Enhanced Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Uncommon Histiocytic Sarcoma of Small Intestine Arising after Gastric Large B-Cell Lymphoma.

Histiocytic sarcoma (HS) is an extremely rare and aggressive malignant neoplasm of hematopoietic origin that shows morphologic and immunophenotypic evidence of histiocytic differentiation. In approximately 25% of the cases, presumed transdifferentiation of a preexisting hematolymphoid disorder can be demonstrated. Various extranodal sites, particularly the gastrointestinal tract, soft tissue, skin, and spleen, can be involved. Enhanced CT and FDG PET/CT findings of extranodal histiocytic sarcoma have been barely reported. We present a case with extranodal HS originating in the small intestine after gastric large B-cell lymphoma, mistaken for prostate cancer metastasis in a 76-year-old man.

Real-World Outcomes of Nivolumab, Pembrolizumab, and Atezolizumab Treatment Efficacy in Korean Veterans with Stage IV Non-Small-Cell Lung Cancer.

PURPOSE: To provide a comprehensive analysis of ICI usage and treatment outcomes in elderly Korean veterans with stage IV NSCLC. METHODS: Patients diagnosed with stage IV NSCLC between 2016 and 2021 were included, and three cohorts were derived according to the type of ICI received. Thereafter, the clinical characteristics and survival outcomes were compared. RESULTS: Of the 180 patients with NSCLC (median age, 76 years) included in this study, 49 (27.7%), 61 (33.9%), and 70 (38.9%) received pembrolizumab, nivolumab, and atezolizumab, respectively, and 19.4%, 36.1%, and 34.4% had PD-L1 expressions < 1%, 1-49%, and ≥50%, respectively. The pembrolizumab, nivolumab, and atezolizumab groups, the objective response rates (ORR), and the disease control rates (DCR) were 22.4%, 8.2%, and 4.3% (p = 0.004), and 59.2, 55.7%, and 30.0% (p = 0.001), respectively. However, no difference in the overall survival (OS) rate was noted among the groups (12.6 months vs. 8.4 months vs. 7.7 months, p = 0.334). Similarly, there was no treatment specific OS benefit with respect to the tumor PD-L1 expression status. Interestingly, multivariate analysis identified bone metastasis as a significant poor prognostic factor for OS (HR = 2.75 [95% CI, 1.31-5.76], p = 0.007). CONCLUSION: Pembrolizumab and nivolumab showed stronger associations with increases in ORR and DCR than atezolizumab, but no statistically significant differences were observed with respect to OS.

A Phase 2 Study of Palbociclib for Recurrent or Refractory Advanced Thymic Epithelial Tumors (KCSG LU17-21).

INTRODUCTION: Thymic epithelial tumors (TETs) are rare but are the most common tumors of the anterior mediastinum. Platinum-based combination chemotherapy is the standard of care for such tumors and is associated with a 50% to 90% objective response rate (ORR) in metastatic disease. Nevertheless, there is no standard chemotherapeutic option after failure of platinum-based combination chemotherapy. Genetic alterations associated with the cell cycle, including pRB, p16INK4A, and cyclin D1, are most often observed in TETs. On the basis of these results, we conducted a phase 2 trial to evaluate the efficacy and safety of palbociclib in patients with recurrent or refractory advanced TETs. METHODS: This is a phase 2, multicenter, open-label, single-arm study of palbociclib monotherapy in patients with recurrent or metastatic advanced TETs who failed one or more cytotoxic chemotherapies. The patients received 125 mg of oral palbociclib daily for 21 days, followed by a 7-day break. The primary end point was progression-free survival (PFS). The secondary end points were ORR, duration of response, overall survival, and safety. RESULTS: Between August 2017 and October 2019, a total of 48 patients were enrolled. The median number of previous chemotherapies was one (range: one to four), and 21 (43.7%) of 48 patients received thymectomy. By the WHO classification, the patients were type A (n = 1), type B1 (n = 2), type B2 (n = 8), type B3 (n = 13), thymic carcinoma (n = 23), and unknown (n = 1). With a median follow-up of 14.5 months (range: 0.8-38.2), the median number of cycles of palbociclib monotherapy was 10 (range: 1-40). The ORR was 12.5% (four partial responses in thymoma and two partial responses in thymic carcinoma). The PFS at 6 months was 60.2%, and the median PFS was 11.0 months (95% confidence interval: 4.6-17.4). The median overall survival was 26.4 months (95% confidence interval: 17.4-35.4). The most common treatment-related adverse events of any grade were neutropenia (62.5%), anemia (37.5%), and thrombocytopenia (29.1%), and the most common grade 3/4 treatment-related hematologic adverse event was neutropenia (41.7%). Neutropenia above grade 3 was reversible, and there were no cases with neutropenic fever. CONCLUSIONS: Palbociclib monotherapy was well tolerated and had encouraging efficacy in patients with TETs who failed platinum-based combination chemotherapy.

