Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

PURPOSE: The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. DESIGN: Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. PARTICIPANTS: Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and 2022. METHODS: Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. MAIN OUTCOME MEASURE: Cumulative incidence of metastatic death. RESULTS: The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P = 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P = 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2 = 0.70, R2 = 0.50, and R2 = 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. CONCLUSIONS: Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population-based study.

BACKGROUND: Errors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging. OBJECTIVE: We sought to investigate precision (number of digits) and terminal digit clustering in Breslow thickness and potential consequences for T category. METHODS: All first primary and morphologically verified invasive melanomas in Norway between 2008 and 2015 were included. A smoothing model was fitted to estimate the underlying Breslow thickness distribution without digit clustering. RESULTS: Thickness was reported for 13,057 (97.5%) patients; the median was 1.0 mm (range, 0.09-85). It was reported as whole numbers (15.6%), to 1 decimal (78.2%) and 2 decimal places (6.2%)-thin tumors with more precision than thick tumors. Terminal digit clustering was found with marked peaks in the observed frequency distribution for terminal digits 0 and 5, and with drops around these peaks. Terminal digit clustering increased proportions of patients classified with T1 and T4 tumors and decreased proportions classified with T2 and T3. LIMITATIONS: Breslow thickness was not reported in 2.5% of cases. CONCLUSIONS: The Norwegian recommendation of measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was marked, with consequences for T category. Pathologists, clinicians, and epidemiologists should know that clustering of thickness data around T category cut points can impact melanoma staging with consequent effect on patient management and prognosis.

T categorization of urothelial carcinomas of the ureter with CT: preliminary study of new diagnostic criteria proposed for differentiating T2 or lower from T3 or higher.

OBJECTIVE: The purposes of this study were to propose and evaluate new diagnostic criteria for the differentiation of category T2 or lower from T3 or higher ureteral urothelial carcinomas on contrast-enhanced CT (CECT) images and to investigate the diagnostic applicability of the criteria. MATERIALS AND METHODS: The study included 30 patients with ureteral urothelial carcinoma who underwent CECT before surgery. For all patients, unenhanced and contrast-enhanced images (nephrographic and excretory phases) were acquired with a 16- or 64-MDCT scanner. The slice thickness of axial images was 5 mm. A grading system was devised that focused on spiculation and mass formation along the ureter on CECT images to differentiate T2 or lower from T3 or higher tumors. Three radiologists not specialized in abdominal radiology participated in an observer performance study to investigate the diagnostic utility of the criteria. Jackknife ROC analysis was used to compare the radiologists' diagnostic performance without and with the proposed diagnostic criteria. In addition, two board-certified radiologists used consensus to determine the CT grade, and the correlation between CT and pathologic findings was assessed. RESULTS: The mean AUCs for the three radiologists without and with the proposed criteria were 0.54 (SD, 0.09) and 0.73 (SD, 0.08), indicating a statistically significant difference (p<0.01). For the CT-pathologic correlation, the diagnostic sensitivity and specificity of the proposed criteria with respect to pT3 and higher tumors were 87.5% (14/16) and 92.9% (13/14). CONCLUSION: The proposed CT grading system was accurate for differentiating T2 or lower from T3 or higher ureteral urothelial carcinoma.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. RESULTS: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. CONCLUSION: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Is adjacent lobe invasion an T category upgrade factor for resected non-small cell lung cancer ≤ 5 cm?

PURPOSE: Controversy exists with regard to the T category of non-small cell lung cancer (NSCLC) with adjacent lobe invasion (ALI), and dispute arises on assigning this subset into T2 or T3 category. We evaluated the effect of ALI on the survival of resected NSCLC ≤ 5 cm, with purpose of determining the most appropriate T category for this population. METHODS: The entire cohort was divided into three subgroups (ALI group, T2 group and T3 group). Kaplan-Meier with log-rank method was carried out to compare overall survival (OS) differences. Propensity score matching (PSM) was performed to minimize bias. RESULTS: A total of 12,564 eligible NSCLC cases (ALI group: 114 cases; T2 group: 10,046 cases; T3 group: 2404 cases) were included in this study. The incidence of ALI was about 0.9%. Before PSM, survival analyses demonstrated that no significant OS differences were observed between ALI group and T2 group, and between ALI group and T3 group, neither in the entire cohort analysis nor in the subgroup analysis. After PSM, there were 102 pairs and 98 pairs in the ALI and T2 matching group and ALI and T3 matching group, respectively. In the matched cohorts, survival curves showed that the OS of ALI group was comparable to that of T2 group (P = 0.950), but superior to that of T3 group (P = 0.012). CONCLUSIONS: The current study proposed that NSCLC with ALI ≤ 5 cm should be still categorized as T2 category, which could improve staging accuracy.

