AJCC 8th Research Articles

Predictors of Sentinel Lymph Node Biopsy in Thin Melanoma: Understanding the Impact of the American Joint Commission on Cancer 8th Edition Staging System.

The definition of T1b cutaneous melanoma was changed in the 8th edition of the AJCC staging system based on survival differences but not risk of sentinel lymph node (SLN) metastases. We sought to evaluate changes in SLN biopsy (SLNB) use and rates of positive SLNB in response to updated staging criteria, and to evaluate the incidence of high-risk features in T1a melanoma in whom SLNB is now recommended. The 2021 National Cancer Database Melanoma PUF was used to obtain SLNB utilization and positivity rates in T1 (thin) melanoma (thickness ≤1.0mm) from 2012 to 2021. Rates were compared between AJCC 7th (2012-2017) and 8th editions (2018-2021). Factors associated with SLNB use in non-ulcerated T1 melanoma were evaluated. The presence of high-risk feature in T1a melanoma were identified and SLN positivity rates were reviewed. A total of 136,966 cases were included with 76,485 (55.8%) cases diagnosed under the AJCC 7th edition era (2021-2017). The overall proportion of patients with thin melanoma undergoing SLNB was relatively stable over the time periods, roughly 30%. In the AJCC 8th edition era, the overall SLNB positivity rate slightly increased from 4.5% to 6.6% (p < 0.001). There was increased SLNB use in melanoma with a thickness of 0.8 to 1.0mm (T1b: OR 2.53 [95% CI 2.31-2.78]) and decreased use when thickness was less than 0.8mm (T1a: OR 0.80 [0.76-0.85]). Rates of SLNB positivity increased in both thickness groups over time. After implementation of the AJCC 8th edition staging criteria, surgeons have become more selective in SLNB use with a resulting increase in SLNB positivity rate. Fewer SLNBs in T1a and more SLNBs in non-ulcerated T1b are being performed.

Pathologic responses and clinical outcomes with neoadjuvant doublet chemotherapy for newly diagnosed, surgically-resectable p16-positive oropharyngeal cancer.

The feasibility and outcomes of neoadjuvant doublet chemotherapy with cisplatin and docetaxel followed by surgical resection of residual disease (NAC+S) for patients with newly diagnosed, resectable p16 positive (+) oropharyngeal squamous cell carcinoma (OPSCC) has been reported from a single institution. Here, we report pathologic responses, need for adjuvant treatment and recurrence-free survival (RFS) following this treatment from a second large academic institution. A retrospective cohort study of patients with p16+OPSCC receiving NAC+S and risk-adjusted adjuvant treatment between January 2017 and March 2024 was performed. Of the 76 patients who met the inclusion criteria, 43 (57%) patients developed clinical-to-pathologic downstaging; all remaining patients had clinical and pathologic stage I disease (AJCC 8th). Thirty-seven (49%) patients experienced complete pathologic response (pCR). Sixty-four (89%) patients avoided adjuvant treatment. Two-year overall survival (OS) and RFS were 93.7% and 75.4%, respectively. Development of a pCR did not statistically associate with improved RFS, but only 8 patients developed disease relapse. Of the 8 (11%) patients that recurred, 3 had developed a pCR and 5 had not. Using risk-adjusted criteria from pathologic analysis, a high proportion of patients with newly diagnosed, resectable p16+OPSCC appear to be able to avoid adjuvant treatment following the NAC+S treatment regimen without sacrificing disease control. Prospective clinical study of the NAC+S treatment strategy with clearly defined inclusion and adjuvant treatment criteria is warranted to determine whether this approach strategy can be safely offered to patients that wish to minimize the need for adjuvant radiation.