A Case of Chronic Neutrophilic Leukemia Incidentally Detected by 18F-FDG PET/CT.

Chronic neutrophilic leukemia (CNL) is a rare, potentially aggressive, myeloproliferative neoplasm. To the best of our knowledge, there are no previous reports dealing with 18F-FDG PET findings in CNL. We describe a case of CNL in a 69-year-old male, imaged with 18F-FDG PET/CT at diagnosis and during treatment.

Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial.

PURPOSE: Limited treatment options exist for patients with thymic epithelial tumor (TET) whose disease progresses after platinum-based chemotherapy. We conducted a phase II study of pembrolizumab in patients with TET to evaluate its efficacy and safety. METHODS: Patients with histologically confirmed TET whose disease progressed after at least one line of platinum-based chemotherapy were eligible for the study. Patients were excluded if they had an active autoimmune disease requiring systemic treatment within the past year or documented history of clinically severe autoimmune disease. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until tumor progression or unacceptable toxicity. The primary objective of response rate was assessed every 9 weeks by investigators. RESULTS: Of 33 patients enrolled, 26 had thymic carcinoma and seven had thymoma. Of seven thymoma, two (28.6%; 95% CI, 8.2% to 64.1%) had partial response, and five (71.6%) had stable disease. Of 26 thymic carcinoma, five (19.2%; 95% CI, 8.5% to 37.9%) had partial response and 14 (53.8%) had stable disease. The median progression-free survival was 6.1 months for both groups. The most common adverse events of any grade included dyspnea (11; 33.3%), chest wall pain (10; 30.3%), anorexia (seven; 21.2%), and fatigue (seven; 21.2%). Five (71.4%) of seven patients with thymoma and four (15.4%) of 26 patients with thymic carcinoma reported grade ≥ 3 immune-related adverse events, including hepatitis (four; 12.1%), myocarditis (three; 9.1%), myasthenia gravis (two; 6.1%), thyroiditis (one; 3.0%), antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis (one; 3.0%), colitis (one; 3.0%), and subacute myoclonus (one; 3.0%). CONCLUSIONS: Pembrolizumab showed encouraging antitumor activity in patients with advanced TET. Given the high incidence of autoimmunity, additional studies are needed to identify those who can benefit from pembrolizumab without immune-related adverse events.

A multicenter, retrospective analysis of elderly patients with acute myeloid leukemia who were treated with decitabine.

Decitabine is widely accepted as the treatment options for elderly acute myeloid leukemia (AML) patients. However, the efficacy has yet been assessed in Asian population. We retrospectively analyzed the outcomes of 80 Korean elderly AML patients who were treated with decitabine. The median age was 74 years (range, 64 to 86 years) and 6 (7.5%), 48 (60.0%), and 25 (31.3%) patients were categorized to favorable, intermediate, and poor risk group, respectively. The median OS was 10.2 months (95% CI 5.0-15.4). Given that decitabine treatment demonstrated improved clinical outcomes, it could be considered as one of the first-line treatment for Korean elderly AML patients.

Clinical features and treatment outcomes of blastic plasmacytoid dendritic cell neoplasm: a single-center experience in Korea.

BACKGROUND/AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal. METHODS: We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014. RESULTS: Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission. CONCLUSIONS: All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.

A retrospective feasibility study of biweekly, reduced-dose docetaxel in Asian patients with castrate-resistant, metastatic prostate cancer.

