An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics.

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.

Potentially functional variants of PARK7 and DDR2 in ferroptosis-related genes predict survival of non-small cell lung cancer patients.

Ferroptosis, a form of regulated cell death, is characterized by iron-dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single-nucleotide polymorphisms (SNPs) within 467 ferroptosis-related genes and survival of non-small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15-1.52, p = .0001) and 1.34 (95% confidence interval = 1.09-1.64, p = .006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (ptrend = .001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis-related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels.

Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.

Artificial intelligence-based digital scores of stromal tumour-infiltrating lymphocytes and tumour-associated stroma predict disease-specific survival in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is known to have a relatively poor outcome with variable prognoses, raising the need for more informative risk stratification. We investigated a set of digital, artificial intelligence (AI)-based spatial tumour microenvironment (sTME) features and explored their prognostic value in TNBC. After performing tissue classification on digitised haematoxylin and eosin (H&E) slides of TNBC cases, we employed a deep learning-based algorithm to segment tissue regions into tumour, stroma, and lymphocytes in order to compute quantitative features concerning the spatial relationship of tumour with lymphocytes and stroma. The prognostic value of the digital features was explored using survival analysis with Cox proportional hazard models in a cross-validation setting on two independent international multi-centric TNBC cohorts: The Australian Breast Cancer Tissue Bank (AUBC) cohort (n = 318) and The Cancer Genome Atlas Breast Cancer (TCGA) cohort (n = 111). The proposed digital stromal tumour-infiltrating lymphocytes (Digi-sTILs) score and the digital tumour-associated stroma (Digi-TAS) score were found to carry strong prognostic value for disease-specific survival, with the Digi-sTILs and Digi-TAS scores giving C-index values of 0.65 (p = 0.0189) and 0.60 (p = 0.0437), respectively, on the TCGA cohort as a validation set. Combining the Digi-sTILs feature with the patient's positivity status for axillary lymph nodes yielded a C-index of 0.76 on unseen validation cohorts. We surmise that the proposed digital features could potentially be used for better risk stratification and management of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Do patients with cN0 oral squamous cell carcinoma benefit from elective neck dissection? A large-scale population-based study.

BACKGROUND: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. METHODS: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. RESULTS: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. CONCLUSION: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.

[Establishment and verification of a prognostic nomogram for survival of tongue squamous cell carcinoma patients who underwent cervical dissection].

OBJECTIVE: To evaluate the prognostic significance of inflammatory biomarkers, prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma (TSCC) patients who underwent cervical dissection. METHODS: The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018. The study population was divided into the training set and validation set by 7 :3 randomly. The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation score (SIS) and prognostic nutritional index (PNI). Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). The nomogram's accuracy was internally validated using concordance index, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration plot and decision curve analysis. RESULTS: According to the univariate Cox regression analysis, clinical TNM stage, clinical T category, clinical N category, differentiation grade, depth of invasion (DOI), tumor size and pre-treatment PNI were the prognostic factors of TSCC. Multivariate Cox regression analysis revealed that pre-treatment PNI, clinical N category, DOI and tumor size were independent prognostic factors for OS or DSS (P < 0.05). Positive neck nodal status (N≥1), PNI≤50.65 and DOI > 2.4 cm were associated with the poorer 5-year OS, while a positive neck nodal status (N≥1), PNI≤50.65 and tumor size > 3.4 cm were associated with poorer 5-year DSS. The concordance index of the nomograms based on independent prognostic factors was 0.708 (95%CI, 0.625-0.791) for OS and 0.717 (95%CI, 0.600-0.834) for DSS. The C-indexes for external validation of OS and DSS were 0.659 (95%CI, 0.550-0.767) and 0.780 (95%CI, 0.669-0.890), respectively. The 1-, 3- and 5-year time-dependent ROC analyses (AUC = 0.66, 0.71 and 0.72, and AUC = 0.68, 0.77 and 0.79, respectively) of the nomogram for the OS and DSS pronounced robust discriminative ability of the model. The calibration curves showed good agreement between the predicted and actual observations of OS and DSS, while the decision curve confirmed its pronounced application value. CONCLUSION: Pre-treatment PNI, clinical N category, DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC. The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection. They are effective tools for predicting survival and helps to choose appropriate treatment strategies to improve the prognosis.

[Translated article] Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas.

BACKGROUND AND OBJECTIVE: Cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. MATERIALS AND METHODS: All cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. RESULTS: A total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. CONCLUSIONS: Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients' survival and was closely associated with tumor skin involvement and stage IIB.

