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Purpose: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach. Methods: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed. Results: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape. Conclusion: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth. [ABSTRACT FROM AUTHOR]

Background: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. Methods: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. Results: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160–23.190) in non-pCRw/mic group and 5.970 (1.840–19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130–34.090) in non-pCRw/mic group, 9.120 (2.850–29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230–21.500) without statistical significance (p = 0.486). Conclusions: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group. [ABSTRACT FROM AUTHOR]

Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T‐cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD‐1, PD‐L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD‐L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD‐1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD‐1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD‐L1 (p < 0.0001), PD‐1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD‐1, and PD‐L1 might have prognostic values in patients with pancreaticobiliary tract cancers. [ABSTRACT FROM AUTHOR]

Appropriate postoperative antibiotic treatment in patients with infective endocarditis (IE) reduces the risks of recurrence and mortality. However, concerns about adverse drug reactions arise due to prolonged antibiotic usage. Therefore, we compared the recurrence and mortality rates according to the duration of postoperative antibiotic therapy in patients with IE. From 2005 to 2017, we retrospectively reviewed 416 patients with IE treated at a tertiary hospital in South Korea; among these, 216 patients who underwent heart valve surgery and received appropriate antibiotics were enrolled. The patients were divided into two groups based on the duration of usage of postoperative antibiotic therapy; the duration of postoperative antibiotic therapy was more than two weeks in 156 patients (72.2%) and two weeks or less in 60 patients (27.8%). The primary endpoint was IE relapse. The secondary endpoints were 1-year IE recurrence, 1-year mortality, and postoperative complication rates. The median age was 53 (interquartile range: 38–62) years. The relapse rate of IE was 0.9% (2/216). There was no statistical difference in relapse (0.0% vs. 1.3%, p = 0.379), 1-year recurrence (1.7% vs. 1.3%, p = 0.829), or 1-year mortality (10.0% vs. 5.8%, p = 0.274) between patients with postoperative antibiotic administration of two weeks or less versus more than two weeks. The duration of postoperative antibiotic therapy did not affect the 1-year mortality rate (log-rank test, p = 0.393). In conclusion, there was no statistically significant difference in recurrence, mortality, or postoperative complications according to the duration of postoperative antibiotic therapy. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Tumor shape as a prognostic factor for the growth of intracanalicular vestibular schwannoma: a long-term observational study" published in the European Archives of Oto-Rhino-Laryngology. The correction states that the captions for Figures 1 and 2 in the original article were mistakenly swapped. The correct captions for Figure 1 show two cases of intracanalicular vestibular schwannoma with different shapes, while Figure 2 shows the association of initial tumor size with tumor growth and cerebellopontine angle extension. The correction notice also includes a statement from the publisher, Springer Nature, emphasizing their neutrality regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is the most common neoplasm originating at the base of the tongue or in the tonsils or soft palate. In this study, we investigated the prognostic value of FOXP3+ regulatory T cells in OPSCC. Methods: Tumor tissues of patients with locally advanced OPSCC were analyzed using quantitative multiplex immunohistochemistry. Staining of CD8+ T cells, conventional CD4+FOXP3- T cells (Tconv cells), CD4+FOXP3+ regulatory T cells (Treg cells), CD20+ B cells, and CD68+ macrophages was performed, and cell density was evaluated in both the tumor and its stroma. Results: Among the 71 patients included in this study, males constituted 93.0% of the cohort, and the median age was 59 years (range: 42–80 years). A total of 56 patients (78.9%) had a smoking history, and 53 (74.6%) patients were positive for human papillomavirus (HPV). The most frequent site of OPSCC was the tonsils (70.4%), followed by the base of the tongue (25.4%). The proportion of Treg cells was lower in the tumors of patients with HPV than in those of patients without HPV. Patients with OPSCC whose tumor Treg cell levels were above the median had longer relapse-free survival (RFS) periods than those with tumor Treg cell levels below the median (HR, 0.12; 95% CI, 0.03–0.46; p = 0.02). Our multivariate analysis identified high Treg levels (HR, 0.13; 95% CI, 0.02–1.00; p = 0.05) as an RFS factor that predicted a good prognosis. Conclusions: Our results demonstrated that high Treg cell density in locally advanced OPSCC tumors was correlated with longer RFS. [ABSTRACT FROM AUTHOR]

Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity. We used immunohistochemistry, ELISA, qPCR, and flow cytometry to investigate the role of PVR in MM. PVR was highly expressed in patients with MM, and membrane PVR expression showed a significant correlation with soluble PVR levels. PVR expression was significantly associated with the Revised-International Staging System stage, presence of extramedullary plasmacytoma and bone lesion, percentage of bone marrow plasma cells (BMPCs), and β2-microglobulin levels, suggesting a possible role in advanced stages and metastasis. Furthermore, TIGIT expression was significantly correlated with the percentage of BMPCs. Patients with high PVR expression had significantly shorter overall and progression-free survival, and PVR expression was identified as an independent prognostic factor for poor MM survival. These findings indicate that PVR expression is associated with MM stage and poor prognosis, and is a potential prognostic marker for MM. [ABSTRACT FROM AUTHOR]

Background: Cereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers. Methods: We evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6. Results: In the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher β2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma. Conclusion: This nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians. [ABSTRACT FROM AUTHOR]

The evaluation of PD‐L1 expression alone has limitations in predicting clinical outcome in immune‐checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associated with response in patients with advanced non‐small cell lung cancer (NSCLC) treated with PD‐1 blockade. Immune cell distribution was heterogeneous and the most dominant immune cell type was T cells. Patients with durable clinical benefit (DCB) showed significantly higher PD‐L1 expression. The ratio of tumor/stroma region of T cell, B cell, and macrophage was significantly higher in patient with DCB. High intratumoral T‐ and B‐cell density (≥median) was associated with DCB in the low PD‐L1 expression (<50%) group. In univariate analyses, the overall survival (OS) benefit was shown according to intratumoral B‐cell density (p = 0.0337). The incidence of hyperprogressive disease (HPD) was 13.0%. The Chi‐square test revealed that HPD was significantly associated with intratumoral B‐cell density but not T‐cell or macrophage density. Our results demonstrate different predictive and prognostic values for infiltrating immune cells in tumor tissue, which may help in selecting patients for ICI. [ABSTRACT FROM AUTHOR]

Background: Immediate breast reconstruction with tissue expander in breast cancer patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander.Methods: We conducted a retrospective study of 1081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1022 patients (94.5%).Results: In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications (p < 0.001). Chemotherapy (p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications.Conclusions: IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR.Trial Registration: Patients were selected and registered retrospectively, and medical records were evaluated. [ABSTRACT FROM AUTHOR]

The Ki-67 labeling index (LI) is an important prognostic factor in breast carcinoma. The Ki-67 LI is traditionally calculated via unaided microscopic estimation; however, inter-observer and intra-observer variability and low reproducibility are problems with this visual assessment (VA) method. For more accurate assessment and better reproducibility with Ki-67 LI, digital image analysis was introduced recently. We used both VA and automated digital image analysis (ADIA) (Ventana Virtuoso image management software) to estimate Ki-67 LI for 997 cases of breast carcinoma, and compared VA and ADIA results. VA and ADIA were highly correlated (intraclass correlation coefficient 0.982, and Spearman’s correlation coefficient 0.966, p<0.05). We retrospectively analyzed cases with a greater than 5% difference between VA and ADIA results. The cause of these differences was: (1) tumor heterogeneity (98 cases, 56.0%), (2) VA interpretation error (32 cases, 18.3%), (3) misidentification of tumor cells (26 cases, 14.9%), (4) poor immunostaining or slide quality (16 cases, 9.1%), and (5) Estimation of non-tumor cells (3 cases, 1.7%). There were more discrepancies between VA and ADIA results in the group with a VA value of 10–20% compared to groups with <10% and ≥20%. Although ADIA is more accurate than VA, there are some limitations. Therefore, ADIA findings require confirmation by a pathologist. [ABSTRACT FROM AUTHOR]