BACKGROUND: The aim of this retrospective study was to evaluate the clinical outcomes of reduced dose, biweekly docetaxel chemotherapy for Korean patients with castrate-resistant prostate cancer (CRPC). METHODS: We retrospectively reviewed the medical records of 48 patients with metastatic CRPC who were treated with a biweekly regimen (intravenous docetaxel 40 mg/m2 on day 1 plus prednisolone 5 mg twice daily) between 2012 and 2015 at Samsung Medical Center (Seoul, Korea). Prior to the adoption of a biweekly regimen in Oct 2013, our institutional standard chemotherapy was docetaxel 75 mg/m2 every 3 weeks for patients with CRPC (n = 24). After Oct 2013, all chemotherapy-naïve patients with CRPC received a 40 mg/m2 biweekly regimen (n = 24). The primary end point was a PSA response, defined as a greater than 50% decline in PSA level from baseline. RESULTS: The baseline characteristics of the patients in the two treatment groups were similar. The most common cause of treatment discontinuation was disease progression, which was exhibited by 17 patients (71%) in the 3-weekly group and 20 (75%) in the biweekly group. PSA responses were observed in 12 (50%) and 11 (46%) patients in the 3-weekly and biweekly groups, respectively (p = 0.683). Time to treatment failure (TTTF, 4.5 vs 3.9 months) and time-to-progression (TTP, 5.0 vs 4.2 months) were not significantly different between the 3-weekly and biweekly groups. CONCLUSIONS: Within the limitations of a retrospective study, the biweekly reduced dose docetaxel regimen was active and well-tolerated in Korean patients with metastatic CRPC.

Patient-Generated Subjective Global Assessment as a prognosis tool in patients with multiple myeloma.

OBJECTIVE: Disease-related weight loss is relatively common in patients with newly diagnosed multiple myeloma (MM), but limited data exist regarding the effects of nutritional status on survival. The aim of this study was to assess the relationship between malnutrition (as measured by Patient-Generated Subjective Global Assessment [PG-SGA]) and clinical characteristics of patients with MM, and to investigate the association between the PG-SGA score before chemotherapy and overall survival in MM patients. METHODS: Using the PG-SGA score, we retrospectively explored the effect of malnutrition on the survival of Asian patients with MM. RESULTS: We divided 216 patients with MM into three groups based on their PG-SGA scores. Of these patients 23% (n = 50) had PG-SGA scores ≥9, indicating severe malnutrition requiring specialist nutrition intervention. Body mass index and serum hemoglobin were independently associated with PG-SGA scores (P < 0.05). The median survival time was not reached in nourished patients with PG-SGA scores of 0 to 3, 58.7 mo in moderately malnourished patients with PG-SGA scores of 4 to 8, and 35 mo in severely malnourished patients with PG-SGA scores ≥9 (P = 0.001). Multivariate analysis revealed that PG-SGA scores ≥9 compared with PG-SGA scores of 0 to 3 (hazard ratio [HR], 2.347; 95% confidence interval [CI], 1.271-4.334; P = 0.006), International Staging System (ISS) stage III compared with ISS stage I (HR, 2.360; 95% CI, 1.271-4.379; P = 0.007), and autologous stem cell transplantation (HR, 0.388; 95% CI, 0.248-0.606; P < 0.001) were associated with overall survival. CONCLUSIONS: A higher PG-SGA score before chemotherapy was associated with reduced survival among patients with MM. Nutritional evaluation should be an integral part of the clinical assessment of MM patients, and the PG-SGA score would be an appropriate tool to evaluate nutritional status.

Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

PURPOSE: Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. MATERIALS AND METHODS: Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. RESULTS: Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. CONCLUSION: In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

Macrophage inflammatory protein 1 alpha (MIP-1α) may be associated with poor outcome in patients with extranodal NK/T-cell lymphoma.

The macrophage inflammatory protein 1α (MIP-1α) is anticipated to have a role in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) because the expression of MIP-1α is related to Epstein-Barr virus (EBV) latency in EBV-related non-Hodgkin lymphoma cells. Thus, we measured the serum level of MIP-1α in 69 patients with ENKTL using frozen serum samples that were archived at diagnosis. As serum level of MIP-1α was not detectable in 19 patients (range: 0-24.37 pg/mL), patients were dichotomized into positive (n = 50) and negative (n = 19) MIP-1α groups according to the presence of detectable level of MIP-1α in serum. MIP-1α-positive group showed a significantly poor overall survival (OS) in comparison with the MIP-1α-negative group (p = 0.004). In the subgroup analysis, the positivity of MIP-1α was significantly associated with OS in patients with stage IIIE/IV and a detectable level of EBV DNA (p = 0.002 and 0.032, respectively). Multivariate analysis also showed that the positivity of MIP-1α was independently associated with worse OS together with bone marrow involvement (p = 0.002). An in vitro study with patient-derived ENKTL tumour cells showed the expression of CCR1 and CCR5 on the surface of tumour cells (28% and 14%, respectively) , and the addition of MIP-1α to the culture media of tumour cells increased cell growth supporting the negative impact of MIP-1α on the prognosis of ENKTL patients. In conclusion, serum levels of MIP-1α could predict survival outcomes in patients with ENKTL. Therefore, MIP-1α should be considered for prognostication and a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd.

