A Multicenter, Prospective, Observational Study to Evaluate Ethanol-Induced Symptoms in Patients Receiving Docetaxel Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms. @*Materials and Methods@#This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day. @*Results@#Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms. @*Conclusion@#The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.

A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. @*Materials and Methods@#Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. @*Results@#After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. @*Conclusion@#Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

A Pilot Study of Peritumor Administration of 5-FU for Preventing Bleeding in Advanced Gastric Cancer / 대한소화기학회지

Five-FU is a potent chemotherapeutic agent for suppressing endothelial cell growth. The purpose of this study was to investigate the usefulness of local peritumor injection of 5-FU for patients with advanced gastric cancer (AGC) for the prevention of anemia. Between January 2020 and January 2022, patients aged 18 years or older with AGC and moderate anemia were included. A total of 200 mg of 5-FU was injected per session at ten points of the lesion (20 mg at each point) every 7 days for 4 to 12 weeks. Patients received a blood test for toxicity at every cycle. From one of these patients, endoscopic biopsy specimens were taken from gastric cancer before and after injecting 5-FU for immunostaining. A total of five AGC patients participated in this study. For most patients, hemoglobin levels were maintained without transfusions during 5-FU injection, and expression levels of thrombospondin-1 was increased after injection compared to those before injection. Blood test results during 5-FU injection showed no significant change in serum glutamic oxalacetic transaminase/glutamic pyruvic transaminase, total bilirubin, or creatinine level. The results of this study showed the possibility of local peritumor 5-FU injection as a treatment for relieving anemia of patients with gastric cancer.

Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. @*Materials and Methods@#Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6. @*Results@#A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups. @*Conclusion@#In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Initial titration with 200 μg fentanyl buccal tablets: a retrospective safety analysis in Korean cancer patients

BACKGROUND/AIMS: Managing breakthrough pain (BTP) is important for many cancer patients because of the rapid onset and unpredictable nature of the pain episodes. Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for BTP management. However, FBT titration is needed to optimize BTP management. In this study, we aimed to evaluate the safety and efficacy of initiating 200 μg FBTs in Korean cancer patients. METHODS: A retrospective analysis of medical records was performed on all advanced cancer patients treated with FBTs for BTP between October 2014 and July 2015. Patients who received initial doses of 200 μg FBTs for at least 3 days and cases in which FBT was available at doses of 200, 400, and 800 μg were included. RESULTS: A total of 56 patients with a median age of 62 years (range, 32 to 80) were analyzed, 61% of whom were male. The median and mean values of morphine equivalent daily doses were 60 mg/day (range, 15 to 540) and 114.8 ± 124.8 mg/day, respectively. The most frequent effective doses of FBT were 200 μg (41 patients, 74%) and 400 μg (12 patients, 21%). Three patients (5%) could not tolerate 200 μg of FBT and discontinued treatment. Nausea, vomiting, somnolence, and dizziness were the most frequent treatment-related adverse events (AEs), and all AEs were grade 1 (mild) or 2 (moderate). CONCLUSIONS: FBT at the initial 200 μg dosage was well-tolerated and effective as a BTP management strategy in Korean cancer patients. Further prospective studies are needed to determine appropriate initiating doses of FBT in Korean patients with opioid tolerance.

Practice Patterns Regarding Multidisciplinary Cancer Management and Suggestions for Further Refinement: Results from a National Survey in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. MATERIALS AND METHODS: Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. RESULTS: We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were “very satisfied” and “satisfied,” respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. CONCLUSION: The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.

Erratum: Field Cancerization in Sporadic Colon Cancer

In the version of this article initially published, the first affiliation (affiliation number 1) was incorrectly stated as "Division of Gastroentorology, Department of Internal Medicine." The correct affiliation is "Department of Internal Medicine."

Field Cancerization in Sporadic Colon Cancer

BACKGROUND/AIMS: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients. METHODS: We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated using methylation-specific PCR. RESULTS: The methylation frequencies of the SFRP2, TFPI2, NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP,TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables. CONCLUSIONS: The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor / Journal of the Korean Cancer Association, 대한암학회지

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

Ethical Attitudes according to Education and Clinical Experience of Do-Not-Resuscitate (DNR) / 한국호스피스완화의료학회지

PURPOSE: Although a Do-Not-Resuscitate (DNR) order is widely in use, it is one of the challenging issues in end-of-life care. This study was conducted to investigate attitudes toward DNR according to education and clinical experience. METHODS: Data were collected using a structured questionnaire comprising 30 items in a tertiary hospital in Seoul, Korea. RESULTS: Participants were 238 nurses and 72 physicians. Most participants (99%) agreed to the necessity of DNR for reasons such as dignified death (52%), irreversible medical condition (23%) and patients' autonomy in decision making (19%). Among all, 33% participants had received education about DNR and 87% had DNR experience. According to participants' clinical DNR experience, their attitudes toward DNR significantly differed in terms of the necessity of DNR, timing of the DNR consent and post-DNR treatments including antibiotics. However, when participants were grouped by the level of DNR education, no significant difference was observed except in the timing of the DNR consent. CONCLUSION: This study suggests that the attitudes toward DNR were more affected by clinical experience of DNR rather than education. Therefore, DNR education programs should involve clinical settings.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

No abstract available.

