Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model.

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.

Anticancer Effect of Benzimidazole Derivatives, Especially Mebendazole, on Triple-Negative Breast Cancer (TNBC) and Radiotherapy-Resistant TNBC In Vivo and In Vitro.

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.

Allogeneic Stem Cell Transplantation for Patients with Natural Killer/T Cell Lymphoid Malignancy: A Multicenter Analysis Comparing Upfront and Salvage Transplantation.

Natural killer (NK)/T cell lymphoid malignancy comprises extranodal NK/T cell lymphoma (ENKTL) and aggressive NK cell leukemia (ANKL), and the outcomes for advanced or relapsed/refractory ENKTL and ANKL remain poor. Allogeneic stem cell transplantation (SCT) can be used as a frontline consolidation treatment to prevent the relapse of advanced disease or as salvage treatment after chemotherapy for relapsed sensitive disease. We retrospectively analyzed 36 patients (ENKTL, n = 26; ANKL, n = 10) who underwent upfront (n = 19) and salvage allogeneic SCT (n = 17) at 6 hospitals. Patients received myeloablative (n = 25) or reduced-intensity (n =11) conditioning regimens depending on the institute's policy. The median age at the time of allogeneic SCT was 37 years (range, 17 to 62), and more patients with ANKL (8/10) received upfront allogeneic SCT than ENKTL patients (11/26). Disease status before allogeneic SCT, conditioning regimen, and donor source did not differ between upfront and salvage allogeneic SCT groups. Febrile neutropenia (n = 20) and acute graft-versus-host disease (n = 16) were common adverse events. The median overall survival (OS) and progression-free survival (PFS) after allogeneic SCT were 11.8 months and 10.0 months, respectively. Twelve patients died from disease relapse and 12 from nondisease-related causes. Ten deaths occurred within 100 days after allogeneic SCT (10/24); these were mostly related to disease relapse (n = 8). The OS after allogeneic SCT did not differ between ENKTL and ANKL (P = .550) or between upfront and salvage SCT (P = .862). Complete chimerism was significantly associated with better PFS (P < .001). No significant differences in PFS were observed based on the conditioning regimen or source of stem cells (P > .05). Allogeneic SCT may be beneficial for patients with ENKTL and ANKL given that some patients were able to maintain their remission after allogeneic SCT. However, allogeneic SCT should only be performed in highly selected patients because the risks of disease relapse and nondisease-related mortality remain high.

Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone-Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single-Blind, Crossover Phase III Trial.

BACKGROUND: To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS: Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS: No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. CONCLUSION: Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. IMPLICATIONS FOR PRACTICE: In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.

Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma.

BACKGROUND: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. METHODS: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. RESULTS: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. CONCLUSIONS: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.

Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer.

PURPOSE: Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR). METHODS: A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR. RESULTS: Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p < 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p < 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001). CONCLUSIONS: In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients.

Prognostic significance of the absolute monocyte counts in lung cancer patients with venous thromboembolism.

We investigated the clinical significance of the absolute monocyte count (AMC) as a predictor of the response to anticoagulation and survival in lung cancer patients with venous thromboembolism (VTE). We retrospectively reviewed 1707 patients with pathologically proven lung cancer who visited the hospital between July 2008 and May 2014. Among them, the clinical data of patients newly diagnosed with VTE and treated with anticoagulation were compared between the low and high AMC groups according to the median value of AMC (640/µL) at the time of VTE diagnosis. The incidence of VTE was 7.9 % during the study period. Most of the patients had non-small-cell lung cancer (82.1 %), stage IV (64.2 %), and pulmonary thromboembolism (76.1 %) and were incidentally diagnosed with VTE (76.9 %). The patients' characteristics and laboratory values were not significantly different between the low and high AMC groups. Among patients available for evaluation of the response to anticoagulation, the high AMC group was significantly more refractory to anticoagulation than the low AMC group (no response to anticoagulation, 21.7 vs. 6.8 %, respectively; p = 0.044). Additionally, the high AMC group showed worse overall survival (OS) than the low AMC group (median, 9.6 vs. 5.9 months; p = 0.038). On multivariate analysis, high AMC, low albumin, and advanced stage were independent poor prognostic factors for OS. High AMC is associated with refractoriness to anticoagulation and poor prognosis in lung cancer patients with VTE.

Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC).

BACKGROUND: Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. METHODS: We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. RESULTS: Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. CONCLUSIONS: Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted.

The clinical impact of the sum of the maximum standardized uptake value on the pretreatment with F-FDG-PET/CT in small-cell lung cancer.

