American Joint Committee Research Articles

DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance

PURPOSE Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival. MATERIALS AND METHODS InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia. Cases are patients who died of melanoma within 5 years from original diagnosis. Controls survived longer than 5 years without evidence of melanoma recurrence or relapse. Methylation classes, distinguished by consensus clustering of 850K methylation data, were evaluated for their clinicopathologic characteristics, 5-year survival status, and differentially methylated gene sets. RESULTS Among 422 InterMEL melanomas, consensus clustering revealed three primary melanoma methylation classes (MethylClasses): a CpG island methylator phenotype (CIMP) class, an intermediate methylation (IM) class, and a low methylation (LM) class. CIMP and IM were associated with higher AJCC stage (both P = .002), Breslow thickness (CIMP P = .002; IM P = .006), and mitotic index (both P < .001) compared with LM, while IM had higher N stage than CIMP ( P = .01) and LM ( P = .007). CIMP and IM had a 2-fold higher likelihood of 5-year death from melanoma than LM (CIMP odds ratio [OR], 2.16 [95% CI, 1.18 to 3.96]; IM OR, 2.00 [95% CI, 1.12 to 3.58]) in a multivariable model adjusted for age, sex, log Breslow thickness, ulceration, mitotic index, and N stage. Despite more extensive CpG island hypermethylation in CIMP, CIMP and IM shared similar patterns of differential methylation and gene set enrichment compared with LM. CONCLUSION Melanoma MethylClasses may provide clinical value in predicting 5-year death from melanoma among patients with primary melanoma independent of other clinicopathologic factors.

Role of Ultrasonographic and Clinicopathological Characteristics in Assessing Stromal Tumor-Infiltrating Lymphocyte Density in Triple-Negative Breast Cancer

A high density of stromal tumor-infiltrating lymphocytes (sTILs) is positively correlated with the pathological complete response rate and favorable survival in patients with triple-negative breast cancer (TNBC). Heterogeneity in stromal lymphocyte distribution and limited tumor sampling may affect the accuracy of sTIL quantification in biopsy samples from patients receiving neoadjuvant therapy. Thus, identifying additional biomarkers to complement sTIL evaluation is essential. To identify biomarkers that could be used to complement sTILs evaluation. Retrospective cohort study. A total of 162 patients with invasive TNBC were enrolled in the study. The following data were gathered: sTIL density, Ki67, nuclear grades of cancer cells, lymphovascular invasion status, the American Joint Committee on Cancer stage, axillary lymph node metastasis status, and ultrasonographic parameters of the tumor (size, shape, orientation, margin, internal echo pattern, posterior feature, and vascularity). The relationship between sTIL density and ultrasonographic or clinicopathological characteristics was investigated using both continuous and categorical analyses. Posterior features of the primary tumors was associated with sTIL density (p = 0.038). Additionally, the Ki67 levels and nuclear grades were also associated with sTIL density (p < 0.001 and p = 0.024, respectively). When stratified according to a 20% cut-off of sTIL density, the posterior features of primary tumors, Ki67 levels, and nuclear grades significantly differed between the high and low sTIL density tumors. Tumors with high Ki67 levels were more likely to exhibit high sTIL density than low sTIL density [odds ratio (OR): 2.75, p = 0.021]. Furthermore, nuclear grade III tumors demonstrated significantly higher sTIL density than nuclear grade I-II tumors (OR: 2.49, p = 0.014). Additionally, tumors with posterior enhancement or no posterior features were more likely to exhibit high sTIL density than tumors with acoustic shadows (OR: 2.91, p = 0.028; OR: 2.74, p = 0.022, respectively). Low sTIL density is frequently observed in tumors exhibiting acoustic shadows on ultrasound. However, high sTIL density is more common in tumors with posterior enhancement or no posterior features. Furthermore, high Ki67 levels (> 40%) and high nuclear grades are positively correlated with high sTIL density. This study findings highlight the need for closer surveillance of these biomarkers to complement sTIL evaluation in TNBC.

