How applicable is the TNM 8 staging for human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) to a UK population of 106 patients? : A cohort comparison of the TNM 7 and TNM8 staging systems for HPV positive oropharyngeal cancer in a UK population.

PURPOSE: TNM8 introduced a new staging system for HPV positive oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to investigate whether the changes made in TNM8 offer the perceived benefit in prognostication when compared to TNM7 in a specific patient population in the North East of England. METHODS: A retrospective cohort comparison study of all patients with HPV positive OPSCC (n = 106) through the Newcastle Head and Neck MDT between January 2012 to December 2014. Overall survival (OS) and Disease specific survival (DSS) data at 3 years was gathered for both TNM7 and TNM8. Log rank test was used to compare survival curves. Harrell's C-index adjusted for age and smoking status was used to assess prognostic ability of the two staging methods. RESULTS: TNM8 downstages disease (TNM7 stage IV patients n = 74, TNM8 stage IV patients n = 2) but gives a more even distribution of patients across disease stages. Survival for TNM8 stage II and III is similar. In our small cohort, the log-rank test detected differences in OS between stages for both scoring methods (TNM7 p = 0.006, TNM8 p < 0.001) and similarly for DSS (TNM7 p = 0.001, TNM8 p < 0.001). Harrell's C-index was similar for both models for OS (TNM7 0.71, TNM8 0.71) and DSS (TNM7 0.74, TNM8 0.70). CONCLUSION: TNM8 downstages disease and prognosticates well for stage I disease but does not differentiate between stage II and III disease when compared to TNM7. Further adaptation is required to address this to make TNM8 a more accurate prognostic tool.

Assessment of the prognostic value and N1b changes of the eighth TNM/AJCC staging system for differentiated thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the prognostic veracity for disease-specific survival (DSS) of the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in a Chinese population of patients with differentiated thyroid carcinoma (DTC) and to evaluate the impact of N1b redefinition and reclassification on prediction of survival. METHODS: A total of 569 DTC patients who underwent thyroid surgery in two Chinese hospitals were included in analysis to assess the predictive accuracy and N1b changes of TNM-8. Data from the Surveillance, Epidemiology and End Results (SEER) program were applied to validate the findings on N1b changes of TNM-8. Unadjusted DSS was calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the association of stage and lymph node metastasis (LNM) status with survival. The proportion of variation explained (PVE), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were evaluated to compare model performance. RESULTS: When TNM-8 was applied, 39.7% of patients were downstaged relative to TMN-7. In comparison of TNM-7 and TMN-8, the PVE was 18.68% and 22.33%, the AIC was 704.22 and 680.50, and the BIC was 702.98 and 679.24, respectively. In 569 Chinese patients with DTC, levels I-V LNM was significantly related to poorer DSS compared with N0 and level VI LNM. Among patients aged ≥ 55 years, those with levels I-V and VII LNM had significantly worse DSS than those with N0 and Level VI LNM. In the SEER dataset, patients with levels I-V and VII LNM had significantly worse DSS compared with those with N0 and Level VI LNM, especially in older patients (age ≥ 55 years). CONCLUSIONS: TNM-8 staged a significant number of Chinese patients into lower stages and improved the accuracy of predicting DSS compared with TNM-7. However, changes in lateral LNM definition and classification of TNM-8 have a significant prognostic implication for patients with DTC, especially older patients (≥ 55 years). Our data suggest that a modified TNM staging system would be more useful for predicting mortality and determining a proper treatment strategy in patients with DTC.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Imaging in Lung Cancer Staging.

Lung cancer remains one of the leading causes of mortality worldwide, as well as in the United States. Clinical staging, primarily with imaging, is integral to stratify patients into groups that determine treatment options and predict survival. The eighth edition of the tumor, node, metastasis (TNM-8) staging system proposed in 2016 by the International Association for the Study of Lung Cancer remains the current standard for lung cancer staging. The system is used for all subtypes of lung cancer, including non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumors.

Population-based survival rates after curative surgical and non-surgical treatment of stage III NSCLC since 2017.