OBJECTIVES: The aim of this study was to investigate the clinical significance of the sum of the maximum standardized uptake value (sumSUVmax) on pretreatment positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in newly diagnosed small-cell lung cancer (SCLC). METHODS: We retrospectively analyzed 145 SCLC patients from March 2005 to June 2013 who underwent pretreatment (18)F-FDG-PET/CT. The sumSUVmax was assessed in all malignant lesions up to a maximum of 5 lesions and a maximum of 2 lesions per organ according to RECIST 1.1. RESULTS: A significant difference was found between the low and high sumSUVmax groups (low vs. high sumSUVmax, 91.5 vs. 77.3%; p = 0.018) in the response rate (RR) following frontline platinum-based chemotherapy. The group with low sumSUVmax showed significantly better overall survival (OS; p < 0.001) as well as better progression-free survival (PFS; p < 0.001) compared with the group with high sumSUVmax. Moreover, multivariate analysis revealed that a high sumSUVmax alone was an independent poor prognostic factor for OS (hazard ratio 2.676; 95% confidence interval, 1.674-4.277; p < 0.001). CONCLUSIONS: This study showed that the sumSUVmax adopted from RECIST 1.1 on pretreatment (18)F-FDG PET/CT was significantly correlated with response to treatment, OS, and PFS in patients with SCLC.

Gemcitabine plus vinorelbine as the second-line treatment and beyond in elderly patients with platinum-pretreated advanced non-small cell lung cancer.

BACKGROUND: The efficacy and tolerance of a gemcitabine and vinorelbine (GV) combination as salvage therapy have not been reported in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: We reviewed elderly patients with advanced NSCLC who had disease progression after one or more chemotherapy regimens, at least one including platinum, and then who were treated with GV as the salvage therapy. RESULTS: In total 40 patients were analyzed. GV was at least the third-line chemotherapy in 24 patients (60.0%). Only 2 patients (5.0%) experienced grade 3 febrile neutropenia. Nonhematologic toxicities were generally mild and there was no treatment-related mortality. Among 29 patients evaluable for treatment response, 10 (34.5%) and 9 (31.0%) achieved a partial response and stable disease, respectively. The median overall survival was 10.3 months and the median progression-free survival was 3.1 months. CONCLUSIONS: GV in combination is an effective and tolerable salvage regimen in elderly and heavily pretreated patients with advanced NSCLC.

Acute Tubular Necrosis Associated with Angiotensin Receptor-neprilysin Inhibitor.

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), significantly reduces mortality and morbidity in patients with chronic heart failure with a reduced ejection fraction (HFrEF). However, a considerable number of patients treated with sacubitril/valsartan experience hypotension, oliguria, progressive azotemia, and renal failure as adverse events. These issues have been linked to significant gaps in the usage and dosing of guideline-directed medical therapy with ARNI in patients with HFrEF. We herein report a relevant case of pathologically proven acute tubular necrosis after the first dose of sacubitril/valsartan, highlighting the importance of optimizing the medical therapy in an outpatient with HFrEF.

Sarcopenia using pectoralis muscle area and lymphocyte-to-monocyte ratio (LMR) are independent prognostic factors in patients for nonmetastatic breast cancer.

Sarcopenia is defined as loss of skeletal muscle mass and strength. This can lead to adverse clinical outcomes in patients with advanced cancer. The lymphocyte-to-monocyte ratio (LMR), a converted inflammatory response, is associated with poor prognosis in patients with malignancies. Herein, we examined the prognostic influence of sarcopenia status assessed by pectoralis muscle area (PMA), inflammatory status calculated by LMR, and its association with disease-free survival (DFS) in a cohort of women diagnosed with nonmetastatic breast cancer. A total of 293 patients with nonmetastatic breast cancer who underwent primary mass resection and radiotherapy between January 2011 and December 2017 were enrolled. The cross-sectional area of the muscle (cm2) at PMA was measured using computed tomography before radiation therapy. Baseline monocyte and lymphocyte counts were obtained from the complete blood count to calculate the LMR. Most of the patients (248/293, 84.6%) underwent breast conservation surgery. Lymph node involvement at diagnosis (hazard ratio [HR], 5.08; P < .001), low LMR (HR, 2.79; P = .007), and low PMA (HR, 3.80; P < .001) were independent poor prognostic factors in multivariate analysis. The mean DFS of sarcopenic and nonsarcopenic patients was 89.8 months and 118.8 months, respectively (P < .001). Sarcopenic patients with low LMR showed the worst outcomes, whereas nonsarcopenic patients with high LMR showed the best outcomes. Low PMA and low LMR were independent poor prognostic factors for DFS in patients with nonmetastatic breast cancer.