Survival risk stratification based on prognosis nomogram to identify patients with esophageal squamous cell carcinoma who may benefit from postoperative adjuvant therapy

ObjectiveThe purpose of the study is to develop a prognosis nomogram for esophageal squamous cell carcinoma (ESCC) patients with radical resection and to identify patients who may benefit from postoperative adjuvant radiotherapy/chemoradiotherapy through survival risk stratification.MethodsWe retrospectively enrolled patients who underwent esophagectomy in the First Affiliated Hospital of Nanjing Medical University from July 2015 to June 2017. Patients with stage I-III esophageal squamous cell carcinoma who received radical R0 resection with or without postoperative adjuvant radiotherapy/chemoradiotherapy were included. Further, patients were randomly allocated into two groups (training and validation cohorts) with a distribution ratio of 7:3. The prognosis nomogram was constructed based on independent factors determined by univariate and multivariate Cox analyses. The area under the receiver operating characteristic curve (AUC) and calibration curve were adopted to evaluate the discriminative ability and reliability of the nomogram. The accuracy and clinical practicability were respectively assessed by C-index values and decision curve analysis (DCA), and further contrasted the nomogram model and the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. In addition, survival risk stratification was further performed according to the nomogram, and the effect of postoperative adjuvant therapy on each risk group was appraised by the Kaplan-Meier survival analysis.ResultsA total of 399 patients with esophageal squamous cell carcinoma were recruited in this study, including the training cohort (n = 280) and the validation cohort (n = 119). The nomogram-related AUC values ​​for 1, 3, and 5-year OS were 0.900, 0.795, and 0.802, respectively, and 0.800, 0.865, 0.829 in the validation cohort, respectively. The slope of the calibration curve for both cohorts was close to 1, indicating good consistency. The C-index value of the nomogram was 0.769, which was higher than that of the AJCC 8th TNM staging system by 0.061 (p < 0.001). Based on the prognosis nomogram, patients were stratified into three risk groups (low, medium, and high), and there were obvious differences in prognosis among the groups (p < 0.001). Furthermore, postoperative adjuvant therapy has been shown to enhance the 5-year survival rate by over 15% among patients classified as medium- and high-risk.ConclusionThe constructed nomogram as developed resulted in accurate and effective prediction performance in survival outcomes for patients with stage I-III esophageal squamous cell carcinoma who underwent radical R0 resection, which is superior to the AJCC 8th TNM staging system. The survival risk stratification had potential clinical application to guide further personalized adjuvant therapy.

Tumor Differentiation is Correlated with Estrogen Receptor Beta (ERβ) Expression but Not with Interleukin-6 (IL-6) Expression in Colorectal Carcinoma

BACKGROUND: Colorectal carcinoma (CRC), the third most common malignant disease worldwide, is associated with estrogen receptor β (ERβ) and interleukin-6 (IL-6). ERβ is known to down-regulate IL-6 in prostate cancer, lung carcinoma, and CRC cell lines; however, its effect on human with CRC remains unclear. Therefore, this study was conducted to investigate the association between ERβ and IL-6 expressions with the clinicopathological features of CRC.METHODS: This was an analytic observational study using 40 paraffin blocks of CRC patients. ERβ and IL-6 expression was measured by immunohistochemistry (IHC) staining. The percentage of immunoreactive tumor cell per 1000 cells was manually recorded and tumor differentiation as well as tumor infiltration were determined. Tumor differentiation was graded according to the World Health Organization (WHO) 2010 criteria, while tumor infiltration was defined based on the American Joint Committee on Cancer (AJCC) 8th edition.RESULTS: Fifty percent of samples were well-differentiated CRC, and 57.5% samples were T3 infiltration tumors. IHC staining showed 35.5% of samples were positive for ERβ expression, while 70.86% were positive for IL-6 expression. There were negative correlation of ERβ expression with tumor differentiation (p=0.018; r=-0.371), but no correlation with tumor infiltration (p=0.836) were found. There was no correlation between ERβ expression with IL-6 expression (p=0.154).CONCLUSION: There is statistically significant correlation between tumor differentiation and ERβ expression, wherein improved tumor differentiation is linked to higher levels of positive ERβ expression. However, there is no discernible relationship between IL-6 and tumor differentiation. These findings suggest that while IL-6 was involved in the growth of the tumor, ERβ expression might have an impact on tumor differentiation.KEYWORDS: colorectal carcinoma, estrogen receptor beta, interleukin-6, cell differentiation

Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer

BackgroundNeoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy...

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.

Prognostic Value and Clinical Implication of Lymph Node-to-Primary Tumor SUV Ratio in Node-Positive Hypopharyngeal Squamous Cell Carcinoma Treated With Radiotherapy With or Without Chemotherapy.

