Efficacy and safety of atezolizumab/bevacizumab in patients with HCC after prior systemic therapy: A global, observational study.

BACKGROUND: Since the introduction of the combination treatment of anti-programmed death-ligand 1 antibody atezolizumab and anti-VEGF antibody bevacizumab (AB), median overall survival in HCC has drastically improved. However, evidence on the efficacy and safety of the novel treatment standard in patients with prior exposure to systemic treatment is scarce. The aim of this global, multicenter, observational study was to evaluate the efficacy and safety of AB in patients after previous systemic therapy. METHODS: We screened our global, multicenter, prospectively maintained registry database for patients who received any systemic therapy before AB. The primary end point was overall survival; secondary end points were time-to-progression, progression-free survival, objective response rate, and safety (rate and severity of adverse events). RESULTS: Among 493 patients who received AB for unresectable HCC, 61 patients received prior systemic therapy and were included in this analysis. The median age of the study population was 66 years, with 91.8% males. Predominant risk factors for HCC were viral hepatitis (59%) and alcohol (23%). Overall survival for AB was 16.2 (95% CI, 14.5-17.9) months, time-to-progression and progression-free survival were 4.1 (95% CI, 1.5-6.6) and 3.1 (95% CI, 1.1-5.1) months, respectively. The objective response rate was 38.2% (7.3% with complete and 30.9% with partial response). Overall survival was not influenced by treatment line (2nd vs. >2nd) or previous systemic treatment modality (tyrosine kinase inhibitors vs. immune checkpoint inhibitors). Treatment-related adverse events of all grades according to Common Terminology Criteria for Adverse Events were documented in 42.6% of patients, with only 13.1% of grade ≥3, including one death. CONCLUSION: In this observational study, AB emerges as a safe and efficacious treatment option in patients with HCC previously treated with other systemic therapy.

Role of C-Reactive Protein in Predicting the Severity and Response of Immune-Mediated Diarrhea and Colitis in Patients with Cancer.

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.

Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis.

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.

Characteristics of appendicitis after immune checkpoint inhibitor therapy among cancer patients.

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.

Immune checkpoint inhibitor-related gastrointestinal toxicity in patients with malignancy involving the luminal gastrointestinal tract and its impact on cancer outcomes.

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs. Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed. Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI irAEs based on clinical symptoms and/or histology. The predominant GI irAE symptom was diarrhea (78%). Ten had non-ulcerative inflammation (56%) and 5 had ulcerative inflammation (28%) on endoscopy. Histologically, 3 patients (17%) had evidence of acute inflammation, 4 (22%) had chronic inflammation, and 9 (50%) had both. Ten patients (56%) received immunosuppressant treatment, which included steroids alone (n=2, 20%), steroids with biologics (infliximab or vedolizumab) (n=7, 70%), or biologics alone (n=1, 10%), with clinical remission in all cases. Of the 6 patients who previously had stable or ICI-responsive cancer and received immunosuppressants, none developed progression of GI luminal malignancy during the study period. Conclusions: GI irAEs occurred in 2.4% of patients treated with ICI for cancer involving the luminal GI tract. Immunosuppressant therapies (e.g., vedolizumab) appear to be effective for GI irAEs, showing no association with further GI luminal cancer progression, recurrence, or a subsequent poor response to ICI therapy.

Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity.

Immune checkpoint blockade (ICB) therapy frequently induces immune-related adverse events. To elucidate the underlying immunobiology, we performed a deep immune analysis of intestinal, colitis, and tumor tissue from ICB-treated patients with parallel studies in preclinical models. Expression of interleukin-6 (IL-6), neutrophil, and chemotactic markers was higher in colitis than in normal intestinal tissue; T helper 17 (Th17) cells were more prevalent in immune-related enterocolitis (irEC) than T helper 1 (Th1). Anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) induced stronger Th17 memory in colitis than anti-program death 1 (anti-PD-1). In murine models, IL-6 blockade associated with improved tumor control and a higher density of CD4+/CD8+ effector T cells, with reduced Th17, macrophages, and myeloid cells. In an experimental autoimmune encephalomyelitis (EAE) model with tumors, combined IL-6 blockade and ICB enhanced tumor rejection while simultaneously mitigating EAE symptoms versus ICB alone. IL-6 blockade with ICB could de-couple autoimmunity from antitumor immunity.

