Disease-specific Survival Rates Research Articles

Survival outcomes and establishment of a novel risk stratification system in patients with ovarian yolk sac tumors

ObjectiveTo evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST). MethodsThe recurrence-free survival (RFS), disease-specific survival (DSS), and prognostic factors were retrospectively evaluated in 151 OYST patients treated in our hospital between 2006 and 2022. A risk stratification system based on the identified prognostic factors was established. ResultsThe median follow-up time was 5.1 years, with a 5-year RFS and DSS rate of 75.5% and 91.2%, respectively. FIGO stage III-IV and the interval between treatment and normalization of AFP were two prognostic predictors. Significant differences in RFS and DSS (both P < 0.001) were identified between patients who had normalized AFP ≤ 3 and ≥ 4 cycles of chemotherapy, or among patients who had normalized AFP after ≤2, 3–4, and ≥ 5 cycles of chemotherapy. FIGO stage I – II and stage III–IV were scored as 0 and 2, respectively. AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. A total score of 0–1, 2–3, and ≥ 4 were stratified patients into low-risk (96 patients), intermediate-risk (35 patients), and high-risk groups (20 patients), respectively. Patients in three risk stratifications manifested significant differences in both RFS and DSS (P < 0.0001). ConclusionThis risk stratification system based on tumor stage and the interval between treatment and normalization of AFP may help to guide clinical management by dividing OYST patients into three risk groups.

SAT630 Analytical Validation Of A Telomerase Reverse Transcriptase (TERT) Promoter Mutation Assay

Abstract Disclosure: P. Iyer: None. R. Dadu: Advisory Board Member; Self; Exelixis, Inc., Bayer, Inc. Research Investigator; Self; Merck, Exelixis, Inc., AstraZeneca. A. Barque: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Z. Cleslei: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. H. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. S. Walsh: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. X. Zheng: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. M. Cabanillas: Advisory Board Member; Self; Exelixis, Inc., Bayer, Inc. Consulting Fee; Self; Lilly USA, LLC, Bayer, Inc. Research Investigator; Self; Genentech, Inc., Merck. TERT promoter mutations are relatively enriched in larger, aggressive thyroid cancers and these malignancies carry an independently decreased rate of disease free and disease specific survival when compared to thyroid cancers with wild type TERT promoter gene sequences. High quality analytical validation of a diagnostic test promotes confidence in the results which inform clinical decision making. TERT promoter mutation testing is now offered as a complement to Afirma Genomic Sequencing Classifier (GSC) testing in thyroid nodules that are not designated as molecularly benign. The Afirma TERT test was developed at Veracyte, Inc. based on the AmpliSeq-for-Illumina technology to detect TERT promoter variants C228T and C250T in genomic DNA (gDNA) extracted from patient thyroid fine needle aspirates (FNAs) sent for Afirma GSC testing, without any need for increased needle passes or sample volume. Herein, we describe the analytical performance of the Afirma TERT test. We examined the analytical sensitivity of the Afirma TERT test to varied input DNA amounts and the limit of detection (LOD) of variant allele frequency (VAF). We determined the negative percent agreement (NPA) and the positive percent agreement (PPA) of the Afirma TERT test against a reference primer pair. We also evaluated the analytical specificity from potential interfering substances such as RNA and blood gDNA. Further, the intra-run, inter-run and inter-laboratory reproducibility of the assay were examined. Analytical sensitivity analysis showed that the Afirma TERT test is tolerant to variation in DNA input amount (7-13 ng) and can detect expected positive TERT promoter variants down to 5% VAF LOD at 7ng DNA input with &amp;gt; 95% sensitivity. Both NPA and PPA were 100% against the reference primer pair. Analytical specificity studies demonstrated that the Afirma TERT test remains accurate in presence of 20% RNA or 80% blood gDNA for an average patient sample that typically has 30% VAF. The Afirma TERT test results are highly reproducible across different operators, runs, reagent lots, and laboratories. The Afirma TERT test also demonstrated a 100% confirmation rate when compared with an external NGS-based reference assay executed in a non-Veracyte laboratory. The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma GSC suspicious or Bethesda V/VI nodules. Presentation: Saturday, June 17, 2023

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink.

Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men ( p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups ( p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Multicenter Retrospective Study of Stereotactic Body Radiotherapy for Patients with Previously Untreated Initial Small Hepatocellular Carcinoma.