The aim of this was to evaluate the prognostic significance of the nodal-to-primary tumor SUVmax ratio (NTR) in patients with node-positive hypopharyngeal squamous cell carcinoma (HPSCC) treated with radiotherapy with or without concurrent chemotherapy. The study aims to enhance prognostic accuracy by incorporating NTR into the American Joint Committee on Cancer (AJCC) staging system. This retrospective study included 191 patients with biopsy-proven node-positive HPSCC treated from 2005 to 2013. NTR was calculated as the ratio of SUVmax of metastatic lymph nodes to the primary tumor's SUVmax. Survival analyses were conducted using Cox regression models and Kaplan-Meier analysis. Receiver operating characteristic analysis compared the prognostic performance of the modified and AJCC staging systems. The median follow-up was 8.27 years, with 135 deaths (70.7%). High NTR (≥0.63) was significantly associated with worse overall survival (OS) and was an independent prognostic factor in multivariable analysis (adjusted hazards ratio [HR] = 1.63, P = 0.007). Median OS for high NTR was 17.4 months, compared with 75.2 months for low NTR. High NTR significantly predicted worse OS within AJCC stage IVA patients (HR = 6.09, P = 0.014). Patients in modified stage IVA (AJCC stage IVA with low NTR) had significantly longer OS than those in modified stage IVB (AJCC stage IVA with high NTR and AJCC stage IVB) (HR = 8.62, P = 0.003). The modified staging system incorporating NTR showed superior prognostic performance compared with the AJCC staging system. NTR is a significant independent prognostic factor for OS in node-positive HPSCC patients. Integrating NTR into the AJCC staging system improves prognostic accuracy.

Depth of invasion and extranodal extension: the influential factors to predict survival rate of patients with oral tongue squamous cell carcinoma

BackgroundCancer staging is essential in determining patients’ prognoses and designing the appropriate treatment strategy. American Joint Committee on Cancer has released the latest version of the staging system for tongue SCC. However, it is interesting to know whether this change in staging and the addition of depth of invasion (DOI) and the extra-nodal extension (ENE) have any influence on patients’ prognosis.MethodsIn this retrospective cohort study, the pathology records of patients with tongue SCC who underwent surgery at the Pathology Department of Cancer Institute Hospital, 2017–2021, were collected by referring to the hospital information system. Then the rate of change of pT, pN, and overall stage were assessed based on American Joint Committee on Cancer 7th and 8th editions.ResultsThe records of 204 patients were included in the final analysis. Significant changes in the staging system 2021 resulted in upstaging 64 patients (31.4%) in the overall stage, 91 patients (44.6%) in pT, and 30 patients (14.7%) in pN. The survival of upstaged patients was inferior compared to those without upstaging. However, this was not statistically significant for tumor and overall upstaging in the univariate analysis, while those with upstaged pN had significantly shorter survival. In the multivariate analysis, pT upstage also significantly impacted survival.ConclusionThis study showed the importance of pathology reports based on the latest edition of the American Joint Committee on Cancer, the accuracy in examining factors such as depth of invasion and extra-nodal extension.

Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification

Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Observed Changes in the Distribution of Colon Cancer Metastasis: A National Cancer Database Review and Institutional Experience.

The University of Louisville has observed a near 70% drop in resectable/borderline resectable metastatic colorectal cancer in the past 5 years. The aim of this study was to evaluate the distribution of colon cancer metastasis at diagnosis and at recurrence. Stage was defined by the American joint committee on cancer (AJCC) eighth edition. Institutional review board approval was granted for post hoc review of stage II and III patients with colon cancer from the University of Louisville prospective hepatic database from 2002 to 2023, as well as for the National cancer database (NCDB) Participant user file (PUF) 2021. The Surveillance epidemiology and end-results (SEER) 22 database was also utilized to corroborate the findings in the NCDB. Between 2018 and 2021 pathological M1a decreased annually (51.9-46.3%), while M1c increased year-over-year (26.6-32.4%) and M1b stayed relatively the same (21.4-21.3%). These differences were significant on chi-squared analysis with a p value of < 0.001. Univariate analysis of the post hoc review between 2017 and 2020 revealed significant differences between stage 4a and 4c in terms of race (p value 0.018), carcinoembryonic antigen (CEA) at diagnosis (p value 0.037), CEA at recurrence (p value 0.012), presence of liver metastasis (p value 0.003), and referral pattern (p value 0.014). Multivariate analysis identified stage 4b as an independent predictor for hepatic metastasis (odds ratio; OR 4.69, p value 0.011). A significant change in the distribution of colon cancer metastases has occurred at an institutional and national level over the past 3-5 years. Interdisciplinary treatment strategies will have to be modified accordingly.