OBJECTIVES: In stage III non-small cell lung cancer (NSCLC), curative treatment approaches used to include neoadjuvant therapy followed by surgery, and definitive chemoradiotherapy followed by consolidation durvalumab (CRT-ICI). Surgical strategies included either neoadjuvant chemotherapy (CTx-surg) or chemoradiotherapy (CRT-surg). We studied the outcomes of these three radical intent strategies in the Netherlands Cancer Registry (NCR) for patients diagnosed from 2017 to 2021. MATERIALS AND METHODS: Patients with clinical stage III NSCLC (TNM edition 8) were identified in the NCR after excluding patients with known driver mutations, ECOG performance status >=2, N3-disease and those undergoing sequential chemoradiotherapy or single modality/palliative treatments. Overall survival (OS) was calculated from date of surgery or start of durvalumab. RESULTS: Treatments delivered were CRT-ICI (n = 1016 patients), CRT-surg (n = 166) and CTx-surg (n = 111). The surgical series comprised 224 lobectomies, 21 bilobectomies and 32 pneumonectomies, with a 90-day postoperative mortality rate of 3.3 %. Use of CRT-surg decreased steeply after 2018, when durvalumab became fully reimbursed, and use of CRT-ICI increased. Three-year OS was better following CRT-surg (78.7 %) compared to CTx-surg (66.7 %) or CRT-ICI (63.2 %). After controlling for age, ECOG performance status and histology, the hazard ratios for CRT-surg and CTx-surg were 0.66 (95 % CI 0.47-0.91) and 0.82 (95 % CI 0.58-1.17), respectively, compared to CRT-ICI. CONCLUSION: Population survivals after curative strategies for clinical stage III NSCLC in The Netherlands exceed those reported historically for both surgical and non-surgical approaches. Use of surgery decreased from 2018 following the formal reimbursement of durvalumab. While variations in case-mix hamper comparison between curative treatment strategies, there is a clear need for randomized studies in subgroups with potentially resectable disease.

Histologic re­evaluation of a population­based series of renal cell carcinomas from The Netherlands Cohort Study according to the 2022 ISUP/WHO classification.

The aim of the present study was to re-evaluate 457 renal cell carcinoma (RCC) cases from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large population-based cohort, according to the new 2022 ISUP, Genitourinary Pathology Society and World Health Organisation (WHO) classifications to assess whether newly recognized subtypes of RCC could be found among these cases. These cases were initially evaluated according to the 2004 WHO classification, the Fuhrman grading system and the 3rd version of the Tumor-Node-Metastasis (TNM). Data on tumor size, laterality and date of diagnosis, among other clinicopathological characteristics, were obtained through record linkage with the Netherlands Cancer Registry and the Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief. Digital slides from the NLCS were reviewed by two urogenital pathologists according to the new ISUP grading and the 2022 WHO classification (5th edition). Immunohistochemistry staining for carbonic anhydrase IX was performed on cases with ambiguous morphology. A total of 373 cases of clear cell RCC (ccRCC), 61 cases of papillary RCC (pRCC), 13 cases of chromophobe RCC, 3 cases of collecting duct carcinoma and 4 cases of oncocytoma were identified. The subtyping showed no discrepancy with the previous diagnoses. A comparison of the WHO/ISUP grading to the original Fuhrman grading showed a similar grading in 245 (56.5%) cases of the total ccRCC and pRCC cases. The staging according to the novel TNM classification 8th edition showed a restaging in 286 cases (65.5%). Lymphovascular (microvascular) invasion (LVI) and tumor necrosis (TN) were present in 14.4% and 33.5% of the total number of cases, respectively. Furthermore, the presence of sarcomatoid differentiation in 5.1% and rhabdoid differentiation in 4.2% of the cases was observed. In conclusion, none of the newly accepted and emerging/provisional RCC entities were identified in the NLCS cases, which could be attributed to the high mean age (71.4 years) at diagnosis of the patients included in the present study. A restaging of the NLCS cases using the TNM 8th edition and regrading using ISUP grading was performed, which showed that it is possible to report on newer features, such as sarcomatoid differentiation and LVI, even in an old sample collection.

Pathological snapshots of thymic epithelial tumors with invasion into neighboring structures: preparing for the forthcoming revision of the TNM classification.