The effectiveness of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been shown in many studies and its therapeutic effect is similar to radiofrequency ablation (RFA). However, many of these studies were done in combination with transcatheter chemoembolization (TACE), for recurrent HCC, or on a small scale. To better understand the specific outcomes of SBRT for HCC, we conducted a multicenter retrospective analysis of SBRT for previously untreated initial HCC at Japanese Society of Clinical Oncology (JCOG) member hospitals. Patientswho underwent SBRT for HCC at JCOG member hospitals between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤ 3 nodules, ≤ 5 cm in diameter; (3) a Child-Pugh (CP) score of A or B; and (4) unsuitability for or refusal of standard treatment, such as surgery, transplantation, RFA and TACE. We evaluated the overall survival (OS), recurrence-free survival (RFS) which was defined as the first instance of intra-hepatic recurrence after SBRT, disease-specific survival (DSS) using Kaplan-Meier analysis. Using Grey's test, patients who died of other diseases were analyzed as competing risks to estimate the cumulative incidence of local recurrence (CLR). Adverse events directly related to SBRT also analyzed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range; 50-89 years), and the median tumor size was 23 mm (range; 6-50 mm). The median radiation dose was 40 Gy (range; 35-60 Gy) in five fractions (range; 4-8). The median follow-up period was 45 months (range; 0-103 months). There were three cases where follow-up was not possible due to unexpected events unrelated to SBRT, while the remaining 70 patients were successfully followed for at least six months. The 2 and 3year OS, RFS, DSS, and CLR rates were 84.3% (95% CI: 75.8-92.8%) and 69.9% (95% CI: 58.7-81%), 67.5% (95% CI: 56.0-79.0%) and 57.9% (95% CI: 45.2-70.5%), 95.1% (95% CI:89.7-100%)/87.6% (95% CI:78.8-96.3%), and 11.4% (95% CI: 5.3-20.0%) and 20.0% (95% CI: 11.2-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: one case of grade 3 laboratory toxicities, one case of grade 3 liver failure, one case of grade 3 portal tumor thrombosis, and one case of grade 4 duodenal ulcer. No grade 5 toxicities were observed. The results of our study demonstrate that SBRT for HCC is highly effective in achieving local control and is safe to administer. In addition, survival outcomes are favorable. SBRT is a promising treatment modality, especially for small HCCs for that is not suitable for standard treatment.

Hyperfractionated and Accelerated Reirradiation for Angiosarcoma Following Breast-Conserving Therapy: Long-Term Clinical Outcomes

Radiation-associated angiosarcoma (RAAS) of the breast is a highly aggressive tumor that can occur in women who have undergone breast conserving therapy (BCT). Due to the rare nature of the disease, no consensus exists regarding the optimum management. Historically, local control and disease-specific survival rates have been poor. In our study, we evaluate the long-term outcomes of a novel approach to treatment of this disease using hyperfractionated and accelerated reirradiation (HART). The fractionation scheme was motivated by the idea that rapidly-growing tumors would benefit from hyperfractionation and previously irradiated tissues would handle smaller doses per fraction better. With IRB approval, charts were retrospectively reviewed and follow-up was obtained for 15 patients treated with HART for angiosarcoma of the breast which developed after BCT between November 1997 and April 2017. Mean time to diagnosis of RAAS after BCT was 7.6 years (range, 4.3 - 11.0). Seven patients were treated for recurrent angiosarcoma after initial surgical resection and 8 were treated for de novo angiosarcoma. Patients were treated to a median of 60 Gy (range, 43-75) using two (n = 2) or three (n = 13) daily treatments. Mean time to beginning of HART after the diagnosis of angiosarcoma was 1.91 months (0.13-8.84). Median follow-up time was 137 months (range, 4.8 - 235.3). Seven patients were alive at the time of follow-up. Fifteen-year cause-specific survival and overall survival rates were 67% (95% CI: 43 - 89%) and 53% (95% CI: 29 - 76%), respectively. Six patients had progression of their disease after HART, none of which were in the radiation field. Two of these patients had evidence of metastatic disease before treatment began. Effects from radiation included skin, musculoskeletal, nerve, and lung toxicities, most of which resolved or were not clinically significant. This suggests that HART can provide relatively high rates of local control and overall survival for RAAS after BCT. Additionally, it highlights the need for multi-institution trials regarding treatment with HART in this disease. To our knowledge, this study contains the longest follow-up available for patients with RAAS of the breast.

RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis.

Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.

Gender Differences in Prognosis After Primary Resection for Retroperitoneal Liposarcoma.

