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Background: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). Methods: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. Results: Forty‐eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty‐nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). Conclusion: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background: This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC). Methods: This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease‐free survival (DFS). Results: In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P <.05). Our new N classification proposed three categories: N0 (0 LN+), N1 (1 LN+), and N2 (≥2 LN+ or ENE). The C‐index of our N classification showed improvement in OS prediction (0.768) compared with the AJCC seventh (0.743) and eighth (0.756) edition N classifications. Conclusions: Our proposed N classification incorporating LN+ number and ENE may improve prediction of post‐treatment survival and recurrence in patients with SGC. [ABSTRACT FROM AUTHOR]

Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression. We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0–3) multiplied by proportion (0–100), ranged from 0 to 300. Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed. Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients. [ABSTRACT FROM AUTHOR]

Objective: Histological grade is the most important factor for defining treatment strategies and predicting prognosis for salivary gland carcinoma (SGC). We examined factors affecting long-term recurrence and survival among intermediate-grade SGC (IGSGC) patients to define optimal treatment modalities and outcomes. Methods: We reviewed the clinical and pathological data on 108 IGSGC patients who underwent definitive surgery with or without postoperative radiotherapy. We compared treatment outcomes by treatment strategies such as surgical extent for the primary tumor, neck dissection, or postoperative radiotherapy. Results: During a 103-month median follow-up, local, regional, and distant recurrences were detected in 14 (13.0%), 3 (2.8%), and 21 (19.4%) patients, respectively. The 10-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 83.1, 76.0, and 80.1%, respectively. Multivariate analyses identified a nonparotid primary site as an independent prognostic factor for LRC (p = 0.018). Adenoid cystic carcinoma and a positive pN classification were significantly unfavorable prognostic factors for DMFS (p = 0.025 and p = 0.030, respectively); overall advanced stage was an independent prognostic factor for OS (p = 0.020). Surgical extent, elective neck dissection, and postoperative adjuvant radiotherapy did not significantly affect treatment outcomes. Conclusion: Patients with early-stage IGSGC of parotid origin can achieve favorable treatment outcomes with conservative surgery alone. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) generally has an indolent course and favorable prognosis. However, an optimal treatment strategy for asymptomatic PTC is not clear. We compared the recurrence and survival outcomes of patients with asymptomatic and symptomatic PTC and identified the associated risk factors. Materials and Methods: Patients with previously untreated PTC of size ≤2 cm and who underwent curative surgery were included in this analysis. Asymptomatic PTC was defined as a tumor detected only by ultrasonography, computed tomography (CT), magnetic resonance imaging, and/or 18F-fluorodeoxyglucose positron emission tomography/CT. Clinical factors, operative and pathologic findings, and posttreatment outcomes were compared between the aforementioned two groups. Univariate and multivariate analyses were performed to identify the factors associated with recurrence-free survival (RFS) and overall survival (OS). Results: Out of 1419 patients, 1259 patients (88.7%) were asymptomatic. Patients with symptomatic PTC had significantly larger tumor size, palpability, extrathyroidal extension, high tumor and node stages, and were more likely to undergo treatment with radioactive iodine therapy compared with patients with asymptomatic PTC ( p < 0.05 each). Recurrence was significantly higher in the symptomatic PTC group than in the asymptomatic group ( p < 0.001). Asymptomatic PTC was an independent predictor of RFS and OS and had higher five-year rates than those associated with symptomatic tumors: 97.3% and 90.6% for RFS ( p < 0.001) and 99.4% and 96.9% for OS ( p < 0.001), respectively. Conclusion: Symptomatic PTC is associated with higher recurrence and lower overall survival rates than asymptomatic PTC. Symptomatic PTC may require total thyroidectomy and close posttreatment surveillance. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Methods: Of 162 patients with OSCC evaluated preoperatively by F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). Results: The median (range) SUV, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV ( P = 0.018) and TLG ( P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV ( P = 0.001) and TLG ( P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV ( P = 0.001), TLG ( P = 0.002) and the involved resection margin ( P = 0.007) were independent predictive factors for OS. Conclusion: Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC. [ABSTRACT FROM AUTHOR]

Conclusions: p16 immunohistochemistry (IHC) status correlated with less exposure to smoking and/or alcohol in Korean patients with locally advanced tonsillar squamous cell carcinoma (TSCC), and was an independent prognostic factor for survival. Objective: TSCC is more likely to be human papillomavirus (HPV)-positive than other head and neck squamous cell carcinoma (HNSCC) subtypes. The objective of this study was to ascertain the HPV status of TSCC in Korean patients and to determine its relationship with clinical parameters and prognosis. Methods: The locally advanced TSCCs of 79 patients who were treated between 2000 and 2008 were tested by p16 IHC and HPV in situ hybridization (ISH) with a tissue microarray. Results: Sixty-three patients (80%) were positive for p16 IHC, while 54 (68%) were positive by HPV ISH. p16 IHC status correlated significantly with lower exposure to smoking and alcohol ( p < 0.05) but did not correlate with T and N stage classification, histological differentiation, age, or gender. The p16-positive group had a significantly higher 5-year overall survival rate in comparison with the p16-negative group (78% vs 63%, hazard ratio (HR) = 0.347, 95% CI = 0.14, 95% C p = 0.025). p16 IHC was a favorable independent prognostic factor for overall survival, even after adjustment for age and T stage (HR = 0.283, 95% CI = 0.103, 95% p = 0.015). [ABSTRACT FROM AUTHOR]

Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1–155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5–103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR. [Copyright &y& Elsevier]

Summary: Tumor hypoxia is associated with poorer outcome in patients with head and neck carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer. We evaluated whether hypoxia biomarkers and clinicopathologic variables were prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection and neck dissection. Tissue samples were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1α, HIF-2α, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR). Locoregional control and survival rates were calculated by the Kaplan-Meier method, and prognostic factors were calculated from uni- and multivariate analyses. Tumor thickness was correlated with expression of CA-9 and GLUT-1 and nodal classification was correlated with GLUT-1 expression. The nodal metastasis rate was 51%, and the 5-year locoregional control and disease-specific survival (DSS) rates were 59% and 69%, respectively. Univariate analysis showed that HIF-1α and EPOR expression were significantly related to DSS. Multivariate analysis showed that EPOR expression was an independent predictor of DSS (P =0.030). EPOR expression may be an independent predictor for DSS in patients with T2-staged SCC of the oral tongue. [Copyright &y& Elsevier]

Background: Human papillomavirus (HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC.Methods: We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type.Results: HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR=19.8; P=0.040) and low CD8/CD4 ratio (HR=7.7, P=0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR=15.2; P=0.03) and low CD8 (+)/CD4 (+) ratio (HR=3.3; P=0.04).Conclusions: The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems.Materials and Methods: This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients.Results: Median follow-up period was 75 months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P < 0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P < 0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group.Conclusion: The revised staging system may not provide an improved risk stratification for survival of HNSTS patients. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. This study was designed to identify valuable prognosticator in MEC. Histopathologic analysis, immunohistochemistry, and in situ hybridization were performed on 128 carcinomas diagnosed as MEC of the head and neck. Expression of p16 was found in 96 cases (76%) of MEC. Lymphoid stroma was identified in 63 cases (49%). There was a significant correlation between loss of p16 expression and absence of lymphoid stroma. Expression of p16 was significantly associated with better clinicopathologic features. Lymphoid stroma was significantly associated with lower histologic grade. Overall survival (OS) was significantly longer in cases expressing p16 (P = 0.00096) and lymphoid stroma cases (P = 0.0023). Multivariate analysis revealed loss of p16 expression as negative prognosticators for OS. Our data showed p16 expression and the presence of lymphoid stroma were significantly associated with good clinical outcomes. Testing for these factors could lead to better prognostication and treatment of patients with MEC. [ABSTRACT FROM AUTHOR]

Background Accurate assessment of the extent of cancer is essential for appropriate treatment planning and outcome prediction. This study prospectively evaluated whether adding 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) to the routine initial staging practice in head and neck squamous cell carcinoma (HNSCC) improved management and prognosis. Methods All consecutive patients with newly diagnosed HNSCC who presented in October 2010 – December 2012 underwent conventional workups (CWU) followed by PET/CT. The clinical stage and management plans before and after PET/CT were compared. PET/CT was deemed to have no/low, moderate, and high impact on management planning depending on whether PET/CT changed the treatment modality or goal. The appropriateness of PET/CT staging and management impact was confirmed by histopathology and clinical follow-up, and its association with survival was analysed. Findings Of the 248 patients, PET/CT changed the Tumour Node Metastasis (TNM) classification in 79 (31.9%). In the patients with discordant staging, PET/CT staging was significantly more sensitive and accurate than CWU staging (both P < 0.001). PET/CT had high or moderate impact on management in 39 (15.7%) patients. Patients with PET/CT upstaged disease had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with no CWU-stage changes (3-year PFS = 56.8% versus 74.5%, P = 0.043; 3-year OS = 61.3% versus 85.3%, P = 0.006). Multivariate analyses revealed that PET/CT staging and second primary cancer were independent predictive factors for both PFS and OS ( P < 0.05, each). Interpretations 18 F-FDG PET/CT added important staging information that improved management and prognostic stratification in HNSCC. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). Methods and Materials: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. Results: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). Conclusion: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated. [Copyright &y& Elsevier]

Abstract: We aimed to assess the ability of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan to predict pathologic complete response (CR) and survival in patients with oesophageal cancer treated with preoperative chemoradiotherapy (CRT). The study cohort consisted of 62 consecutive patients with operable oesophageal cancer who were treated with preoperative CRT followed by oesophagectomy. Endoscopy, computed tomography (CT) and PET were performed before and after CRT. Of the 62 patients, 56 (90%) patients responded to preoperative CRT. FDG-PET-determined complete metabolic response (CMR) was achieved by 33 patients (54.1%), whereas pathologic CR was achieved by 28 patients (45.2%). Compared with endoscopic biopsy or CT scan, CMR by FDG-PET showed the highest correlation with pathologic CR (concordance, 71%). At a median follow-up of 19.3 months (range, 3.9–57.1 months), median overall survival (OS) was not reached in patients with CMR compared to 22.4 months in patients who did not achieve CMR. Median disease free survival (DFS) was not reached in patients with CMR compared to 17.4 months in patients who did not achieve CMR. By multivariate analysis, CMR by FDG-PET was significantly associated with better DFS and OS (P =0.006, P =0.033, respectively). The variables associated with pre-CRT PET scan were not predictive of survival. In conclusion, CMR by FDG-PET has a significant correlation with pathologic CR and can predict the long-term outcome in oesophageal cancer patients undergoing CRT. Although surgery is standard treatment for respectable oesophageal cancer, currently even in patients with CMR, the addition of 18F-FDG-PET could be used to select the patient subgroup not requiring surgery. [Copyright &y& Elsevier]