Comparison Between AJCC 8th Edition Gastric and Esophageal ypTNM Classification System in Siewert II Esophagogastric Junction Adenocarcinomas: A Retrospective Study Based on Eastern and Western Data

Multimodal therapy has become the standard treatment for curable upper gastrointestinal cancers. However, it remains unclear which 8th edition AJCC post-neoadjuvant therapy pathological classification system, esophageal (ypTNM-EC) or gastric (ypTNM-GC), can predict the overall survival (OS) of patients with Siewert II adenocarcinomas better. Patients diagnosed with Siewert II adenocarcinomas receiving neoadjuvant therapy plus curative resection at the University Medical Center Utrecht (UMC Utrecht) and the Peking University Cancer Hospital (PUCH) between the 2001 and 2022 were included in this study. The patients from two institutions were analyzed separately. Predictive univariable and multivariable Cox models based on ypTNM-EC and ypTNM-GC were constructed. The C-index and calibration curves were used to compare the predictive abilities of ypTNM-EC and ypTNM-GC Cox models. A total of 125 patients from UMCU and 145 from PUCH were included. There was no significant difference in the C-index between the ypTNM-EC and the ypTNM-GC univariable and multivariable Cox models in the UMC Utrecht (p-value=0.883; p-value=0.681) and PUCH (p-value=0.808; p-value=0.548) cohorts, and no significant difference was observed between their calibration curves in the two cohorts. The AJCC 8th edition ypTNM prognostic classification systems for esophageal and gastric cancer demonstrated no difference in predicting OS for patients with Siewert II adenocarcinomas both in the Western and Eastern data. The ypTNM-GC, with fewer stage groups, may offer greater convenience for clinical application.

Abstract C028: Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence

Abstract There have been improvements in clinical risk stratifications for oral cavity squamous cell carcinoma (OSCC) with the AJCC 8th edition staging system. Other studies suggest the addition of a metric of specific immune interactions in and around the tumor may be helpful to further stratify patients, with mixed findings. The advent of spatial imaging has allowed a global view for assessing tumor features in the context of all surrounding cell interactions. We hypothesize that the lack of architectural information could contribute to varied clinical outcomes in previous studies, such as tumor recurrence. This highlights how spatial technologies could aid in understanding the role of tissue architecture and its influence on biology and medicine. To study tissue remodeling spatially, we focused on multiplexed-ion beam imaging (MIBI), a spatial proteomics platform to visualize 40 immuno-onco proteins simultaneously. Our banked patient cohort consists of 20 recurrent and 49 non-recurrent OSCC primary surgery samples. Clinical metadata capturing pathologic stage, alcohol use, smoking history, survival data, and more were also collected. With our pathologist, we curated 290 field-of-views (FOVs) of matched primary tumors, uninvolved lymph nodes, and metastatic lymph nodes (if any). Downstream computational analysis using existing MIBI codebases augmented with in-house spatial analytics has revealed a robust spatial dataset. After using machine-learning algorithms to cell segment our images, we validated these assigned cells and marker staining to further annotate cell populations. When we analyzed direct cell interactions, there was a decrease in heterogeneity in immune interactions within recurrent patients compared to non-recurrent patients. To ascertain how the loss of these interactions affected recurrence prognosis, we investigated their prevalence within the tumor border vicinity. We hypothesize that the proximity and cell-cell interactions near the border will promote a tumor-suppressive environment. Utilizing centroid-to-centroid distance measurements, we distilled the top 30 cell-cell interactions within a 100-micron distance from the tumor border. Cell pairs involving macrophage tissue-resident memory cells and CD8 T memory resident cells were more abundant in recurrent patients, while pairs involving CD4 T regulatory and CD8 cells were found in non-recurrent patients. Reassuringly, cell pairings involving myeloid cells were upregulated in the recurrent cohort as expected. Interestingly, cancer-associated fibroblast cell pairings were upregulated indiscriminately in both patient sub- cohorts. This suggests that the impact of certain known immunosuppressive changes may contribute in varying amounts to disease control. Our data demonstrates differences in the architecture of tumors with known divergent outcomes, which suggests global tissue-level changes could be a predictive factor. Clinically, interrogating these interactions of interest could guide treatment escalation or de-escalation in the future. Citation Format: Connie J. Zhou, Jane Lee, Rebecca Jaszczak, Steven R. Long, Patrick K. Ha, Matthew H. Spitzer. Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C028.

Prognostic model for resected borderline and locally advanced pancreatic cancer after neoadjuvant chemotherapy.