Treatment decision-making of thymic epithelial tumors (TETs) after surgery is based on the pathological stage. Currently, most institutions use both the Masaoka-Koga system and the 8th edition of the tumor, node, metastasis (TNM) classification. Because these two systems separate each stage according to the same concept, namely, the "levels" of tumor extension, precise pathological evaluation of the presence or absence of tumor invasion into stage-defining structures is necessary. This review provides representative pathological snapshots of tumors invading neighboring structures to provide references that might be helpful to readers; the snapshots will cover features that correspond to those of "locally advanced TETs", the topic of this series. Tumor subtype, whether thymoma or thymic carcinoma, is another factor influencing treatment decisions. Accumulating evidence has indicated that most thymomas and thymic carcinomas have biologically distinct features. Representative results were achieved by a study conducted as part of The Cancer Genome Atlas (TCGA) project, and subsequent studies with the help of the TCGA data have further reported on these distinctive features. Here, we also introduce newly recognized features of TETs, mainly focusing on the difference between epithelial-rich thymomas and thymic squamous cell carcinoma. The new (9th) edition of the TNM classification will be launched in January 2024. Therefore, sharing current pathological features of TETs will help readers, not only in their daily practice but also in preparing for the upcoming classification system.

Development and external validation of a dynamic nomogram to predict the survival for adenosquamous carcinoma of the pancreas.

Objective: We aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP). Background: Adenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance. Methods: Histologically confirmed ASCP patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis. Results: A total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8th) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis. Conclusion: The nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans.

Primary temporal bone squamous cell carcinoma: Comparing the prognostic value of the American Joint Committee on Cancer TNM classification (8th edition) with the revised Pittsburgh staging system.

BACKGROUND: Retrospectively considering a temporal bone squamous cell carcinomas (TBSCCs) series, our aim was to compare the predictive power of the American Joint Committee on Cancer (AJCC) staging system (8th edition) with the revised Pittsburgh staging system (rPSS) in terms of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). METHODS: Forty-three TBSCCs consecutively treated surgically were reviewed. The prognostic performance of AJCC and rPSS was compared. RESULTS: The areas under the curves for the prediction of DFS, DSS, and OS did not differ significantly between both staging systems (p = 0.518, p = 0.940, and p = 0.910, respectively). Harrel's C-indexes for respectively the AJCC and rPSS were 0.76 and 0.70 for DFS, 0.73 and 0.76 for DSS, 0.66 and 0.63 for OS. CONCLUSION: Comparable prognostic accuracy was observed between AJCC and rPSS. Levels of prognostic performance were only acceptable for both systems, according to Hosmer-Lemeshow scale. Further efforts are needed to define new TBSCC staging modalities with higher prognostic reliability.

Selection of Digestive Tract Reconstruction After Partial Gastric Sparing Surgery in Patients With Adenocarcinoma of the Esophagogastric Junction of cT2-T3 Stage.

Objective: To investigate the appropriate reconstruction method of the digestive tract after partial gastric sparing surgery for adenocarcinoma of the esophagogastric junction of stage cT2-T3. Methods: A retrospective analysis of the clinical data of patients with adenocarcinoma of the esophagogastric junction from January 2015 to January 2019 in the General Surgery Department of Zhengzhou University Affiliated Tumor Hospital was performed. Patients with intraoperative double tract anastomosis composed the double tract reconstruction (DTR) group, and patients with intraoperative oesophagogastrostomy with a narrow gastric conduit group composed the oesophagogastrostomy by a narrow gastric conduit (ENGC) group. We analysed and compared the short-term postoperative complications and long-term postoperative nutritional status of the two groups of patients. Result: There were no statistically significant differences between the two groups of patients in terms of age, sex, preoperative haemoglobin level, albumin level, cT, cN, neoadjuvant therapy or not, pathological type and Siewert type. In terms of BMI and body weight, the ENGC group was higher than the DTR group, but the difference was not statistically significant (p = 0.099, p = 0.201). There was no significant difference between the two groups of patients in terms of upper resection margin, operation time, blood loss, tumor diameter, pT, pN and postoperative hospital stay. The gastric resection volume of the DTR group was much larger than that of the ENGC group, and there was a significant difference between the two (p = 0.000). The length of the lower resection margin of the DTR group was also significantly greater than that of the ENGC group (p = 0.000). In terms of surgical approach, the proportion of the DTR group with the abdominal approach was significantly higher than that of the ENGC group, and the difference between the two was statistically significant (p = 0.003). The postoperative exhaust time in the ENGC group was significantly shorter than that in the DTR group (p = 0.013). However, there was no statistically significant difference between the two groups in terms of anastomotic leakage, anastomotic bleeding, intestinal obstruction, abdominal infection, pneumonia, pancreatic leakage, lymphatic leakage,death within 30 days after surgery, or overall complications. In terms of anastomotic stenosis, the incidence in the ENGC group was higher than in the DTR group, and the difference was statistically significant (p = 0.001). There was no significant difference in oral PPI, haemoglobin or albumin levels in patients at 3 months, 6 months, or 12 months after surgery. Comparing reflux/heartburn symptoms at 3 months and 6 months after surgery, we found no statistically significant difference between the two, while in terms of reflux/heartburn symptoms at 12 months after surgery, the findings of the ENGC group were higher than those of the DTR group, and the difference was statistically significant (p = 0.045). In terms of poor swallowing, the ENGC group was always higher than the DTR group, and the difference between the two groups was statistically significant (p < 0.05). There was no statistically significant difference in body weight between the two groups at 3 months or 6 months after surgery. At 12 months after surgery, the body weight of the patients in ENGC group was significantly higher than that in the DTR group, and the difference between the two groups was statistically significant (p = 0.039). Conclusions: For patients with cT2-T3 stage oesophagogastric junction adenocarcinoma with tumours less than 4 cm in diameter, ENGC anastomosis is recommended for patients with a high tumour upper boundary, with obesity, short mesentery, or disordered vascular arch, and for routine patients, DTR anastomosis is recommended.