Genetic Status Affects Disease-Specific Mortality But Not the Incidence of Local Recurrence in Patients with Uveal Melanoma.

PURPOSE: Increased disease-specific mortality has been observed among patients with local recurrence (LR) from uveal melanoma (UM), but the underlying mechanism is unknown. The purpose of this study was to determine if copy number alterations of chromosomes 3 and/or 8q, at the time of diagnosis, increase the incidence of LR and if disease-specific mortality among patients with LR depends on the chromosome status of the primary tumor. DESIGN: Retrospective cohort study. PARTICIPANTS: The study included 239 consecutive patients with primary UM (choroidal or ciliary body) treated with Ruthenium-106 (Ru-106) brachytherapy from January 2009 to December 2019 at a single national referral center. METHODS: Cox regression modeling and Kaplan-Meier analyses were used to assess the effect of the status of chromosomes 3 and 8q on the incidence of LR and disease-specific mortality after the event of LR. Multistate models were used to illustrate the probabilities over time of patients being alive and disease-free, alive with LR, dead from UM metastases, or dead from other causes split on the status of chromosomes 3 and 8q. MAIN OUTCOME MEASURES: Incidence of LR and disease-specific mortality. RESULTS: Local recurrence was observed in 42 patients (16%). Overall incidence of LR was not affected by aberrations of chromosomes 3 and/or 8q (P = 0.87). Although LR occurred earlier in patients with aberrations of chromosomes 3 and/or 8q compared with patients with a normal copy number of chromosomes 3 and 8q, the median time from primary diagnosis to LR was 1.6 years (interquartile range [IQR], 1.0-2.0) and 3.2 years (IQR, 2.1-5.0), respectively. Cox regression found LR to be an independent risk factor for disease-specific mortality (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-5.0) among all patients, but multistate models demonstrated a low risk of disease-specific death among patients with normal chromosomes 3 and 8q status, even after an LR. CONCLUSIONS: Copy number alterations of chromosome 3 and/or 8q in the primary UM did not increase the overall incidence of LR. However, the development of an LR enhanced the risk of disease-specific mortality among patients with copy number alterations of chromosomes 3 and/or 8q. Even after an LR, disease-specific mortality remained low among patients with normal copy numbers of chromosomes 3 and 8q. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinical outcome in metastatic prostate cancer after primary radiotherapy.

PURPOSE: To describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions. METHODS AND MATERIALS: We included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60-81.4 Gy to the prostate, and 45-50.4 Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy. RESULTS: We included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5­year biochemical recurrence-free rates were 52% and 24%, respectively (p < 0.0001); the 5­year disease-specific survival rates were 92% and 61%, respectively (p = 0.001); and the 5­year OS rates were 77% and 48%, respectively (p = 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (p = 0.01). CONCLUSIONS: DM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low.

The impact of the COVID-19 pandemic in 2020 on the diagnosis, treatment, and outcomes of invasive cutaneous melanoma: A retrospective national cohort study.

BACKGROUND: Prior multiinstitutional studies demonstrate that patients diagnosed with melanoma during the Coronavirus Disease 2019 (COVID-19) pandemic presented with more advanced melanomas. OBJECTIVES: To further characterize patients diagnosed with melanoma during the COVID-19 pandemic. METHODS: Retrospective population-based cohort study of the Surveillance, Epidemiology, and End-Results (SEER) registry of patients diagnosed with cutaneous melanoma from 2018-2020. RESULTS: Patients diagnosed with melanoma in 2020 were more likely to have increased Breslow depth, more ulceration, nodular tumors, and more advanced stage at diagnosis despite less treatment delays. Patients tended to be from wealthier, more urban areas. Primary surgical treatment was more likely to be with Mohs surgery. Diagnosis in the year 2020 was not correlated with overall or disease specific survival. LIMITATIONS: This is a retrospective cohort review and limited by short follow-up times, which could affect survival outcomes. There was a 15.5% drop in melanoma diagnosis in 2020 compared to prior years, which could relate to delayed presentation. CONCLUSIONS AND RELEVANCE: Patients diagnosed with melanoma in 2020 tended to have thicker, more ulcerated, and more advanced tumors, but this was not associated with survival. Further studies are needed to characterize outcomes for patients diagnosed with melanoma during the COVID-19 pandemic.

Tumour budding in cutaneous squamous cell carcinoma: A novel prognosis risk factor.