The current AJCC 8th has been reported to have a poor ability to predict the prognosis in patients with resected borderline resectable pancreatic cancer and locally advanced pancreatic cancer following neoadjuvant chemotherapy. This study was aimed to develop an improved prognostic model by incorporating pathology and parameters of biologic response (BR). A retrospective cohort study was conducted including patients who underwent curative-intent surgery following chemotherapy. We developed a modified ypT staging system and incorporated the BR, involving normalization of carbohydrate antigen 19-9 and reduction in the maximum standardized uptake value simultaneously after chemotherapy. The prognostic performance of the current pathologic system, modified pathologic system, and newly developed system incorporating pathology and BR were compared. In this study, 171 patients underwent surgery following chemotherapy. The modified T stage, which unified ypT2 and ypT3, demonstrated improved prognostic performance than the current staging system (area under the curve: 0.706 vs. 0.661). Biologic unresponsiveness was an independent prognostic factor for worse survival (hazard ratio 2.31, 95% confidence interval 1.50-3.55, P<0.001). The modified pathology with BR system demonstrated the highest discriminative ability in predicting 5-year overall survival than the current pathologic system (area under the curve: 0.785 vs. 0.661, P=0.010) and modified pathologic staging system (area under the curve: 0.785 vs. 0.706, P=0.002). The prognostic model, incorporating modified ypT staging and elevated carbohydrate antigen 19-9 levels and maximum standardized uptake value simultaneously, demonstrated improved results in predicting oncologic outcomes for patients who underwent surgery following neoadjuvant chemotherapy.

Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for hepatocellular carcinoma.

Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, the authors adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, their model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data. The authors conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA. The authors recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5 years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model. The authors' modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.

Cutaneous Toxicities of Advanced Treatment for Cutaneous Melanoma: A Prospective Study from a Single-Center Institution.

The landscape of advanced melanoma treatments has shifted dramatically in recent years. Target therapy and immunotherapy have changed the management of patients with both metastatic (stage IV according to AJCC 8th ed.) and nodal (stage IIB/C and III) disease. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, high-grade or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining a patient's quality of life is of paramount importance. We undertook a prospective, monocentric, and descriptive study in Bologna, Italy, including patients referred to the Oncologic Dermatology Unit of IRCCS AOU of Bologna who developed biopsy-proven cutaneous adverse events (AE) under treatment with immunotherapy for cutaneous melanoma with nodal (stage IIB/C, III) and metastatic (stage IV) disease from January 2016 to April 2024. In 202 identified patients, 75 (37.5%) developed skin AEs. Ipilimumab was causal for 48.1% of skin AEs, followed by nivolumab (37%) and pembrolizumab (31.4%). Recorded types of skin AEs included erythematous rash, vitiligo, alopecia, lichenoid, maculopapular, acneiform, urticarial, psoriasiform, granulomatous, eczematous, and severe cutaneous AEs, such as Erythema multiforme/Stevens-Johnson syndrome and bullous autoimmune dermatoses. Most AEs were low-grade [CTCAE 1-2] (97%) and typically occurred after 10 weeks of treatment. This study comprehensively describes skin AEs occurring during systemic treatment with ICIs for cutaneous melanoma at a single center.

Prognostic value of a modified pathological staging system for gastric cancer based on the number of retrieved lymph nodes and metastatic lymph node ratio.

