5-year Disease-specific Survival Research Articles

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients

BackgroundThe validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients.MethodsThe clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed.ResultsThe mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups.ConclusionsESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient’s general condition.

Incidence and survival outcomes of patients with high-grade appendicular bone sarcoma and isolated regional lymph node metastasis: A national cohort database study

BackgroundWhile distant metastases in primary bone sarcomas have been extensively studied, the impact of isolated regional lymph node (LN) metastasis on survival remains unknown. In patients with primary bone sarcomas, we sought to assess the prevalence of isolated regional LN metastasis and the survival of this population. MethodsA total of 6651 patients with histologically-confirmed high-grade osteosarcoma, Ewing sarcoma, or chondrosarcoma were retrieved from the SEER database. We defined four subgroups for our analysis: localized disease (N0 M0), isolated regional LN metastasis (N1 M0), isolated distant metastasis (N0 M1), and combined regional LN and distant metastasis (N1 M1). Disease-specific survival (DSS) was assessed using the Kaplan-Meier method. ResultsPrevalence of isolated regional LN metastasis (N1 M0) was highest in Ewing sarcoma (27/1097; 3.3 %), followed by chondrosarcoma (18/1702; 1.4 %) and osteosarcoma (26/3740; 0.9 %). In all three histologies, patients with isolated regional LN metastasis had a worse 2-year, 5-year, and 10-year DSS than those with localized disease. Chondrosarcoma patients with isolated regional LN (N1 M0) metastasis had a significantly higher DSS in comparison to those with only distant metastasis (N0 M1) at the 5- and 10-year marks; for osteosarcoma and Ewing sarcoma, only a pattern towards higher survival was seen. Risk factors for presenting isolated regional LN metastasis included tumor location in lower-limb (OR = 2.01) or pelvis (OR = 2.49), diagnosis of Ewing sarcoma (OR = 2.98), and tumor >10 cm (OR = 1.96). ConclusionsIsolated regional LN metastases in primary bone sarcomas is an infrequent presentation associated with worse survival than localized disease. Level of evidenceIII.

A retrospective study of clinical outcomes for patients with esophageal cancer who were treated with radiotherapy alone

Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80 – 11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43 – 3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28 – 2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25 – 2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78 – 0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10 – 2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

The histological spectrum and immunoprofile of head and neck NUT carcinoma: A multicentre series of 30 cases.

Head and neck nuclear protein of testis carcinoma (HN-NUT) is a rare form of carcinoma diagnosed by NUT immunohistochemistry positivity and/or NUTM1 translocation. Although the prototype of HN-NUT is a primitive undifferentiated round cell tumour (URC) with immunopositivity for squamous markers, it is our observation that it may assume variant histology or immunoprofile. We conducted a detailed clinicopathological review of a large retrospective cohort of 30 HN-NUT, aiming to expand its histological and immunohistochemical spectrum. The median age of patients with HN-NUT was 39 years (range = 17-86). It affected the sinonasal tract (43%), major salivary glands (20%), thyroid (13%), oral cavity (7%), larynx (7%), neck (7%) and nasopharynx (3%). Although most cases of HN-NUT (63%) contained a component of primitive URC tumour, 53% showed other histological features and 37% lacked a URC component altogether. Variant histological features included basaloid (33%), differentiated squamous/squamoid (37%), clear cell changes (13%), glandular differentiation (7%) and papillary architecture (10%), which could co-exist. While most HN-NUT were positive for keratins, p63 and p40, occasional cases (5-9%) were entirely negative. Immunopositivity for neuroendocrine markers and thyroid transcription factor-1 was observed in 33 and 36% of cases, respectively. The outcome of HN-NUT was dismal, with a 3-year disease specific survival of 38%. HN-NUT can affect individuals across a wide age range and arise from various head and neck sites. It exhibits a diverse spectrum of histological features and may be positive for neuroendocrine markers, potentially leading to underdiagnosis. A low threshold to perform NUT-specific tests is necessary to accurately diagnose HN-NUT.

Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Average log change rate of pretreatment squamous cell carcinoma antigen after concurrent chemoradiotherapy in stage IIIC1 cervical squamous cell carcinoma

We aimed to determine whether pretreatment squamous cell carcinoma antigen (SCC-Ag) levels and the average logarithmic change in SCC-Ag levels (ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document}) after concurrent chemoradiotherapy (CCRT) could predict treatment outcomes in patients with stage IIIC1 cervical squamous cell carcinoma (SCC). We analyzed 168 patients with stage IIIC1 cervical SCC who underwent primary CCRT and collected data on age, local extension, treatment details, hematological parameters, and tumor markers such as SCC-Ag and carcinoembryonic antigen 21-1 (Cyfra). Predictive performances of pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} were assessed using receiver operating characteristic curves. Survival analysis was performed using the Cox regression model and Kaplan–Meier plots. The combination of pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} showed higher area under the curve values than pretreatment SCC-Ag levels alone (area under the curve; 95% confidence interval [CI] 0.708 [0.581–0.836] vs. 0.666 [0.528–0.804], respectively). Pretreatment SCC-Ag (≥ 5 ng/ml and Cyfra levels (≥ 3.15 ng/ml) and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} (≥ − 1.575) were significant predictors of disease-specific survival. The 5-year disease-specific survival rates significantly differed among the low-, intermediate-, and high-risk groups. Risk stratification using both pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} may predict treatment outcomes of patients with stage IIIC1 SCC.

Plasma IL-1 and IL-6 Family Cytokines with Soluble Receptor Levels at Diagnosis in Head and Neck Squamous Cell Carcinoma: High Levels Predict Decreased Five-Year Disease-Specific and Overall Survival.

Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.

Impact of gene expression profiling on diagnosis and survival after metastasis in patients with uveal melanoma.

Surveillance frequency for metastasis is guided by gene expression profiling (GEP). This study evaluated the effect of GEP on time to diagnosis of metastasis, subsequent treatment and survival. A retrospective study was conducted of 110 uveal melanoma patients with GEP (DecisionDx-UM, Castle Biosciences, Friendswood, Texas, USA) and 110 American Joint Committee on Cancer-matched controls. Surveillance testing and treatment for metastasis were compared between the two groups and by GEP class. Rates of metastasis, overall survival and melanoma-related mortality were calculated using Kaplan-Meier estimates. Baseline characteristics and follow-up time were balanced in the two groups. Patients' GEP classification was 1A in 41%, 1B in 25.5% and 2 in 33.6%. Metastasis was diagnosed in 26.4% (n = 29) in the GEP group and 23.6% (n = 26) in the no GEP group (P = 0.75). Median time to metastasis was 30.5 and 22.3 months in the GEP and no GEP groups, respectively (P = 0.44). Median months to metastasis were 34.7, 75.8 and 26.1 in class 1A, 1B and 2 patients, respectively (P = 0.28). Disease-specific 5-year survival rates were 89.4% [95% confidence interval (CI): 81.0-94.2%] and 84.1% (95% CI: 74.9-90.1%) in the GEP and no GEP groups respectively (P = 0.49). Median time to death from metastasis was 10.1 months in the GEP group and 8.5 months in the no GEP group (P = 0.40). There were no significant differences in time to metastasis diagnosis and survival outcomes in patients with and without GEP. To realize the full benefit of GEP, more sensitive techniques for detection of metastasis and adjuvant therapies are required.

Recurrence morbidity of olfactory neuroblastoma.

With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence. A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses. A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p<0.001), overall stage (p<0.001), and modified Kadish scores (p<0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio=5.62; p=0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence. Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.

Relationship between aggressive features of oral squamous cell carcinoma and the immunoexpression of CX3CR1, CX3CL1 and ITGAV