Current evidence regarding gender difference in retroperitoneal liposarcoma (RLPS) is scarce, so we sought to investigate whether gender may affect prognosis after primary resection of RLPS. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify RLPS patients from January 1973 to December 2015. Multivariate cox proportional hazard analysis was adopted to generate adjusted hazard ratio (AHR) and 95% confidence intervals (CIs) of survival outcomes. In total, 2108 RLPS patients, including 971 women and 1137 men, were identified, with a median follow-up of 45.0 (17.0-92.0) months. The 5-year and 10-year overall survival rates were 50.5% and 31.5% for men and 60.4% and 42.5% for women. The 5-year and 10-year disease-specific survival rates for men and women were 71.5%, 57.3% and 76.3%, 62.1%, respectively. We found men were associated with an increased risk of all-cause mortality (AHR 1.3, 95% CI 1.0-1.6, P = .017) but not disease-specific mortality (AHR 1.2, 95% CI .9-1.6, P = .246). The subgroup analyses revealed that men were associated with an increased risk of all-cause mortality in patients with low-grade tumors (AHR 1.8, 95% CI 1.3-2.5) or patients who received non-radical resection (AHR 1.6, 95% CI 1.2-2.1). In the subgroup of low-grade tumors, men were also associated with an increased risk of disease-specific mortality (AHR 2.0, 95% CI 1.2-3.3). Men may have worse survival after primary resection of RLPS compared with women, especially in patients with low-grade tumors or patients who received non-radical resection. Gender-based disparities may deserve more attention in patients with RLPS.

The Prognostic Impact of Preoperative Osteopenia in Patients With Colorectal Cancer.

Osteopenia, a condition in which bone mineral density is lower than normal, is a noted risk factor that leads to a shortened healthy life expectancy. To investigate the prognostic impact of preoperative osteopenia in patients with colorectal cancer. This was a retrospective study. This study was conducted at a university hospital. A total of 1086 patients with stage I to III colorectal cancer who underwent curative resection. Osteopenia was evaluated with CT. Overall survival, disease-specific survival, and recurrence-free survival were the primary end points. Osteopenia was identified in 300 patients (27.6%). Compared with the no osteopenia group, the 5-year overall survival (74.0% vs 93.4%, p < 0.001), disease-specific survival (81.6% vs 97.2%, p < 0.001), and recurrence-free survival rates (57.1% vs 88.3%, p < 0.001) were significantly lower in the osteopenia group. Multivariate analyses showed that preoperative osteopenia was significantly associated with worse overall survival (HR: 4.135; 95% CI, 2.963-5.770; p < 0.001), disease-specific survival (HR: 7.673; 95% CI, 4.646-12.675; p < 0.001), and recurrence-free survival (HR: 5.039; 95% CI, 3.811-6.662; p < 0.001). The prognosis of the osteopenia group was poorer than that of the no osteopenia group in every stage: 5-year overall survival (stage I: 89.4% vs 96.9%, p = 0.028; stage II: 76.5% vs 91.9%, p < 0.001; stage III: 56.4% vs 90.8%, p < 0.001) and 5-year recurrence-free survival (stage I: 85.4% vs 96.6%, p = 0.002; stage II: 62.0% vs 86.5%, p < 0.001; stage III: 26.4% vs 80.0%, p < 0.001). The main limitations are retrospective single-institutional features and races of the study population. Preoperative osteopenia could be a strong predictive marker for long-term prognosis in colorectal cancer regardless of stage. ANTECEDENTES:La osteopenia, una afección en la que la densidad mineral ósea es más baja de lo normal, es un relevante factor de riesgo que conduce a una expectativa menor de vida saludable.OBJETIVO:Investigar el impacto pronóstico de la osteopenia preoperatoria en pacientes con cáncer colorrectal (CCR).DISEÑO:Un estudio retrospectivo.AJUSTE:Estudio realizado en un hospital universitario.PACIENTES:Un total de 1.086 pacientes con CCR en estadio I-III sometidos a una resección curativa.PRINCIPALES MEDIDAS DE RESULTADO:La osteopenia se evaluó con imágenes de tomografía computarizada. La supervivencia global la supervivencia específica de la enfermedad y la supervivencia libre de recurrencia fueron los criterios de valoración primaria.RESULTADOS:Se identificó osteopenia en 300 pacientes (27,6%). En comparación con el grupo sin osteopenia, las tasas de supervivencia global a 5 años (74,0% frente a 93,4%, p < 0,001), supervivencia especifica de la enfermedad (81,6 % frente a 97,2%, p < 0,001) tasas de supervivencia libre de recurrencia (57,1% frente a 88,3%, p < 0,001) fueron significativamente más bajas en el grupo de osteopenia. Los análisis multivariados mostraron que la osteopenia preoperatoria se asoció significativamente con una peor supervivencia global (HR 4,135; IC 95% 2,963-5,770; p < 0,001), supervivencia especifica de la enfermedad (HR 7,673; IC 95% 4,646-12,675; p < 0,001) y tasas de supervivencia libre de recurrencia (HR 5,039; IC 95% 3,811-6,662; p < 0,001). El pronóstico del grupo con osteopenia fue peor que el del grupo sin osteopenia en todos los estadios: supervivencia global a 5 años (estadio I: 89,4% frente a 96,9%, p = 0,028; estadio II: 76,5% frente a 91,9%, p < 0,001; estadio III: 56,4% frente a 90,8%, p < 0,001) y tasas de supervivencia libre de recurrencia a 5 años (estadio I: 85,4% frente a 96,6%, p < 0,002; estadio II: 62,0% frente a 86,5%, p < 0,001; estadio III: 26,4% frente a 80,0%, p < 0,001).LIMITACIONES:Las principales limitaciones son las características retrospectivas de una sola institución y las razas de la población de estudio.CONCLUSIONES:La osteopenia preoperatoria puede ser un fuerte marcador predictivo para el pronóstico a largo plazo en CCR independientemente de la etapa. (Traducción-Dr. Fidel Ruiz Healy ).