Clinicopathological Features and Prognostic Factors Affecting Survival Outcomes in Isolated Locoregional Recurrence of Breast Cancer: Single-Institutional Series.

PURPOSE: The purpose of this study was to investigate the clinicopathologic features and prognostic factors affecting outcome in patients with isolated locoregional recurrence of breast cancer (ILRR). METHODS: We retrospectively analyzed the medical records of 104 patients who were diagnosed with ILRR and underwent curative surgery from January 2000 to December 2010 at Samsung Medical Center. RESULTS: Among 104 patients, 43 (41%) underwent total mastectomy and 61 (59%) underwent breast-conserving surgery for primary breast cancer. The median time from initial operation to ILRR was 35.7 months (4.5-132.3 months). After diagnosis of ILRR, 45 (43%) patients were treated with mastectomy, 41 (39%) with excision of recurred lesion, and 18 (17%) with node dissection. During a median follow-up of 8.9 years, the 5-year overall survival was 77% and 5-year distant metastasis-free survival (DMFS) was 54%. On multivariate analysis, younger age (< 35 years), higher stage, early onset of elapse (≤ 24 months), lymph node recurrences, and subtype of triple negative breast cancer (TNBC) were found to be independently associated with DMFS. Patients in the no chemotherapy group showed a longer DMFS after surgery for ILRR than those treated with chemotherapy (median 101.5 vs. 48.0 months, p = 0.072) but without statistical significance. CONCLUSION: Our analysis showed that younger age (< 35 years), higher stage, early onset of relapse (≤ 24 months), lymph node recurrence, and subtype of TNBC are the worst prognostic factors for ILRR.

Value of volume-based early metabolic response in patients with unresectable thymic epithelial tumor.

OBJECTIVE: We conducted this study to investigate the value of early metabolic responses assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in predicting prognosis and monitoring treatment response in patients with unresectable thymic epithelial tumors (TETs). PATIENTS AND METHODS: Study subjects were selected from the prospective dataset of a phase II clinical trial for cisplatin plus Cremorphor EL-free paclitaxel. A total of thirty patients with unresectable TETs who underwent baseline and early post treatment scan after two cycles of chemotherapy were enrolled (22 Male; mean age 55.0±15.0years). Metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the tumor lesions were measured. RESULTS: Multivariate analysis using Cox proportional hazards regression model showed that percent decrease of MTV (HR=0.995 by 1% decrease, P=0.037) and TLG (HR=0.996 by 1% decrease, P=0.044) were significant predictors of progression-free survival (PFS). Receiver operating characteristic curve identified an 88.0% decrease in MTV and a 92.0% decrease in TLG as the optimal cut-off value for disease progression. Responders with ≥88% of ΔMTV and ≥92% of Δ TLG had significantly longer PFS than non-responders (P=0.012, 0.026, respectively). CONCLUSION: The percent decrease in MTV and TLG of tumor lesions measured by early post treatment FDG PET/CT significantly associated with disease progression in this study. Early metabolic response based on these volumetric parameters has the potential to monitor treatment response and predict prognosis in patients with unresectable TETs.

Assessment of objective responses in thymic epithelial tumors using ITMIG modified criteria.

