AJCC Stage Research Articles

Clinical Presentation and Treatment Strategies for Laryngeal Neuroendocrine Carcinoma: Insights from a Rare Case

Intriduction -Neuroendocrine neoplasms (NEN) of the larynx are very rare, accounting for <1% of all laryngeal carcinomas. Based on the 2022 IARCH/WHO classification, NENs are characterised as well-differentiated neuroendocrine tumours (NET), which can further be divided into grades 1-3 based on Ki-67 levels and mitotic count, or poorly differentiated neuroendocrine carcinomas (NEC) consisting of small cell carcinoma and large cell carcinoma. In this case report, we describe a rare presentation of NEC of the larynx encountered in a 54-year-old man and how diagnostic and therapeutic dilemmas unfolded. Case description: A 6-month history of breathing and swallowing difficulties led to a tracheostomy due to stridor, in the emergency department. Imaging revealed a soft tissue mass involving the supraglottic larynx but no significant associated cervical lymphadenopathy. The biopsy from the growth was suggestive of poorly differentiated NEC as an AJCC stage cT3N0M0. However, there was local progression post-initial treatment with vincristine, doxorubicin and cyclophosphamide (VAC). The chemotherapy regimen was switched to carboplatin and etoposide. The patient received definitive radiation therapy and completed the planned dose of radiation.After 10 months of disease-free interval, there was local recurrence with lung nodules that prompted rechallenge with platinum and etoposide. The patient is doing well and remains clinically and radiologically stable to maintenance therapy with carboplatin & etoposide. Conclusion: NENs of the larynx and especially NECs, are difficult to diagnose as they are rare and have varied molecular profiles. Its management frequently calls for multimodal approaches with chemotherapy and radiation therapy. Due to the developments in diagnostic and therapeutic modalities, our knowledge of NENs has been enhanced which contributed to better practice standards. Nevertheless, standardized treatment strategies remain to be determined by large cohort studies and comprehensive molecular profiling that can determine improved clinical outcomes.

Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma: a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker

BackgroundOral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT).MethodsIn this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III–IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy.ResultsAfter a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT.ConclusionsThis randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting.Trial registrationwww.ClinicalTrials.gov. NCT02923258 (date of registration: October 4, 2016)

Minimum number of lymph nodes to maximize survival in non-metastatic appendiceal adenocarcinoma

IntroductionIn non-metastatic appendiceal adenocarcinoma, the relationship between the number of lymph nodes harvested and overall survival is unknown. The objective of this study was to determine whether the number of lymph nodes harvested impacts survival in patients with mucinous and non-mucinous appendiceal cancer. MethodsRetrospective cohort analysis was conducted in patients who underwent surgery for appendiceal adenocarcinoma in the SEER database from 2000–2019. Exclusion criteria included patients without the number of regional nodes harvested/node positivity, missing survival data, stage IV disease, and certain subtypes of appendiceal tumors. The primary outcome was 10-year overall survival. ResultsA total of 1651 patients were identified, 1101 with mucinous and 550 with non-mucinous cancer. The majority of patients were male (54 %) and between the ages of 50–74 (52 %). Mean ± SD number of lymph nodes harvested was 17.04 ± 10.41. The ten-year survival rates for patients with mucinous appendiceal cancer were 43–74 % and 25–68 % for non-mucinous cancer, depending on AJCC stage. Multivariate Cox-regression analysis displayed that the number of lymph nodes harvested was an independent predictor of survival (p < 0.0001). The optimal threshold predicted by Cox-regression for maximal survival benefit was harvest of a minimum of 15 nodes for mucinous and 12 for non-mucinous cancer. Additionally, for mucinous cancer, per each additional 3 nodes harvested past 15, the 10-year risk of mortality decreased by 7 % (HR 0.93 (0.88 to 0.98), p < 0.001). ConclusionsThe number of lymph nodes harvested is an independent predictor of survival for patients with appendiceal adenocarcinoma. To maximize this survival benefit, a minimum of 15 regional lymph nodes must be harvested for mucinous and 12 for non-mucinous cancer.