Racial and Ethnic Disparities in the Diagnosis and Treatment of Thyroid Disease.

There are differences in diagnosis, treatment, and outcomes for thyroid between racial and ethnic groups that contribute to disparities. Identifying these differences and their causes are the key to understanding and reducing disparities in presentation and outcomes in endocrine disorders. The present study reviews original studies identifying and exploring differences between benign and malignant thyroid diseases. A PubMed, Web of Science, and Scopus search was conducted for English-language studies using the terms "thyroid," "thyroid disease," "thyroid cancer," "race," "ethnicity," and "disparities" from inception to December 31, 2022. Many racial and ethnic disparities in the diagnosis, presentation, treatment, and outcomes of thyroid disease were found. Non-White patients are more likely to have a later time to referral, to present with more advanced disease, to have more aggressive forms of thyroid cancer, and are less likely to receive the appropriate treatment than White patients. Overall and disease-specific survival rates are lower in Black and Hispanic populations when compared to White patients. Extensive disparities exist in thyroid disease diagnosis, treatment, and outcomes that may have been overlooked. Further work is needed to identify the causes of these disparities to begin to work toward equity in the care of thyroid disease.

Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma.

Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive, lipid mediator, produced by sphingosine kinase 1 (SphK1). In this study, we evaluated the expression of phosphorylated SphK1 (pSphK1) in patients with pancreatic ductal adenocarcinoma (PDAC) and investigated its clinical significance. A total of 111 patients who underwent curative-intent resection for PDAC were enrolled. We investigated pSphK1 (Ser-225) expression in surgically resected specimens of PDAC using immunohistochemistry. The patients were divided into two groups according to pSphK1 immunoreactive expression: a pSphK1-high group (n=63) and a pSphK1-low group (n=48). Logistic regression analyses revealed that lymphatic invasion (p=0.007) was a significantly independent factor associated with high pSphK1 immunoreactive expression. The pSphK1-high group showed significantly worse disease-specific survival (DSS) than the pSphK1-low group (5-year DSS rate, 19.6% vs. 58.7%; p=0.001). High pSphK1 immunoreactive expression (hazard ratio=2.547; 95% confidence interval= 1.434-4.527; p=0.001) was an independent prognostic factor for DSS. High pSphK1 expression is independently associated with lymphatic invasion and unfavorable prognosis in PDAC patients. Thus, the SphK1-S1P axis may be important in mechanisms of tumor progression, such as lymphatic invasion, in PDAC patients.

Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma.

Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

Analysis of risk factors affecting long-term survival in elderly patients with advanced gastric cancer.