Investigation of the non-small cell lung cancer patients with bronchus involvements: A population-based study.

BACKGROUND: We aimed to explore the prognostic differences among T1-4N0-2M0 non-small cell lung cancer (NSCLC) patients with bronchus involvements and to validate the T category of these patients in an external cohort. METHODS: Univariable and multivariable Cox analysis was performed to determine the prognostic factors. Kaplan-Meier method with a log-rank test was used to compare overall survival differences between groups. Propensity score matching method was used to minimize the bias caused by the imbalanced covariates between groups. RESULTS: A total of 169 390 eligible T1-4N0-2M0 NSCLC cases were included. There were 2354, 3367, 1638, 75, 87 585, 42 056, 19 246, and 13 069 cases in the group of superficial tumors of any size with invasive component limited to bronchial wall (T1-bronchus), tumors involving main stem bronchus ≥2 cm from carina (T2-main bronchus [≥2 cm]), tumors involving main stem bronchus <2 cm from carina (T2-main bronchus [<2 cm]), tumors with carina invasion (T4-carina), T1, T2, T3, and T4, respectively. Multivariable Cox analysis indicated that T1-bronchus patients had the best prognosis; T2-main bronchus (≥2 cm) and T2-main bronchus (<2 cm) patients had similar prognosis both in the entire cohort and in several subgroups. Survival curves showed that T1-bronchus and T1 patients had similar survival rates; the survivals of T2-main bronchus patients regardless of the distance from carina were comparable to those of T2 patients, and the survivals of T4-carina patients were also similar to those of T4 patients. CONCLUSIONS: Our results validated and supported the current T category for the patients with bronchus involvements, which might provide certain reference value for the revisions of T category in the next version of the tumor-node-metastasis stage classification.

Impact of anatomic resection on long-term survival in patients with hepatocellular carcinoma with T1-T2 disease or microscopic vascular invasion.

BACKGROUND: This study aimed to clarify potential candidates for anatomic resection (AR) among patients with pathological T1-T2 (pT1-T2) hepatocellular carcinoma (HCC) and to determine whether AR is effective for HCC with microscopic vascular invasion (MVI). METHODS: We retrospectively analyzed 288 patients with pT1a (n = 50), pT1b (n = 134) or pT2 (n = 104) HCC who underwent curative-intent resection between 1990 and 2010. Surgical outcomes were compared between patients who underwent AR (n = 189) and those who underwent nonanatomic resection (NAR; n = 99) according to pT category and MVI status. RESULTS: Patients who underwent AR were more likely to have good hepatic functional reserve and an aggressive primary tumor than those who underwent NAR. When patients were stratified according to pT category, AR had a more favorable impact on survival than NAR only in patients with pT2 HCC in univariate (5-year survival, 51.5% vs. 34.6%; p = 0.010) and multivariate analysis (hazard ratio 0.505; p = 0.014). However, AR had no impact on survival in patients with pT1a or pT1b HCC. In patients with MVI (n = 57), AR achieved better survival than NAR (5-year survival, 52.0% vs. 16.7%; p = 0.019) and was an independent prognostic factor (hazard ratio 0.335; p = 0.020). In patients without MVI (n = 231), there was no significant difference in survival between the two groups (p = 0.221). CONCLUSION: AR was identified as an independent factor in improved survival in patients with pT2 HCC or HCC with MVI.

Reappraisal of the T Category for Solitary Intrahepatic Cholangiocarcinoma by Tumor Size in 611 Early-Stage (T1-2N0M0) Patients After Hepatectomy: a Surveillance, Epidemiology, and End Results (SEER) Analysis.