Sentinel lymph node biopsy for early oral cancer - accuracy and considerations in patient selection.

Sentinel lymph node biopsy (SLNB) for staging oral squamous cell carcinoma (OSCC) patients presenting with early (T1 and T2 N0) disease in preference to elective neck dissection (END) remains controversial worldwide. A retrospective analysis of 145 patients who underwent sentinel lymph node biopsy for a previously untreated early oral cancer between 2010 and 2020 was performed. The primary outcome measures were predictors of occult metastases, accuracy of SLNB and disease specific plus overall survival. The negative predictive value, the false negative rate, and sensitivity for SLNB were 97%, 7.8%, and 92%, respectively. Depth of invasion (DOI) was a significant predictor of N status, overall survival, and disease specific survival. There was a significant difference in the incidence of the neck node metastasis in patients with DOI <5mm compared to those with DOI >5mm. For tumours >5mm there was a moderate to good correlation between radiological depth on contrast enhanced computed tomography (CECT) and histopathological DOI. Preoperative estimation of DOI may be a useful tool in the counselling of patients in the selection of either SLNB or END for N staging purposes in early OSCC.

Proposed modification of the eighth edition of the AJCC-ypTNM staging system of esophageal squamous cell cancer treated with neoadjuvant chemotherapy: Unification of the AJCC staging system and the Japanese classification.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer (AJCC) tumor node metastasis (AJCC-TNM 8th) system adopted the newly separate post-neoadjuvant pathologic stage group (ypTNM). However, it is not compatible with the Japanese pathologic classification after neoadjuvant chemotherapy (JPN-CT-pTNM). The aim of this study is to clarify the subjects of the AJCC-ypTNM 8th and propose a unification of the AJCC and Japanese systems to create novel AJCC-CT-pTNM 8th. METHODS: Participants were 304 esophageal squamous cell carcinoma (ESCC) patients who underwent neoadjuvant chemotherapy followed by 3 stage esophagectomy between 2010 and 2019. Predictive probabilities of pN, pM in AJCC-ypTNM 8th and JPN-CT-pTNM 11th systems were evaluated to propose novel system. RESULTS: In training data from 234 patients, the overall survival rate was statistically better for ypStage IIIA than ypStage II (P = 0.040) resulting in staging inversion in AJCC-ypTNM 8th. Predictive probability of pathological N status in AJCC-ypTNM 8th (Akaike Information Criterion: AIC = 979.53) was superior to that in JPN-CT-pTNM 11th (AIC = 999.07). In AJCC-ypTNM 8th, 71% (15/21) of ypM1 diseases were supraclavicular lymph nodes (No. 104 L/N as regional in JPN-CT-pTNM 11th) metastases with considerably good prognosis. The predictive probability of the novel AJCC-CT-pTNM 8th [unification of ypStage II and IIIA, conversion of supraclavicular L/Ns metastases from ypM to ypN] (AIC = 1054.24) was superior to that of the existing AJCC-ypTNM 8th (AIC = 1070.74). The feasibility of novel system was validated using test data from 70 patients. CONCLUSIONS: Unification of the AJCC and Japanese systems yields a simpler and more precise predictive system after neoadjuvant chemotherapy.

Comparison of a Tumor-Ratio-Metastasis Staging System and the 8th AJCC TNM Staging System for Gastric Cancer.