Factors predicting postoperative complications after gastrectomy for elderly patients with gastric cancer have been analyzed in several previous studies. However, there is limited research available on risk factors related to long-term survival. This study aimed to analyze factors affecting long-term survival after curative gastrectomy in elderly patients with advanced gastric cancer. This study included patients aged > 75years with histologically confirmed advanced gastric cancer stage II or greater. Before analysis, risk factors were categorized into four groups: baseline characteristics, underlying diseases, surgical and pathologic factors, and nutritional factors. The mean follow-up duration was 71.0months. The 5-year overall survival and disease-specific survival rates were 51.5% and 58.3%, respectively. Kaplan-Meier curves showed that patients who were female and overweight had significantly longer survival rates than those who were male and underweight. Elderly patients who underwent a total gastrectomy had poorer survival rates than those who underwent a distal gastrectomy. Multivariate analysis demonstrated that tumor stage, extent of gastrectomy, overweight status and overall complication were independent risk factors for overall survival. Our study show that the overweight patients, the extent of gastrectomy, tumor stage and overall complications are significant risk factors affecting long-term survival. Therefore, surgeons may be cautious in performing total gastrectomy in elderly gastric cancer patients. Additionally, it is important to focus on improving nutritional status and mitigating overall complications.

Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma.

Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.

Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan.

Head and neck mucosal melanomas are rare malignancies. Although the prognosis is poor owing to the high incidence of distant metastases, locoregional control remains important. It is difficult to obtain results in a large cohort because of its rarity. This study aimed to elucidate the survival outcomes of patients with head and neck mucosal melanoma treated with surgery in Japan. Patients with head and neck mucosal melanoma who were surgically treated between 2007 and 2021 at the National Cancer Center Hospital were retrospectively analyzed. A total of 47 patients were included in this study. The 5-year overall survival, disease-specific survival, locoregional control and relapse-free survival rates were 42%, 50%, 79% and 13%, respectively. The disease-specific survival of the oral mucosal melanoma group was significantly better than that of the sinonasal mucosal melanoma group (5-year disease-specific survival rate: 70% versus 37%, respectively; P=0.04). Multivariate analyses revealed that sinonasal mucosal melanoma were independently significant adverse prognostic factor, for overall survival and disease-specific survival. Patients with oral mucosal melanoma patients had a higher incidence of lymph node metastasis than those with sinonasal mucosal melanoma patients (P<0.0001). This study demonstrated the survival outcomes of the largest cohort of patients with head and neck mucosal melanomas treated surgically at a single institution within the past 20years in Japan. We found that survival outcomes and incidence of nodal metastases varied by site.

What is a useful marker for predicting survival in patients with high-grade soft tissue sarcoma who have non-inflammatory conditions?

BackgroundThe modified Glasgow prognostic score (mGPS) is a reliable system for identifying patients at high risk of death among patients with soft tissue sarcoma (STS). The scoring systems use a combination of C-reactive protein (CRP) and albumin levels. Although patients with high-grade STS are at risk of metastasis and death, even if their mGPS is 0, the prognostic indicators in these patients are unknown. Therefore, we investigated useful prognostic indicators for survival and the development of metastasis in patients with high-grade STS and an mGPS of 0. MethodsOne hundred and four patients with CRP and albumin levels of <1.0 mg/dl and >3.5 g/dl, respectively, indicating an mGPS of 0, were included. The mean follow-up period was 79 months. ResultsThe 5-year disease-specific survival (DSS) rate was 79.2%. Cox proportional analysis showed that tumor size and absolute neutrophil count (ANC) were prognostic variables in multivariate analyses. Patients with higher ANC (ANC>3370/μl) had a worse DSS than those with lower ANC. The 5-year DSS was 74.7% vs. 91.7%, respectively (p = 0.0207). The 5-year metastasis-free survival was 67.2%. Tumor size and ANC remained significant variables for predicting the development of metastasis in the multivariate analysis. Patients with higher ANC had a worse metastasis-free survival than those with lower ANC. The 5-year metastasis-free survival was 59.5% vs. 87.3%, respectively (p = 0.00269). ConclusionsWhen patients with high-grade STS have an mGPS of 0, the ANC and tumor size should be carefully evaluated. A higher neutrophil count and larger tumor size may increase the risk of metastasis development.

A comparison between p16-positive head and neck cancer of unknown primary (HPV-HNCUP) and oropharyngeal squamous cell carcinoma (HPV-OPSCC): are they the same disease?