Treatment and management of medullary thyroid microcarcinoma: a 10-year retrospective study from a single center.

To explore individualized treatment and management methods for medullary thyroid microcarcinoma (MTMC). Clinical data of patients with medullary thyroid carcinoma with a diameter ≤1 cm admitted to the First Affiliated Hospital of Kunming Medical University from June 2013 to June 20× were collected. Combined with different treatment guidelines for medullary thyroid carcinoma, factors affecting lymph node metastasis and postoperative disease status were analyzed. Twenty-nine patients with MTMC were included in the analysis, including 24 patients who underwent total thyroidectomy, 5 who underwent thyroid gland lobectomy, and 13 who experienced postoperative lymph node metastasis. Multifocal tumor and calcitonin (Ctn) were the influencing factors, while multifocal tumor, Ctn, lymph node metastasis, and AJCC stage affected the dynamic risk stratification of postoperative disease. Calcitonin detection is an important method for detecting MTMC. A tumor diameter ≤1 cm does not indicate that the tumor is in the early stage. The presence of multifocal tumors and Ctn should be used as important indicators for preoperative evaluation. Dynamic stratified risk assessment is critical in postoperative follow-up.

Development and validation of a diagnostic nomogram for frailty in cancer patients

BackgroundThe presence of frailty decreases the overall survival of cancer patients. An accurate and operational diagnostic method is needed to help clinicians choose the most appropriate treatment to improve patient outcomes. MethodsData were collected from 10 649 cancer patients who were prospectively enrolled in the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers (INSCOC) project in China from July 2013 to August 2022. The training cohort and validation cohort were randomly divided at a ratio of 7:3. The multivariable logistic regression analysis, multivariate Cox regression analyses, and the least absolute shrinkage and selection operator (LASSO) method were used to develop the nomogram. The concordance index and calibration curve were used to assess the diagnostic utility of the nomogram model. ResultsThe 10 risk factors associated with frailty in cancer patients were age, AJCC stage, liver cancer, hemoglobin, radiotherapy, surgery, hand grip strength (HGS), calf circumference (CC), PG-SGA score and QOL from the QLQ-C30. The diagnostic nomogram model achieved a good C index of 0.847 (95% CI, 0.832–0.862, P < 0.001) in the training cohort and 0.853 (95% CI, 0.83–0.876, P < 0.001) in the validation cohort. The prediction nomogram showed 1-, 3-, and 5-year mortality C indices in the training cohort of 0.708 (95% CI, 0.686–0.731), 0.655 (95% CI, 0.627–0.683), and 0.623 (95% CI, 0.568–0.678). The 1-, 3-, and 5-year C indices in the validation cohort were similarly 0.743 (95% CI, 0.711–0.777), 0.680 (95% CI, 0.639–0.722), and 0.629 (95% CI, 0.558–0.700). In addition, the calibration curves and decision curve analysis (DCA) were well-fitted for both the diagnostic model and prediction model. ConclusionsThe nomogram model provides an accurate method to diagnose frailty in cancer patients. Using this model could lead to the selection of more appropriate therapy and a better prognosis for cancer patients.

Can We Go beyond Pathology? The Prognostic Role of Risk Scoring Tools for Cancer-Specific Survival of Patients with Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices.

Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States.

