Conventional Staging Research Articles

The prognostic value of adding systemic inflammation response index to Epstein–Barr virus DNA in childhood nasopharyngeal carcinoma: A real‐world study

To assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein-Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC). A total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS). Elevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low- and high-risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low- and high-risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05). The combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC.

Small Cell Lung Cancer Staging: Prospective Comparison of Conventional Staging Tests, FDG PET/CT, Whole-Body MRI, and Coregistered FDG PET/MRI.

BACKGROUND. Whole-body MRI and FDG PET/MRI have shown encouraging results for staging of thoracic malignancy but are poorly studied for staging of small cell lung cancer (SCLC). OBJECTIVE. The purpose of our study was to compare the performance of conventional staging tests, FDG PET/CT, whole-body MRI, and FDG PET/MRI for staging of SCLC. METHODS. This prospective study included 98 patients (64 men, 34 women; median age, 74 years) with SCLC who underwent conventional staging tests (brain MRI; neck, chest, and abdominopelvic CT; and bone scintigraphy), FDG PET/CT, and whole-body MRI within 2 weeks before treatment; coregistered FDG PET/MRI was generated. Two nuclear medicine physicians independently reviewed conventional tests and FDG PET/CT examinations in separate sessions, and two chest radiologists independently reviewed whole-body MRI and FDG PET/MRI examinations in separate sessions. Readers assessed T, N, and M categories; TNM stage; and Veterans Administration Lung Cancer Study Group (VALSG) stage. Reader pairs subsequently reached consensus. Stages determined clinically during tumor board sessions served as the reference standard. RESULTS. Accuracy for T category was higher (p < .05) for whole-body MRI (94.9%) and FDG PET/MRI (94.9%) than for FDG PET/CT (85.7%). Accuracy for N category was higher (p < .05) for whole-body MRI (84.7%), FDG PET/MRI (83.7%), and FDG PET/CT (81.6%) than for conventional staging tests (75.5%). Accuracy for M category was higher (p < .05) for whole-body MRI (94.9%), FDG PET/MRI (94.9%), and FDG PET/CT (94.9%) than for conventional staging tests (84.7%). Accuracy for TNM stage was higher (p < .05) for whole-body MRI (88.8%) and FDG PET/MRI (86.7%) than for FDG PET/CT (77.6%) and conventional staging tests (72.4%). Accuracy for VALSG stage was higher (p < .05) for whole-body MRI (95.9%), FDG PET/MRI (95.9%), and FDG PET/CT (98.0%) than for conventional staging tests (82.7%). Interobserver agreement, expressed as kappa coefficients, ranged from 0.81 to 0.94 across imaging tests and staging endpoints. CONCLUSION. FDG PET/CT, whole-body MRI, and coregistered FDG PET/MRI outperformed conventional tests for various staging endpoints in patients with SCLC. Whole-body MRI and FDG PET/MRI outperformed FDG PET/CT for T category and thus TNM stage, indicating the utility of MRI for assessing extent of local invasion in SCLC. CLINICAL IMPACT. Incorporation of either MRI approach may improve initial staging evaluation in SCLC.

Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma.

As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n=208) or validation set (n=108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.

Methods of Sentinel Lymph Node Detection and Management in Urinary Bladder Cancer-A Narrative Review.

Introduction: Detection of lymph node status in bladder cancer significantly impacts clinical decisions regarding its management. There is a wide range of detection modalities for this task, including lymphoscintigraphy, computed tomography, magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, and fluoroscopy. We aimed to study the pre- and intraoperative detection modalities of sentinel lymph nodes in urinary bladder cancer. Method: This narrative review was performed by searching the PubMed and EMBASE libraries using the following search terms: (“Transitional cell carcinoma of the bladder” OR “urothelial cancer” OR “urinary bladder cancer” OR “bladder cancer”) AND ((“sentinel lymph node”) OR (“lymphatic mapping”) OR (“lymphoscintigraphy”) OR (“lymphangiography”) OR (“lymph node metastases”)). Studies analysing the effectiveness and outcomes of sentinel lymph node detection in bladder cancer were included, while non-English language, duplicates, and non-article studies were excluded. After analysing the libraries and a further manual search of bibliographies, 31 studies were included in this paper. We followed the RAMESES publication standard for narrative reviews to produce this paper. Results: Of the 31 studies included, 7 studies included multiple detection methods; 5 studies included lymphoscintigraphy; 5 studies included computed tomography and/or single-photon emission computed tomography; 5 studies included fluoroscopy; 4 studies included magnetic resonance imaging; and 5 studies included positron emission tomography. Discussion: Anatomical, radioactive, and functional detection modalities have been studied independently and in combination. The consensus is that preoperative detection with imaging helps guide surgical management and intraoperative detection methods help capture any lymph nodes that may have been missed. Each of these types of detection represent their own set of benefits and drawbacks, but there is currently limited evidence to support any change in overall practice to replace conventional staging.