IntroductionThe following study aimed to answer the question if HPV-HNCUP and HPV-OPSCC are the same disease. Propensity score matching (PSM) was used to compare the oncological outcomes of both groups, in particular the 5-year overall survival rate (OS), the 5-year disease specific survival rate (DSS) and the 5-year progression free survival rate (PFS).Materials and methodsFirstly, between January 1st, 2007, and March 31st, 2020 a total of 131 patients were treated with HNCUP at our Department. Out of these, 21 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. Secondly, between January 1st, 2000, and January 31st, 2017, a total of 1596 patients were treated with an OPSSC at our Department. Out of these, 126 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. After PSM, 84 patients with HPV-OPSCC and 21 HPV-HNCUP remained in the study for further comparison.ResultsThe OS was 63.5% (95% CI 39.4–87.6) for HPV-HNCUP and 88.9% (95% CI 90.4–100.0) for HPV-OPSCC patients and therefore, significantly lower for the first mentioned (p = 0.013). The DSS was also significantly impaired for HPV-HNCUP (71.0%, 95% CI 46.3–95.7), in comparison with HPV-OPSCC patients (95.5%, 95% CI 90.4–100.0; p = 0.002). The PFS for HPV-HNCUP patients was lower (75.6%, 95% CI 54.0–97.2) yet not significantly different to HPV-OPSCC (90.4%, 95% CI 83.5–97.3; p = 0.067).ConclusionsThe results presented demonstrate a significant reduced OS and DSS for HPV-HNCUP patients. Accordingly, in our study HPV-HNCUP and HPV-OPSCC are two different entities with a different oncological outcome.

A systematic investigation and network interaction analysis on preventive treatments against HepG2 cancer cells from a genomic-level perspective

Worldwide, the fourth most common malignancy leading to death via cancer transformation is hepatocellular carcinoma (HCC). Notwithstanding various preventive approaches, the incidence and mortality of patients with HCC continue to increase. However, a successful early diagnosis of HCC is beneficial given a potentially curative treatment. We systematically searched the publicly available NCBI microarray database to extract the required information on different preventive treatments and their affected genes and signaling pathways on HCC. Furthermore, the significant genes were analyzed through the Kaplan-Meier tool for overall survival, relapse-free survival, progression-free survival, and disease-specific survival rates. Subsequently, we assessed the protein-protein network interaction analysis and their corresponding drugs and diseases. The thorough screening of the literature microarray gene datasets revealed that various compounds could be implicated in HCC prevention. The results showed that nine genes (i.e., FGA, FGG, TP53, HELLS, CCNA2, MCM10, MCM2, PCTP, and CYP24A1) modulated the four above-mentioned survival rates. Furthermore, the associations between genes, drugs, and related diseases discovered 39 out of 61 medications covered potential anticancer agents. Finally, we demonstrated that numerous signaling pathways were simultaneously modulated in HCC. In conclusion, this work underlines the importance of the genomic-level perspective in studying HCC treatment and development.

Clinical Outcomes of Follow-Up Observation After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma Invading the Muscularis Mucosa Without Lymphovascular Involvement.

The therapeutic approach after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) diagnosed as pathological T1a-muscularis mucosa (pT1a-MM) without lymphovascular involvement (LVI) remains uncertain. We aimed to determine whether observation after ESD is acceptable for patients without LVI showing pT1a-MM cancer. We retrospectively registered 566 ESCC patients who were treated with ESD at ten institutions between January 2007 and December 2015. Of those, 447 cases showing pT1a-epithelium/lamina propria mucosa (EP/LPM) without LVI and vertical margin (VM) (EP/LPM group), and 41 cases showing pT1a-MM without LVI and VM (MM group) were analyzed in this investigation. The clinical outcomes were assessed between the groups. The 5year cumulative incidence of metastatic recurrence was 0.5% and 3.3% in the EP/LPM and MM groups, respectively (P = 0.121). Two cases showing pT1a-EP/LPM and one showing pT1a-MM experienced lymph node recurrence. The 5year cumulative incidence of local recurrence was 1.5% and 3.8% in the EP/LPM and MM groups, respectively (P = 0.455). The 5year disease-specific survival (DSS) rate was 99.3% and 96.6% in the EP/LPM and MM groups, respectively (P = 0.118), whereas the 5year overall survival rate was significantly higher in the EP/LPM group than in the MM group (92.6% versus 81.1%, respectively; P = 0.021). As regards metastatic recurrence and DSS, ESCC patients with pT1a-MM without LVI showed favorable outcomes that were equivalent to those with pT1a-EP/LPM, even when they were not treated with additional therapy after ESD.

Comparison of Clinical Outcomes, Pathologic Characteristics, and Immune-Related Features of Postradiation vs Sporadic Oral Cavity Squamous Cell Carcinoma

Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation. To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC. This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022. Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC. The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed. A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-β compared with sporadic OCSCC. This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.