toxicity). Twenty-two (11%) required hospitalization, and 71 (37%) developed recurrence of symptoms. Compared to bortezomib or carfilzomib, ixazomib had a longer interval from PI initiation to the onset of gastrointestinal symptoms (313 days vs 58 days vs 89 days, p = 0.002) and a significantly lower percentage of diarrhea-predominant presentation of gastrointestinal toxicity (71% vs 96% vs 91%, p = 0.048). CONCLUSION: While PI-related gastrointestinal toxicities have various presentations and courses based on different regimens, the vast majority of patients presented with milder disease behavior. Despite a considerably high rate of hospitalization and recurrence after treatment necessitating optimization of clinical management, our cohort demonstrates favorable outcomes without long-term consequences.
Assuntos
Compostos de Boro , Bortezomib , Gastroenteropatias , Glicina , Inibidores de Proteassoma , Humanos , Inibidores de Proteassoma/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Compostos de Boro/efeitos adversos , Compostos de Boro/uso terapêutico , Idoso , Glicina/análogos & derivados , Glicina/efeitos adversos , Bortezomib/efeitos adversos , Bortezomib/administração & dosagem , Gastroenteropatias/induzido quimicamente , Oligopeptídeos/efeitos adversos , Adulto , Idoso de 80 Anos ou maisRESUMO
Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.
RESUMO
PURPOSE: Exposure to immune checkpoint inhibitors (ICIs) can predispose to immune-related adverse events (irAEs) involving the gastrointestinal tract. The association between ICIs and bowel perforation has not been well studied. We aimed to describe the clinical course, complications, treatment, and outcomes of patients experiencing bowel perforation during or after ICI treatment. METHODS: This retrospective, single-center study included adult cancer patients with bowel perforation that occurred between the first dose of ICI treatment and up to 1 year thereafter between 1/1/2010 and 4/30/2021. Patients' clinical course, imaging, treatment, and outcomes related to bowel perforation were collected and analyzed. RESULTS: Of the 13,991 patients who received ICIs during the study period, 90 (0.6%) met the inclusion criteria. A majority were male (54.4%), the most common cancer type was melanoma (23.3%), and most patients had received PD-1/L1 inhibitor treatment (58.8%). Onset of perforation occurred after a median of four ICI treatment cycles. The most common symptom was abdominal pain (95.5%). The colon was the most common location for the perforation (37.7%). Evidence of diverticulitis, enterocolitis, or appendicitis was seen in 32 (35.6%) patients, and 6 (6.6%) patients had luminal cancer involvement at the time of perforation. The overall hospitalization rate related to perforation was 95.5%, with mortality of 15.5% during the same admission. Antibiotics were given in 95% of our sample; 37.8% of patients also required surgical/interventional radiology intervention. Forty-six patients (51.1%) had perforation-related complications (e.g., sepsis, fistula, abscess), which were associated with a higher mortality rate (30%). CONCLUSION: Our findings suggest a low incidence of bowel perforation after ICI treatment (0.6%), with 40% of patients having coexisting bowel inflammation as a potential contributing factor. Patients with bowel perforation had an aggressive disease course and high rates of hospitalization, complications, and mortality. Early recognition and prompt intervention is critical to improve patient outcomes. Future studies are warranted to further investigate the cause, predictive markers, and optimal treatment for this patient population.
Assuntos
Antineoplásicos Imunológicos , Perfuração Intestinal , Neoplasias , Adulto , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Progressão da DoençaRESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment. METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded. RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4 years, with 1 patient on budesonide within 2 months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis. CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.
Assuntos
Antineoplásicos Imunológicos , Colite Microscópica , Colite , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Colite Microscópica/induzido quimicamente , Colite Microscópica/tratamento farmacológicoRESUMO
PURPOSE: A variety of tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of solid tumors and hematological cancers. However, TKIs are often associated with gastrointestinal (GI) adverse effects (AEs), especially diarrhea. Therefore, in the present study, we aimed to describe the clinical features and outcomes of TKI-associated lower GI AEs. METHODS: This was a retrospective single-center cohort study of patients with cancer treated with TKIs from March 2016 to September 2020 who experienced diarrhea without other identifiable causes. Basic and GI AE-related characteristics and outcomes were compared using χ2 and Mann-Whitney U tests. RESULTS: Of 2172 patients who received TKIs over the study period, we included 228 in the final analysis. Of these, 166 (72.8%) had hematological cancers. Besides diarrhea, GI symptoms included nausea (36.4%), vomiting (21.9%), abdominal pain (15.4%), and bleeding (3.1%). Symptoms were typically mild, with 209 patients (91.7%) presenting with Common Terminology Criteria for Adverse Events grade 1-2 diarrhea. Only 5 patients (2.2%) received immunosuppressants for diarrhea treatment, 83 (36.4%) received no treatment, 29 (12.7%) received antibiotics, 101 (44.3%) received supportive antidiarrheal medications, and 17 patients (7.5%) needed TKI dose reduction or cessation of TKI use. When compared with patients with hematological cancers, those with solid tumors had a higher rate of hospitalization (29.0% vs. 7.2%; p < 0.001) and