Burnt-out Metastatic Prostate Cancer / 영남의대학술지

A burnt-out prostate cancer tumor is a very rare clinical entity. The term 'burnt-out' refers to a primary tumor that has spontaneously and nearly completely regressed without treatment. Since metastasis of prostate cancer is usually encountered in the presence of advanced disease, distant metastasis with an undetectable primary tumor is very rare. We report herein a case of a burnt-out prostate cancer tumor that metastasized to the thoracic (T) spine and caused cord compression. A 66-year-old man visited the Emergency Department due to weakness of both legs for the past two days. His blood and urine tests were normal at the time. His spine magnetic resonance imaging (MRI) scans looked like bone metastasis that involved the T-7 vertebral body and a posterior element, and caused spinal cord compression. Other images, including from the brain MRI, neck/chest/abdomino-pelvic computed tomography (CT) scan and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and endoscopy, revealed no lesions that suggested malignancy. After total corpectomy T-7 and screw fixation/fusion at T5 to T10, the pathology report revealed a metastatic carcinoma that was strongly positive for prostate-specific antigen (PSA). The serum PSA value was 1.5 ng/mL. The transrectal 12-core prostate biopsy and ultrasonography showed no definitive hypoechoic lesion, but one specimen had slight (only 1%) adenocarcinoma with a Gleason score of 6 (3+3). The final diagnosis was burned-out prostate cancer with an initial normal PSA value. Although metastatic disease with an unknown primary origin was confirmed, a more aggressive approach in seeking the primary origin could provide a more specific treatment strategy and greater clinical benefit to patients.

Long-term Follow-up of Hb Madrid Patient / 임상소아혈액종양

We report a long-term follow-up of unstable hemoglobin (Hb) patient. He was diagnosed as Hb Madrid [beta115(G17)Ala-->Pro] by direct DNA sequencing and restriction enzyme analysis. Hydroxyurea had been given for beta-chain hemoglobinopathies through activation of gamma(gamma)-chain synthesis. Nowadays he still needs transfusion three or four times per year, but he had been free of hemolytic crisis after hydroxyurea. Although he has been treated for hemochromatosis with parenteral and oral iron-chelating agents, liver cirrhosis complicated by esophageal varix was developed and treated with endoscopic ligation. In addition, he is on warfarin maintenance for anticoagulation therapy for extensive portal vein and superior mesenteric vein thrombosis which presented with abdominal pain and diagnosed by CT scan. In management of unstable Hb patients, physician should monitor and control the serum ferritin level with iron-chelating agents, and be aware of possible long-term complication including hemochromatosis, cirrhosis or thromboembolism.

Long-term Follow-up of Hb Madrid Patient / 임상소아혈액종양

We report a long-term follow-up of unstable hemoglobin (Hb) patient. He was diagnosed as Hb Madrid [beta115(G17)Ala-->Pro] by direct DNA sequencing and restriction enzyme analysis. Hydroxyurea had been given for beta-chain hemoglobinopathies through activation of gamma(gamma)-chain synthesis. Nowadays he still needs transfusion three or four times per year, but he had been free of hemolytic crisis after hydroxyurea. Although he has been treated for hemochromatosis with parenteral and oral iron-chelating agents, liver cirrhosis complicated by esophageal varix was developed and treated with endoscopic ligation. In addition, he is on warfarin maintenance for anticoagulation therapy for extensive portal vein and superior mesenteric vein thrombosis which presented with abdominal pain and diagnosed by CT scan. In management of unstable Hb patients, physician should monitor and control the serum ferritin level with iron-chelating agents, and be aware of possible long-term complication including hemochromatosis, cirrhosis or thromboembolism.

Diagnosis and Treatment of Gastrointestinal Stromal Tumor / 대한내과학회지

Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.

Diagnosis and Treatment of Gastrointestinal Stromal Tumor / 대한내과학회지

Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.

Prognostic Value of Immunohistochemical Biomarkers at Different Cut-off Values in Patients with Diffuse Large B-cell Lymphoma Treated with CHOP Chemotherapy

Many predictive models have been proposed for better stratification of diffuse large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins. However, there have been disagreements in the literature regarding its prognostic significance. Here, we retrospectively analyzed Hans' algorithm and the individual immunohistochemical biomarkers at different cut-off values (5%, 30%, 50% or 75%) in 94 Korean patients with DLBCL treated with combination chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No significant differences were observed between the GCB (18 patients, 19.1%) and non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%) positivity was an independent good prognostic marker in overall survival irrelevant of international prognostic index. The present study showed the lack of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may have diverse prognostic significance at different cut-off values. Our results suggest that the proposed cut-off value may not be applied universally, and that the optimal cut-off value may need to be optimized for individual laboratory.