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1-4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. Methods: A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). Results: PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2–12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1–11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2–87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. Conclusion: In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding the role of anthropometrics in prostate cancer survival is inconsistent. We examined the associations between anthropometric measures and survival outcomes.Methods: Men diagnosed with prostate cancer (n=987) were recruited into a population-based case-control study between 1997 and 2000 then a prospective cohort study between 2000 and 2002 where anthropometric measurements (weight, height, body mass index, waist circumference, waist-hip ratio) were taken and participants were followed up to 19 years for survival outcomes. Cox proportional hazards were used to examine these associations.Results: Survival analyses suggested no clear pattern of associations between post-diagnosis anthropometric measurements and all-cause mortality, prostate-specific mortality, first recurrence/progression or new primary cancer.Conclusions: We did not find a significant trend relating anthropometrics to survival outcomes after prostate cancer diagnosis. Continued assessment of objective measurements of body composition over the life-course is warranted to determine true associations between anthropometrics and survival after prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Given that immune-related response in non-small cell lung cancer (NSCLC) has not been well evaluated, we assessed tumor response using the response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1) and immune-related response criteria (irRC) to identify atypical responses in patients with advanced NSCLC treated with immunotherapeutic agents.Methods: Patients received immune-checkpoint inhibitors (pembrolizumab, atezolizumab, nivolumab, and durvalumab plus tremelimumab) to treat metastatic or recurrent NSCLC after failed platinum-based chemotherapy. Tumor response was assessed according to both RECIST v1.1 and irRC.Results: Responses by 41 patients were analyzed. The overall response rate (ORR) was 29.2% (95% CI 17.6-44.5) assessed by RECIST v1.1 and 34.1% (95% CI 21.6-49.4) by irRC, showing similar results from the two methods (p = 0.923). Two patients (4.9%) were defined as having progressive disease as assessed by RECIST but not by irRC. The patients eventually experienced tumor regression, suggesting delayed pseudoprogression. For all patients, the median PFS was 5.1 months (95% CI 3.4-6.7) and OS was 18.3 months (95% CI 6.7-29.8). In multivariate analysis, ex- or current smokers (HR 0.34, p = 0.14) and EGFR mutation negativity (HR 0.16, p = 0.05) were associated with significantly longer PFS.Conclusion: Our study found that pseudoprogression was not frequently observed in NSCLC. Conventional RECIST v1.1 might underestimate the benefit of immune-checkpoint inhibitors. Given the small number of patients studied, further study is warranted on whether treatment with immune-checkpoint inhibitors beyond RECIST progression benefits patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung.Methods: Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of > 5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500 mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity.Results: All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%-23.8%) and the disease control rate was 50% (95% CI, 30.8%-69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months, ≥ 5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95% CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95% CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).Conclusions: Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted. Cancer 2016;122:3024-3031. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The efficacy and/or tolerability of pazopanib in patients with metastatic renal cell carcinoma (mRCC) have been found to differ in Western and Asian populations. This retrospective multicenter study analyzed the results of first-line pazopanib treatment in 93 consecutive patients with mRCC who were treated at the medical oncology departments of three tertiary cancer centers in Seoul, Korea.Methods: The decision to administer pazopanib as first-line therapy was at the discretion of the treating physician in all patients with mRCC. Patients enrolled in clinical trials were excluded to ensure that the results would reflect real-world outcomes representative of daily clinical settings. All patients received 800 mg/day pazopanib. Outcomes included response rate, progression-free survival (PFS), overall survival (OS), and safety.Results: The 93 patients included72 (77 %) male and 21 (23 %) female individuals, of median age 65 years (range, 19-84 years). The median number of metastatic sites per patient was two (range, 1-5), with the lungs being the most frequently involved site. Most patients had favorable (n = 46) or intermediate (n = 36) risk as determined by Memorial Sloan Kettering Cancer Center criteria. Pazopanib was generally welltolerated: the major hematologic adverse effect was grade 1/2 anemia (14 %); and the most frequently observed non-hematologic toxicity was grade 1/2 mucositis (22 %), followed by hair discoloration and hypertension. Of the 93 patients, three (3 %) showed complete response, 52 (56 %) showed partial response, and 21 (23 %) showed stable disease, making the objective response rate 59 % and the disease control rate 82 %. At a median follow-up of 21 months, the estimated median PFS and OS were 12.2 months (95 % confidence interval, 7.1-17.4 months) and 21.9 months (95 % confidence interval, 12.9-30.9 months), respectively.Conclusions: In this retrospective study, first-line therapy with pazopanib demonstrated clinically relevant efficacy and tolerability in unselected real-world Korean patients with mRCC. OS and PFS of these Korean patients were similar to those reported in phase III trials. [ABSTRACT FROM AUTHOR]

