Immune-related Adverse Events: Overview and Management Strategies for the Use of Immune Checkpoint Inhibitors

Recent studies on T cell immunology have been instrumental in developing therapies to overcome cancer immune escape, and immune checkpoint inhibitors have emerged as one of the most promising therapeutic tools in advanced cancer patients. Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that modulate the effects of immune checkpoints. These include cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1, which are co-inhibitory signals responsible for immune suppression. Despite their clinical benefits, ICPIs behave as general immune activators, exerting to several toxic effects called immune-related adverse events attributed to organ-specific inflammation. Here, we review ICPI toxicities, highlighting the importance of their early identification and proper management.

Validity and Reliability of Korean Version of Simplified Nutritional Appetite Questionnaire in Patients with Advanced Cancer: A Multicenter, Longitudinal Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m² (range, 15.6 to 39.6 kg/m²). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.

Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma

PURPOSE: This study aimed to determine the prognostic value of new quantitative parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC). MATERIALS AND METHODS: In total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent 18F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors. RESULTS: In univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUVmt max (the highest SUV among the metastatic lesions) (p=0.040) and MTVtotal (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTVtotal (hazard ratio: 2.07; 95% confidence interval: 1.23–3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039). CONCLUSION: In locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTVtotal, were found to be useful for the identification of patients with poor prognosis.

Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients. MATERIALS AND METHODS: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis. RESULTS: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively). CONCLUSION: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

A Case of Combined Hepatocellular-Cholangiocarcinoma with Favorable Response to Systemic Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary liver cancer composed of cells with histopathologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of its low incidence, the information on clinical outcomes of cHCC-CC is very limited and there are no published reports describing non-surgical treatment options for cHCC-CC. We report a case of cHCC-CC exhibiting a favorable response to systemic chemotherapy with doxorubicin and cisplatin. A 62-year-old man who recurred after a right lobectomy for cHCC-CC received sorafenib for palliative systemic therapy, but follow up imaging studies showed disease progression. He received 2nd line chemotherapy with doxorubicin at 60 mg/m2 together with cisplatin at 70 mg/m2. After 2 cycles of chemotherapy, a computed tomography scan of the chest showed markedly decreased size and number of the multiple lung metastases. After completing 8 cycles of 2nd line therapy, we changed the regimen to a fluorouracil (5-FU) mono therapy because of the toxicities associated with doxorubicin and cisplatin. To date, the patient has completed his 15th cycle of 5-FU mono therapy with the disease status remaining stable during 18 months of follow-up.

Wernicke's Encephalopathy in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: With their prolonged survival and malnutrition, cancer patients, and especially gastrointestinal (GI) tract cancer patients, can develop Wernicke's encephalopathy (WE). The aim of this study is to remind physicians of the importance of WE and prompt management in patients with GI tract cancer. MATERIALS AND METHODS: This study is a retrospective review of 2 cases of WE in advanced gastric cancer (AGC) patients, and we review the literature for cases of GI tract cancer related to WE. RESULTS: A 48-year-old female with AGC presented dizziness and diplopia for 5 days and a 20 kg weight loss. Neurologic exam showed nystagmus and gaze disturbance. Her symptoms improved after daily parenteral injection of thiamine 100 mg for 17 days. A 58-year-old female with AGC presented with sudden disorientation, confusion and 15 kg weight loss. Neurologic exam showed gaze limitation and mild ataxia. Despite daily parenteral injection of thiamine 100 mg for 4 days, she died 5 days after the onset of neurologic symptoms. Combining the cases noted in the literature review with our 2 cases, the 7 gastric cancer cases and 2 colorectal cancer cases related to WE showed similar clinical characteristics; 1) a history of long-period malnutrition and weight loss, 2) relatively typical neurologic signs and symptoms and 3) specific magnetic resonance image findings. Except for 2 patients who had irreversible neurologic symptoms, the other 7 patients were improved with prompt thiamine treatment. CONCLUSION: It is important to consider WE in GI tract cancer patients with acute neurologic symptoms and who are in a state of malnutrition. Thiamine should be given as soon as possible when WE is suspected.

Docetaxel versus Paclitaxel Combined with 5-FU and Leucovorin in Advanced Gastric Cancer: Combined Analysis of Two Phase II Trials / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m2) or docetaxel (DFL; 75 mg/m2) on day 1, followed by a bolus of LV (20 mg/m2 days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m2 days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. RESULTS: Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade > or =3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. CONCLUSION: Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.