The prognosis for gastric cancer (GC) remains grim, underscoring the importance of accurate staging and treatment. Given the potential benefits of using lymph node ratio (LNR) for improved prognostication and treatment planning, it is critical to incorporate examined lymph nodes (ELN) count in an integrated GC staging system. Patients data from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 was utilized as training set. The Mantel-Cox survival test was used to calculate chi-square values for 40 LNR segments with a 0.025 interval, defining a novel LNR-based N (rN) classification based on the cutoff points. A revised AJCC (rAJCC) staging system was established by replacing the 8th AJCC N staging with a rN classification. The relationship between the ELN count and prognosis or positive lymph node detection was conducted by using multivariable models. The series of the odds ratios and hazard ratios were fitted with a locally weighted scatterplot smoothing (LOWESS) smoother, and the structural break points were determined by Chow test to clarify an optimal minimum ELN count. The integrated GC staging system incorporated both rAJCC system and the ideal ELN count. Discriminatory ability and prognostic homogeneity of the rAJCC and integrated staging system was compared with AJCC staging system in the SEER validation set (2016-2017), the Cancer Genome Atlas Program (TCGA) database, and the Third Affiliated Hospital of Sun Yat-sen University database. The current study found that LNR and ELN count are both significantly associated with the prognosis of GC patients (HR = 0.98, p < 0.001 and HR = 2.51, p < 0.001). Four peaks of the chi-square value were identified as LNR cut-off points at 0.025, 0.175, 0.45 and 0.6 to define a novel rN stage. In comparison to the 8th AJCC staging system, the rAJCC staging system demonstrated significant prognostic advantages and discriminatory ability in the training set (5-Y OS AUC: 71.7 vs. 73.0; AIC: 57,290.7 vs. 57,054.9). The superiority of the rAJCC staging system was confirmed in all validation sets. Using a LOWESS smoother and Chow test, a threshold ELN count of 30 was determined to maximum improvement in the prognosis of node-negative patients without downgrading due to potential metastasis, while also maximizing the detection efficiency of at least one involved lymph node. The integrated staging system, combining the refined rAJCC classification with an optimized ELN count threshold, has demonstrated superior discriminatory performance compared to the standalone rAJCC or the traditional AJCC system. The development of a novel GC staging system, which integrated the LNR-based N classification and the minimum ELN count, has exhibited superior prognostic accuracy, holding promise as a valuable asset in the clinical management of GC. However, it is crucial to recognize the limitations from the retrospective database, which should be addressed in subsequent analyses.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

Prognostic significance of anatomic site-specific depth of invasion in oral squamous cell carcinoma - An eastern Indian multi-center study

A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), >5 to ≤10 mm(B) and >10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0–1.2, p < 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was >20 % for all intra-oral sites combined. DOI <5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8–49.9) and DSS (OR = 14.7 % CI: 5.9–37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and > 5 mm for advanced cases across all evaluated oral anatomic sites.

430. PROGNOSTIC PATTERNS OF LYMPH NODES WITH COMPLETE TREATMENT RESPONSE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY AND NEOADJUVANT CHEMOTHERAPY

Abstract Background The prognostic significance of lymph nodes with pathological complete treatment response (pcr-LN) has not been well investigated in esophageal squamous cell carcinoma (ESCC). We aimed to determine the prognostic impact of pcr-LNs in ESCC after either neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). Methods 578 patients with ESCC from two medical facilities were analyzed retrospectively, with 303 patients receiving nCRT and 275 receiving nCT. Pcr-LNs were defined as LNs exhibiting regression changes, such as fibrosis, mucin lakes, keratinization, and giant cell responses but no evidence of living tumor cells. 5 LN status subgroups were identified based on the ypN category in 8th AJCC: ypN0/pcr-LN-, ypN0/pcr-LN+, ypN1, ypN2, and ypN3. The Kaplan-Meier approach was used to analyze the overall survival (OS), and subgroup findings were compared using the log-rank test. Multivariate analysis of OS was performed using a Cox proportional hazard model. Results 45 patients were classified into ypN0/pcr-LN+ (7.8%), 33 in the nCRT group, and 12 in the nCT group (p = 0.006). Compared to the nCRT group, the nCT group underwent a more thorough LN dissection (LN (mean (SD)): nCRT, 21.05 (8.77); nCT, 26.08 (11.66); p = 0.001). Survival analysis of OS showed the subgroup ypN0/pcr-LN+ had a significantly worse prognosis than ypN0/pcr-LN- in the nCRT group (p = 0.047), but no difference was seen in the nCT group. Multivariable analysis revealed that ypN0/pcr-LN+ patients in the nCRT group had a greater risk of mortality than ypN0/pcr-LN- patients (p = 0.0487). Conclusion The nCRT group had a more noticeable complete treatment response in LNs than the nCT group. However, in comparison to the nCT group, the nodal downstaging with radiotherapy in the nCRT group may not translate into improved outcomes. More aggressive systemic therapy might be required to improve the overall survival in esophageal cancer patients receiving neoadjuvant treatment.