Context The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma ( MTC). Objective We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors. Design This was a retrospective analysis from 1982 to 2012. Patients Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012). Measurements These included recurrence and mortality as well as biochemical remission ( BCR) of serum calcitonin. Results Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po- BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po- BCR was the strongest predictive factor associated with recurrence (hazard ratio [ HR] = 58·04, 95% CI 7·14-472·11; P < 0·001). Male gender ( HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 cm ( HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis ( HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality. Conclusions Clinicopathological characteristics and recurrence of MTC improved with time. Po- BCR was the best predictive factor for recurrence-free survival. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis. Epidermal growth factor receptor (EGFR) overexpression in TNBC indicates poor prognosis. However, there is no previous study of the relationship between expression of the entire human epidermal growth factor receptor (HER) family genes and patient prognosis in TNBC. Accordingly, we investigated the expression profiles of HER family genes in patients with TNBC to determine the prognostic value and clinical implications of HER family expression.Methods: We used the nCounter expression assay (NanoString®) to measure the expression of EGFR, erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, and estrogen receptor 1 (ESR1) genes using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Our data were validated using a separate cohort of 84 TNBC patients.Results: A total of 203 TNBC patients who received adjuvant chemotherapy after curative surgery from 2000 to 2004 formed the training set. The 84 TNBC patients in the validation consort were selected from breast cancer patients who received curative surgery since 2005 to 2010. Analysis of the expression profiles of the HER family genes in TNBC tissue specimens revealed that increased expression of ERBB4 was associated with poor prognosis according to survival analysis (5-year distant relapse free survival [5Y DRFS], low vs. high expression [cut-off: median]: 90.1% vs. 80.2%; p = 0.022). This trend was also observed in the validation set of TNBC patients (5Y DRFS, low vs. high: 69.4% vs. 44.7%; p = 0.053). In a multivariate Cox regression model, ERBB4 expression was identified as a indicator of long-term prognosis in patients with TNBC.Conclusions: The expression profile of ERBB4, a member of the HER family, might serve as a prognostic marker in patients with TNBC. [ABSTRACT FROM AUTHOR]