Can an anti-Xa assay for unfractionated heparin be used to assess the presence of rivaroxaban in critical situations?

OBJECTIVE: Although rivaroxaban has recently become widely used for thrombosis treatment, it is difficult for clinicians to make clinical decisions in critical situations, such as emergent surgery or interventions, because a specific anti-Xa assay is not available in many laboratories. This study assessed the relationships between rivaroxaban-specific anti-factor Xa activity (AXA) and unfractionated heparin (UFH)-specific AXA and determined the cutoff level for UFH-specific AXA in critical situations for patients undergoing rivaroxaban therapy. METHODS: Thirty-eight blood samples were collected from patients with cancer-associated thrombosis receiving rivaroxaban therapy. All samples were assessed using both rivaroxaban-specific and UFH-specific anti-Xa assays. Routine coagulation studies, including prothrombin time (PT) and activated partial thromboplastin time, were also conducted on the samples. RESULTS: A positive dose-dependent correlation between rivaroxaban-specific and UFH-specific AXA was evident (R = 0.97; P < .0001). Rivaroxaban-specific AXA was also positively correlated with PT (R = 0.95; P < .0001) but only weakly with activated partial thromboplastin time (R = 0.67; P < .0001). Patients with plasma rivaroxaban concentrations <100 ng/mL were found to have UFH-specific AXA <1.41 IU/mL and PT <17.3 seconds, with sensitivities of 100% and 93.3% and specificities of 87.0% and 95.7%, respectively. CONCLUSIONS: Our study demonstrates that UFH-calibrated AXA correlates strongly with plasma rivaroxaban concentration. This assay appears to be sensitive to the presence of rivaroxaban, which may be advantageous in the setting of assessing drug levels for critical events. These findings suggest that if a rivaroxaban-specific anti-Xa assay is unavailable, the chromogenic anti-Xa assay for UFH may be useful to assess the anticoagulant effects of rivaroxaban.

Bilateral ovarian granulocytic sarcoma as the primary manifestation of acute myelogenous leukemia treated with allogenic stem cell transplantation: A case report.

RATIONALE: Granulocytic sarcoma (GS), also known as chloroma, is a tumor comprising myeloblasts or monoblasts, potentially occurring as an extramedullary mass. Systemic chemotherapy should be used to induce complete remission. However, such patients with chloroma have a poorer treatment outcome than those without extramedullary myeloid sarcomas. PATIENT CONCERNS: A 30-year-old woman who initially presented with bilateral ovarian masses and splenomegaly was admitted to hospital. Also, her complete blood cell counts showed pancytopenia and blood smear revealed a few immature cells (3%). DIAGNOSES: A bone marrow biopsy demonstrated acute myelomonocytic leukemia, and the chromosomal analysis revealed a 46, XX, del18 (p11) [20] karyotype and cytogenetics and molecular markers showed all negative results. INTERVENTIONS: Since this diagnosis, she received remission-inducing chemotherapy comprising anthracycline and cytarabine, which is a standard regimen for acute myeloid leukemia (AML), and followed by allogenic hematopoietic stem cell transplantation from Human leukocyte antigen (HLA)-identical sibling donor. OUTCOMES: After transplantation, the bone marrow engrafted successfully without complications. She visited our clinic regularly with no evidence of leukemia relapse or graft-versus host disease. LESSONS: This report represents the first case of ovarian GS, wherein treatment was successful with high-dose chemotherapy, followed by allogenic hematopoietic stem cell transplantation without oophorectomy.

Romiplostim-related myelofibrosis in refractory primary immune thrombocytopenia: A Case report.

RATIONALE: Primary immune thrombocytopenia (ITP) is an immune-mediated disease that is defined as increased platelet destruction and impaired platelet production. Treatment is recommended for highly selected patients, the standard regimen includes glucocorticoid, intravenous immunoglobulin (IVIG). The recombinant thrombopoietin (TPO) receptor agonists, romiplostim, stimulate platelet production and have approved for glucocorticoid or IVIG, splenectomy-refractory chronic ITP patients. PATIENT CONCERNS: A patient has been diagnosed with ITP, reftractory to steroid, IVIG, splenectomy, danazol, and cyclosporine. The patient received romiplostim to normalize his platelet count, however, over the course of the following year, his platelet counts progressively decreased despite increasing the romiplostim dosing. DIAGNOSES: A peripheral blood smear showed a severe leukoerythroblastic reaction and bone marrow biopsy demonstrated myelofibrosis due to romiplostim. OUTCOMES: Since this diagnosis, romiplostim was discontinued for a while, after 3 months, romiplostim was re-administered to improve thrombocytopenia. His platelet count recovered to 70,000/mm after the administration of romiplostim at 2 µg/kg, and he did not experience complications for 6 months. LESSONS: This report represents the first evidence of romiplostim-induced myelofibrosis, which was associated with increased levels of bone marrow reticulin and Masson trichrome staining.