BACKGROUND: The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy is controversial, and the T category in the American Joint Committee on Cancer (AJCC) stage for ICC is a topic of debate. METHODS: Data from 611 T1-2N0M0 ICC patients classified by the AJCC 8th edition who underwent hepatectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 1988-2015. Cancer-specific survival was evaluated using Kaplan-Meier analysis. The optimal cutoff value of solitary tumor size was used an adjusted p value approach to discriminating patient survival. RESULTS: In the AJCC 8th staging system, using a 5-cm cut-off value of tumor size for solitary ICC without vascular invasion (S/VI-) was not associated with survival in T1 category (p = 0.201), and multifocal ICC with vascular invasion had a worse survival than solitary ICC with vascular invasion (S/VI+) in T2 category (p = 0.014). Tumor size was a prognostic factor for both S/VI- and S/VI+, the optimal cutoff value of tumor size was obtained 8 cm for S/VI- and 3 cm for S/VI+. S/VI- ≤ 8 cm had a similar survival to S/VI+ ≤ 3 cm (p = 0.126), S/VI- > 8 cm had a similar survival to S/VI+ > 3 cm (p = 0.655), and multifocal ICC had a similar survival with S/VI- > 8 cm (p = 0.159) and S/VI+ > 3 cm (p = 0.196). When the cohort was divided into two groups-new T1 (S/VI- ≤ 8 cm and S/VI+ ≤ 3 cm) and new T2 (S/VI- > 8 cm, S/VI+ > 3 cm and multifocal ICC)-significant survival difference was observed (p < 0.0001). CONCLUSIONS: The discriminatory power of the AJCC 8th edition for solitary ICC could be further enhanced by subdividing tumors according to size and vascular invasion (8 cm for S/VI- and 3 cm for S/VI+).

Extent of paranasal sinus involvement and its prognostic value in nasopharyngeal carcinoma: Proposed modification in the current UICC/AJCC staging system.

PURPOSE: This study aimed to evaluate the prognostic value of paranasal sinus involvement (PSI) in NPC and to explore its appropriate position in the current AJCC staging system. MATERIALS AND METHODS: Pretreatment MRI of 1317 patients with NPC treated with intensity-modulated radiotherapy (IMRT) between January 2010, and January 2013, were reviewed retrospectively. Survival was compared between patients with PSI-slight (sinus bone wall erosion only) and PSI-severe (tumor penetrated into sinus cavity). Multivariable analysis was performed to identify the independent predictors of survival. RESULTS: The study included 1317 patients (median age 46 years; range, 11-78 years). PSI-slight was present in 15.2% (200/1317) patients and PSI-severe in 20.0% (263/1317) patients. Overall survival (OS), distant metastasis-free survival (DMFS), loco-regional recurrence-free survival (LRFS), and progression-free survival (PFS) were significantly lower in patients with PSI-severe (all P < .05). In multivariable analysis, PSI-severe was an independent prognostic factor for OS, DMFS, LRFS, and PFS (all P < .05). 96 AJCC T3 category patients with PSI-severe were reclassified as T4 category. The revised T category had significantly better predictive value (higher C-index) than that the AJCC system for survival (OS, 0.661 vs. 0.652; DMFS, 0.655 vs. 0.650; and PFS, 0.625 vs. 0.625; P < .05 for all). CONCLUSION: PSI-severe is an independent negative prognostic factor in nasopharyngeal carcinoma, which is recommended to be classified as T4 category in the 8th AJCC staging system for NPC.

Evaluation of Depth of Invasion and Tumor Thickness as a Prognostic Factor for Early-Stage Oral Squamous Cell Carcinoma: A Retrospective Study.

The aim of this study was to compare the effect of using depth of invasion (DOI) versus tumor thickness (TT) as a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). A total of 57 patients with early-stage OSCC treated surgically from 2009 to 2014 at our institution were reviewed retrospectively. Histopathological measurement of DOI and TT was performed. The validation of DOI and TT as prognostic factors was conducted using a Kaplan-Meier survival analysis. TT had no association with disease-specific survival (DSS) or progression-free survival (PFS) in this cohort; however, increased DOI was significantly associated with decreased DSS but not correlated to decreased PFS. The T category of the 7th edition of AJCC was statistically associated with both DSS and PFS; however, the T category of the 8th edition of the AJCC was only associated with DSS. In this study group, TT could not be used as a prognostic factor, and DOI was not by itself sufficient to predict prognosis for early-stage OSCC. The T category in AJCC 8th Edition cannot be considered the sole prognostic factor for early OSCC, so additional prognostic factors may need to be considered.