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are frequently found in brain tumors, and the resulting onco–metabolite, 2–hydroxyglutarate (2HG), has been suggested to be a potential diagnostic and prognostic biomarker of the diseases. Indeed, recent studies have demonstrated the feasibility of non–invasively detecting 2HG by using proton magnetic resonance spectroscopy (1H–MRS). Due to severe spectral overlaps of 2HG with its background metabolites and spectral baselines, however, the majority of those previous studies employed spectral editing methods with long echo times (TEs) instead of the most commonly used short TE approach with spectral fitting. Consequently, the results obtained with spectral editing methods may potentially be prone to errors resulting from substantial signal loss due to relaxation. Given that the spectral region where the main signal of 2HG resides is particularly sensitive to spectral baseline in metabolite quantification, we have investigated the impact of incorporating voxel–specifically measured baselines into the spectral basis set on the performance of the conventional short TE approach in 2HG detection in rodent models (Fisher 344 rats; n = 19) of IDH1/2 mutant–overexpressing F98 glioma at 9.4T. Metabolite spectra were acquired (SPECIAL sequence) for a tumor region and the contralateral normal region of the brain for each animal. For the estimation of spectral baselines metabolite–nulled spectra were obtained (double–inversion–recovery SPECIAL sequence) for each individual voxels. Data were post–processed with and without the measured baselines using MRUI and LCModel—the two most widely used data post–processing packages. Our results demonstrate that in–vivo detection of 2HG using the conventional short TE approach is challenging even at 9.4T. However, incorporation of voxel–specifically measured spectral baselines may potentially improve its performance. Upon more thorough validation in a larger number of animals and more importantly in human patients, the potential utility of the proposed short TE acquisition with voxel–specific baseline measurement approach in 2HG detection may need to be considered in the study design. [ABSTRACT FROM AUTHOR]

Purpose PBRM1 , a SWI/SNF chromatin remodeling complex gene, is the second most frequently mutated gene in clear cell renal cell carcinoma. Although previous studies showed that loss of PBRM1 expression was associated with poor prognosis of renal cell carcinoma, these studies were performed on earlier stage, surgically resected renal cell carcinoma. Accordingly we investigated the PBRM1 expression profile in patients with stage IV renal cell carcinoma to determine the prognostic and predictive value of PBRM1. Materials and Methods A total of 53 patients with stage IV or recurrent renal cell carcinoma were included in analysis. Immunohistochemistry was performed for PBRM1 using formalin fixed, paraffin embedded tissue microarrays. Results Overall 25 of 53 patients (47%) had high PBRM1 expression in the tumor. On analysis comparing survival rates and treatment responses of patients with renal cell carcinoma high PBRM1 expression in the tumor was associated with reduced overall survival (mean ± SD 45.0 ± 4.8 vs 23.0 ± 8.3 months, p = 0.022, and for clear cell renal cell carcinoma 46.0 ± 4.1 vs 27.0 ± 6.7 months, p = 0.053). Regarding treatment outcome higher PBRM1 expression tended to indicate a poorer response to mTOR inhibitor (median progression-free survival 3.0 ± 0.2 vs 1.9 ± 2.3 months, p = 0.101). On subgroup analysis according to the Heng score this trend was more significant in the higher risk group than in the low risk group (progression-free survival for low risk mean 11.6 ± 1.2 vs 7.4 ± 7.4 months, p = 0.157, and for intermediate risk 7.1 ± 24.7 vs 2.9 ± 0.9 months, p = 0.060). Conclusions Our study shows that the PBRM1 expression level is a potential prognostic marker for advanced renal cell carcinoma. We suggest that determining the tumor PBRM1 expression level may be used to inform the prognosis and treatment of metastatic renal cell carcinoma. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the pre- and post-treatment neutrophil to lymphocyte ratio (pre- and post-NLR) in combination with immunologic profiles in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). A total of 447 newly diagnosed patients with DLBCL treated with R-CHOP were analyzed retrospectively. A pre-NLR ≥ 3 was independently associated with poor progression-free survival (PFS) (hazard ratio [HR] = 2.19, p < 0.001) and overall survival (OS) (HR = 2.89, p < 0.001). In patients with high pre-NLR, reduction of the post-NLR to < 3 after R-CHOP was correlated with improved survival. Low pre-NLR (< 3) was also associated with a higher number of peripheral CD19 + lymphocytes ( p = 0.049) and NK cells ( p = 0.031). In conclusion, a pre-NLR ≥ 3 was an independent prognostic factor for PFS and OS in patients with DLBCL treated with R-CHOP. [ABSTRACT FROM AUTHOR]

