Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report.

BACKGROUND: Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. CASE PRESENTATION: A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. CONCLUSION: To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Computed tomography-based radiomic model predicts radiological response following stereotactic body radiation therapy in early-stage non-small-cell lung cancer and pulmonary oligo-metastases.

PURPOSE: Radiomic models elaborate geometric and texture features of tumors extracted from imaging to develop predictors for clinical outcomes. Stereotactic body radiation therapy (SBRT) has been increasingly applied in the ablative treatment of thoracic tumors. This study aims to identify predictors of treatment responses in patients affected by early stage non-small cell lung cancer (NSCLC) or pulmonary oligo-metastases treated with SBRT and to develop an accurate machine learning model to predict radiological response to SBRT. MATERIALS AND METHODS: Computed tomography (CT) images of 85 tumors (stage I-II NSCLC and pulmonary oligo-metastases) from 69 patients treated with SBRT were analyzed. Gross tumor volumes (GTV) were contoured on CT images. Patients that achieved complete response (CR) or partial response (PR) were defined as responders. One hundred ten radiomic features were extracted using PyRadiomics module based on the GTV. The association of features with response to SBRT was evaluated. A model using support vector machine (SVM) was then trained to predict response based solely on the extracted radiomics features. Receiver operating characteristic curves were constructed to evaluate model performance of the identified radiomic predictors. RESULTS: Sixty-nine patients receiving thoracic SBRT from 2008 to 2018 were retrospectively enrolled. Skewness and root mean squared were identified as radiomic predictors of response to SBRT. The SVM machine learning model developed had an accuracy of 74.8%. The area under curves for CR, PR, and non-responder prediction were 0.86 (95% confidence interval [CI], 0.794-0.921), 0.946 (95% CI, 0.873-0.978), and 0.857 (95% CI, 0.789-0.915), respectively. CONCLUSION: Radiomic analysis of pre-treatment CT scan is a promising tool that can predict tumor response to SBRT.

Clinical outcome and toxicity for immunotherapy treatment in metastatic cancer patients.

BACKGROUND: Immunotherapy (IO) is known to improve survival and outcome in various types of solid tumours. However, nonspecific activation of the immune system also affects various organ systems leading to the immune-related adverse events (irAEs). Systematic reviews of IO trials show that the actual incidence of irAEs may be higher than expected. Little is known about the impact of these irAEs on patients' clinical outcome, palliative care (PC) needs and hospice service use. METHODS: This is a single centre, retrospective review study of metastatic cancer patients between June 2016 to June 2017 who consecutively received immune checkpoint inhibitors with anti-PD1 in our institution. The computerized medical record, body weight chart, blood test results and in-patient assessment records were reviewed. The study was approved by the Institutional Review Board of the University of Hong Kong/ Hospital Authority Hong Kong West Cluster and conducted in compliance with the Declaration of Helsinki. RESULTS: Fifty patients received immune checkpoint inhibitors with anti-PD1 consecutively between June 2016 to June 2017 were retrospectively reviewed. The median age was 64 years old (range: 22 to 87 years old). Thirty-three of them were male (66%) patients. Twenty-five patients (50%) experienced any grade irAE. Ten patients (20%) experienced grade III/IV irAE among which 7 patients (14%) discontinued IO treatment permanently and 2 patients (4%) died due to grade III/IV toxicity. The development of grade III/ IV irAE required in-patient management, with a median duration of hospitalization of 6.5 days (range: 1 to 38 days). The response rate was 36% vs. 4% (P=0.01), median PFS (15.8 vs. 6.2 months, P=0.26), median OS (21.0 vs. 12.9 months, P=0.05) for patients with or without irAEs, respectively. The occurrence of any grade irAE was associated with a trend of improved overall survival (OS) on IO (P=0.05). Five patients (10%) developed hyper-progressive disease and received only one course of treatment before they died. Only 2 patients (4%) developed pseudo-progressive disease during treatment. Thirty-five mortalities (70%) occurred at the time of assessment of the study, of which 18 patients (36%) received PC consultations and 12 patients (24%) received hospice care before they passed away. CONCLUSIONS: Our study underscored the need for enhanced selection criteria to identify patient subgroups which benefit most from IO, and the need to involve PC and hospice services early for those non-responders or unlikely responders. Patient education and a dedicated multi-disciplinary team approach is needed to identify and treat irAE timely to prevent severe morbidities and mortalities.

Revisiting oral fluoropyrimidine with cetuximab in metastatic colorectal cancer: Real-world data in Chinese population.

BACKGROUND: Cetuximab in combination with oral fluoropyrimidine (FP) remains controversial in metastatic colorectal cancer (mCRC). In view of the regional variation in the tolerability of FP, we conducted a retrospective analysis to compare oral FP with infusional FP in combination with cetuximab in Chinese population. AIM: To compare the efficacy and safety profile of cetuximab in combination with oral FP and infusional FP in Chinese population in the real-world setting. METHODS: A retrospective cohort study was done to analyse consecutive patients with Kras wild-type mCRC who received first-line treatment with cetuximab and FP-based chemotherapy in our unit from January 2010 to December 2015. Ninety-five eligible patients were included. The median follow-up of our cohort was 65.0 mo. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) of the entire cohort were 9.66 mo (95%CI: 7.72-12.5) and 25.8 mo (95%CI: 18.7-35.6), respectively. Between oral FP and infusional FP, there was no statistical significant difference in the mPFS [9.79 mo (95%CI: 7.49-12.7) vs 9.63 mo (95%CI: 6.34-13.4); P = 0.72] and mOS [25.8 mo (95%CI: 15.2-35.6) vs 26.3 mo (95%CI: 18.7-41.2); P = 0.63]. Grade 3 or above adverse events were reported in 28.4% of patients, being similar with oral and infusional FP, and included 10.5% of neutropenia and 2.1% of diarrhoea events. CONCLUSION: The current analysis demonstrates comparable efficacy and safety profiles of cetuximab in combination with oral and infusional FP in Chinese population. The results expand treatment options for Chinese patients and invite revision of existing treatment guidelines to incorporate oral FP-based chemotherapy plus cetuximab.