Palliative care plays essential roles in cancer care. However, differences in receipt among individuals identifying as Asian American, Native Hawaiian, and Other Pacific Islanders (AA&NHPI) with cancer are not well-characterized, especially when these diverse groups are disaggregated. We characterized disparities in receipt of palliative care among AA&NHPI patients with AJCC Stage IV prostate, breast, or lung cancer. We performed multivariable logistic regressions were performed in this retrospective cohort analysis, using deidentified data from the National Cancer Database (NCDB) of patients diagnosed with AJCC analytic group stage IV breast, lung, or prostate cancer (2004-2018) who were White or of Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. We conducted multivariable logistic regression analyses in a retrospective cohort study using deidentified data from the National Cancer Database (NCDB). The study included patients diagnosed with AJCC analytic group Stage IV breast, lung, or prostate cancer between 2004 and 2018, who were White or identified as Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. Adjusted odds ratios and 95% confidence intervals of receiving palliative care were measured when comparing White vs. AA&NHPI patients as one cohort and White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates. Among 775,289 individuals diagnosed with cancer (median age: 68years), no significant differences in palliative care receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate, breast, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for breast cancer patients of Asian Indian/Pakistani descent (AOR 0.75, 95% CI, 0.60-0.94, P = 0.011) and for lung cancer patients of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR 0.88, [0.81-0.94], P = 0.001; Vietnamese AOR 0.89, [0.80 to 0.99], P = 0.032; Thai AOR 0.64, [0.44-0.92], P = 0.016; Asian Indian/Pakistani AOR 0.83, [0.74-0.93], P = 0.001). Palliative care was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR 1.92, [1.32-2.75], P = 0.001; Hawaiian AOR 2.09, [1.20-3.66], P = 0.009), breast cancer (Japanese AOR 1.72, [1.21-2.43], P = 0.001; Hawaiian AOR 1.70, [1.08-2.67], P = 0.021), and lung cancer (Japanese AOR 1.92, [1.70-2.17], P < 0.001; Hawaiian AOR 2.95, [2.5-3.5], P < 0.001), as well as patients of Other Pacific Islander descent with lung cancer (AOR 1.62, [1.34-1.96], P < 0.001). Our findings demonstrate disparities in receipt of palliative care upon disaggregation of diverse AA&NHPI groups, the need for disaggregated research and targeted interventions that address the unique cultural, socioeconomic, and healthcare system barriers to palliative care receipt.

Implications of tumor-positive sentinel lymph nodes in single vs multiple nodal basins in melanoma.

Melanoma patients' prognosis is based on the primary tumor characteristics and the tumor status of the regional lymph nodes. The advent of lymphoscintigraphy with SLN biopsy (SLNB) has shown that melanoma can drain to multiple nodal basins but the significance of multiple basins (vs. one basin) with tumor-positive sentinel lymph node(s) (+SLN) of similar tumor burden has not been shown. We examined the impact of the number of nodal basins with +SLN (+basin) in melanoma patients and its significance for patients' prognosis and survival. We identified 1,915 patients with +SLN from two randomized surgical clinical trials: Multicenter Selective Lymphadenectomy Trials I and II. Patient groups were divided based on number of +SLNs and number of +basins. Disease-free survival (DFS), distant disease-free survival (DDFS) and melanoma-specific survival (MSS) were compared with the Kaplan-Meier method and log-rank tests. Univariable and multivariable analyses were performed using Cox proportional hazard regressions. Among the 1,915 patients, 1,501 had only one +SLN (78%) in one basin and 414 (22%) had multiple +SLNs: 340 located in one basin and 74 in multiple basins. Among patients with multiple +SLNs, those with multiple +basins have a worse DFS, DDFS and MSS than those with a single basin (p ≤ 0.0001 for all comparisons). MSS was significantly different based on AJCC stages: AJCC IIIA and IIIB (p ≤ 0.001 and 0.0287, respectively). Our results suggest that the number of tumor-positive basins may be important for staging and in understanding the biology of lymph node metastases.