Mucosal Melanoma: Review from a Pathologist Point of View

Mucosal melanomas are rare malignant tumors arising from the epithelia lining the inner mucosal surfaces of the body. Unlike cutaneous melanoma, we have a limited understanding of mucosal melanomas is currently limited. Mucosal melanomas are characterized by genetic alterations quite distinct from cutaneous melanomas; however, their causative and promoting factors are unknown. These melanomas are characteristically diagnosed at a later stage due to their occult locations, leading to a worse prognosis. Dedicated staging systems for mucosal melanomas exist only for sinonasal and conjunctival melanomas. Therefore, risk stratification of patients with mucosal melanomas, particularly those arising from the anogenital area, is challenging. Recent studies have shown that minor modifications of the AJCC 8th Edition cutaneous melanoma staging system can group patients fairly robustly; however, the proposed T-categorization systems have yet to be validated in larger cohorts. We summarize the demographic, clinical, histopathologic, and molecular features of common subtypes of mucosal melanomas and highlight the outstanding needs in this field.

235. A NOVEL TUMOR STAGING SYSTEM INCORPORATING CN STATUS FOR STRATIFYING EARLY STAGE ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS AFTER TRIMODAL THERAPY

Abstract Background This study aims to assess the prognostic significance of cN status in early-stage esophageal squamous cell carcinoma (ESCC) patients following neoadjuvant chemoradiotherapy (nCRT) and develop a novel staging model for personalized survival prediction. Methods Patients with ESCC who underwent nCRT and esophagectomy were included. The Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) were employed to evaluate the validity of various oncological staging systems. A reduction in AIC and BIC values indicates improved predictive capability and accuracy. Results We established a novel staging model by incorporating ypTNM stage and cN status, effectively stratifying ypI ESCC patients. Cox regression analysis showed that only cN status was an independent prognostic factor for both overall survival (p = 0.030) and disease-free survival (p = 0.019) in patients with stage ypI. The newly developed ypTNM-cN staging exhibited a superior alignment with overall survival trends compared to the AJCC 8th ypTNM staging, with a significantly lower AIC of 3143.014 versus 3149.950. This superiority was further supported by a BIC of 3146.605 compared to 3153.541. In terms of disease-free survival outcomes, the emerging ypTNM-cN staging, with AIC and BIC values of 3196.057 and 3199.648, respectively, outperformed the AJCC 8th ypTNM staging, which recorded values of 3203.853 and 3207.444. Conclusion We have devised a novel staging system based on ypTNM stage and cN status to accurately categorize patients with ypI stage. Our ypTNM-cN staging system offers valuable insights into the classification of ypI ESCC and demonstrates reliable classification efficacy for all ESCC patients following nCRT and surgery.

Tumor Apparent Diffusion Coefficient is Associated with Early Recurrence of Intrahepatic Cholangiocarcinoma

Rationale and ObjectivesIdentifying intrahepatic cholangiocarcinoma (iCCA) patients who are at high risk for early recurrence (ER) can guide personalized treatment strategy and improve survival. This study aimed to investigate the value of preoperative MRI, especially diffusion-weighted imaging, in predicting ER, including in patients receiving neoadjuvant therapy. Materials and methodsThis study included 175 pathologically-confirmed iCCA patients who underwent curative resection (114 men, 61 women; mean age 59.0±9.56 years). MRI features, particularly apparent diffusion coefficient (ADC), were analyzed and compared between ER and non-ER cases. Survival analyses of ER were evaluated using Cox regression and Kaplan-Meier analysis. ResultsER occurred in 54.3% (95/175) of patients. Multivariate logistic regression analysis identified tumor ADC as the only independent predictor of ER (odds ratio=0.034, P<0.001), with AUCs of 0.758 (95%CI 0.664, 0.836) in the testing cohort and 0.779 (95%CI 0.622, 0.893) in the validation cohort. The optimal ADC threshold was 1.273×10-3mm2/s. Tumor ADC was comparable to the AJCC 8th staging system in predicting ER (AUC 0.758 vs 0.650 in testing cohort and 0.779 vs 0.661 in validation cohort). Multivariate Cox analysis identified high tumor burden score (HR=1.109, P=0.009), non-smooth margin (HR=2.265, P=0.008) and tumor ADC (HR=0.111, P<0.001) as independent risk factors for ER. Lower ADC values were linked to shorter RFS in both testing and validation cohorts (P<0.001 and 0.0219), as well as in patients receiving neoadjuvant therapy (P=0.003). ConclusionPreoperative MRI, particularly ADC, can help predict ER in iCCA, regardless of the application of neoadjuvant therapy, comparable to the AJCC 8th staging system.