INTRODUCTION: Most cutaneous squamous cell carcinomas (cSCC) have a good prognosis, there is a small group where metastasis and death occur and the evaluation of this risk is still cause for controversy. Tumour budding is a pattern of histological invasion that is an emerging risk factor in other solid tumours. OBJECTIVE: To examine the association between tumour budding and other known high-risk predictors in cSCC. In addition, the impact of tumour budding on overall survival (OS) and disease-specific survival (DSS) was analysed. METHOD: Retrospective study. It included patients with a diagnosis of non-genital cSCC by excisional biopsy at a university hospital, between 2010 and 2020. A pathologist re-analysed their histological slides and evaluated budding. Univariate and multivariate analyses were made to study the associations. RESULTS: 156 cSCC biopsies were found, and positive tumour budding was found in 13.5%. This correlated with worse DSS and OS. On univariate analysis, budding was correlated with the diameter, thickness of the tumour, histological grade, level of invasion, perineural and lymphovascular invasion, previous radiotherapy, recurrent tumours and lymph node metastasis (LNM). Multivariate analysis: tumour budding was associated with poorly differentiated tumours, prior radiotherapy and LNM. CONCLUSION: An association was found between tumour budding and most known risk factors in cSCC. We found findings that indicate that the presence of tumour budding is associated with a worse prognosis in terms of LNM, OS and DSS. This supports the results of previous work which has suggested that budding could be related to high-risk cSCC.

Risk factors and prognostic models of lymph node metastatic hypopharyngeal squamous cell carcinoma.

PURPOSE: To explore the risk factors for lymph node metastasis (LNM) and establish nomograms for predicting survival outcomes and assessing individual risk in patients with LNM and hypopharyngeal squamous carcinoma (HSCC). METHODS: Clinical data of patients with HSCC were retrospectively reviewed. The study's primary endpoints were overall survival (OS) and disease-specific survival (DSS). Nomograms were established based on Cox regression analyses. The accuracy and calibration ability of the nomograms were evaluated using the C-index, area under the curve, calibration curves, and decision curve analysis. RESULTS: Overall, 2888 patients were enrolled, and the LNM rate was 74.2%. Age ≤ 60 years, male sex, unmarried status, pyriform sinus location, grade III-IV, tumor larger than 4 cm, and advanced T stage increased the risk of LNM. In addition, LNM was a negative prognostic factor for OS and DSS. Ten variables were identified and incorporated into nomograms to estimate OS and DSS. Our nomograms outperformed the traditional staging system in training and validation cohorts. Patients were stratified into risk subgroups based on the OS- and DSS-nomogram scores. Patients in the high-risk subgroup had a higher risk of death and disease-specific mortality than those in the low- and intermediate-risk subgroups. CONCLUSIONS: LNM worsens the prognosis of HSCC. This study identified the independent prognostic factors for HSCC with LNM and developed satisfactory OS- and DSS-monogram to provide individual prediction and risk classification for patients with this diagnosis.

Prognostic significance of minor high grade component in non-invasive papillary urothelial carcinoma of urinary bladder: (A study of 273 consecutive cases over a period of 3 years).

PURPOSE: Our study aimed to determine the prognostic significance of minor high-grade components (HGC) in non-invasive papillary urothelial carcinomas compared with pure low-grade and high-grade tumors. MATERIAL AND METHODS: We retrospectively retrieved 273 in-house cases of non-invasive papillary urothelial carcinomas (pTa) from 2016 to 2018 for which follow up data was available in hospital archives. We stratified our data into four main groups (G). G1, pure low-grade (n = 164); G2, HGC ≤5 % (n = 17); G3, HGC >5 % to ≤25 % (n = 14); and G4, pure high-grade (n = 78). Prognosis was assessed in terms of recurrence, grade and stage of progression, metastasis, and death. The mean follow up duration was 34.72 ± 20 months (range 20-60 months). RESULTS: All four groups showed no difference in tumor recurrence (G1 81.7 %, G2 88.2 %, G3 92.9 %, G4 92.3 % p-value 0.183). In terms of grade progression, there was no significant difference in G2 35.3 % and G3 35.7 % and both groups showed worst prognosis compared to G1 16.5 % p-value 0.04. Regarding stage progression (G1 6.7 %, G2 23.5 %, G3 28.6 %, G4 41% p-value 0.001), metastasis (G1 5.5 %, G2 5.9 %, G3 7.1 %, G4 17.9 % p-value 0.01) and death (G1 4.3 %, G2 5.9 %, G3 7.1 %, G4 15.4 % p-value 0.02) there was no significant difference in G2 and G3 and both groups showed worst prognosis than G1 and better than G4. CONCLUSION: Urothelial carcinomas with minor high-grade component ≤25 % behaved worst than pure low grade and better than pure high grade and should be treated as distinct grade entity.