Anemia Severity Associated with Increased Healthcare Utilization and Costs in Inflammatory Bowel Disease.

BACKGROUND: Anemia is a common systemic complication of inflammatory bowel disease (IBD) and is associated with worse disease outcomes, quality of life, and higher healthcare costs. AIMS: The purpose of this study was to determine how anemia severity impacts healthcare resource utilization and if treatment of anemia was associated with reduced utilization and costs. METHODS: Retrospective chart review of adult patients managed by gastroenterology between 2014 and 2018 at a tertiary referral center. RESULTS: The records of 1763 patients with IBD were included in the analysis, with 966 (55%) patients with CD, 799 (44%) with UC, and 18 (1%) with unspecified IBD. Of these patients, 951 (54%) had anemia. Patients with anemia had significantly more hospitalizations, increased length of stays, more ER, GI, and PCP visits, as well as higher costs when compared to patients with IBD without anemia. Patients with more severe anemia had more healthcare utilization and incurred even higher total costs. Treatment with IV or oral iron did not lower overall utilization or costs, when compared to patients with anemia who did not receive treatment (p < 0.0001). CONCLUSIONS: Our results demonstrate that the presence of anemia is correlated with increased resource utilization in patients with IBD, with increase in anemia severity associated with higher utilization and costs. Anemia has been associated with increased disease activity and could represent a marker of more severe disease, possibly explaining these associations. Our results suggest that treating anemia is associated with increased resource utilization; however, further research is needed to investigate this relationship.

Left ventricular rupture: a rare complication and an unusual presentation.

Myocardial infarction (MI) is a relatively common medical condition in the community. A rare complication of acute MI is left ventricular rupture (LV) rupture. This usually follows a transmural infarct. The incidence of this is 2%-4% and this usually happens within 3-7 days of MI. The anterolateral wall is involved in the majority of cases. Atypical presentations can occur several weeks after the initial event. Symptoms may mimic gastrointestinal disorder. The prognosis of this condition is very grim. However, with appropriate treatment, they can make an excellent recovery. The definitive treatment for this is surgical repair. We present the case of a 70-year-old man who had LV rupture and his clinical journey.

Diabetic muscle infarction.

Diabetic muscle infarction (DMI) is a rare complication of longstanding, poorly controlled diabetes. Only a few cases have been reported in the literature. The case of a 34-year-old man with a 7-year history of type 2 diabetes mellitus, with sudden onset of left thigh pain, is described here. A final diagnosis of DMI was made, the pathophysiology of which remains unclear. MRI findings were diagnostic and characteristic. The management of this condition is usually symptomatic. Short-term prognosis is very good; however, the recurrence rate is high. Long-term prognosis is poor, with most patients dying from cardiovascular complications of diabetes within 5 years of diagnosis. This case supports the need for a high index of suspicion, when a poorly controlled patient with diabetes presents with non-traumatic limb pain.

Diabetic muscle infarction.

Diabetic muscle infarction (DMI) is a rare complication of longstanding, poorly controlled diabetes. Only a few cases have been reported in the literature. The case of a 34-year-old man with a 7-year history of type 2 diabetes mellitus, with sudden onset of left thigh pain, is described here. A final diagnosis of DMI was made, the pathophysiology of which remains unclear. MRI findings were diagnostic and characteristic. The management of this condition is usually symptomatic. Short-term prognosis is very good; however, the recurrence rate is high. Long-term prognosis is poor, with most patients dying from cardiovascular complications of diabetes within 5 years of diagnosis. This case supports the need for a high index of suspicion, when a poorly controlled patient with diabetes presents with non-traumatic limb pain.

Therapeutic bronchoscopy: endobronchial laser resection and airway stenting.

Lung cancer is the leading cause of cancer death among both men and women. About 30% of lung cancers cause obstruction of the major bronchus leading to severe complications such as postobstructive pneumonia, hemoptysis, and progressive dyspnea. Endobronchial laser treatment and airway stenting is an interventional pulmonary treatment offered to patients with lung tumors that obstruct the main airways. This article will provide an overview of endobronchial laser resection and airway stenting with a particular focus on procedural techniques and care of the patient.