Development and validation of a practical score to predict 3-year distant metastatic free survival in nasopharyngeal carcinoma incorporating the number of lymph node regions.

The improvement in diagnosis and treatment for nasopharyngeal carcinoma (NPC) has shifted the pattern of failure toward distant metastasis. This study aimed to develop a simplified prognostic scoring model to predict distant metastatic free survival (DMFS) for NPC patients. Patients with non-metastatic NPC were identified from a retrospective cohort diagnosed between 2010 and 2018. Flexible parametric survival analysis was used to identify potential predictors for DMFS and establish a scoring model. The prognostic accuracy between the 8th AJCC system and the scoring model was compared using Harrell's C-index. Of the total 393 patients, the median follow-up time was 85 months. The 3-year DMFS rate was 83.3%. Gender, T-stage, pre-EBV (cut-off 2300 copies/ml), and the number of metastatic lymph node regions were identified as independent risk factors for distant metastasis and were included in the final scoring model. Our established model achieved a high C-index in predicting DMFS (0.79) and was well-calibrated. The score divided patients into two categories: low-risk (score 0-4) and high-risk (score 5-7), corresponding with the predicted 3-year DMFS of 96% and 64.5%, respectively. A feasible and applicative prognostic score was established and validated to discriminate NPC patients into low- and high-risk groups.

Does liver cirrhosis affect outcomes in non-metastatic esophageal squamous cell carcinoma (ESCC) undergoing radiotherapy-based treatment?

89 Background: Liver cirrhosis frequently coexists with esophageal squamous cell carcinoma (ESCC), as both conditions share alcohol consumption as a common etiological factor. Surgical intervention is often contraindicated or associated with significant morbidity in patients with non-metastatic ESCC and liver cirrhosis. Consequently, radiotherapy-based therapy is commonly employed. This study aims to investigate prognostic factors for overall survival in such patients undergoing radiotherapy-based therapy. Additionally, we will evaluate predictors for the 90-day mortality rate, proposed as a measure to mitigate treatment-related toxicity and prevent unwarranted or excessive medical interventions. Methods: From January 2001 to December 2021, we conducted a retrospective review of the medical records of 1298 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Within this cohort, we identified 103 patients with concomitant liver cirrhosis, diagnosed through abdominal ultrasonography, computerized tomography, and/or liver biopsy, as appropriate. Of these individuals, 78 patients with non-metastatic ESCC and liver cirrhosis were included in our analysis. We collected clinicopathologic parameters and examined their correlation with overall survival and the 90-day mortality rate. Results: Univariate analysis revealed several factors significantly associated with inferior overall survival: Child-Pugh classification B/C (P&lt;0.001, compared to A), radiotherapy alone (P=0.03, compared to chemoradiotherapy), prothrombin time prolonged by ≥2 seconds (P=0.024), albumin levels ≤3.5g/dl (P&lt;0.001), controlled/refractory ascites (P=0.01, compared to no ascites), and total bilirubin levels ≥1.5mg/dl (P=0.004). In multivariate analyses, albumin levels ≤3.5g/dl (P=0.001, odds ratio: 2.500) and total bilirubin levels ≥1.5mg/dl (P=0.019, odds ratio: 2.012) were identified as independent prognostic factors. Among the 78 patients receiving radiotherapy-based therapy, the 90-day mortality rate was 10.3% (n=8). Clinical 8th AJCC stage IVA (P=0.02), clinical T classification T3/4 (P=0.049), prothrombin time prolonged by ≥4 seconds (P=0.009), and albumin levels ≤3.5g/dl (P=0.027) were significantly correlated with higher 90-day mortality rate. The logistic model indicated that albumin levels ≤3.5g/dl (P=0.015, odds ratio: 16.129) and clinical 8th AJCC stage IVA (P=0.012, odds ratio: 17.544) were independently associated with higher 90-day mortality rate. Conclusions: In patients undergoing radiotherapy-based therapy for non-metastatic esophageal squamous cell carcinoma (ESCC) and liver cirrhosis, pretreatment hypoalbuminemia has been associated with increased 90-day mortality and unfavorable prognosis.