Visual prognosis in retinoblastoma patients with multimodality treatments: Visual Prognosis in Retinoblastoma Patients

PurposeThis study evaluates factors associated with globe preservation and long-term visual outcomes according to clinical characteristics and treatment modalities in intraocular retinoblastoma patients. DesignA retrospective review of medical records enrolled intraocular retinoblastoma patients between January 1, 2007, and June 30, 2020. Methods•Setting: Single-centered.•Patient or study population: Intraocular retinoblastoma patients treated at Ramathibodi Hospital, Bangkok, Thailand.•Main outcome measure: A statistically significant factor associated with visual prognosis corresponds to baseline characteristics, staging, anatomical involvement, and multimodal treatments. Results86 patients (124 eyes) were included. Median age of disease bilaterality onset was significantly younger than unilaterality. Three-quarters of patients were in advanced stages (groups D or E in either ICRB or IIRC and up to cT2a from AJCC). Globe salvage rate was 54.0 % (67 eyes). ICRB Groups D-E, IIRC Groups D-E, and AJCC cT2a and more advanced stages are the globe removal-associated independent risk factors (adjusted odds ratio [AOR] [95 % CI] = 7.40 [1.36, 40.09], 8.33 [1.55, 44.73], 14.73 [1.55, 139.79], respectively). Compared to other classification, IIRC provided the highest statistical correlation from univariate analysis. IIRC Groups A-C is a good visual acuity-associated independent risk factor (AOR [95 % CI] = 4.64 [1.05, 20.43] and P = 0.042). Macular involvement is a worse visual acuity-associated independent risk factor (AOR [95 % CI] = 0.14 [0.02, 0.82] and P = 0.03). Systemic chemotherapy (86.29 %) is the mainstay treatment in our study and is the only good visual outcome-associated treatment. Subgroup analysis of all eyes receiving systemic chemotherapy reveals statistically significant preventive factors for globe removal for tumor staging with ICRB and IIRC groups A-C and AJCC stages cT1a–cT1b (odds ratio [95 % CI] = 15.75 [4.38, 56.65], 15.67 [4.34, 56.53], 9.97 [2.75, 36.18], respectively; P=<0.001) and prevents the worse visual outcome in these stages, (odds ratios [95 % CI] = 4.57 [1.28, 16.27], 6.61 [1.74, 25.11], and 7.50 [1.86, 30.16], respectively; P =< 0.05). ConclusionsAll recent advanced clinical stagings are globe removal outcome-associated independent risk factors. IIRC staging is the best visual results predictor. IIRC Groups A-C were associated with a good visual outcome. Macular involvement tumors are strongly associated with poor visual outcome, despite successful globe preservation from multimodality treatment. Systemic chemotherapy remains a crucial globe-saving treatment and prevents worse vision–especially in ICRB and IIRC Groups A-C and AJCC stage cT1a-cT1b.

Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- (“Triple”) wild type melanomas

BackgroundMelanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as “triple wild-type” (tWT) melanomas. They constitute 5–10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date. MethodsTargeted next-generation sequencing of the TERT promoter and 29 melanoma-associated genes were performed on 3109 melanoma tissue samples of the prospective multicenter study ADOREG/TRIM of the DeCOG revealing 292 patients suffering from tWT-melanomas. Clinical characteristics and mutational patterns were analyzed. As subgroup analysis, we analyzed 141 tWT-melanoma patients receiving either anti-CTLA4 plus anti-PD1 or anti PD1 monotherapy as first line therapy in AJCC stage IV. Results184 patients with cutaneous melanomas, 56 patients with mucosal melanomas, 34 patients with acral melanomas and 18 patients with melanomas of unknown origin (MUP) were included. A TERT promoter mutation could be identified in 33.2 % of all melanomas and 70.5 % of all tWT-melanomas harbored less than three mutations per sample. For the 141 patients with stage IV disease, mPFS independent of melanoma type was 6.2 months (95 % CI: 4–9) and mOS was 24.8 months (95 % CI: 14.2–53.4) after first line anti-CTLA4 plus anti-PD1 therapy. After first-line anti-PD1 monotherapy, mPFS was 4 months (95 %CI: 2.9–8.5) and mOS was 29.18 months (95 % CI: 17.5–46.2). ConclusionsWhile known prognostic factors such as TERT promoter mutations and TMB were equally distributed among patients who received either anti-CTLA4 plus anti-PD1 combination therapy or anti-PD1 monotherapy as first line therapy, we did not find a prolonged mPFS or mOS in either of those. For both therapy concepts, mPFS and mOS were considerably shorter than reported for melanomas with known oncogene mutations.