BACKGROUND: Despite the implementation of the 8th American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer (GC) in 2017, it still holds a significant level of stage migration which affects patients' proper classification and accurate prognosis. Here, to reduce this effect, we evaluated the prognostic value of a lymph node ratio (LNR) and established a novel tumor-ratio-metastasis (TRM) staging system. METHOD: The data of 15,206 GC patients from the Sun Yat-sen University Cancer Center (Training set; n=2,032) and the US Surveillance, Epidemiology, and End Results (SEER) database (Validation set; n=13,174) were analyzed. The training set was classified into 5 LNR categories, based on which the novel TRM staging system was constructed. The overall survival (OS) between the TRM and AJCC TNM systems was compared in the training set and validated in the validation set. The likelihood ratio x 2, liner trend x 2, C-index, and Akaike information criterion (AIC) values were used to measure the discriminatory ability between the two different staging systems. Decision curve analyses (DCAs) were conducted to test the clinical value of the two staging systems. RESULT: The patients were classified into the following categories: LNR0: 0%, LNR1: 0%60%. Univariate analyses demonstrated that the log-rank x 2 of the LNR stage (Training/Validation set: x 2 = 463.1/2880.8) was larger than the AJCC pN stage (Training/Validation set: x 2 = 281.5/2240.8). For both the training set and validation set, stratified analyses using the Kaplan-Meier method identified significantly heterogeneous OS in every pN category but only one using the LNR. The TRM staging system had higher likelihood ratio x 2, liner trend x 2, C-index and smaller AIC values than the TNM system. CONCLUSION: The TRM staging system demonstrated improved homogeneity and discriminatory ability in predicting the prognosis of GC patients compared with the AJCC TNM staging system.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Comparison of model fit and discriminatory ability of M category as defined by the 7th and 8th editions of the tumor-node-metastasis classification of colorectal cancer and the 9th edition of the Japanese classification.

BACKGROUND: In transitioning from the 7th edition of the tumor-node-metastasis classification (TNM-7) to the 8th edition (TNM-8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC-9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. METHODS: The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. RESULTS: According to TNM-8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC-9) tumors. Among the three classification systems, JPC-9 had the lowest AIC value (JPC-9: 10546.3; TNM-7: 10555.9; TNM-8: 10585.5), highest C-index (JPC-9: 0.608; TNM-7: 0.598; TNM-8: 0.599), and superior time-dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. CONCLUSIONS: While the revised M category definition did not improve model fit and discriminatory ability from TNM-7 to TNM-8, further subdivision of M1c in JPC-9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system.

Survival of patients with oropharyngeal squamous cell carcinomas (OPSCC) in relation to TNM 8 - Risk of incorrect downstaging of HPV-mediated non-tonsillar, non-base of tongue carcinomas.

BACKGROUND: TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and -unrelated OPSCC based on p16INK4a overexpression (p16+), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16+ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite. PATIENTS AND METHODS: All 932 patients, treated with curative intent in Stockholm 2000-2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively. RESULTS: Patients with p16+ otherOPSCC had significantly poorer OS compared to patients with p16+ TSCC/BOTSCC (p = 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16+ otherOPSCC had a significant poorer OS compared to patients with p16+ TSCC/BOTSCC and similar stage (p = 0.02). Lastly, patients with otherOPSCC and low TNM-7 stage had a significant better OS, as compared to those with a high stage (p = 0.019) while no hazard discrimination was observed with TNM-7 in TSCC/BOTSCC. CONCLUSION: Our results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.

A 15 year institutional experience of well-differentiated follicular cell-derived thyroid carcinomas; impact of the new 2017 TNM and WHO Classifications of Tumors of Endocrine Organs on the epidemiological trends and pathological characteristics.

PURPOSE: Our study aimed to describe the evolution of the rate of pathological subtypes of well-differentiated follicular-cell derived thyroid carcinomas (DTCs) in the Department of Pathology, Emergency County Hospital Targu-Mures, Romania over a 15 year period and to assess the impact the new 2017 WHO and TNM classifications of thyroid tumors had on our cases. METHODS: The pathological data were retrieved from the original pathological reports. After applying the exclusion criteria the remaining cases were reviewed on a double-headed microscope and reclassified according to the 2017 WHO and TNM staging system. The follow-up data were collected from the Institute of Oncology Cluj-Napoca, Romania. RESULTS: Our study included 396 cases of DTCs (375 papillary, 11 follicular, and 10 Hürthle cell carcinomas). PTCs revealed a significant increasing trend over the study period, whereas follicular and Hurthle cell carcinomas remain rare; 125/131 of noninvasive encapsulated follicular variant PTC (EFVPTC) were reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), resulting in a 33.3% reduction in the number of PTCs. According to 2017 TNM stage-grouping 31% of 271 patients with DTC were downstaged. Follow-up data were available for most of the patients (65.7%, mean period 58.1 months). All patients with noninvasive EFVPTC were disease free at the last clinical assessment. CONCLUSIONS: The increasing rate of PTC was maintained even after exclusion of NIFTP. By applying 2017 TNM criteria, a significant number of DTC cases were downstaged into a more favorable group. Follow-up data highlight the indolent behavior of noninvasive EFVPTCs reclassified as NIFTPs.

