Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea / Journal of the Korean Cancer Association, 대한암학회지

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea / Journal of the Korean Cancer Association, 대한암학회지

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Primary Malignant Melanoma of the Breast: A Report of Two Cases

Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. MATERIALS AND METHODS: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). RESULTS: Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. CONCLUSION: Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.

A Phase II Study of Weekly Paclitaxel Plus Gemcitabine as a Second-Line Therapy in Patients with Metastatic or Recurrent Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen. MATERIALS AND METHODS: Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m2) and G (1,000 mg/m2) on days 1 and 8 of each cycle of 21 days until disease progression. RESULTS: Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia. CONCLUSION: Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy.

Giant esophageal schwannoma / 영남의대학술지

Esophageal schwannoma is a very rare submucosal tumor. We report successful management of esophageal schwannoma in a 41-year-old man who complained of progressively worsening dysphagia. A huge submucosal tumor was found via endoscopy and a chest computed tomography scan. Esophagectomy was performed with no post-operative complications. Post-operative immunohistochemistry staining showed a positive result for S-100 and negative results for c-kit and CD34. The post-operative mild dysphagia persisted, and the follow-up endoscopic findings revealed anastomosis site stenosis. Approximately 2 months later, we performed endoscopic balloon dilatation. We report herein a case of esophageal schwannoma with reviews.

Small Cell Lung Cancer with Mutation of Epidermal Growth Factor Receptor in Patients with Lung Adenocarcinoma Resistant to Gefitinib / 대한내과학회지

Most epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinomas. In contrast, these mutations have rarely been reported in small cell lung cancer (SCLC). We herein report two cases of EGFR-mutant SCLC transformed from and combined with lung adenocarcinoma. In one case, SCLC appeared to be transformed from EGFR mutant 19-del adenocarcinoma when the patient became resistant to gefitinib. The other patient had combined EGFR-mutant 19-del SCLC and adenocarcinoma at the initial diagnosis, which was resistant to gefitinib at multiple sites. Further comparative molecular analyses of these histologically distinct tumors would provide useful information regarding the role of EGFR mutation in the pathogenesis of SCLC. In conclusion, despite the presence of the same EGFR mutation, gefitinib was not effective in treatment of SCLC. Therefore, confirmation of SCLC cell morphology may become an important means of predicting resistance to EGFR tyrosine kinase inhibitors in addition to common secondary genetic alterations.

A Case of Myocardial Infarction Occurred after Endoscopic Submucosal Dissection under Bridging Therapy with Low Molecular Weight Heparin

Myocardial infarction (MI) is a complication that can occur after endoscopic submucosal dissection (ESD). However, very few reports are available about this complication. A 71-year-old male, who had two drug eluting stents inserted due to ischemic heart disease, was referred to the Division of Gastroenterology for ESD of a lesion suspicious of early gastric cancer. ESD was performed after dual antiplatelet agents were discontinued and bridging therapy with low molecular weight heparin (LMWH) was initiated. However, MI occurred immediately after the ESD procedure. A coronary angiogram did not show any significant stent thrombosis or restenosis. The patient recovered spontaneously. Here, we report a case of MI that occurred after ESD under bridging therapy with LMWH.

A Case of Patient with Lung Adenocarcinoma with Double Rare EGFR Mutation of G719C and L861Q / 계명의대학술지

The vast majority of epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinoma. EGFR mutations are the strongest predictor of response to EGFR tyrosine kinase inhibitor (TKI) treatment in patient with advanced non-small cell lung cancer. Of these, exon 19 deletions and exon 21 L858R point mutations account for more than 80% of mutations detected in tumor with EGFR mutations, which called classical EGFR mutations, and double mutations mainly composed of classical and uncommon EGFR mutations are reported to be present in 13% of total EGFR mutations. But there has been no report to date of patient with double mutation of TKI sensitive uncommon EGFR mutations (G719C and L861Q). We experienced a case of patient with lung adenocarcinoma with double mutation of G719C and L861Q, the first case on our literature review, and showing partial response to TKI treatment.

Recurrent Hypoglycemia Triggered by Sorafenib Therapy in a Patient with Hemangiopericytoma

Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.

Clinical outcome of high-dose-rate interstitial brachytherapy in patients with oral cavity cancer

PURPOSE: To evaluate the clinical outcome of high-dose-rate (HDR) interstitial brachytherapy (IBT) in patients with oral cavity cancer. MATERIALS AND METHODS: Sixteen patients with oral cavity cancer treated with HDR remote-control afterloading brachytherapy using 192Ir between 2001 and 2013 were analyzed retrospectively. Brachytherapy was administered in 11 patients as the primary treatment and in five patients as salvage treatment for recurrence after the initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25 fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was administered as the sole treatment in three patients with a total dose of 50 Gy/10 fractions and as postoperative adjuvant treatment in one patient with a total of 35 Gy/7 fractions. RESULTS: The 5-year overall survival of the entire group was 70%. The actuarial local control rate after 3 years was 84%. All five recurrent cases after initial surgery were successfully salvaged using IBT +/- external beam radiotherapy. Two patients developed local recurrence at 3 and 5 months, respectively, after IBT. The acute complications were acceptable (< or =grade 2). Three patients developed major late complications, such as radio-osteonecrosis, in which one patient was treated by conservative therapy and two required surgical intervention. CONCLUSION: HDR IBT for oral cavity cancer was effective and acceptable in diverse clinical settings, such as in the cases of primary or salvage treatment.

Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib

Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (> or = 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.