356 The Role of Cancer Cachexia in Influencing Outcomes in Pancreatic &amp; Biliary Malignancy

Abstract Aim To investigate the influence of cancer cachexia on outcomes and clinicopathological variables in pancreatico-biliary malignancies. Method Patients who underwent pancreaticoduodenectomy for malignancy from 2007-2020 at the Glasgow Royal Infirmary were included in this study. Pre-operative single-slice CT scan images were collected for cross sectional analysis of body composition using the semi-automated segmentation programme, SliceOmatic. Body composition measurements were represented as z-scores to account for age and sex. Results Subcutaneous fat radiodensity (SFD) was significantly lower in ampullary adenocarcinoma (-0.17+/-0.95), duodenal adenocarcinoma (-0.03+/-1.08), and cholangiocarcinoma (-0.18+/-1.00) groups compared to the pancreatic cancer group (0.12+/-1.00) (P=0.09). Skeletal muscle index (SMI) was significantly higher in those diagnosed with cholangiocarcinoma compared to all other indications (0.20+/-0.91 vs -0.04+/-1.02, P=0.05). Disease-specific and recurrence-free median survival was lower in those with low SMI compared to those with high SMI for all indications (35 months vs 41 months, 13 months vs 18 months).When comparing those who underwent up-front resection to those who received neoadjuvant therapy, visceral fat index (VFI) was found to be higher (0.06+/-1.00 vs -0.21+/-0.99, P=0.03) and skeletal muscle density was found to be lower (-0.05+/-1.01 vs 0.18+/-0.96, P=0.04). SFD was also found to be significantly lower in those with AJCC stage 1 compared to all other stages (-0.21+/-0.86 vs 0.07+/-1.01, P=0.03). Conclusions Adverse body composition may influence outcomes in pancreatic and biliary malignancy; however, this influence appears to be modest at best. Clinical applications of body composition analysis may be limited to serial monitoring of patients within the context of their treatment pathway.

Preoperative neutrophil–to–lymphocyte ratio after chemoradiotherapy for esophageal squamous cell carcinoma associates with postoperative pulmonary complications following radical esophagectomy

ObjectivesEsophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy.MethodsWe retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival.ResultsPostoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively. Preoperative neutrophil-to-lymphocyte ratio was not associated with the oncological stratification such as pathological T classification, pathological N classification, and pathological AJCC stage. The 3-year overall survival rates were 70% and 34% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0026). The 3-year disease-free survival rates were 57% and 29% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0055). The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 was independently associated with more pulmonary complications, inferior overall survival, and worse disease-free survival.ConclusionsElevated preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy is independently associated with higher pulmonary complication rate following radical esophagectomy and poor prognosis in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy. Preoperative neutrophil-to-lymphocyte ratio is routinely available in clinical practice and our findings suggest it can be used as a predictor for pulmonary complications after esophagectomy in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy.

MCM8 promotes gastric cancer progression through RPS15A and predicts poor prognosis.

Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Minichromsome maintenance proteins family member 8 (MCM8) assists DNA repair and DNA replication. MCM8 exerts tumor promotor function in multiple digestive system tumors. MCM8 is also considered as a potential cancer therapeutic target. Bioinformatics methods were used to analyze MCM8 expression and clinicopathological significance. MCM8 expression was detected by immunohistochemistry (IHC) staining and qRT-PCR. MCM8 functions in GC cell were explored by Celigo cell counting, colony formation, wound-healing, transwell, and annexin V-APC staining assays. The target of MCM8 was determined by human gene expression profile microarray. Human phospho-kinase array kit evaluated changes in key proteins after ribosomal protein S15A (RPS15A) knockdown. MCM8 functions were reassessed in xenograft mouse model. IHC detected related proteins expression in mouse tumor sections. MCM8 was significantly upregulated and predicted poor prognosis in GC. High expression of MCM8 was positively correlated with lymph node positive (p < 0.001), grade (p < 0.05), AJCC Stage (p < 0.001), pathologic T (p < 0.01), and pathologic N (p < 0.001). MCM8 knockdown inhibited proliferation, migration, and invasion while promoting apoptosis. RPS15A expression decreased significantly after MCM8 knockdown. It was also the only candidate target, which ranked among the top 10 downregulated differentially expressed genes (DEGs) in sh-MCM8 group. RPS15A was identified as the target of MCM8 in GC. MCM8/RPS15A promoted phosphorylation of P38α, LYN, and p70S6K. Moreover, MCM8 knockdown inhibited tumor growth, RPS15A expression, and phosphorylation of P38α, LYN, and p70S6K invivo. MCM8 is an oncogene and predicts poor prognosis in GC. MCM8/RPS15A facilitates GC progression.

Multi-omics data analysis reveals the complex roles of age in differentiated thyroid cancer

AimsAge is a major risk factor for differentiated thyroid cancer (DTC); however, the mechanisms underlying aging-regulated progression of DTC remains unclear. MethodsBased on multi-omics data (transcriptional files, somatic mutation files, methylation files) derived from the TCGA database, we comprehensively investigated the genomic and biological features associated with aging in patients with DTC. ResultsWe confirmed that age was an independent risk factor for overall survival and progression-free survival of patients with DTC, and confirmed that 55 years of age (adopted in the 8th AJCC staging system) is an appropriate cutoff for patients with DTC rather than 45 years (adopted in the 7th AJCC staging system). Using 55 years as the cutoff, we demonstrated DNA methylation-driven transcriptional regulation during aging, and identified the landscape of somatic mutations in young and old patients with DTC along with two aging-related mutations: TTN and EIF1AX. Subsequently, we investigated the infiltration of immune cells in DTC, and found that old patients exhibited decreased CD8+ T cells infiltration with lower cytotoxicity. Finally, we constructed a prognosis prediction model based on three age-related genes (PTK2B, E2F1, and GHR) that showed satisfactory performance in predicting patients prognosis. ConclusionsWe comprehensively investigated the complex interplay between age and biological features of DTC, which may provide new insights into the role of aging in DTC.

Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation.

To evaluate the application value of a new TLNRM staging prediction model based on lymph node ratio (LNR) in patients with Pyriform Sinus and Hypopharyngeal and Laryngeal cancer (PHLC). A total of 2,257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEE database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1,094 people in our hospital were included for external verification and validation. We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1-5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year OS difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system's prediction line. The smaller AIC and BIC suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center. Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients, and can independently guide postoperative chemoradiotherapy in patients.

Prognostic risk stratification value of MACC1 expression in patients with gastric cancer.

The prognostic significance of metastasis-associated in colon cancer-1 (MACC1) has been explored in a variety of malignancies. However, its clinical relevance in patients with gastric cancer (GC) is limited, also remains controversial. In this study, we retrospectively evaluated the prognostic value of lesion MACC1 expression in 347 GC patients. Lesion MACC1 expression was analyzed with immunohistochemistry and grouped as MACC1low (n = 172) and MACC1high (n = 175) cases. Data revealed that the degree of MACC1 expression is not related to patient sex, age and disease stage (all p > 0.05). Survival analysis showed that only post-operation advanced pT (p = 0.018), pN (p < 0.001), pM (p = 0.001) and AJCC stages (p < 0.001) are significantly associated with shorter survival, while no obvious difference was observed between MACC1low and MACC1high cases (p = 0.158). However, we found that survival for female (p = 0.032), older (p = 0.028), and early disease stage (pT stage I + II, p = 0.033) patients with MACC1high are remarkably worse than those with MACC1low. In summary, our findings revealed that, though MACC1 expression is not associated with the survival of the whole cohort, the prognostic risk stratification value of lesion MACC1 expression in subgroups of patients with gastric cancer should be noted.