A Novel Echocardiographic Risk Score in AL-Amyloidosis

Prognosis in light chain (AL) amyloidosis is often determined by the severity of cardiac involvement. Conventional (Mayo) staging includes 1) hs troponin 2) N-terminal pro-beta natriuretic peptide (NT-pro BNP) and 3) free light chain difference.

Prospective study to assess the role of FDG PET/CT in detecting systemic metastatic spread in rectal cancers with lateral pelvic lymph nodes

IntroductionThe utility of positron emission tomography (PET) in detecting additional M1 patients over conventional staging modalities is not known in rectal cancer patients with enlarged lateral pelvic nodes. MethodsProspective, single center, single-arm interventional study of consecutive rectal cancer patients that had baseline lateral pelvic nodes on MRI (>10 mm) between February 2017 to December 2018. Such patients underwent PET after confirming non-metastatic status on CT of thorax and abdomen. Primary outcome measure was additional M1 sites detected on PET. A 10% distant metastasis rate was expected with 80% confidence interval (CI) set at 5% as the lower limit. Results44 patients were included and the concordance between MRI and PET in detection of lateral nodes was 97.7% (43 patients). Additional sites of metastasis were detected in 5 patients (11.36%; 80% CI - 5.63%–20.6%), and there was a change in treatment plan in 7 (15.9%). The number needed to treat (NNT) for PET scans to detect additional metastatic sites and change treatment were 9 and 6 respectively. There was a change in treatment intent (curative to palliative) in 2 patients (4.5%, NNT – 22). ConclusionIn rectal cancer patients with LPLN, the use of FDG-PET-CT over conventional staging studies led to the detection of additional extra-pelvic metastasis in 11.4% and changed the treatment plan in 15.9%. This met the pre-defined threshold to endorse the use of PET-CT in patients that match the study characteristics.

Effects of Total Pancreatectomy on Survival of Patients With Pancreatic Ductal Adenocarcinoma: A Population-Based Study.

Background: Total pancreatectomy (TP) seems to be experiencing a renaissance in recent years. In this study, we aimed to determine the long-term survival of pancreatic ductal adenocarcinoma (PDAC) patients who underwent TP by comparing with pancreaticoduodenectomy (PD), and formulate a nomogram to predict overall survival (OS) for PDAC individuals following TP.Methods: Patients who were diagnosed with PDAC and received PD (n = 5,619) or TP (n = 1,248) between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. OS and cancer-specific survival (CSS) of the PD and TP groups were compared using Kaplan-Meier method and log-rank test. Furthermore, Patients receiving TP were randomly divided into the training and validation cohorts. Univariate and multivariate Cox regression were applied to identify the independent factors affecting OS to construct the nomogram. The performance of the nomogram was measured according to concordance index (C-index), calibration plots, and decision curve analysis (DCA).Results: There were no significant differences in OS and CSS between TP and PD groups. Age, differentiation, AJCC T stage, radiotherapy, chemotherapy, and lymph node ratio (LNR) were identified as independent prognostic indicators to construct the nomogram. The C-indexes were 0.67 and 0.69 in the training and validation cohorts, while 0.59 and 0.60 of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The calibration curves showed good uniformity between the nomogram prediction and actual observation. DCA curves indicated the nomogram was preferable to the AJCC staging system in terms of the clinical utility. A new risk stratification system was constructed which could distinguish patients with different survival risks.Conclusions: For PDAC patients following TP, the OS and CSS are similar to those who following PD. We developed a practical nomogram to predict the prognosis of PDAC patients treated with TP, which showed superiority over the conventional AJCC staging system.