Validation of the Eighth Edition Clinical T Categorization System for Clinical Stage IA, Resected Lung Adenocarcinomas: Prognostic Implications of the Ground-Glass Opacity Component.

INTRODUCTION: There is controversy regarding the clinical T (cT) category of lung adenocarcinomas that manifest as part-solid nodules (PSNs). We aimed to validate the cT category and to evaluate the independent prognostic role of the nodule type (i.e., part-solid versus solid). METHODS: We retrospectively evaluated the prognostic value of clinico-radiologic factors regarding the overall survival of patients with clinical stage IA lung adenocarcinomas that were resected between 2008 and 2014. cT Category, nodule type, and their interaction term were included in the multivariable Cox regression analysis with other variables. In addition, a mixture cure model analysis was performed to investigate the association between the covariates and long-term survival. RESULTS: A total of 744 patients (420 women; 362 PSNs; median age, 63 y) were included. The multivariable-adjusted hazard ratio (HR) of the nodule type was not significant (1.30, 95% confidence interval [CI]: 0.80-2.10, p = 0.291). However, the cT categories were significantly associated with overall survival (HR of cT1b, 2.33 [95% CI: 1.07-5.06, p = 0.033]; HR of cT1c, 5.74 [95% CI: 2.51-13.12, p < 0.001]). There were no interactions between the nodule type and the cT categories (all p > 0.05). The multivariable mixture cure model revealed that solid nodules were associated with a decreased probability of long-term survival (OR = 0.40, 95% CI: 0.18-0.92, p = 0.030). In addition, cT1c was a negative predictor of long-term survival (OR = 0.26, 95% CI: 0.07-0.94, p = 0.040). CONCLUSIONS: The cT categorization system is valid for PSNs and solid nodules. Nevertheless, PSNs are a prognostic factor associated with long-term survival.

Radiomic Nomogram Improves Preoperative T Category Accuracy in Locally Advanced Laryngeal Carcinoma.

Surgical decision-making on advanced laryngeal carcinoma is heavily depended on the identification of preoperative T category (T3 vs. T4), which is challenging for surgeons. A T category prediction radiomics (TCPR) model would be helpful for subsequent surgery. A total of 211 patients with locally advanced laryngeal cancer who had undergone total laryngectomy were randomly classified into the training cohort (n = 150) and the validation cohort (n = 61). We extracted 1,390 radiomic features from the contrast-enhanced computed tomography images. Interclass correlation coefficient and the least absolute shrinkage and selection operator (LASSO) analyses were performed to select features associated with pathology-confirmed T category. Eight radiomic features were found associated with preoperative T category. The radiomic signature was constructed by Support Vector Machine algorithm with the radiomic features. We developed a nomogram incorporating radiomic signature and T category reported by experienced radiologists. The performance of the model was evaluated by the area under the curve (AUC). The T category reported by radiologists achieved an AUC of 0.775 (95% CI: 0.667-0.883); while the radiomic signature yielded a significantly higher AUC of 0.862 (95% CI: 0.772-0.952). The predictive performance of the nomogram incorporating radiomic signature and T category reported by radiologists further improved, with an AUC of 0.892 (95% CI: 0.811-0.974). Consequently, for locally advanced laryngeal cancer, the TCPR model incorporating radiomic signature and T category reported by experienced radiologists have great potential to be applied for individual accurate preoperative T category. The TCPR model may benefit decision-making regarding total laryngectomy or larynx-preserving treatment.

The development and external validation of simplified T category classification for nasopharyngeal carcinoma to improve the prognostic value in the intensity-modulated radiotherapy era.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. METHODS: We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. RESULTS: In the training set, local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c-indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0-1 as stage II; proT3N0-2/proT1-2N2 as stage III; and proT1-3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. CONCLUSIONS: In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0-2 (the 8th edition T4N0-2) should be down-staged to stage III.

Evaluation of maximum standardized uptake value at fluorine-18 fluorodeoxyglucose positron emission tomography as a complementary T factor in the eighth edition of lung cancer stage classification.