OBJECTIVES: Pleural metastases of thymic epithelial tumors (TETs) are relatively common, and this unique growth pattern makes the use of RECIST (response evaluation criteria in solid tumors) response criteria difficult. To standardize tumor measurement in TETs, the International Thymic Malignancy Interest Group (ITMIG) has proposed newly developed criteria. We compared evaluation of objective response between ITMIG modified criteria and RECIST 1.1 in patients with TET treated with systemic chemotherapy. PATIENTS AND METHODS: We retrospectively evaluated the tumor response of 40 patients with unresectable TET who were enrolled in a phase II clinical trial using ITMIG modified criteria, and compared the findings with prospectively evaluated tumor response assessed by RECIST 1.1. Agreement analyses for the response at each time point, including overall response and declaring progression, were performed and the time to progression (TTP) was also assessed using the two different measurements. RESULTS: The overall response rate assessed by the two methods did not differ significantly, with kappa value of 0.897. Agreement analysis for declaring progression of disease (PD) at the date of RECIST 1.1-designated PD showed 95% concordance rate with ITMIG modified criteria (p=1.000, kappa index=0.875). The median TTP according to RECIST 1.1 and ITMIG modified criteria was 8.4 and 7.9 months (p=0.983), respectively. Validation with another cohort of 27 TET patients treated with neoadjuvant chemotherapy also showed a 96% concordance rate in overall response between the two different criteria. CONCLUSIONS: ITMIG modified criteria showed a high concordance rate with RECIST 1.1 criteria in response assessment of TETs. Given the rarity of TETs, further evaluation of ITMIG modified criteria in a larger number of patients will be required before their implementation in clinical trials.

MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis.

Monocarboxylate transporters (MCTs) play a major role in up-regulation of glycolysis and adaptation to acidosis. However, the role of MCTs in gastric cancer (GC) is not fully understood. We investigated the potential utilization of a new cancer therapy for GC. We characterized the expression patterns of the MCT isoforms 1, 2, and 4 and investigated the role of MCT in GC through in vitro and in vivo tests using siRNA targeting MCTs. In GC cell lines, MCT1, 2, and 4 were up-regulated with different expression levels; MCT1 and MCT4 were more widely expressed in GC cell lines compared with MCT2. Inhibition of MCTs by siRNA or AR-C155858 reduced cell viability and lactate uptake in GC cell lines. The effect of inhibition of MCTs on tumor growth was also confirmed in xenograft models. Furthermore, MCT inhibition in GC cells increased the sensitivity of cells to radiotherapy or chemotherapy. Compared with normal gastric tissue, no significant alterations of expression levels in tumors were identified for MCT1 and MCT2, whereas a significant increase in MCT4 expression was observed. Most importantly, MCT4 was highly overexpressed in malignant cells of acsites and its silencing resulted in reduced tumor cell proliferation and lactate uptake in malignant ascites. Our study suggests that MCT4 is a clinically relevant target in GC with peritoneal carcinomatosis.

Clinicopathologic Features and Long-Term Outcomes of Elderly Breast Cancer Patients: Experiences at a Single Institution in Korea.

PURPOSE: The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. MATERIALS AND METHODS: Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables. RESULTS: Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer-specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. CONCLUSION: Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.

The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: a retrospective analysis.

BACKGROUND: KRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy. METHODS: Patients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6 year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients' outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis. RESULTS: KRAS mutations were identified in 37.8% of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank p = 0.425 for TTR; log-rank p = 0.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (G > A vs. G > T vs. G > C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung. CONCLUSIONS: KRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.

The Impacts of Inclusion in Clinical Trials on Outcomes among Patients with Metastatic Breast Cancer (MBC).

BACKGROUND: Metastatic breast cancer (MBC) remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes. METHODS: We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery) metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center. RESULTS: Among the 806 patients selected for inclusion, 188 (23%) had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000-2004), clinical trial enrollment significantly increased over time (n = 103 for 2005-2009, P = 0.024; n = 110 for 2010-2014, P = 0.046). Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI), and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59-0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC). CONCLUSIONS: Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival.

Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non-Small Cell Lung Cancer.

T790M mutation is most common resistant mechanism to epidermal growth factor receptor gene (EGFR) tyrosin kinase inhibitor (TKI). Several third-generation EGFR-mutant selective TKI, such as AZD9291 (AstraZeneca), Rociletinib (Clovis), or HM61713 (Hanmi) have been developed. Acquired resistant C797S mutation was known to be one of the resistance mechanisms of AZD9291, which has not been reported for HM61713 yet. This is the first case report of C797S mutation as resistance mechanism of HM61713.

Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. MATERIALS AND METHODS: Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. RESULTS: Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. CONCLUSION: PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.