The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. @*Methods@#The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. @*Results@#All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient’s prognosis unless immediate intervention is given within 24–48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4–6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. @*Conclusion@#It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. @*Methods@#The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. @*Results@#The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. @*Conclusion@#It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Treatment of Opioid Withdrawal Syndrome Triggered by Oxycodone/Naloxone with Dexmedetomidine / 한국호스피스완화의료학회지

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodonealoxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodonealoxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodonealoxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodonealoxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient’s condition.

Safe use of opioids

Opioids are effective analgesics for cancer pain and refractory non-cancer pain. Although they are essential medication, problematic issues on aberrant behavior and adverse events have rapidly emerged as social problems in Korea. This study aimed to describe the mechanisms, efficacy, and adverse events, especially how to deal with opioid dependency.Current Concepts: Opioid-induced aberrant behavior includes physical and psychological dependences (addiction), abuse, and diversion (giving prescribed opioids to another person). Most physicians are unfamiliar with how to handle patients presenting these problematic issues. Physical and psychological dependences develop through different pathophysiologic mechanisms, i.e., noradrenergic and dopaminergic pathways, respectively. Motivational enhancement therapy, psychosocial support, substitution therapy with buprenorphine, and adjunctive medications, including alpha-2 adrenergic agonist, antidepressants, and non-steroidal antiinflammatory drugs, are the mainstay of treatment for opioid dependency. Constipation, nausea/vomiting, drowsiness/sedation, delirium, itching sensation, voiding difficulty, dry mouth, opioid-induced hyperalgesia, and respiratory depression are well-known physical side effects of opioid consumption.Discussion and Conclusion: Research on the development history, epidemiology of opioid dependency, and its treatment are warranted to avoid an opioid crisis in Korea. Above all, thorough knowledge for physicians and patients is urgently needed.

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy: Results of the Korean South West Oncolog / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. RESULTS: Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). CONCLUSION: Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

Exosomal miR-181b-5p Downregulation in Ascites Serves as a Potential Diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites

PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.

The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC. MATERIALS AND METHODS: With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9-negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67–high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling. RESULTS: The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016). CONCLUSION: This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Successful Treatment with Transdermal Buprenorphine Patch in Opioid-Dependent Cancer Patients: Case Series / 한국호스피스완화의료학회지

Opioid aberrant behavior is an emerging problem as strong opioid is increasingly used to alleviate cancer pain in patients with cancer. Although the treatment of opioid addiction and physical dependence for non-cancer pain is well known, few studies have been conducted with cancer patients, particularly in the Korean population. Presented here are ten cases of cancer patients who were physically dependent on strong opioid and successfully treated with a partial mu-opioid receptor agonist, buprenorphine. This is the first report showing the efficacy of transdermal buprenorphine as a treatment for physical dependence on opioid medication in cancer patients.

Adjuvant Chemotherapy for Advanced Gastric Cancer in Elderly and Non-elderly Patients: Meta-Analysis of Randomized Controlled Trials / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study evaluated the benefits of adjuvant chemotherapy on elderly patients with advanced gastric cancer (AGC) using meta-analysis of well-designed randomized controlled clinical studies. MATERIALS AND METHODS: PubMed, Embase, and Cochrane were searched to retrieve clinical studies evaluating the benefits of adjuvant chemotherapy in the elderly with AGC. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a fixed-effects model. RESULTS: Two studies were included in this meta-analysis to estimate HR for the overall survival (OS), and relapse-free survival (RFS) between adjuvant chemotherapy and surgery in elderly and non-elderly patients. HR for OS in the elderly and non-elderly was 0.745 (95% CI, 0.552 to 1.006, p=0.055) and 0.636 (95% CI, 0.522 to 0.776; p < 0.001), respectively, which showed no heterogeneity regarding HR between the two groups (p(interaction)=0.389). HR for RFS in the elderly and non-elderly was 0.613 (95% CI, 0.466 to 0.806; p < 0.001) and 0.633 (95% CI, 0.533 to 0.753; p < 0.001), respectively (p(interaction)=0.846). CONCLUSION: Meta-analysis suggests that the benefit of adjuvant chemotherapy to the elderly is not big enough to reach statistical significance while the HR for OS is less than 1 (0.745) and no heterogeneity are observed regarding the HR between the elderly and non-elderly patients.