mortality (75.8% vs. 43.4%; p < 0.001) but a lower rate of recurrence of GI AEs (21.0% vs. 42.8%; p = 0.003. Only 15 patients (6.6%) underwent colonoscopy, with normal endoscopic findings in 8 patients (53.3%) and nonulcerative inflammation in 5 patients (33.3%). The inflammation universally involved the left colon. Twelve of the 15 patients who underwent colonoscopy had active colitis. In the hematological cancer group, patients with acute myeloid leukemia had a lower GI AE recurrence rate than did patients with other hematological cancers (7.2% vs. 30.1%; p = 0.001). CONCLUSION: Ten percent of cancer patients receiving TKIs experienced lower GI AEs, which were usually mild. Symptoms TKI-related GI adverse effects were nonspecific, often overlapping those of other cancer therapy-related GI AEs. Treatment of GI AEs was largely supportive, with limited roles for antibiotics and immunosuppressants.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Hematológicas , Neoplasias , Humanos , Estudos de Coortes , Estudos Retrospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Inflamação/induzido quimicamente , ImunossupressoresRESUMO
PURPOSE: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer care but is associated with immune-related adverse events (irAEs). Recent case reports raised the concern that acute appendicitis may be an irAE. In this study, we sought to describe the disease course of post-ICI therapy appendicitis and its associated complications. METHODS: Adult patients who had an International Classification of Diseases code for appendicitis within the first 2 years after initiating ICI therapy from January 2010 to April 2021 and who had imaging evidence of appendicitis were studied retrospectively. RESULTS: 13,991 patients were identified who had ICI exposure during the study period, 44 had codes for appendicitis, 10 of whom met the inclusion criteria. Their median age at the time of diagnosis was 59 years. The median time from ICI therapy initiation to appendicitis onset was 188 days. The most common presenting symptoms were abdominal pain (70%) and fever (40%). Abscesses were present in two patients, and a perforation was present in one. All 10 patients received broad-spectrum antibiotics. Five patients needed surgery or interventional radiology drainage. Nine patients had resolution of appendicitis symptoms after treatment. CONCLUSION: Post-ICI therapy appendicitis is rare but presents similarly to and has similar complications rates as conventional appendicitis. Appendectomy remains the mainstay of treatment, but its use can be limited in cancer patients. The decision to continue ICI therapy remains at the discretion of the clinician. Further studies are needed to bring awareness to and advance the understanding of this clinical entity.
Assuntos
Antineoplásicos Imunológicos , Apendicite , Neoplasias , Adulto , Humanos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/efeitos adversos , Apendicite/cirurgia , Apendicite/induzido quimicamente , Apendicite/tratamento farmacológico , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs. METHODS: This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed. RESULTS: The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients). CONCLUSION: Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.
Assuntos
Doenças Autoimunes , Inibidores de Checkpoint Imunológico , Neoplasias , Exacerbação dos Sintomas , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVES: Immune checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs) such as colitis. irAEs can be managed by selective immunosuppressive therapy (SIT) agents such as infliximab and vedolizumab. We aimed to elucidate the incidence of subsequent new irAEs after exposure to SIT by describing patients' clinical course. METHODS: We conducted a retrospective chart review of adult patients at a tertiary cancer center diagnosed with ICI-mediated colitis (IMC) treated with SIT from February 2013 through October 2021. Patients' clinical courses, treatments, and outcomes of new irAEs after SIT were collected and analyzed. RESULTS: The study included 156 patients. Most were male (67.3%), 44.8% had melanoma, and 43.5% received anti-PD1/L1 ICIs. For IMC treatment, 51.9% received infliximab and 37.8% received vedolizumab. Twenty-six patients (16.6%) resumed ICI treatment after their colitis event. Twenty-five patients (16%) developed a new irAE after receiving SIT. The most common new irAE involved skin (44%), and most (60%) were treated with steroids. Higher diarrhea grade and ≥2 doses of SIT were associated with lower incidence of post-SIT irAEs ( P =0.038, P =0.050). However, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs. CONCLUSIONS: New irAEs usually occur more than 6 months after SIT completion for initial colitis event. Severe diarrhea grade and higher number of SIT infusions appeared to have protective effect to lower the occurrence of new irAEs. Otherwise, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs.
Assuntos
Antineoplásicos Imunológicos , Colite , Melanoma , Adulto , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Infliximab/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Colite/induzido quimicamente , Terapia de Imunossupressão/efeitos adversos , Diarreia/induzido quimicamenteRESUMO
Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3-4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.
RESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS). METHODS: This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1 year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26. RESULTS: Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p < 0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p < 0.05). Immunosuppression has no effect on PFS (p < 0.05). CONCLUSION: Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.