Background: Despite the advances in acute myeloid leukemia (AML) treatment, the prognosis of elderly patients remains poor and no definitive treatment guideline has been established. In the present study, we aimed to evaluate the effectiveness of intensive chemotherapy in elderly AML patients and to determine which subgroup of patients would be most responsive to the therapy. Methods: We retrospectively analyzed 84 elderly patients: 35, 19, and 30 patients were administered intensive chemotherapy, low-dose chemotherapy, and supportive care, respectively. Results: Among those who received intensive chemotherapy, there were 17 cases of remission after induction chemotherapy; treatment-related mortality was 22.9%. The median overall survival was 7.9 months. Multivariate analysis indicated that the significant prognostic factors for overall survival were performance status, fever before treatment, platelet count, blast count, cytogenetic risk category, and intensive chemotherapy. Subgroup analysis showed that intensive chemotherapy was markedly effective in the relatively younger patients (65-70 years) and those with de novo AML, better-to-intermediate cytogenetic risk, no fever before treatment, high albumin levels, and high lactate dehydrogenase levels. Conclusions: Elderly AML patients had better outcomes with intensive chemotherapy than with low-intensity chemotherapy. Thus, appropriate subgroup selection for intensive chemotherapy is likely to improve therapeutic outcome. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Although the optimal treatment of frail glioblastoma patients is still controversial, previous randomized trials have excluded such patients. This study aimed to evaluate the feasibility and safety of hypofractionated radiotherapy (RT) with concomitant temozolomide for glioblastoma patients with poor prognostic features. Methods: We retrospectively reviewed 33 glioblastoma patients who underwent postoperative hypofractionated chemoradiotherapy. The patient criteria were either ≥70 years or <70 years with one or more risk factors: pre-RT performance status (ECOG score) ≥3, biopsy only, or rapid disease progression immediately after surgery. The median RT dose was 45 Gy (range 30-45) with a fraction size of 3 Gy. Results: The median age was 66.0 years. Eighteen patients (55 %) had poor pre-RT performance status (ECOG ≥3), and 16 patients (48 %) underwent stereotactic biopsy only. The median overall survival (OS) and progression-free survival were 10.6 and 7.5 months, respectively. Poor pre- and post-RT performance status [hazard ratio (HR) 3.12, 95 % confidence interval (CI) 1.21-8.07 and HR 4.51, 95 % CI 1.44-14.12, respectively] and no pseudoprogression (HR 5.43, 95 % CI 1.58-18.61) were associated with poorer OS. While acute neurologic symptoms were reported in 5 patients (15 %), toxicity profiles were acceptable without treatment-related aggravation of performance status. Conclusions: Concurrent chemoradiotherapy with temozolomide, the current standard treatment after surgery for glioblastoma, could be shortened without increasing side effects for patients with poor prognostic features. [ABSTRACT FROM AUTHOR]

Background Concurrent endocrine therapy with chemotherapy had a concern of potential antagonism. However, gonadotropin-releasing hormone (GnRH) agonist has been used concurrently with chemotherapy to prevent premature ovarian failure for young breast cancer patients. The aim of this study was to determine the impact of concurrent use of GnRH agonists on relapse-free and overall survival, and to establish the oncologic safety of ovarian protection with GnRH agonists. Methods Premenopausal women aged between 20 and 40 years who received adjuvant chemotherapy for breast cancer from January 2002 to April 2012 were classified into two groups; One treated with GnRH agonists for ovarian protection during chemotherapy, and the other without ovarian protection. A propensity score matching strategy was used to create matched sets of two groups with age, pathologic stage, hormone receptor, and Her2 status. Results A total of 101 patients treated with concurrent GnRH agonist during chemotherapy were compared with 335 propensity score matched patients. Among them, 81.2% were younger than 35 years and 58.4% were hormone responsive. Survival analysis using stratified Cox regression showed that women treated with concurrent GnRH agonists had better recurrence-free survival (adjusted Hazard ratio 0.21, p = 0.009; unadjusted Hazard ratio 0.33, p = 0.034). Conclusions Ovarian protection using GnRH agonists can be safely considered for young women with breast cancer in terms of oncologic outcomes. Further studies are needed to assess the long-term outcomes of concurrent GnRH agonist use with chemotherapy. [ABSTRACT FROM AUTHOR]