Recent advance in tailored treatment of gastric cancer / 대한내과학회지

Even the overall incidence is decreasing and the proportion of early gastric cancer is increasing from the national mass screening program, still gastric cancer is the major issue in Korea. Multimodality approach and the development of novel therapeutic agents enabled us to improve the survival rate of gastric cancer. However, the proper treatment strategy for the subgroups of patients is necessary, which is now categorized based on the clinicopathologic parameters. We need more in-depth information regarding the molecular biology of gastric cancer, and the development of novel targeted biological agents and the biomarkers for the future. Currently, the recent chemotherapeutic agents showed the improved response in advanced gastric cancer. Hence, the basic concept of adjuvant chemotherapy, palliative chemotherapy, neoadjuvant treatment with or without incorporation of radiotherapy become settle down with more evidences from several phase III trials. Especially, after understanding the difference between Asia and Western countries including biology, ethnic difference, operation technology, and the treatment approaches, the qualified, well-designed multinational clinical trials are on-going. Based on the current results, here, I describe the current status of gastric cancer treatment strategy.

Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction

Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival.

Prognosis of pN3 Stage Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to determine the prognosis of pN3 stage gastric cancer patients after they have undergone curative resection, and we also wanted to identify the prognostic factors according to the clinico-pathologic features. MATERIALS AND METHODS: Between January 2000 and December 2004, we retrospectively reviewed the medical records of the patients with histologically confirmed pN3 stage gastric cancer. They underwent both gastrectomy and lymphadenectomy with a curative aim. We categorized the pN3 stage patients into 2 groups; one with pN3 only (pN3M0) and the other with pN3 combined with M1 stage (pN3M1) that included peritoneal seeding, hepatic metastasis or para-aortic LN metastasis. RESULTS: Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 78 patients were classified as the pN3/M1 stage. For all the patients, the median follow-up period was 19 months (range: 1~108 months) and the median overall survival time was 16.2 months (95% CI, 14.1~18.3%). The 5-year survival rate of the pN3/M0 group was significantly higher than that of the pN3/M1 group (12.6% vs. 2.6%, respectively, p<0.0001). The identified predictor for a worse prognosis was an advanced T4 stage (HR: 3.38, 95% CI, 1.4~8.3, p=0.008) for the pN3 patients. CONCLUSION: The survival for the pN3 gastric cancer patients after curative gastrectomy was significantly longer in the pN3/M0 group as compared to that of the pN3/M1 group. An advanced T stage was a predictor for a poor prognosis for the pN3 patients. Therefore, diverse treatment strategies for these heterogeneous pN3 gastric cancer patients are needed for improving their survival.

S-1 Monotherapy as a Neoadjuvant Treatment for Locally Advanced Gastric Cancer

S-1, a novel oral fluoropyrimidine, is an effective therapeutic agent for gastric cancer. Herein, we report a case with locally advanced gastric cancer that achieved a curative resection after S-1 monotherapy as neoadjuvant treatment. A 68-year-old man was diagnosed with gastric cancer and massive lymphadenopathy involving the perigastric, celiac axis and splenic hilum. His clinical stage was cT3N2H0P0M0. Considering his relatively poor performance (ECOG 2, severe weight loss) and advanced age, we started the patient on S-1 monotherapy at a dose of 35 mg/m2 bid for 4 consecutive weeks followed by a 2-week rest. Follow-up study after 4 treatment cycles revealed disappearance of the lymphadenopathy of the perigastric and celiac axis with diminished extension of the stomach mass. The patient had a partial response (PR) with a 72% tumor reduction, according to the Response Evaluation Criteria in Solid Tumors (RECIST). His performance status was improved to an ECOG 1 and he gained 7 kg. A curative (R0) resection was achieved with a radical total gastrectomy and D2 dissection. The pathological stage was pT3N2M0, stage IIIB. In conclusion, S-1 neoadjuvant chemotherapy aided in the treatment of gastric cancer in this patient.

An Attempt for Combining Microarray Data Sets by Adjusting Gene Expressions / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The diverse experimental environments in microarray technology, such as the different platforms or different RNA sources, can cause biases in the analysis of multiple microarrays. These systematic effects present a substantial obstacle for the analysis of microarray data, and the resulting information may be inconsistent and unreliable. Therefore, we introduced a simple integration method for combining microaray data sets that are derived from different experimental conditions, and we expected that more reliable information can be detected from the combined data set rather than from the separated data sets. MATERIALS AND METHODS: This method is based on the distributions of the gene expression ratios among the different microarray data sets and it transforms, gene by gene, the gene expression ratios into the form of the reference data set. The efficiency of the proposed integration method was evaluated using two microarray data sets, which were derived from different RNA sour-ces, and a newly defined measure, the mixture score. RESULTS: The proposed integration method intermixed the two data sets that were obtained from different RNA sources, which in turn reduced the experimental bias between the two data sets, and the mixture score increased by 24.2%. A data set combined by the proposed method preserved the inter-group relationship of the separated data sets. CONCLUSION: The proposed method worked well in adjusting systematic biases, including the source effect. The ability to use an effectively integrated microarray data set yields more reliable results due to the larger sample size and this also decreases the chance of false negatives.

A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.