Assuntos
Colite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunossupressores/efeitos adversos , Neoplasias/terapia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
PURPOSE: Sclerosing mesenteritis (SM), a fibroinflammatory process of the mesentery, can rarely occur after immune checkpoint inhibitor (ICI) therapy; however, its clinical significance and optimal management are unclear. We aimed to assess the characteristics and disease course of patients who developed SM following ICI therapy at a single tertiary cancer center. METHODS: We retrospectively identified 12 eligible adult cancer patients between 05/2011 and 05/2022. Patients' clinical data were evaluated and summarized. RESULTS: The median patient age was 71.5 years. The most common cancer types were gastrointestinal, hematologic, and skin. Eight patients (67%) received anti-PD-1/L1 monotherapy, 2 (17%) received anti-CTLA-4 monotherapy, and 2 (17%) received combination therapy. SM occurred after a median duration of 8.6 months from the first ICI dose. Most patients (75%) were asymptomatic on diagnosis. Three patients (25%) reported abdominal pain, nausea, and fever and received inpatient care and corticosteroid treatment with symptom resolution. No patients experienced SM recurrence after the completion of corticosteroids. Seven patients (58%) experienced resolution of SM on imaging. Seven patients (58%) resumed ICI therapy after the diagnosis of SM. CONCLUSIONS: SM represents an immune-related adverse event that may occur after initiation of ICI therapy. The clinical significance and optimal management of SM following ICI therapy remains uncertain. While most cases were asymptomatic and did not require active management or ICI termination, medical intervention was needed in select symptomatic cases. Further large-scale studies are needed to clarify the association of SM with ICI therapy.
Assuntos
Inibidores de Checkpoint Imunológico , Mediastinite , Neoplasias , Esclerose , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Mediastinite/diagnóstico por imagem , Mediastinite/tratamento farmacológico , Mediastinite/imunologia , Esclerose/diagnóstico por imagem , Esclerose/tratamento farmacológico , Esclerose/imunologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Corticosteroides/uso terapêuticoRESUMO
BACKGROUND: RICAP is a recognized adverse effect of radiation therapy (RT) that can adversely affect cancer patients' quality of life. Data on the clinical characteristics and outcomes of RICAP are scarce. We aimed to analyze the clinical and endoscopic characteristics of acute or chronic radiation-induced colitis and proctopathy (ARICAP and CRICAP) based on symptom onset after RT (≤ or >45 days, respectively). METHODS: This is a retrospective observational study of a single tertiary cancer center, from January 2010 and December 2018, of cancer patients with endoscopically confirmed ARICAP and CRICAP. We conducted univariate and multivariate logistic regression analyses to associate clinical variables with endoscopic and medical outcomes. RESULTS: One hundred and twelve patients were included (84% Caucasian; 55% female; median age of 59 years); 46% had ARICAP with non-bloody diarrhea as the predominant symptom, whereas 55% had CRICAP with mostly bloody diarrhea. Neovascularization was the most frequent finding on endoscopy, followed by bleeding. ARICAP patients more often received medical management (p < 0.001), whereas CRICAP patients with bleeding more often received argon plasma coagulation (APC) (p = 0.002). Female sex and undergoing less-intense RT treatments were more associated with medical treatment; bleeding clinically and during the endoscopy was more associated with APC treatment. However, APC treatment did not significantly reduce bleeding recurrence or RICAP symptoms. CONCLUSION: Patients with ARICAP and CRICAP experience different symptoms. Medical management should be considered before endoscopic therapy. APC may be useful in patients with endoscopically apparent bleeding.
RESUMO
Background: Immune-mediated diarrhea and colitis (IMDC) frequently develop after treatment with immune checkpoint inhibitors. C-reactive protein (CRP) is a serum inflammatory biomarker used to stratify and monitor disease severity in many inflammatory conditions. However, CRP level is not specific and is widely influenced by various factors non-specific to bowel inflammation. We aimed to study the utility of CRP as a predictor of disease severity and therapy response in IMDC. Methods: We performed a retrospective analysis of patients diagnosed with IMDC who had CRP measured at IMDC onset and after treatment with selective immunosuppressive therapy (SIT: infliximab and vedolizumab), between 01/2016 and 02/2022 at MD Anderson Cancer Center. Patient demographics, clinical characteristics, and IMDC data were collected and analyzed. Results: Our sample of 128 patients had a median age of 67 years; most were white (89.8%); and male (65.6%). Prior to development of IMDC, 15 (11.7%) were initially treated with anti-CTLA-4, 42 (32.8%) with anti-PD-1 or PD-L1, and 71 (55.5%) with a combination of both. We found higher CRP level was associated with higher CTCAE grade of clinical symptoms such as diarrhea (p=0.015), colitis (p=0.013), and endoscopic findings (p=0.016). While CRP levels decreased after IMDC treatment, there was no significant association between CRP levels with clinical remission, endoscopic remission or histologic remission. There also was no significant correlation between CRP level and recurrence of IMDC, or with fecal calprotectin levels. Conclusion: CRP level may be useful to assess initial severity of IMDC, including grade of diarrhea and colitis and degree of endoscopic inflammation. However, CRP is not a robust surrogate biomarker for assessing treatment response or disease recurrence. Despite the reduction of CRP levels observed following IMDC treatment, this finding might be nonspecific and potentially confounded by concurrent clinical factors, such as underlying malignancy, other inflammatory processes, and systemic anti-cancer therapy. Further studies of the role of CRP are warranted in patients with cancer and IMDC.