This study investigated the prognostic factors of Castleman disease (CD) and focused specifically on multicentric CD (MCD). Seventy patients with CD were studied. Forty-three patients (61.5%%) had unicentric CD (UCD) and 27 patients (38.5%%) had MCD. Thirty-six patients with UCD (83.7%%) underwent surgical excision, and 25 patients with MCD (92.6%%) received systemic treatment, including corticosteroids and combination chemotherapy. In the patients with MCD, age >60 years and the presence of splenomegaly were prognostic factors for progression-free survival (hazard ratio [[HR]] 9.01, 95%% confidence interval [[CI]] 2.64--30.83 and HR 4.32, 95%% CI 1.16--16.09) as well as overall survival (OS) in MCD (HR 8.7, 95%% CI 2.83--26.84 and HR 2.9, 95%% CI 0.95--9.02, respectively). Patients ≤≤60 years old without splenomegaly showed better OS than patients >60 years old or with splenomegaly (71.4%% vs. 10.8%% for 5-year OS). MCD might be dissected clinically by the simple parameters of age and presence of splenomegaly. [ABSTRACT FROM AUTHOR]

Simple Summary: The high-grade pattern (micropapillary or solid pattern, MPSol) in lung adenocarcinoma affects the patient's poor prognosis. We aimed to develop a deep learning (DL) model for predicting any high-grade patterns in lung adenocarcinoma and to assess the prognostic performance of model in advanced lung cancer patients who underwent neoadjuvant of definitive concurrent chemoradiation therapy (CCRT). Our model considering both tumor and peri-tumoral area showed area under the curve value of 0.8. DL model worked well in independent validation set of advanced lung cancer, stratifying their survival significantly. The subgroup with a high probability of MPSol estimated by the DL model showed a 1.76-fold higher risk of death. Thus, our DL model can be useful in estimating high-grade histologic patterns in lung adenocarcinomas and predicting clinical outcomes of patients with advanced lung cancer who underwent neoadjuvant or definitive CCRT. We aimed to develop a deep learning (DL) model for predicting high-grade patterns in lung adenocarcinomas (ADC) and to assess the prognostic performance of model in advanced lung cancer patients who underwent neoadjuvant or definitive concurrent chemoradiation therapy (CCRT). We included 275 patients with 290 early lung ADCs from an ongoing prospective clinical trial in the training dataset, which we split into internal–training and internal–validation datasets. We constructed a diagnostic DL model of high-grade patterns of lung ADC considering both morphologic view of the tumor and context view of the area surrounding the tumor (MC3DN; morphologic-view context-view 3D network). Validation was performed on an independent dataset of 417 patients with advanced non-small cell lung cancer who underwent neoadjuvant or definitive CCRT. The area under the curve value of the DL model was 0.8 for the prediction of high-grade histologic patterns such as micropapillary and solid patterns (MPSol). When our model was applied to the validation set, a high probability of MPSol was associated with worse overall survival (probability of MPSol >0.5 vs. <0.5; 5-year OS rate 56.1% vs. 70.7%), indicating that our model could predict the clinical outcomes of advanced lung cancer patients. The subgroup with a high probability of MPSol estimated by the DL model showed a 1.76-fold higher risk of death (HR 1.76, 95% CI 1.16–2.68). Our DL model can be useful in estimating high-grade histologic patterns in lung ADCs and predicting clinical outcomes of patients with advanced lung cancer who underwent neoadjuvant or definitive CCRT. [ABSTRACT FROM AUTHOR]