7478 Effects of RAI on Papillary Thyroid Carcinoma with Positive Lymph Nodes

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

Evaluation of lymph node ratios and log odds of positive nodes as prognostic indicators in primary organ malignancy

BackgroundStaging of malignant tumours based on positive lymph node number and not taking into account the actual number of examined lymph nodes during surgery may lead to bias and fallacious results. The ratio of positive and resected lymph nodes (LNR) and log odds of positive nodes (LODDS) emerged as novel prognostic markers in deciding the future course of management better than the parameter pN in predicting cancer-specific survival. We aim to evaluate and compare the prognostic value of pN, LNR and LODDS in common primary organ malignancies like breast, head and neck, gastric and cervical cancers. MethodsThis was an ambidirectional observational study conducted from September 2018 to August 2021 with one year (from 2017 to 2018) for retrospective data collection archived from records. It included patients affected by breast, head and neck, gastric and cervical cancers and were followed up for a period of 3 years from the date of diagnosis to perform a holistic survival analysis. The sample was grouped by American Joint Committee on Cancer N stage, LNR and LODDS, and analysed using Kaplan–Meier and multivariate Cox proportional hazard models. ResultsThe study included 202 breast cancer patients, 85 head and neck cancer patients, 100 gastric cancer patients and 52 cervical cancer patients. Multivariate Cox regressions analysis demonstrated a lower Akaike Information Criterion (AIC) value for LODDS and LNR followed by pN stage. ConclusionThe novel indicators LNR and LODDS better predicted the biological behaviour irrespective of lymph node number and allowed clinicians to correctly stratify patients for better postoperative management.

Establishment of a clinical model based on vessels encapsulating tumour clusters that could efficiently predict recurrence of patients with hepatocellular carcinoma after curative hepatectomy

According to previous studies, vessels encapsulating tumor clusters (VETC) could promote metastasis of hepatocellular carcinoma (HCC) in a manner independent from epithelial-mesenchymal transition (EMT). However, the prognostic significance of VETC among patients undergoing curative hepatectomy has not been fully explored. This study was performed to assess the prognostic significance of VETC among patients undergoing curative hepatectomy.81 patients undergoing curative hepatectomy were included in this study. A predictive model based on VETC was established. Then this predictive model based on VETC was compared with American Joint Committee on Cancer Tumor Nodal Metastasis (AJCC TNM) and Barcelona Clinic Liver Cancer (BCLC) system.It was revealed by multivariate Cox regression analysis that high neutrophil lymphocyte ratio (NLR) (P=0.013, HR=6.175, 95%CI: 1.468-25.977), number of tumors (P＜0.001, HR=4.119, 95%CI 1.886-8.995) and VETC positivity (P=0.010, HR=2.440, 95%CI 1.235-4.821) were independent predictive factors for disease-free survival (DFS). Additionally, by Kaplan-Meier analysis, we revealed that VETC positivity was associated with worse DFS (P=0.018). Then the clinical predictive model combining NLR, number of tumors, and VETC was compared with AJCC TNM stage and BCLC classification system by performing time-dependent receiver operating curve (td-ROC) analysis, revealing that the clinical predictive model was superior to AJCC TNM stage and BCLC system at different time points. Additionally, we demonstrated that the clinical model could well predict DFS by plotting calibration curves.VETC could be utilized as an efficient prognostic factor for HCC and the clinical predictive model combining NLR, number of tumors, and VETC was superior to AJCC TNM stage and BCLC system in predicting cancer recurrence.

Nutritional support after hospital discharge reduces long-term mortality in patients after gastric cancer surgery: secondary analysis of a prospective randomized trial