Objective: We aimed to describe the association between CX3CR1, CX3CL1 and ITGAV immunoexpression with PNI and adverse oncological outcomes in OSCC patients. Study design: Expression CX3CR1, CX3CL1 and ITGAV was assessed by immunohistochemistry in a cohort of 50 paraffin-embedded resections of OSCC. Survival analysis, Cox, and binary logistic regressions were undertaken to determine the impact on patient survival and predictive value for PNI. Results: CX3CL1 positive nerves exhibited a significant association with tumor budding (TB) (p=0.043), whereas nerves positive for ITGAV were associated with PNI (p=0.021), T3-T4 tumor size (p=0.029), and III-IV stage (p=0.044). Cases with ITGAV-positive nerves exhibited an odds ratio of 9.603 (p=0.008) for PNI, while cases with CX3CL1-positive nerves exhibited and odds ratio of 4.682 (p=0.033) for TB. A trend towards decreased 5-year overall survival (p=0.078) and 5-year disease-specific survival (p=0.09) was observed in relation to ITGAV-positive nerves. However, no independent predictors for poor survival were identified. Conclusion: The expression of ITGAV was associated with PNI and advanced disease, while the expression of CX3CL1 was related to TB, suggesting that ITGAV and CX3CL1 are involved in their respective developments. Therefore, further investigations are encouraged to assess the potential utility of targeted therapies against CX3CL1 receptors in OSCC.

Surgical management of advanced sinonasal cancer: a 10-year mono-institutional experience

Surgical management of advanced sinonasal cancer: a 10-year mono-institutional experience

A 22-year single institution review of 119 cases of salivary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level 3.

Abstract 2452: Clinical importance of nicotinamide nucleotide transhydrogenase in obesity-associated colorectal cancer

Abstract Background: Obesity is increasing worldwide, and many associated diseases are emerging as global health problems. There is a relationship between body mass and the risk of developing colorectal cancer (CRC). However, predictive biomarkers of survival with body mass remain elusive. Therefore, we aimed to identify novel clinically relevant biomarkers for obesity-associated CRC. Methods: We searched for biomarker candidates in The Cancer Genome Atlas CRC cohort. We divided the TCGA CRC cohort (n=268) data into 3 groups (healthy weight CRC group [HT], adjacent normal tissue from the HT group [AN]), and obesity CRC group [OT]). Candidates were validated by survival analysis after immunohistochemistry in an independent cohort of 420 patients. Results: The gene expression levels of NNT, PANK3, PPARGC1B, RTL6, FAM220A, and TMEM9 were associated with survival in overweight and obese patients with CRC from TCGA cohort. These findings were validated using protein expression data from our independent cohort. In our patient cohort, the hazard ratio (HR) of the subgroup of low NNT versus that of high NNT in terms of 5-year event-free survival (EFS) was 2.20 (adjusted for age and sex, 95% CI: 1.01-4.80, p &amp;lt; 0.05) among patients of obesity-associated CRC. When both TNM staging and NNT expression were considered, patients of obesity-associated CRC with low NNT expression and advanced stage III-IV cancer had a HR of 21.20 (adjusted for age and sex, 95% CI: 2.88-156.08, p &amp;lt; 0.01) compared to those with high NNT expression and early stage I-II cancer. However, when patients of obesity-associated CRC with high NNT expression and advanced stage III-IV cancer were compared to those with high NNT expression and early stage I-II cancer, the former subgroup had a HR of 8.39 (adjusted for age and sex, 95% CI: 1.03-68.39, p &amp;lt; 0.05) in terms of the 5-year EFS. Finally, when the 5-year disease-specific survival analysis was performed, the patients of obesity-associated CRC with low NNT expression and advanced stage III-IV cancer were found to have a HR of 14.05 (adjusted for age and sex, 95% CI: 1.89-104.38, P = 0.01) compared to those with high NNT expression and early stage I-II cancer. Furthermore, low NNT expression results in the inactivation of several metabolic pathways, including ROS-related pathways. Conclusions: NNT is a novel and promising CRC prognostic biomarker for overweight and obese patients. It can provide clinicians with early indicators of patient prognosis and aid in appropriate treatment selection. Citation Format: Soyeon Jeong, Sungjin Park, Jungsuk An, Myunghee Kang, Seungyoon Nam, Jung Ho Kim. Clinical importance of nicotinamide nucleotide transhydrogenase in obesity-associated colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2452.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study

AimsTo evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). MethodsA retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. ResultsYolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I–II and stages III–IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1–2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). ConclusionDistinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

Clinicopathological features of cholangiolocarcinoma and impact of tumor heterogeneity on prognosis: A single institution retrospective study.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor: A SEER-Based Study.

Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood. The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients. The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C -indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively. The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BackgroundWhile several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. MethodsBetween 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. ResultsThe group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). ConclusionsOCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.