Prognostic performance of TNM8 staging rules in oral cavity squamous cell carcinoma.

BACKGROUND: Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination. METHODS: Retrospective study of 297 patients with OCSCC who underwent surgery at our institution. Clinical and pathological data were previously populated from review of medical charts and histological reports. Slides were re-reviewed for depth of invasion measurements. Patients were staged using both TNM7 and TNM8 with overall survival statistics analysed. RESULTS: Overall 118 patients (39.7%) were upstaged using TNM8. Both TNM7 and TNM8 stage categories were highly significant for OS (all p values < 0.0001). Hazard discrimination analysis showed that TNM7 could only differentiate stage III from stage IV disease with significance (OS p = 0.01). In comparison TNM8 could distinguish between stage II and III disease (OS p = 0.047) and between stage III and IV disease (OS p = 0.004). Subsite analysis suggested that both editions of the staging system perform best for tongue primaries. CONCLUSIONS: Although TNM8 showed improved hazard discrimination in comparison to TNM7, problems with discriminative ability persisted with 8th edition staging criteria. Large scale validation studies will be required to direct future refinement of the staging rules and to establish if the continued use of a single staging system for all oral cavity subsites is appropriate.

A Relook at the T Stage of Differentiated Thyroid Carcinoma with a Focus on Gross Extrathyroidal Extension.

BACKGROUND: The recently published eighth edition of the American Joint Committee on Cancer (AJCC) staging system has emphasized the importance of gross extrathyroidal extension (gETE) while classifying the tumor (T) stage in differentiated thyroid carcinoma (DTC). However, the clinical impact of gETE invading only the strap muscles or the recurrent laryngeal nerve (RLN) remains unclear due to scarce and conflicting data. METHODS: A retrospective cohort study was carried out in patients with DTC who underwent thyroid surgery from 1996 to 2005. In total, 3104 patients were included, and disease-specific survival (DSS) was compared according to the degree of gETE, with a median follow-up duration of 10 years. RESULTS: Patients with gETE invading only the strap muscles and with a tumor size ≤4 cm (T3b [≤4 cm]) showed no difference in DSS compared to patients with T2 stage disease (hazard ratio [HR] = 0.81 [confidence interval (CI) 0.24-2.77]; p = 0.737) but rather showed a better DSS than patients with T3a disease (HR = 0.19 [CI 0.05-0.72]; p = 0.014). Conversely, patients with gETE invading to the posterior direction showed significantly poorer DSS than patients with T3 stage disease, even when only the RLN was invaded (HR = 7.78 [CI 3.41-17.75]; p < 0.001). However, there was no difference in DSS between gETE invading only the RLN and that invading other posterior organs beyond the RLN (p = 0.563). A modified T classification was suggested to downgrade patients with T3b (≤4 cm) disease to the T2 stage, which revealed higher predictability of survival than the T classification according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (proportion of variation explained: 3.6% vs. 2.65%). CONCLUSIONS: gETE invading only the strap muscles did not significantly affect DSS, while that invading the posterior organs significantly affected DSS, even when only the RLN was invaded. The data support the applicability of downgrading patients with T3b (≤4 cm) disease to the T2 stage for a better predictability of survival.

Staging Lung Cancer: Metastasis.

The updated eighth edition of the tumor, node, metastasis (TNM) classification for lung cancer includes revisions to T and M descriptors. In terms of the M descriptor, the classification of intrathoracic metastatic disease as M1a is unchanged from TNM-7. Extrathoracic metastatic disease, which was classified as M1b in TNM-7, is now subdivided into M1b (single metastasis, single organ) and M1c (multiple metastases in one or multiple organs) descriptors. In this article, the rationale for changes in the M descriptors, the utility of preoperative staging with PET/computed tomography, and the treatment options available for patients with oligometastatic disease are discussed.