Sedation for terminally ill cancer patients: A multicenter retrospective cohort study in South Korea.

Sedation therapy is a potential solution to providing relief from refractory symptoms at end of life. The aim of this study was to investigate actual sedation practice and physician characteristics associated with the use of sedation for terminally ill cancer patients in South Korea.A retrospective review was conducted on consecutive patients who had died from cancer at seven tertiary medical centers between January 2010 and October 2015. The use of sedation was defined as the administration of sedative agents to relieve intolerable symptoms within the last 2 weeks preceding death. Patients and physician characteristics and information on the use of sedation were collected.A total of 8309 patients were included in the study. Sedatives were administered in 1334 patients (16.1%) for the following indications: delirium in 39.3%, intractable pain in 23.1%, and dyspnea in 21.9%. Median duration of sedation from initiation to death was 3 days. The use of sedation depended on physician specialty and experience. Family physicians used sedation most often (57.6%), followed by medical oncologists (13.9%), other internists (10.7%), and surgical oncologists (9.4%). The use of sedation was highest for physicians with >5 to 10 years practice experience (22.1%) and lowest for those in practice for 5 years or less (10.2%). The proportion of patients receiving sedation also varied markedly across participating institutions (range, 7.0%-49.7%).This large cohort study provides insight into sedation practice for terminally ill cancer patients in South Korea. Our study shows that the use of sedation depends on physician background and institution. A nation-wide guidelines and continued education on end-of-life sedation are required in South Korea.

Craving Behavior from Opioid Addiction Controlled with Olanzapine in an Advanced Cancer Patient: A Case Report.

Opioid addiction, although uncommon in cancer patients, can be a significant challenge for optimal pain management in certain patients. We present a case of a 59-year-old man with advanced colon cancer whose compulsive craving for the buccal tablet of fentanyl citrate (BTFC) was improved with the use of olanzapine. He was hospitalized for abdominal pain caused by disease progression. He had visited several times at outpatient follow-up to obtain a prescription for BTFC because he took all medications before the appointed times. After admission, intravenous infusion of oxycodone and opioid rotation were applied to the patient to control his pain. However, he complained that the pain was not relieved at all and persistently asked for only BTFC 7 to 15 times per day. With the diagnosis of opioid addiction, the transdermal buprenorphine patch was applied, but was ineffective for controlling the addictive behaviors. Finally, olanzapine (10 mg/day per os), a dopamine receptor antagonist, was given to control the craving behavior because psychological dependence is mediated by the dopaminergic system. Three days later, opioid craving was reduced from five to one on a 5-point Likert scale. The pain was well controlled to numeric rating scale 1 or 2 without cravings for BTFC. Craving behavior as a result of opioid addiction may be controlled with olanzapine. Further prospective studies on this issue are warranted.

Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report.

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis.

PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

Neutrophil-lymphocyte ratio and a dosimetric factor for predicting symptomatic radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVES: To identify the factors that predict the progression of radiological radiation pneumonitis (RP) to symptomatic RP, and to evaluate the usefulness of the neutrophil-lymphocyte ratio (NLR) as a marker of RP severity and prognosis in stage III non-small cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively reviewed 61 patients treated between January 2010 and December 2015. Patients' demographic characteristics, clinical data, laboratory findings and treatment parameters were analyzed to determine the predictive factors associated with progression from radiological RP to symptomatic RP. RESULTS: Forty-seven patients (77%) exhibited radiological RP at a median of 78 days after radiation therapy (RT) completion, and 15 (32%) of these patients developed symptomatic RP. The interval between RT completion and radiological RP presentation was shorter in patients who progressed to symptomatic RP (P = .001); progression was highly probable if this latency period was ≤2 months (P = .002). Stage and RT technique correlated with symptomatic RP development (P = .046 and P = .046, respectively). Among dosimetric factors, a V20 (defined as the lung volume receiving ≥20 Gy) of >30% was the most significant predictor of symptomatic RP (P = .001). The NLR and C-reactive protein level at radiological RP were higher in patients who developed symptomatic RP (P = .067 and P = .012, respectively). On multivariate analysis, a V20 >30% and an NLR at radiological RP >6 were associated with symptomatic RP development. CONCLUSION: The NLR at radiological RP is a useful biomarker for predicting symptomatic RP development after CCRT in stage III NSCLC patients.