ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. @*Materials and Methods@#Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. @*Results@#193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. @*Conclusion@#Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Management of the adverse effects of cancer immunotherapy with a focus on the gastrointestinal and hepatic systems

Immunotherapy has become established as a new cancer treatment that enhances patients’ immune systems’ ability to fight cancer. Immune checkpoint inhibitors (ICI) have demonstrated remarkable benefits in the treatment of a range of cancer types. The increasing use of immune-based therapies has exposed a discrete group of immune-related adverse effects. Effective recognition and treatment of ICI-induced toxicities have emerged as essential goals of ICI management.Current Concepts: Gastrointestinal (GI) and hepatic adverse effects of ICI treatment are relatively common. Immune-related GI or hepatic toxicities occur in approximately 30% of patients. The incidence of grade 3 or 4 adverse effects ranges from 0.5% to 2%. The management strategy for immune-related adverse effects depends on their severity. In general, ICI treatment can be continued with close monitoring for mild (grade 1) GI/hepatic toxicities. ICI treatment should be interrupted for most grade 2 to 4 toxicities, and systemic steroid administration is recommended. If steroids are ineffective, immunosuppressive agents such as infliximab may be used. When symptoms and laboratory values revert to grade 1 or less, ICI treatment may be resumed with caution. Grade 4 toxicities warrant permanent discontinuation of ICI treatment.Discussion and Conclusion: Most immune-related GI and hepatic adverse effects are mild to moderate in severity and can be managed with supportive care, steroid therapy, and other immunomodulatory agents. Management of ICI-related toxicities in the GI and hepatic systems requires close collaboration between the patient, the treating oncologist, and other specialists.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Immune Checkpoint Inhibitors in Advanced Colorectal Cancer / 대한소화기암학회지

no abstract available.

Feasibility Study of Physician Orders for Life-Sustaining Treatment for Patients with Terminal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Physician Orders for Life-Sustaining Treatment (POLST) form is a legal document for terminally ill patients to make medical decisions with physicians near the end-of-life. A multicenter prospective study was conducted to evaluate the feasibility of POLST administration in actual oncological practice. MATERIALS AND METHODS: Patients with terminal cancer, age ≥ 20 years, and capable of communicating were eligible. The primary endpoint was the completion rate of POLST. Data about physicians' or patients' barriers were also collected. RESULTS: From June to December 2017, 336 patients from seven hospitals were eligible. Median patient age was 66 years (range, 20 to 94 years); 52.7% were male; and 60.4% had poor performance status. Primary cancer sites were hepato-pancreato-biliary (26.2%), lung (23.2%), and gastrointestinal (19.9%). Expected survival duration was 10.6±7.3 weeks, with 41.2% receiving hospice care, 37.9% showing progression after cancer treatment, and the remaining patients were under active treatment (15.8%) or initially diagnosed with terminal cancer (5.1%). POLST forms were introduced to 60.1% of patients, and 31.3% signed the form. Physicians' barriers were reluctance of family (49.7%), lack of rapport (44.8%), patients' denial of prognosis (34.3%), lack of time (22.7%), guilty feelings (21.5%), and uncertainty about either prognosis (21.0%) or the right time to discuss POLST (16.6%). The patients' barriers were the lack of knowledge/understanding of POLST (65.1%), emotional discomfort (63.5%), difficulty in decision-making (66.7%), or denial of prognosis (14.3%). CONCLUSION: One-third of patients completed POLST forms, and various barriers were identified. To overcome such barriers, social engagement, education, and systematic support might be necessary.

Secondary amyloidosis complication of Crohn disease treated with infliximab / 영남의대학술지

Secondary systemic (AA) amyloidosis is a severe complication of progressed Crohn disease (CD) characterized by the deposition of amyloid A in body organs and tissues. Various therapeutic approaches have been recommended, however there is still no effective treatment. Recently, several case reports have demonstrated the effects of anti-tumor necrosis factor-alpha therapy in patients with AA amyloidosis associated with CD. We report on a 35-year-old female patient with CD complicated by AA amyloidosis in the gastrointestinal tract and renal involvement, who was treated with infliximab. The infliximab therapy improved the gastrointestinal symptoms and decreased the serum creatinine.

Malignant mesothelioma mistaken for tuberculous pleurisy / 영남의대학술지

Malignant mesothelioma is a common, primary tumor that can invade pleura, and is associated with previous exposure to asbestos. However, it poses considerable difficulties regarding its diagnosis and treatment, and thus, accurate history taking with respect to exposure to asbestos, and radiologic and pathologic examinations are essential. In addition, the involvement of a multidisciplinary team is recommended in order to ensure prompt and appropriate management using a framework based on radiotherapy, chemotherapy, surgery, and symptom palliation with end-of-life care. Because lymphocyte-dominant, exudative pleural effusion can occur in malignant mesothelioma, adenosine deaminase values may be elevated, which could be mistaken for tuberculous pleurisy, and lead to an incorrect diagnosis and suboptimal treatment. The authors describe a case of malignant mesothelioma initially misdiagnosed as tuberculous pleurisy. As evidenced by the described case, malignant mesothelioma should be considered during the differential diagnosis of patients with lymphocyte-dominant, exudative pleural effusion with a pleural lung lesion.

Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the Treatment of Metastatic Spermatocytic Seminoma with Extensive Rhabdomyosarcomatous Transformation / Journal of the Korean Cancer Association, 대한암학회지

A 52-year-old man was presented with a huge left testicular mass and palpable cervical lymphadenopathy with retroperitoneal lymph node enlargement on an abdominal computed tomography. A left radical orchiectomy and an ultrasound-guided neck node biopsy were performed. A pathological examination revealed spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a condition known to be highly resistant to platinum-based chemotherapy. The patient received four cycles of etoposide, ifosfamide and cisplatin (VIP) chemotherapy. A repeat computed tomography revealed a substantial regression consistent with a partial response. Retroperitoneal lymph node dissection was attempted, which revealed rhabdomyosarcoma; however, complete microscopic resection was not achieved. After surgery, the residual abdominal lymph node progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy was employed, which again achieved a partial response. Here, we present a first case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous transformation and multiple metastatic lymphadenopathies that showed a favorable response to platinum-based systemic chemotherapy.

Recurrence of Tuberculosis after Resuming a TNF-Inhibitor in a Patient with Crohn's Disease / 대한내과학회지

The use of tumor necrosis factor inhibitors (TNFi) increases a patient's risk of developing tuberculosis (TB). There is no consensus on whether restarting a TNFi after treating an active TB infection caused by previous TNFi exposure is safe. We report the first case of TB recurrence after recommencing a TNFi in a 37-year-old woman with a history of active TB infection caused by previous TNFi treatment.

A Case of Polyostotic Fibrous Dysplasia Masquerading as a Mulptile Bone Metastases / 계명의대학술지

Fibrous dysplasia is a benign, bony abnormality that is usually asymptomatic. A 41-year-old male with minimal symptoms presented at this hospital with abnormal findings incidentally seen in his ribs on the chest radiograph. A skeletal survey showed numerous, osteolytic lesions throughout multiple bones. Diagnostic processes for malignancy of undefined primary origin (MUO) were performed in order to identify the underlying primary neoplasm, although abnormal findings were not seen except for multiple bone lesions. A computed tomography guided bone biopsy was performed on his left rib. The final diagnosis was fibrous dysplasia. This case demonstrates that fibrous dysplasia should be considered in the differential diagnosis in young patients with multiple, osteolytic lesions and without a prior history suggesting malignancy.