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study.

Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

Patient-reported and clinical outcomes among patients with pancreatic cancer.

e23200 Background: Pancreatic cancer is associated with poor survival, high symptom burden, and psychological distress. Conventional assessments such as performance status (PS) have relied on provider-generated data to evaluate the selection of treatment and prognosis. Patient-reported outcome measures (PROMs) represent a patient-centric representation of the patient experience and are increasingly applied as tools to help improve outcomes and quality of life. However, little is known about the correlation of PROMs with ECOG PS and clinical outcomes in pancreatic cancer. Methods: We performed a retrospective analysis of patients with pancreatic cancer seen at the Henry Ford Health System between 09/2020 and7/2023, using ICD codes. The NIH’s validated and standardized Patient-Reported Outcomes Measurement Information System was used to capture 4 core domains: fatigue, pain interference, physical function, and depression. Patient-level variables and disease-specific variables were obtained by chart review from EHR. Kruskal-Wallis tests for continuous variables and or Fisher’s exact tests for categorial variables were used to compare the different ECOG scores and PROM scores and patient-level and disease-specific variables. Results: 176 patients were analyzed, with a median age of 65, 58% were male. Most patients had Stage 1 32.9% followed by Stage 4 25.9%, stage 3 22.9%, 1 32.9%. The majority had an ECOG score of 1, followed by, 0, 2, and only 10 had an ECOG PS of 3. There was no statistically significant difference in PS scores according to smoking status, race, or AJCC Stage but differed by age (P = 0.0007). PS score was not significantly associated with PROMscores on depression, fatigue, or pain interference. However, increasing PS scores were associated with a significant increase in low physical function PROM scores (P &lt; 0.0001). Conclusions: Clinician-assessed PS is a single assessment of the patient’s tolerance to therapies subject to physician bias; our study provides encouraging data on the association between PS and patients’ reported physical function. The other PROM domains did not provide additional meaningful information on the patient’s function although are part of clinical decision-making. [Table: see text]

End of life (EOL) care in head and neck squamous cell carcinoma (HNSCC) compared to other solid tumors (OST) in Washington (WA) State.

11147 Background: Real world data describing EOL care in HNSCC is limited. We performed a retrospective study evaluating EOL in HNSCC vs OST in a population-based sample of patients in WA. Methods: We used a database linking WA state cancer registry records with claims records from Medicare, Medicaid, and two large commercial insurers. Patients with HNSCC (oral cavity, oropharynx, hypopharynx, or larynx) were compared to OST (any solid tumor diagnosis). Adults with AJCC stage II-IV or SEER stage Regional/Distant who died in 2011-2021 with continuous insurance enrollment 6 months before death were included. We compared proportions of patients with &gt;1 ED visits in the last 30 days of life, ICU admission in the last 30 days of life, chemotherapy in the last 14 days of life, and hospice enrollment at least 3 days prior to death. We performed multivariate regression analysis to determine factors associated with hospice enrollment. Results: 1,389 patients with HNSCC and 41,412 patients with OST were identified. Demographics for HNSCC vs OST included median age 68 vs 73, white race 91.5% vs 90.1%, stage IV 57.5% vs 45.3%. Insurance types for HNSCC vs OST were commercial 8.4% vs 9.8%, Medicaid 16.6% vs 8.8%, Medicare 59.1% vs 65.5%, multiple 15.8% vs 15.9% (p&lt;0.0001). HNSCC patients had lower rates of &gt;1 ED visits compared to OST (14.1% vs 16.4%, p=0.02); there was no significant difference in ICU admission (25.1% vs 24.0%, p=0.3) or chemotherapy receipt (6.3% vs 5.1%, p=0.056). Hospice enrollment was significantly lower in HNSCC patients (49.0% vs 56.4%, p&lt;0.0001). A stratified analysis limited to stage IV patients yielded consistent findings in all categories. HNSCC patients died more at home and less in hospice (20.2% vs 12.7% and 41.5% vs 52.0%, p&lt;0.0001). In a multivariate regression analysis (Table) HNSCC, black race, living with a partner, or living in neighborhoods with higher area deprivation index (ADI) was associated with lower hospice enrollment. Patients with Medicare or multiple insurance types were more likely to enroll in hospice; AJCC stage was not significant. Conclusions: In this population-based sample, compared to OST, a greater proportion of HNSCC patients were insured by Medicaid at EOL and were less likely to enroll in hospice prior to death. The reasons driving these observed disparities in hospice enrollment warrant further study to optimize EOL care among patients with HNSCC. [Table: see text]