Background & aimsNutritional support after hospital discharge was found to enhance the nutritional condition of patients after cancer surgery. However, the effect of nutritional support after hospital discharge in patients after cancer surgery on long-term clinical outcomes is controversial. We aimed to investigate the effect of nutritional support after hospital discharge on long-term clinical outcomes in patients after gastric cancer surgery. MethodsThis study conducted a secondary analysis on individuals at nutritional risk who underwent gastric cancer surgery included in a randomized controlled trial. The intervention group received oral nutritional supplements combined with dietary advice, and the control group received dietary advice alone. The long-term mortality (primary outcome) and other clinical outcomes were compared between groups. ResultsIn total, 321 patients were included in this analysis, with a median follow-up duration of 60.5 months. According to the Nutritional Risk Screening 2002 (NRS 2002), the presence of nutritional risk was found to be a significant predictor of death. This association remained independent even after adjusting for age, sex, comorbidity, and American Joint Committee on Cancer stage (AJCC). The adjusted hazard ratio (HR) for mortality increased by 1.30 [95% confidence interval (CI) 1.05-1.60, P= 0.016] for each additional point rise in NRS. During the follow-up, a total of 64 individuals (39.5%) in the intervention group and 81 patients (50.9%) in the control group died. Consequently, the adjusted HR for mortality between two groups was 0.69 (95% CI 0.50-0.96, P=0.026). The results of interaction tests did not yield statistically significant variations in fatality rates through the age, sex, comorbidity, NRS, and AJCC stage subgroups. Nutritional support after hospital discharge significantly improved handgrip strength (adjusted coefficient 5.05, 95% CI 3.01-7.08, P=0.000) among other functional outcomes. ConclusionsNutritional support after hospital discharge reduced long-term mortality and improved handgrip strength among patients at nutritional risk after gastric cancer surgery. The current investigation provides the guarantee of nutritional support after hospital discharge for patients after surgery in cancer management guidelines.

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

The prognostic value of the 8th American Joint Committee on cancer anatomic and prognostic stage groups for penile cancer: A multicenter collaboration study

ObjectiveThe aim of this study was to investigate the value of 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. MethodsThe clinical and histopathologic data from 16 centers between 2000 and 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan–Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). ResultsThe 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV (stage 0 to stage IV) disease were 100 %, 98.9 %, 85.5 %, 81.1 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–IIA<0.001, pIIA–IIB=0.486, pIIB–IIIA<0.001, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 98.9 %, 87.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–II<0.001, pII–IIIA=0.002, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 99.0 %, 85.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.757, pI–II<0.001, pII–IIIA=0.008, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). The C-index of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. ConclusionThere is still room for improvement about 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, had a similar predictive value.

Validation of clinical tumor depth of invasion measure in patients with oral cavity cancer

ObjectivesThe 8th edition of the American Joint Committee on Cancer (AJCC) for head and neck malignancies incorporated depth of invasion (DOI) for oral cavity squamous cell carcinoma (OCSCC). Currently, there is no standardized method to determine clinical DOI (cDOI). We aim to validate radiologic DOI (rDOI) utilizing contrast-enhanced computed tomography (CECT) imaging. Materials and MethodsRadiographic DOI was defined as the coronal measurement of the deepest margin parallel to the expected normal mucosal plane. To establish a valid, accurate and repeatable rDOI, a retrospective cohort at a single institution tertiary hospital underwent preoperative CECT. Radiographic DOI was independently assessed by 2 neuroradiologists. Correlation was determined between rDOI and pDOI. A prospective pilot study of 49 patients with newly diagnosed OCSCC underwent rDOI assessment compared to final pDOI to assess our rDOI method clinical applicability. ResultsNeuroradiologists demonstrated a high degree of predictability between rDOI and pDOI with as great as 90.91% accuracy for readable CECTs. Inter-observer correlations were strong in the retrospective (Session 1: ICC= 0.956; Session 2: ICC= 0.932) and prospective cohorts (Session 1: ICC= 0.859; Session 2: ICC=0.913) illustrating reliability. Intraobserver correlations were also strong (Retrospective Reader 1 ICC=0.968, Reader 2 ICC=0.941; prospective Reader 1 ICC=0.965, Reader 2 ICC=0.800, p<0.001). T1 lesions were immeasurable 25-62.5% of the time. ConclusionsUsing CECT, the coronal measurement of the deepest margin parallel to the expected normal mucosal plane can enhance determination of a reliable cDOI in OCSCC corresponding to pDOI without change in staging for T2 and greater lesions.

Prognostic utility of the modified albumin-bilirubin score among patients undergoing curative-intent surgery for gallbladder cancer