OBJECTIVES: This retrospective cohort study aimed to analyze the prognostic effect of maximum standardized uptake value (SUVmax) as a complementary T factor in addition to the clinical T category of the eighth-edition staging system for the prediction of disease-free survival (DFS) in patients with resected lung adenocarcinomas. MATERIALS AND METHODS: A total of 572 patients (male:female = 235:337; median age, 64 years) with clinical stage I (T1-T2aN0M0) adenocarcinomas underwent preoperative fluorine-18 fluorodeoxyglucose positron emission tomography and subsequent lobectomy between 2009 and 2015. The prognostic values of SUVmax and PETT category [categorized SUVmax; PETT1 (SUVmax ≤2), PETT2 (2< SUVmax ≤7), and PETT3 (SUVmax >7)] in conjunction with the clinical T category were analyzed using a multivariable Cox regression and a likelihood-ratio test, respectively. The clinical T category was then upstaged or downstaged (cTModified) based on PETT. This new categorization system was evaluated using a Cox regression and then compared with the clinical T category. RESULTS: Multivariable-adjusted Cox regression revealed that SUVmax and PETT were independent and significant predictors with the current clinical T category for DFS. Regarding SUVmax, the adjusted hazard ratio (HR) was 1.048 (95% CI: 1.009, 1.089; P = 0.017). Regarding PETT, the adjusted HRs were 2.365 (95% CI: 1.034, 5.406; P = 0.041) in PETT2 and 3.005 (95% CI: 1.258, 7.179; P = 0.013) in PETT3. The inclusion of the PET-derived factors substantially improved the model fit (P < 0.05). cTModified was a significant predictor of DFS, which improved the prognostic discrimination of lung adenocarcinomas. CONCLUSION: SUVmax and PETT are independent prognostic factors after adjustment for the clinical T category. The PETT category could be used to adjust the clinical T category preoperatively.

Consolidation-to-tumor ratio and tumor disappearance ratio are not independent prognostic factors for the patients with resected lung adenocarcinomas.

OBJECTIVES: Our study aimed to investigate the independent prognostic values of consolidation-to-tumor ratio (CTR) and tumor disappearance ratio (TDR) after adjustment for the conventional prognostic factors and the eighth edition clinical T category for patients with resected lung adenocarcinomas. MATERIALS AND METHODS: This retrospective study included 691 patients (281 men and 410 women; median age, 63 years) with resected lung adenocarcinomas (clinical T1N0M0). The prognostic implications for disease-free survival (DFS) of CTR and TDR in continuous and categorical forms were analyzed using multivariable-adjusted Cox regression analysis, including multiple clinico-radiological prognostic factors and the clinical T category based on the solid portion measurement. Analysis was performed for the total study population and for two part-solid nodule subgroups (cT1mi/cT1a to cT1c and cT1mi/cT1a to cT1b, respectively). RESULTS: For the total study population, CTR and TDR were not selected in the multivariable Cox regression models, which indicated that these are not independent prognostic factors. Age (adjusted HR: 1.026; P = 0.022) and clinical T category (adjusted HR for cT1b: 3.475; P = 0.019; adjusted HR for cT1c: 9.938; P < 0.001) were independently associated with DFS. For the part-solid nodule subgroups, multivariable-adjusted HRs for CTR and TDR were not statistically significant (all P > 0.05). CONCLUSION: CTR and TDR were not independent prognostic factors. Preoperative prognostication based on clinical T category would be sufficient without further stratification according to CTR or TDR.

Multiplicity of Advanced T Category-Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma.

BACKGROUND: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. METHODS: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. RESULTS: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). CONCLUSIONS: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Prognostic significance of subclassification of stage IIB lung cancer: a retrospective study of 226 patients.