Population-Based Regional Cancer Incidence in Korea: Comparison between Urban and Rural Areas / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate differences in organ-specific cancer incidence according to the region and population size in Korea. MATERIALS AND METHODS: We reviewed the data of the cancer registration program of Gyeongnam Regional Cancer Center between 2008 and 2011. Age-standardized rates of cancer incidence were analyzed according to population size of the region and administrative zone. RESULTS: Incidence of thyroid cancer has been increasing rapidly in both urban and rural areas. However, the thyroid cancer incidence was much lower in rural areas than in urban areas and megalopolis such as Seoul. Gastric cancer was relatively more common in rural areas, in megalopolis near the sea (Ulsan, Busan, and Incheon), and other southern provinces (Chungcheongnam-do, Gyeongsangbuk-do, and Gyeongsangnam-do). A detailed analysis in Gyeongsangnam-do revealed that rural areas have relatively low incidence of thyroid and colorectal cancer, and relatively high incidence of gastric and lung cancer compared to urban areas. CONCLUSION: This study suggests that there are some differences in cancer incidence by population size. Thyroid and colorectal cancer incidence was increasing, and gastric and lung cancer was slightly decreasing in urban areas, whereas gastric and lung cancer incidence still remains high in rural areas.

Usefulness of neutrophil to lymphocyte ratio in patients with chronic obstructive pulmonary disease: a prospective observational study

BACKGROUND/AIMS: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker. However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the usefulness of NLR in patients with COPD. METHODS: NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28). NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period. The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression. RESULTS: NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001). NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs. 11.5 ± 8.8, p < 0.001). NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale. NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079). Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization. CONCLUSIONS: NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD.

CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. MATERIALS AND METHODS: With various gastric tissues, we performed immunohistochemical staining for CD44v9. RESULTS: The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. CONCLUSION: This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.

Is There a Role for Adjuvant Therapy in R0 Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection. MATERIALS AND METHODS: Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors. RESULTS: In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups. CONCLUSION: The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.

Cyclosporine A as a Primary Treatment for Panniculitis-like T Cell Lymphoma: A Case with a Long-Term Remission / Journal of the Korean Cancer Association, 대한암학회지

Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a distinctive cutaneous lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic T cells, similar to panniculitis. It is well-established that patients who are diagnosed with SPTL usually respond poorly to chemotherapy, showing fatal outcome. As a first line treatment for SPTL, anthracycline-based chemotherapy was most frequently used. For the treatment of SPTL, the efficacy of cyclosporine A has been recently reported in relapsed SPTL after anthracycline-based chemotherapy. However, it is still not clear whether cyclosporine A can be used as a first-line treatment against SPTL. Here, we report a case of SPTL, which achieved complete remission for nine years after first-line cyclosporine A therapy. This study suggests that cyclosporine A can induce a complete long-term remission as a first-line treatment.

Cyclosporine A treatment for relapsed subcutaneous panniculitis-like T-cell lymphoma: a case with long-term follow-up / 대한혈액학회지

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a distinctive lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic cytotoxic T cells. There was no distinction between TCR alpha/beta phenotype and TCR gamma/delta phenotype, and anthracycline-based chemotherapy was usually used for both. Here, we report a patient with recurrent SPTL who achieved a second long-term complete remission by repeated cyclosporine A (CsA) treatment. From 2000 to 2001, the patient received anthracycline-based combination chemotherapy. However, the treatment did not induce long-term remission. In 2002, he received cyclosporine treatment for about 6 months. This resulted in a 5-year remission that ended in relapse in 2008. He received CsA treatment once again and attained a second long-term remission. This case suggests that re-treatment with CsA can be a good option for relapsed SPTL cases and can result in long-term remission.

Usefulness of Real-time PCR to Detect Mycobacterium tuberculosis and Nontuberculous Mycobacteria / 결핵및호흡기질환

BACKGROUND: The purpose of this study was to evaluate recently developed real-time polymerase chain reaction (PCR) assay kit to detect Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) in respiratory specimens. METHODS: We assessed the positive rate of the real-time PCR assay to detect MTB and NTM in 87 culture-positive specimens (37 sputum, 50 bronchial washing), which were performed real-time PCR by using Real-Q(TM) MTB&NTM Kit from January 2009 to June 2009, at Gyeongsang University Hospital. To compare the efficacy with the TB-PCR assay, we evaluated 63 culture-positive specimens (19 sputum, 44 bronchial washing) for MTB or NTM, which were performed TB-PCR by using ABSOLUTE(TM) MTB II PCR Kit from March 2008 to August 2008. RESULTS: Among 87 specimens tested using real-time PCR, MTB and NTM were cultured in 58 and 29, respectively. The positive rate of real-time PCR assay to detect MTB was 71% (22/31) and 92.6% (25/27) in AFB stain-negative and stain-positive specimens. For NTM, the positive rate of real-time PCR was 11.1% (2/18) and 72.7% (8/11) in AFB stain-negative and stain-positive specimens. Among 63 specimens performed using TB-PCR, MTB and NTM were cultured in 46 and 17, respectively. The positive rate of TB-PCR was 61.7% (21/34) and 100% (12/12) in AFB stain-negative and stain-positive specimens. TB-PCR was negative in all NTM-cultured 17 specimens. CONCLUSION: TB/NTM real-time PCR assay is useful to differentiate MTB and NTM in AFB stain-positive respiratory specimens and it is as effective in detecting MTB with TB-PCR.