Long-term Survival after Surgical Resection for Liver Metastasis from Gastric Cancer: Two Case Reports / Journal of the Korean Cancer Association, 대한암학회지

Surgical resection of colorectal cancer metastasis to the liver results in a 5-year survival rate of around 40%. Liver metastasis from other cancers such as neuroendocrine carcinoma and genitourinary tumors are also treated effectively with combined liver resection. However, hepatic metastasectomy for liver tumor from gastric cancer hasn't been considered as a standard treatment, and the benefit for this treatment has not been established. We report here on two cases of gastrectomy and combined liver resection for synchronous liver metastasis without any evidence of other metastatic lesions, and these two patients have survived for more than 7 years without evidence of disease recurrence. In conclusion, for patients with hepatic metastasis from gastric cancer, combined surgical resection of the liver metastasis should be considered as a treatment option when metastasis to other sites can be excluded.

Significant Gene Selection Using Integrated Microarray Data Set with Batch Effect

In microarray technology, many diverse experimental features can cause biases including RNA sources, microarray production or different platforms, diverse sample processing and various experiment protocols. These systematic effects cause a substantial obstacle in the analysis of microarray data. When such data sets derived from different experimental processes were used, the analysis result was almost inconsistent and it is not reliable. Therefore, one of the most pressing challenges in the microarray field is how to combine data that comes from two different groups. As the novel trial to integrate two data sets with batch effect, we simply applied standardization to microarray data before the significant gene selection. In the gene selection step, we used new defined measure that considers the distance between a gene and an ideal gene as well as the between-slide and within-slide variations. Also we discussed the association of biological functions and different expression patterns in selected discriminative gene set. As a result, we could confirm that batch effect was minimized by standardization and the selected genes from the standardized data included various expression pattems and the significant biological functions.

A case of toxoplasmosis mimicking systemic recurrence in a patient treated with breast cancer / 대한내과학회지

Left cervical lymphadenopathy was found in a 48-year-old Korean female patient who had been treated for breast cancer 3 years ago. A presumative diagnosis was lymph nodal and lung metastasis of breast cancer during chest CT and neck CT. Core needle biopsy was undertaken. Pathological examination of lymph node revealed reactive hyperplasia consistent with toxoplasmosis, and toxoplasma Ig M antibody was also positive. Finally, she was diagnosed as toxoplasmosis, not metastasis of breast cancer. As she had no symptoms, no specific treatment was necessary. Follow up chest and neck CT scan after 5 months later showed resolved lung lesion, and size decrement of cervical lymph node. So, she has no evidence of recurrence and is now under clinical follow up. Recognition that toxoplasmosis can mimic metastasis is important in reaching the correct diagnosis and treatment.

Chemotherapy in Cancer Patients with Comorbidity

This report attempts to explain the (i) implications of comorbidity for research and practice in the fieldo of oncology, (ii) the approach for dosing of anti-cancer drugs in the presence of comorbidity, as an example of its clinical application, and finally (iii) the dosing guidelines for the anticancer drugs clinically active in gastric cancer in the presence of renal or liver dysfunction. This has resulted from the idea of approaching comorbidity in a systematic way and of integrating it with oncologic decisions. Various methods have been used to assess comorbidity. However, significant work remains to be done to analyze how various diseases combine to influence the oncologic outcome. The main end-point explored so far has been mortality, but a largely open challenge remains to correlate comorbidity with treatment tolerance and functional and quality of life, as well as to integrate it in clinical decision-making. Cancer chemotherapy in comorbidity should be considered as an example of the need for dose optimization in individual patients, and it should be determined by considering the basic principles of the pharmacokinetics and the pharmacodynamics of the agents. This review analyzes the available data on the pharmacokinetics and the toxicities of anti-cancer agents in the comorbidity population.

Leptomeningeal Carcinomatosis in Solid Tumors; Clinical Manifestation and Treatment / 대한암학회지

PURPOSE: Leptomeningeal carcinomatosis occurs in about 5% of patients with solid tumor and is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. In general, the most commom cancers that involved the leptomeninges are breast cancer, lung cancer, and malignant melanoma. MATERIALS AND METHODS: We investigated 25 patients presented with multiple neurologic symptoms and signs who were diagnosed with leptomeningeal carcinomatosis at the Yonsei Cancer Center from January 1990 to December 1999. RESULTS: The primary disease of leptomeningeal carcinomatosis were stomach cancer (10 cases), breast cancer (7 cases), lung cancer (5 cases), unknown primary cancer (2 cases) and common bile duct cancer (1 case). All patients were presented with multiple neurologic symptoms and signs involving the central nervous system (CNS), cranial nerve or spinal nerves. Twenty-one of twenty- five patients were treated with intrathecal chemotherapy, radiotherapy, or combination therapy. Fourteen of them (66.7%) experienced improvement or stabilization of neurologic symptom and sign. The median survival was 122 days (10-2190). CONCLUSION: In conclusion, although early diagnosis and active treatment of leptomeningeal carcinomatosis may improve the quality of life in selected patients, the median survival was relatively short. Therefore, new diagnostic and therapeutic strategy for leptomeningeal carcinomatosis were needed.

Efficacy of Pre- and Postoperative Chemotherapy in Patients with Osteosarcoma of the Extremities / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.