Management of the adverse effects of cancer immunotherapy with a focus on the respiratory and nervous systems

The incidence of adverse toxic reactions to immunotherapy using immune checkpoint inhibitors is 2-10% in the respiratory system and 3.9% to 12% in the neurologic system. The severity of adverse effects increases when combined immunotherapeutic agents are administered.Current Concepts: In cases of high-grade toxicity, it is important to discontinue immunotherapy immediately. In cases of grade 3 to 4 toxicity, immunosuppressive corticosteroid therapy is the first-line treatment. Short-term steroid treatment does not affect anti-tumor efficacy. It is thus necessary to use steroids for an appropriate period then carefully taper the steroid dose to prevent recurrence. If no improvement is achieved within 48-72 hours after the administration of steroids, it is essential to initiate multidisciplinary treatment involving related departments and add immunosuppressive drugs. If the patient is administrated immunotherapy again, it may be necessary to permanently discontinue the immunotherapy depending on the toxicity grade that first occurred.Discussion and Conclusion: The primary goals for effective management of immunotherapy-related adverse events are early recognition of symptoms and immediate treatment.

EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. MATERIALS AND METHODS: A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2–, luminal B and HR+/HER2+, HR–/HER2+ and HER2–enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS. RESULTS: In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation–related discordant breast cancer including the VHL gene in the HR+/HER2– group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01). CONCLUSION: A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.

Investigation of Emergency Department Violence: Resident Survey

PURPOSE: The Korean Intern Resident Association and Korean Society of Emergency Medicine announced the 'Hospital violence response system' to secure patient safety and provide a health care provider countermeasures against hospital violence. The aim of this study is to investigate the response to hospital violence in the ER and which measures could improve the current status. METHODS: Emergency medicine residents in the Seoul, Incheon, Kyung-gi area participated in the survey. The questionnaire included 4 categories (1. Awareness of protocol, 2. Experience and countermeasure for hospital violence, 3. Understanding of protocol, 4. Suggestions to improve against hospital violence) RESULTS: Among 362 candidates, 236 (65.2%) participated in the survey. Only 7.6% of residents have not experienced hospital violence. In the group of people who were aware of the protocol, participants tended to be more familiar with processes of the hospital violence response protocol, and willing to deal with violence using a better systematic support. People did not counteract to hospital violence because the process was thought to be too complicated. Only 63 participants were actively involved in an official course for countermeasure. Participants suggested that police should deal more appropriately with hospital violence. CONCLUSION: The hospital violence response protocol is thought to have a positive effect on appropriate management of hospital violence. However, a multi-disciplinary approach to hospital violence from the hospital, police, and judicial authority should be developed.

Risk Factors and Efficacy of Adjuvant Therapy After Surgery of Elderly Colon Cancer Patients 70 Years of Age or Older

BACKGROUND: Colon cancer affects largely elderly populations. Elderly patients treated with adjuvant chemotherapy is lower than younger patients in colon cancer. We aim to evaluate the survival and prognostic factors in accordance with adjuvant chemotherapy in elderly colon cancer patients undergoing curative resection. METHODS: We retrospectively reviewed 86 patients 70 years of age or older with stage II, III colon cancer who were underwent surgical resection between 2005 and 2013 at single-center. We examined demographic factors, comorbidities at the time of diagnosis, factors associated with colon cancer, and factors associated with treatment, and analyzed associations survival and these factors divided into adjuvant chemotherapy group (chemotherapy group) and the conservative treatment group (observation group). RESULTS: Among 86 patients 70 years of age or older, 58 patients (67.4%) administered adjuvant chemotherapy and 28 patients (32%) underwent conservative treatment. There are significant differences in respect to the age of 75 in order to select conservative treatment or adjuvant chemotherapy for patients with surgery (p=0.008). There was no significant difference of median overall survival between both groups (chemotherapy group versus observation group: 20 months vs. 24 months, p=0.000). Poor ECOG PS score was independent prognostic factor for overall survival (95% confidential interval 0.016-0.205; hazard ratio, 0.58; p<0.001). CONCLUSION: Adjuvant chemotherapy did not affect the overall survival in stage II, III elderly colon cancer after surgical resection. There was the tendency to determine whether undergoing adjuvant chemotherapy according to chronologic age. It is thought to be necessary to perform a comprehensive geriatric assessment for decision of adjuvant chemotherapy in elderly patients.

Complication of Amebic Liver Abscess: Biliary Fistula / 고신대학교의과대학학술지

In amebic liver abscess, communication between liver abscess and intrahepatic bile ducts is an uncommon cause of bile leak. This condition can be treated surgically or endoscopically. However, these treatment modalities are related with high morbidity and mortality. A 49-year-old man was diagnosed with amebic liver abscess. Percutaneous drainage was performed due to poor medical response and for the purpose of preventing abscess rupture. Liver abscess-biliary communication was found at follow-up imaging study. He was treated successfully with medical therapy and supportive care without further interventions.