BackgroundGallbladder cancer (GBC) has been associated with high rates of recurrence and dismal prognosis even after curative-intent resection. The prognostic utility of the modified albumin-bilirubin (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined. MethodsPatients who underwent radical resection for GBC between 2000 and 2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship among mALBI score, overall survival (OS), and recurrence-free survival (RFS) was examined. ResultsAmong 269 patients who underwent radical resection for GBC, 161 (59.9%) had mALBI grade 1, 48 (17.8%) had grade 2a, 47 (17.5%) had grade 2b, and 13 (4.8%) had mALBI grade 3. After surgery, compared with patients with a low mALBI grade (grade 1/2a), individuals with a high mALBI grade (grade 2b/3) had worse 5-year OS (54.4% vs 19.2%, respectively; P < .001) and RFS (42.0% vs 17.8%, respectively; P < .001). On multivariable analysis, after controlling for relevant clinicopathologic variables, individuals with a high mALBI score remained independently associated with higher risks of death and recurrence (OS: hazard ratio [HR], 2.38 [95% CI, 1.50–3.79]; RFS: HR, 2.12 [95% CI 1.41–3.20]) versus patients with a low mALBI score after curative-intent resection for GBC. Of note, mALBI score was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic American Joint Committee on Cancer subclassifications failed to distinguish patients with long-term survival. ConclusionThe mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool for patients undergoing curative-intent resection for GBC.

Prognostic value of three clinical nutrition scoring system (NRI, PNI, and CONUT) in elderly patients with prostate cancer.

Most of patients with prostate cancer (PCa) are elderly and have a long course of disease. Preoperative assessment of the patient's clinical nutritional status facilitates early intervention and improves patient prognosis. We assessed the nutritional status of PCa patients utilizing the Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) scoring systems. Survival comparisons between groups were conducted using Kaplan-Meier curve analysis and log-rank tests, while Cox proportional hazards regression analysis was employed to identify independent prognostic factors. Furthermore, we implemented bootstrap-based optimism correction methods to validate the scoring systems and applied decision curve analysis to evaluate the non-inferiority of these three clinical nutrition scoring systems relative to the conventional American Joint Committee on Cancer (AJCC) staging. In this study, malnutrition was diagnosed in 31.51% of the patients using the NRI, 13.02% using the PNI, and 88.28% using the CONUT score. After adjusting for confounders, normal nutritional status as defined by NRI and PNI emerged as an independent prognostic factor for prostate-specific antigen progression-free survival (PSA-PFS). However, nutritional status assessed by CONUT inaccurately predicted PSA-PFS. Normal nutritional status, as determined by all three scoring systems, was found to be an independent prognostic factor for progression-free survival (PFS). Following adjustments for optimistic estimates, the C-index for NRI in predicting both PSA-PFS and PFS remained the highest among the three scoring systems. The results of the DCA indicated that the C-index of all three scoring systems was higher than that of AJCC stage. NRI, PNI, and CONUT are convenient and clinically applicable scoring systems. A clinical malnutrition intervention may improve the prognosis of prostate cancer patients.

Impact of location and size of minimal extrathyroidal extension on lymph node metastasis in papillary thyroid cancer: a retrospective analysis.

The 8th edition of the American Joint Committee on Cancer (AJCC)'s T-stage for differentiated thyroid cancer (DTC) removes minimal extrathyroidal extension (mETE), while ignoring the risk of mETE would lead to overtreatment or inadequate treatment. The aim of this study was to investigate the impact of location and size of mETE on lymph node metastasis in papillary thyroid cancer (PTC). A retrospective analysis of 267 patients who underwent unilateral radical surgery for PTC was conducted. According to the postoperative pathology, they were divided into mETE group (121 patients) and non-mETE group (146 patients). The number of lymph nodes dissected and the number of lymph nodes metastasized were compared between the two groups. The linear regression analysis and the receiver operating characteristic (ROC) curves were performed to evaluate the impact of the locations and sizes on lymph node metastasis. There was no significant difference in the number of lymph node dissected between the mETE group and the non-mETE group. The tumor located at the upper part and the size <1.0 cm in mETE group showed a higher number of lymph node metastasis (0.78±0.88 vs. 0.25±0.45, P=0.03). Meanwhile, in the mETE group, the number of patients with lymph node metastasis was higher than that in the non-mETE group. Further subgroup analysis revealed that for PTC patients with tumors at the upper part and size <1.0 cm, the number of those with lymph node metastasis in the mETE group was also greater than that in the non-mETE group. Furthermore, the Spearman correlation analysis showed a positive correlation between tumors located at the upper part with a size <1.0 cm and lymph node metastasis rate (R=0.647, P=0.004). Additionally, if the upper part tumor was within 1 cm, the tumor's size was able to identify the lymph node metastasis, with the optimal cut-off point of 0.45 cm (Youden index =0.650). When tumors combine with mETE, the probability of lymph node metastasis increases in tumors located at the upper part with a size <1.0 cm. Especially, when the upper part tumor is within 1 cm, the tumors of size ≥0.45 cm are more likely to have lymph node metastasis.