We investigated the prognostic significance of subclassification of stage IIB lung cancer according to the eighth tumor-node-metastasis (TNM) classification. To this purpose, the prognostic outcomes of 226 stage IIB lung cancer patients who underwent surgery without adjuvant therapies between 2001 and 2010 were evaluated retrospectively based on the eighth TNM classification. Of the 226 patients, 23, 30, 118 and 55 had pT1b, pT1c, pT2a, and pT2b stage cancers, respectively. Their 5-year survival rates were 67%, 33%, 21%, and 27%, respectively. There was no significant difference in the 5-year survival between T1b and T1c, between T1c and T2a, and between T2a and T2b (p = 0.128, 0.105, and 0.403, respectively). There were significant differences in the 5-year survival between T1b and T2a, between T1b and T2b, and between T1c and T2b (p = 0.005, 0.002, and 0.042, respectively). The 5-year survival of patients with pleural invasion and vessel invasion was significantly worse than that of their counterparts (p = 0.009 and <0.001, respectively). Subclassification of stage IIB lung cancer is of prominent prognostic significance. It is recommended that the current stage be subclassified, in order to more accurately predict the prognosis of patients.

Tumor thickness versus depth of invasion - Analysis of the 8th edition American Joint Committee on Cancer Staging for oral cancer.

OBJECTIVES: The primary aim of this study is to compare the effect of using tumor thickness versus depth of invasion (DOI) to determine the 8th edition AJCC T-category on survival in a large cohort of OSCC. MATERIALS AND METHODS: A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively into a dedicated head and neck database. 927 patients with oral SCC were identified in this cohort, with the final study population including 456 patients with complete information on DOI, tumor thickness, T and N staging and follow-up. RESULTS: 26 (5.7%) patients had a different AJCC 8 T category when using thickness instead of depth. 15 were upstaged from T1 to T2, 10 upstaged from T2 to T3 and 1 down staged from T2 to T1. Additionally, similar stratification of disease-specific and overall survival curves were found for T category based on DOI and thickness. CONCLUSION: The T category and TNM stage prognostic performance of 8th edition AJCC staging of oral cancer is similar regardless of whether DOI or thickness is used as the T-category modifier. In centers without complete DOI data it is reasonable to impute thickness for retrospective survival analyses using the 8th edition of the AJCC staging system.

Gene expression analysis supports tumor threshold over 2.0 cm for T-category breast cancer.

Tumor size, as indicated by the T-category, is known as a strong prognostic indicator for breast cancer. It is common practice to distinguish the T1 and T2 groups at a tumor size of 2.0 cm. We investigated the 2.0-cm rule from a new point of view. Here, we try to find the optimal threshold based on the differences between the gene expression profiles of the T1 and T2 groups (as defined by the threshold). We developed a numerical algorithm to measure the overall differential gene expression between patients with smaller tumors and those with larger tumors among multiple expression datasets from different studies. We confirmed the performance of the proposed algorithm by a simulation study and then applied it to three different studies conducted at two Norwegian hospitals. We found that the maximum difference in gene expression is obtained at a threshold of 2.2-2.4 cm, and we confirmed that the optimum threshold was over 2.0 cm, as indicated by a validation study using five publicly available expression datasets. Furthermore, we observed a significant differentiation between the two threshold groups in terms of time to local recurrence for the Norwegian datasets. In addition, we performed an associated network and canonical pathway analyses for the genes differentially expressed between tumors below and above the given thresholds, 2.0 and 2.4 cm, using the Norwegian datasets. The associated network function illustrated a cellular assembly of the genes for the 2.0-cm threshold: an energy production for the 2.4-cm threshold and an enrichment in lipid metabolism based on the genes in the intersection for the 2.0- and 2.4-cm thresholds.

Correlation of tumor-associated macrophages and NK cells with bladder cancer size and T stage in patients with solitary low-grade urothelial carcinoma.

OBJECTIVE: The aim of the present study was to correlate the level of tumor-infiltrating immune cells with bladder cancer size and T category in patients with solitary low-grade non-muscle invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Between 1996 and 2006, 115 patients with solitary low-grade NMIBC after transurethral resection of the bladder without adjuvant therapy were retrospectively identified from the institutional database. Tumor specimens were retrieved and tissue microarrays were constructed. Immunhistochemical staining for tumor-infiltrating immune cells with anti-CD3, CD4, CD8, CD20, CD56, CD68, and granzyme B (Gr B) was performed. RESULTS: Immune cells were predominantly observed within the cancer stroma. Statistically significant higher levels of CD56 cells in small tumors and CD68 cells in T1 tumors (p = 0.0310, 0.0151, respectively) were established. CONCLUSION: The current study propose a possible correlation of CD56+ and CD68+ cells with bladder cancer size and stage in patients with solitary low-grade NMIBC.