Multi-feature next-generation liquid biopsy for diagnosis and prognosis in HPV-associated head and neck cancer.

6064 Background: Human papillomavirus-associated head and neck squamous cell carcinoma (HPV+HNSCC) releases circulating tumor HPV DNA (ctHPVDNA) into the blood which is a highly accurate biomarker of disease status. Existing approaches based on droplet digital PCR (ddPCR) have limitations in sensitivity, genotype coverage, and do not annotate additional prognostic genomic features. In this study, we tested the diagnostic and prognostic performance of a custom HPV whole-genome next-generation sequencing (NGS) liquid biopsy, termed HPV-DeepSeek, at the time of diagnosis with HPV+HNSCC, compared to ctHPVDNA ddPCR, HPV serology, and clinical work-up. Methods: 304 participants (152 untreated HPV+HNSCC patients, 152 population-level controls) were prospectively enrolled in this single-center prospective cohort study. Plasma samples were analyzed using HPV-DeepSeek, a multiplexed serology assay, single-plex ddPCR, and a 5-genotype multiplexed ddPCR assay. We tested the hypothesis that HPV-DeepSeek would have the highest diagnostic accuracy. We secondarily examined the accuracy of HPV-DeepSeek for prognostic feature annotation including high-risk HPV16 single nucleotide polymorphisms (SNPs), integration events, and PIK3CA mutations. Results: Of 152 cases, 114 (75%) were AJCC stage 1 and 138/152 (91%) were oropharynx primary site cancers. The sensitivity (98.7%), specificity (98.7%), and diagnostic accuracy (0.974) of HPV-DeepSeek was superior (P&lt;0.001) to singleplex ddPCR (94.2%, 98.6%, 0.928), multiplex ddPCR (90.6%, 96.3%, 0.869), HPV serology (86.4%, 96.3%, 0.827), and first attempt clinical diagnostic biopsy (78% sensitive). Utilizing HPV-DeepSeek, 8 different genotypes were detected. 4 patients were found to have multi-genotype infections. 137/152 cases were classified as HPV16, with A1 the most common sub-lineage (90/137). 21 of 137 HPV+HNSCC HPV16 cases (15%) displayed high risk SNPs. Head-to-head comparison of HPV SNP genotyping by HPV-DeepSeek, with the gold-standard tissue-based HPV whole genome sequencing assay, demonstrated 89% concordance in tissue and 85% in blood. The internal concordance rate for HPV-DeepSeek between tissue and blood was 91%. 48 of 152 cases (32%) had at least one viral integration event detected and 36 of 152 cases (24%) had a PIK3CA mutation detected by HPV-DeepSeek. Fragmentomic analysis demonstrated a mean ctHPVDNA fragment size of 148bp for ctHPVDNA versus 167bp for human cell free (cf)DNA from HPV+HNSCC patients and 168bp for control patient cfDNA. Baseline ctHPVDNA quantity was strongly correlated with viral integration status, T stage and N stage (P&lt;0.001). Conclusions: HPV-DeepSeek has improved diagnostic accuracy relative to ddPCR, HPV serology and clinical work-up at the time of diagnosis and demonstrates detection of prognostic features including high-risk HPV16 SNPs, viral integration events, and PIK3CA mutations.