Targeted therapy and tailored chemotherapy for advanced non-small cell lung cancer / 대한내과학회지

The prognosis of advanced non-small cell lung cancer (NSCLC) is very poor and the median overall survival is 10 to 12 months, despite the use of chemotherapy and targeted therapy. Recently, many targeted agents for NSCLC have been developed and tested in clinical trials. Of these, chemotherapeutic agents targeting epidermal growth factor receptor (EGFR), such as gefitinib, erlotinib and cetuximab, have been very efficacious in the treatment of NSCLC. Many phase III trials have evaluated the efficacy of these agents in combination with cytotoxic chemotherapy. Based on the results of these trials, clinical and molecular predictors of the response to EGFR-targeted agents, such as EGFR mutations or gene amplification, have been elucidated. Recent advances in understanding the biologic basis of acquired resistance to these agents have potential to improve the clinical effectiveness of agents targeting EGFR. Another agent, bevacizumab, targets an angiogenesis inhibitor, and has improved the survival in advanced NSCLC when used in combination with chemotherapy. In addition, many agents targeting tyrosine kinase inhibitors are being used in clinical trials. This review summarizes the outcomes of clinical trials evaluating agents targeting EGFR, angiogenesis inhibitors, and other molecules used alone or in combination with chemotherapy for the treatment of advanced NSCLC. Also, the predictive role of NSCLC histology for chemotherapy response will be summarized from the results of phase III studies.

Phase II Study of Low-dose Paclitaxel and Cisplatin as a Second-line Therapy after 5-Fluorouracil/Platinum Chemotherapy in Gastric Cancer

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.

Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation with Non-Myeloablative Conditioning: Experiences at a Single Center / 대한혈액학회지

BACKGROUND: The use of non-myeloablative stem cell transplantation (NST) has recently been increasing for treating the patients who cannot tolerate ablative hematopoietic stem cell transplantation (HSCT). Although graft-versus-host disease (GVHD) is one of the greatest problems in HSCT, the clinical effect of GVHD following NST is not clear. We undertook this study to evaluate the clinical manifestations of GVHD and the outcomes after NST. METHODS: From October 2000 to October 2004, 61 patients underwent NST with a fludarabine-based conditioning regimen. The cumulative incidence of GVHD and the survival rates were obtained from the Kaplan-Meier curves. RESULTS: With a median follow-up of 195 days, the estimate for overall three-year survival was 32%. The cumulative incidences of grades II~IV acute GVHD and chronic GVHD were 33% (18/53) and 78% (29/37), respectively. The response rates for acute and chronic GVHD were 33% and 89%, respectively. The survival rates of patients with acute and chronic GVHD were 27% and 89%, respectively. The median survival time was 6.5 months CONCLUSION: The incidence of GVHD after NST did not differ from that after ablative HSCT. This study suggests that the aggressive treatment of acute GVHD should be considered to improve the overall survival after NST.

Acute myelogenous leukemia in the elderly (>or=60): retrospective study of 115 patients / 대한내과학회지

BACKGROUND: Acute myelogenous leukemia (AML) is frequently encountered in elderly patients whereas intensive chemotherapy yield lower rate of complete remission (CR) and survival than young patients. This study was aimed to review the clinical features and treatment outcomes of elderly patients (>or=60) with AML. METHODS: We respectively reviewed the clinical features, laboratory findings and outcomes of treatment from the medical records of 115 patients with the elderly AML (>or=60), admitted in Seoul National University Hospital, between Jan.1995 and Dec.2004. RESULTS: Their median age was 66 (60~86) years with male predominance (M:F=68:47). Complete response rate in patients with conventional chemotherapy was 66.7% (42 of 63 patients; 95% CI 50.2~78.4). Median overall survival (OS) was 5.2 months with clinical benefit in the conventional chemotherapy group, compared to supportive or palliative group (11.5 vs 0.9months; p<0.0001). In between two age groups, the sixties (n=69) showed higher CR rate (69.0 vs 61.9%; p=0.9) and longer median overall survival (7.0 vs 4.4months; p=0.8) than patients group of the seventies (n=38) but without statistical significance. CONCLUSIONS: Conventional induction chemotherapy improved survival rate than palliative or supportive treatment.

A Pilot Study of Bortezomib in Korean Patients with Relapsed or Refractory Myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.

A case of blastic natural killer cell lymphoma presented as disseminated cutaneous lesions / 대한내과학회지

Reports of blastic natural killer (NK)-cell lymphoma are rare. In previous reports, primary cutaneous blastic NK-cell lymphomas were even rarer. In Asian patients, most CD56+ lymphomas are classified as nasal type extranodal NK/T-cell lymphoma and mostly associated with the presence of Epstein-Barr virus (EBV) and have an aggressive clinical course. Few cases of blastic NK-cell lymphoma were reported previously in Korea but there was no report about blastic NK-cell lymphoma initially presented as disseminated skin lesions without any other organ involvement. We report such a young patient who was treated by systemic chemotherapy.

Renal, gastric, and multiple intestinal metastases of invasive ductal carcinoma of breast / 대한내과학회지

We describe a 53-year-old woman with renal, gastric, and multiple intestinal metastases of invasive ductal carcinoma of breast. She was diagnosed as left breast cancer of stage II, received left modified radical mastectomy 10 years ago and has been followed up without any evidence of residual disease. During investigation for indigestion and lower abdominal pain, we found multiple masses in left kidney, multiple levels of colon, ovary, peritoneum and bone. The histology of the tissue taken from renal mass was adenocarcinoma, which had identical features with those of masses resected from her left breast 10 years ago. During 28 month palliative chemotherapy, we found gastric metastasis of breast cancer and finally, the colonic metastatic masses caused intestinal obstruction. The diagnosis of gastrointestinal metastases of breast cancer is very important in the view of improvement of survival and quality of life because they can lead to intestinal obstruction, bleeding, and perforation.