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Purpose: We investigated the change in pupil size and pupil light reflex (PLR) using a pupillography capable of continuous measurement both during CPR and immediately following the return-of-spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) comatose patients in an emergency department.Methods: Pupil size and PLR were continuously measured both during CPR and immediately following ROSC until intensive care unit (ICU) admission. The changes in pupil sizes during CPR were categorized into three groups (no change - N, decreased - D, and increased - I groups).Results: Pupillography was applied for 118 and 60 patients during CPR and immediately following ROSC, respectively. Only two patients had a PLR during CPR. The number of patients included each group were 58 (N-group), 21 (D-group) and 39 (I-group). In the D-group, the proportion of witnessed arrest was higher than in the N-group and I-group (81% vs. 55% and 49%, respectively; p = 0.049). There were statistically significant shorter prehospital time in the D-group than the N-group and I-group (13 vs. 23 and 24 min, respectively; p = 0.012). PLR was observed immediately following ROSC in 14 patients. PLR was maintained in seven of these patients until admission to intensive care unit. Six of the seven patients who remained with PLR until ICU admission had survival to hospital discharge, and three of them had good neurological recovery.Conclusion: Our study demonstrated that measurement of the continuous pupillary response can be feasible. Patients with the presence of PLR following ROSC had better outcomes. [ABSTRACT FROM AUTHOR]

Background: The long-term prognosis of patients with variant angina presenting with aborted sudden cardiac death (ASCD) is unknown.Objectives: The purpose of this study was to evaluate the long-term mortality and ventricular tachyarrhythmic events of variant angina with and without ASCD.Methods: Between March 1996 and September 2014, 188 patients with variant angina with ASCD and 1,844 patients with variant angina without ASCD were retrospectively enrolled from 13 heart centers in South Korea. The primary endpoint was cardiac death.Results: Predictors of ASCD manifestation included age (odd ratio [OR]: 0.980 by 1 year increase; 95% confidence interval [CI]: 0.96 to 1.00; p = 0.013), hypertension (OR: 0.51; 95% CI: 0.37 to 0.70; p < 0.001), hyperlipidemia (OR: 0.38; 95% CI: 0.25 to 0.58; p < 0.001), family history of sudden cardiac death (OR: 3.67; 95% CI: 1.27 to 10.6; p = 0.016), multivessel spasm (OR: 2.06; 95% CI: 1.33 to 3.19; p = 0.001), and left anterior descending artery spasm (OR: 1.40; 95% CI: 1.02 to 1.92; p = 0.04). Over a median follow-up of 7.5 years, the incidence of cardiac death was significantly higher in ASCD patients (24.1 per 1,000 patient-years vs. 2.7 per 1,000 patient-years; adjusted hazard ratio [HR]: 7.26; 95% CI: 4.21 to 12.5; p < 0.001). Death from any cause also occurred more frequently in ASCD patients (27.5 per 1,000 patient-years vs. 9.6 per 1,000 patient-years; adjusted HR: 3.00; 95% CI: 1.92 to 4.67; p < 0.001). The incidence rate of recurrent ventricular tachyarrhythmia in ASCD patients was 32.4 per 1,000 patient-years, and the composite of cardiac death and ventricular tachyarrhythmia was 44.9 per 1,000 patient-years. A total of 24 ASCD patients received implantable cardioverter-defibrillators (ICDs). There was a nonsignificant trend of a lower rate of cardiac death in patients with ICDs than those without ICDs (p = 0.15).Conclusions: The prognosis of patients with variant angina with ASCD was worse than other patients with variant angina. In addition, our findings supported ICDs in these high-risk patients as a secondary prevention because current multiple vasodilator therapy appeared to be less optimal. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed the prognostic factors from 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease. Based on multivariate analysis, significant prognostic factors are recovery of neutropenia, respiratory infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on the fifth day after antibiotic treatment. From these variables, we derived a predictive model for the prognosis of febrile neutropenia using baseline serum albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy. Further studies in prospective setting are needed for the validation of this model. [Copyright &y& Elsevier]