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.

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic. @*Materials and Methods@#In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time. @*Results@#The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88. @*Conclusion@#The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

Screening for Lung Cancer Using Low-dose Chest Computed Tomography in Korean Long-term Colorectal Cancer Survivors

BACKGROUND: The National Lung Screening Trial (NLST) and NELSON trial showed that low-dose chest computed tomography (LDCT) screening significantly reduced the mortality form lung cancer. Although cancer survivors are known to have high risk for second malignant neoplasm (SMN), the usefulness of LDCT screening for lung cancer in cancer survivors is not clear. METHODS: Between August 2016 and August 2017, 633 long-term colorectal cancer (CRC) survivors visited the survivorship clinic in Cancer Prevention Center, Yonsei Cancer Center, Seoul, Republic of Korea. We surveyed the smoking status and recommended LDCT screening to ever-smoking CRC survivors aged 55–80 years. The participants were classified into three risk groups: risk group 1 (RG1) who met the NLST criteria (Age 55–74 years, ≥ 30 pack-years of smoking, smoking cessation < 15 years); risk group 2 (RG2) who would not meet the NLST criteria but were at increased 6-year risk of lung cancer (PLCOM2012 ≥ 0.0151); risk group 3 (RG3) who did not meet any of the criteria above. RESULTS: Among 176 ever-smoking CRC survivors, 173 (98.3%) were male, 32 (18.2%) were current-smoker, and median age was 66 years (range, 55–79 years). We found 38 positive findings (non-calcified nodule ≥ 4 mm), 8 clinically significant findings, 66 minor abnormalities, and 64 negative findings on LDCT. Positive findings were identified in 15 of 79 (19.0%) of RG1, in 9 of 36 (25%) of RG2, and in 14 of 61 (23.0%) of RG3. Second primary lung cancers were found in 2 patients of RG2, and in 1 patient of RG3. SMN was most frequently found in RG2 (11 of 36 patients, 30.6%), compared with RG1 (12.7%) or RG3 (9.8%) (P = 0.016). CONCLUSIONS: LDCT screening for lung cancer in Korean CRC survivors is feasible. Well-designed clinical trial for defining high risk patients for lung cancer among CRC survivors is needed.

Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Design of a Hospice Referral System for Terminally Ill Cancer Patients Using a Standards-Based Health Information Exchange System / 대한의료정보학회지

OBJECTIVES: The demand for hospice has been increasing among patients with cancer. This study examined the current hospice referral scenario for terminally ill cancer patients and created a data form to collect hospice information and a modified health information exchange (HIE) form for a more efficient referral system for terminally ill cancer patients. METHODS: Surveys were conducted asking detailed information such as medical instruments and patient admission policies of hospices, and interviews were held to examine the current referral flow and any additional requirements. A task force team was organized to analyze the results of the interviews and surveys. RESULTS: Six hospices completed the survey, and 3 physicians, 2 nurses, and 2 hospital staff from a tertiary hospital were interviewed. Seven categories were defined as essential for establishing hospice data. Ten categories and 40 data items were newly suggested for the existing HIE document form. An implementation guide for the Consolidated Clinical Document Architecture developed by Health Level 7 (HL7 CCDA) was also proposed. It is an international standard for interoperability that provides a framework for the exchange, integration, sharing, and retrieval of electronic health information. Based on these changes, a hospice referral scenario for terminally ill cancer patients was designed. CONCLUSIONS: Our findings show potential improvements that can be made to the current hospice referral system for terminally ill cancer patients. To make the referral system useful in practice, governmental efforts and investments are needed.

PTEN Methylation Dependent Sinonasal Mucosal Melanoma / Journal of the Korean Cancer Association, 대한암학회지

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

PTEN Methylation Dependent Sinonasal Mucosal Melanoma / Journal of the Korean Cancer Association, 대한암학회지

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

Prognostic Significance of Volume-Based FDG PET/CT Parameters in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation Therapy

PURPOSE: We investigated the prognostic role of volume-based parameters measured on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scans in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiation therapy (CRT). MATERIALS AND METHODS: We enrolled 60 patients with LAPC who underwent FDG PET/CT before CRT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary pancreatic cancers were measured on FDG PET/CT scans. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to determine independent prognostic factors. RESULTS: The progression-free survival (PFS), locoregional progression-free survival (LRFPS), and overall survival (OS) for this population were 6.2, 10.9, and 13.2 months, respectively. The overall treatment response rate was 16.7% at 4 weeks after CRT, and the disease control rate (DCR) was 80.0%. DCR was significantly higher in patients with low SUVmax, MTV, or TLG, and showed strong correlation with longer survival times. On univariate analysis, MTV and TLG were significant prognostic factors for PFS, LRPFS, and OS, together with pre-CRT and post-CRT CA19-9 levels. Multivariate analyses demonstrated that MTV together with the pre-CRT CA19-9 level were independent prognostic factors for PFS, LRPFS, and OS, as was TLG for LRPFS and OS. CONCLUSION: MTV and the pre-CRT CA19-9 level provided independent prognostic information in patients with LAPC treated with CRT. Volume-based PET/CT parameters may be useful in identifying which subgroup of patients would benefit from radiation therapy as a part of CRT.

Radiation Recall Dermatitis Induced by Gefitinib / 이화의대지

Radiation recall dermatitis refers to an acute inflammatory reaction in a previously irradiated field triggered by the administration of certain drugs days to years after the exposure to radiation. Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor and is an effective treatment for patients with advanced stage of non small cell lung cancer (NSCLC). Here, we report a rare case of gefitinib induced radiation recall dermatitis. A 52-year-old woman with a metastatic NSCLC had received a palliative radiation therapy of 20 cGy on spine metastasis area (C6-T6). After 24 days of receiving radiation therapy, she had started to take gefitinib. Eight months after taking drug, pain, swelling and erythema of skin were occurred on previously irradiated field. These symptoms were resolved after the cessation of gefitinib for 6 days and the topical use of steroid.

Radiation Recall Dermatitis Induced by Gefitinib / 이화의대지

Radiation recall dermatitis refers to an acute inflammatory reaction in a previously irradiated field triggered by the administration of certain drugs days to years after the exposure to radiation. Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor and is an effective treatment for patients with advanced stage of non small cell lung cancer (NSCLC). Here, we report a rare case of gefitinib induced radiation recall dermatitis. A 52-year-old woman with a metastatic NSCLC had received a palliative radiation therapy of 20 cGy on spine metastasis area (C6-T6). After 24 days of receiving radiation therapy, she had started to take gefitinib. Eight months after taking drug, pain, swelling and erythema of skin were occurred on previously irradiated field. These symptoms were resolved after the cessation of gefitinib for 6 days and the topical use of steroid.

Isolated Pulmonary Arterial Hypertension-Janus' Faces of Hyperthyroidism

We describe a 54-year-old woman with isolated pulmonary arterial hypertension accompanied by hyperthyroidism due to Graves' disease. Her pulmonary artery hypertension resolved spontaneously after restoration of euthyroidism. This case suggests that hyperthyroidism should be considered a reversible cause of pulmonary arterial hypertension.