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas.

OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.

American Joint Committee on Cancer Tumor Staging System Predicts the Outcome and Metastasis Pattern in Conjunctival Melanoma.

PURPOSE: To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM). DESIGN: Retrospective, single-center cohort study. PARTICIPANTS: Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021. METHODS: We reviewed the clinical and histologic parameters and used Kaplan-Meier survival curves and Cox proportional hazards regression models for risk factor analyses. MAIN OUTCOME MEASURES: Time to nodal/distant metastasis, disease-specific survival, metastatic pattern, and metastatic site. RESULTS: At presentation, 5 patients (6%) had clinical tumor (cT)1 disease, 34 patients (41%) had cT2 disease, and 44 patients (53%) had cT3 disease. Four patients (5%) had nodal metastasis (N1), and none had distant metastasis (M1). During follow-up, 12 patients (14%) developed nodal metastasis, 29 patients (35%) developed distant metastasis, and 26 patients (31%) died of disease. The brain, liver, and lung were common distant metastasis sites. Higher cT category was associated with increased risks of distant metastasis (P < 0.001) and disease-specific death (P = 0.002). The separate analysis of primary and recurrent tumors at presentation showed that the patients with cT3 tumors had a higher risk of distant metastasis than those with cT2 tumors. Greater tumor thickness, ulceration, and the presence of regression were correlated with distant metastasis. Previously unreported mutations were detected in the tumor suppressor genes FAT atypical cadherin 4 (FAT4) and spleen associated tyrosine kinase (SYK). Among the 29 patients who developed distant metastasis, we analyzed 2 patterns of metastasis: Eleven patients (38%) developed nodal metastasis before distant metastasis, and 18 patients (62%) developed distant metastasis without previously known nodal metastasis. The patients with cT3 tumors were more likely to follow the latter metastasis pattern (P = 0.02). CONCLUSIONS: Conjunctival melanoma presented with mostly advanced stages and high rates of distant metastasis in the current Chinese cohort. This study confirmed the prognostic value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, for Chinese patients. Histologic features, such as tumor thickness and ulceration, should be emphasized when assessing prognosis and guiding the treatment of CM.

Level IV neck dissection in cN0 HPV-negative oropharyngeal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: As opposed to observation of the neck, elective neck dissection has a survival benefit for cN0 oropharyngeal squamous cell carcinoma (OPSCC). However, there are limited date on level IV neck dissection in human papillomavirus (HPV)-negative OPSCC because most earlier studies did not stratify by P16 or HPV status. Thus, whether to exclude level IV from selective dissection (SND) of cN0 HPV-negative OPSCC remains controversial. METHODS: In this single-center retrospective cohort study, disease-free survival (DFS) was estimated as the primary endpoint for 124 cN0 HPV-negative OPSCC patients who received SND of levels I-III (Group A) and I-IV (Group B). Overall survival (OS) and disease-specific survival (DSS) were considered secondary endpoints. RESULTS: For the entire cohort, the 5-year DFS rates of Groups A and B were 55.0% and 60.1%, respectively. Five-year OS rates were 58.9% and 61.5%, and 5-year DSS rates were 74.0% and 64.8%, respectively. Group B did not show higher 5-year DFS, OS, or DSS than Group A. CONCLUSIONS: This retrospective cohort study validated that in cN0 HPV-negative OPSCC, SND including level IV does not have substantial benefits regarding DFS, OS or DSS.

The clinicopathological characteristics of POLE-mutated/ultramutated endometrial carcinoma and prognostic value of POLE status: a meta-analysis based on 49 articles incorporating 12,120 patients.