Screening high-risk individuals for primary gastric carcinoma: evaluating overall survival probability score in the presence and absence of lymphatic metastasis post-gastrectomy

ObjectiveThe aim of this study was to develop and validate prognostic models for predicting overall survival in individuals with gastric carcinoma, specifically focusing on both negative and positive lymphatic metastasis.MethodsA total of 1650 patients who underwent radical gastric surgery at Shanxi Cancer Hospital between May 2002 and December 2020 were included in the analysis. Multiple Cox Proportional Hazards analysis was performed to identify key variables associated with overall survival in both negative and positive lymphatic metastasis cases. Internal validation was conducted using bootstrapping to assess the prediction accuracy of the models. Calibration curves were used to demonstrate the accuracy and consistency of the predictions. The discriminative abilities of the prognostic models were evaluated and compared with the 8th edition of AJCC-TNM staging using Harrell’s Concordance index, decision curve analysis, and time-dependent receiver operating characteristic curves.ResultsThe nomogram for node-negative lymphatic metastasis included variables such as age, pT stage, and maximum tumor diameter. The C-index for this model in internal validation was 0.719, indicating better performance compared to the AJCC 8th edition TNM staging. The nomogram for node-positive lymphatic metastasis included variables such as gender, age, maximum tumor diameter, neural invasion, Lauren classification, and expression of Her-2, CK7, and CD56. The C-index for this model was 0.674, also outperforming the AJCC 8th edition TNM staging. Calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis for both nomograms demonstrated excellent prediction ability. Furthermore, significant differences in prognosis between low- and high-risk groups supported the models’ strong risk stratification performance.ConclusionThis study provides valuable risk stratification models for lymphatic metastasis in gastric carcinoma, encompassing both node-positive and negative cases. These models can help identify low-risk individuals who may not require further intervention, while high-risk individuals can benefit from targeted therapies aimed at addressing lymphatic metastasis.

Radiotherapy for patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0–1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2–4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1–14, 29–42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7–27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0–21.9 months) and 20.5 months (95% CI 11.8–27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33–NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77–26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27–1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72–2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.

Association between the Worst Pattern of Tumor Invasion and Epithelial-mesenchymal Transition and their Prognostic Impact on Early-stage Oral Tongue Squamous Cell Carcinoma.

We aimed to determine the association between the worst pattern of tumor invasion (WPOI) and epithelial-mesenchymal transition (EMT) in early-stage oral tongue squamous cell carcinoma (OTSCC) with no adverse features and their impact on 2-year disease-free survival (DFS) and overall survival (OS) rates. This prospective observational study included treatment-naive 50 patients who underwent primary surgery for OTSCC (pT1T2N0M0; AJCC 8th edition, with no adverse features) from June 1, 2020, to March 31, 2021 (minimum follow-up period, 2 years). WPOI (low- or high-invasive) and EMT (E-cadherin, N-cadherin, and vimentin expression at the tumor invasive front) were assessed. High invasive WPOI was seen in 66% and low invasive in 34%. 80% of the patients had EMT. No statistically significant association was found between WPOI and EMT. The OS and DFS at 2 years were 90% and 80% respectively. WPOI had statistically significant impact on 2-year DFS (100% for low & 69.7% for high, p-value 0.014). EMT did not significantly affect DFS or OS rates. In early stage OTSCC with no adverse features, WPOI can be a promising predictor for disease recurrence. However, this should be validated for modifying treatment guidelines.

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.