OBJECTIVE: This study was designed to investigate the frequency and clinicopathological characteristics of POLE-mutated/ultramutated (POLEmut) in endometrial carcinoma (EC) and assess the prognostic values of POLE status. METHODS: Electronic databases were screened to identify relevant studies. Meta-analysis was used to yield the pooled frequency of POLEmut and prognostic parameters by 95% confidence interval (CI), odd ratio (OR), and hazard ratio (HR). RESULTS: Totally, 12,120 EC patients from 49 studies were included. The pooled frequency of POLEmut was 7.95% (95% CI: 6.52-9.51%) in EC, 7.95% (95% CI: 6.55-9.46%) in endometrioid endometrial carcinoma, and 4.45% (95% CI: 2.63-6.61%) in nonendometrioid endometrial carcinoma. A higher expression occurred in grade 3 (OR = 0.51, 95% CI: 0.36-0.73, P = 0.0002), FIGO stage I-II (OR = 1.91, 95% CI: 1.29-2.83, P = 0.0013), and myometrial invasion< 50% (OR = 0.66, 95% CI: 0.50-0.86, P = 0.0025). Survival analyses revealed favorable OS (HR = 0.68, 95% CI: 0.55-0.85, P = 0.0008), PFS (HR = 0.74, 95% CI: 0.59-0.93, P = 0.0085), DSS (HR = 0.61, 95% CI: 0.44-0.83, P = 0.0016), and RFS (HR = 0.47, 95% CI: 0.35-0.61, P <  0.0001) for POLEmut ECs. Additionally, the clinical outcomes of POLEmut group were the best, but those of p53-abnormal/mutated (p53abn) group were the worst, while those of microsatellite-instable (MSI)/hypermutated group and p53-wild-type (p53wt) group were medium. CONCLUSIONS: The POLEmut emergered higher expression in ECs with grade 3, FIGO stage I-II, and myometrial invasion< 50%; it might serve as a highly favorable prognostic marker in EC; the clinical outcomes of POLEmut group were the best one among the four molecular subtypes.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Basal cell carcinoma with bone invasion: A systematic review and pooled survival analysis.

BACKGROUND: Although basal cell carcinoma (BCC) tends to follow an indolent course, some tumors can exhibit locally aggressive behavior and invade into bone. OBJECTIVE: To analyze all published demographic, clinical, and treatment data on recurrence patterns, disease progression, disease-specific death, and overall mortality of BCC with bone invasion. METHODS: A systematic review and pooled-survival analysis was performed, including case reports and case series of BCC with bone invasion. RESULTS: The study included 101 patients from 70 publications. BCC tumors invading into bone were most often large, neglected tumors located in high-risk face areas. At 5 years, patients had a 30% risk probability of disease recurrence (after negative margins), a 72.1% risk of disease progression or death (with ambiguous margin status), an 18.2% risk of BCC-related death, and a 20.7% overall probability of death. LIMITATIONS: Limitations include the reliance on case reports and series for individual patient data, which has the potential to introduce selection bias. CONCLUSION: The high rate of disease progression and suboptimal 5-year survival rate highlights the poor prognosis of BCC with bone invasion and further underscores the importance of early detection and treatment.

Clinical characteristics of undifferentiated pleomorphic sarcoma of bone and the impact of adjuvant chemotherapy on the affected patients: a population-based cohort study.

BACKGROUND: Clinical characteristics of undifferentiated pleomorphic sarcoma of bone are not elucidated. Herein, we clarify its clinical features and analyze the efficacy of adjuvant chemotherapy in patients with undifferentiated pleomorphic sarcoma of bone. METHODS: Prognostic factors and estimated disease-specific survival in 247 patients with primary undifferentiated pleomorphic sarcoma of bone were identified from a registry in Japan. The effect of adjuvant chemotherapy was evaluated in localized resectable cases, and the characteristics of the two groups treated with or without chemotherapy were adjusted using propensity score matching. RESULTS: The 5-year disease-specific survival rates were 47.4% in the entire cohort and 56.4 and 16.9% in the M0 and M1 groups, respectively. Multivariate disease-specific survival analysis revealed that metastasis on initial presentation and age ≥ 65 years were poor prognostic factors. Overall, 132 localized and resectable primary lesions were extracted. Adjuvant chemotherapy administration was a favorable prognostic factor (hazard ratio: 0.43, P = 0.04), and it significantly prolonged disease-specific survival compared with no adjuvant chemotherapy (5-year disease-specific survival: 78.8% vs. 51.8%, P = 0.008). Adjuvant chemotherapy prolonged disease-specific survival in patients with tumor size <8 cm (5-year disease-specific survival: 100% vs. 54.6%, P = 0.02); however, its efficacy decreased in those with tumor size ≥8 cm (5-year disease-specific survival: 68.7% vs. 42%, P = 0.09). After propensity score matching, adjuvant chemotherapy was significantly associated with good disease-specific survival (P = 0.02). CONCLUSIONS: Metastasis in the initial presentation was the poorest prognostic factor. On evaluating localized and resectable cases only, adjuvant chemotherapy significantly improved disease-specific survival, although its effect decreased in cases with large tumors.