Development and validation of a nomogram to predict cancer-specific survival in patients with hypopharyngeal squamous cell carcinoma treated with primary surgery.

ObjectiveWe aimed to develop a nomogram to predict cancer-specific survival (CSS) in patients with hypopharyngeal squamous cell carcinoma (HSCC) treated with primary surgery to provide more accurate risk stratification for patients.MethodsWe retrospectively collected data of 1144 eligible patients with HSCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Patients were randomly divided into training and validation groups (ratio 6:4) and we used univariate and multivariate Cox analysis. We developed and validated a nomogram using calibration plots and time-dependent receiver operating characteristic, Kaplan–Meier, and decision curves.ResultsAge; marital status; T, N, and M stage; and postoperative adjuvant therapy were independent factors associated with CSS, which were included in the nomogram. The nomogram’s C-index was 0.705 to 0.723 in the training group and 0.681 to 0.736 in the validation group, which were significantly higher than conventional American Joint Committee on Cancer (AJCC) staging. Calibration curves showed good agreement between prediction and observation in both groups. Kaplan–Meier and decision curves suggested the nomogram had better risk stratification and net benefit than conventional AJCC staging.ConclusionsWe established a nomogram that was superior to conventional AJCC staging in predicting CSS for HSCC.

A Novel Clinical-Radiomics Model Based on Sarcopenia and Radiomics for Predicting the Prognosis of Intrahepatic Cholangiocarcinoma After Radical Hepatectomy.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with a poor prognosis. This study aimed to establish a novel clinical-radiomics model for predicting the prognosis of ICC after radical hepatectomy.MethodsA clinical-radiomics model was established for 82 cases of ICC treated with radical hepatectomy in our hospital from May 2011 to December 2020. Radiomics features were extracted from venous-phase and arterial-phase images of computed tomography. Kaplan-Meier survival analysis was generated to compare overall survival (OS) between different groups. The independent factors were identified by univariate and multivariate Cox regression analyses. Nomogram performance was evaluated regarding discrimination, calibration, and clinical utility. C-index and area under the curve (AUC) were utilized to compare the predictive performance between the clinical-radiomics model and conventional staging systems.ResultsThe radiomics model included five features. The AUC of the radiomics model was 0.817 in the training cohort, and 0.684 in the validation cohort. The clinical-radiomics model included psoas muscle index, radiomics score, hepatolithiasis, carcinoembryonic antigen, and neutrophil/lymphocyte ratio. The reliable C-index of the model was 0.768, which was higher than that of other models. The AUC of the model for predicting OS at 1, and 3 years was 0.809 and 0.886, which was significantly higher than that of the American Joint Committee on Cancer 8th staging system (0.594 and 0.619), radiomics model (0.743 and 0.770), and tumor differentiation (0.645 and 0.628). After stratification according to the constructed model, the median OS was 59.8 months for low-risk ICC patients and 10.1 months for high-risk patients (p < 0.0001).ConclusionThe clinical-radiomics model integrating sarcopenia, clinical features, and radiomics score was accurate for prognostic prediction for mass-forming ICC patients. It provided an individualized prognostic evaluation in patients with mass-forming ICC and could helped surgeons with clinical decision-making.

Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema

Precise staging of breast cancer-related lymphedema (BCRL) is important to guide treatment-decision making. Recent studies have suggested staging of BCRL using indocyanine green lymphangiography (ICG-L) based on the extent of lymphatic injury and dermal backflow patterns. Currently, the benefits of ICG-L compared to conventional clinical staging are unknown. For this study, we included 200 patients with unilateral BCRL. All BCRL patients were staged using ICG-L and clinical exam. The amounts of excess arm volume, fat mass and lean mass were compared between stages using Dual Energy X-Ray Absorptiometry. Multivariate regression models were used to adjust for confounders. For each increase in the patient's ICG-L stage, the excess arm volume, fat mass and lean mass was increased by 8, 12 and 6.5 percentage points respectively (P < 0.001). For each increase in the patient's clinical ISL stage, the volume was increased by 3.5 percentage points (P < 0.05), however no statistically significant difference in the lean and fat mass content of the arm was observed for ascending stages. However, the residual plots showed a high degree of variance for both ICG-L and clinical staging. This study found that ICG-L staging of BCRL was superior to clinical staging in forecasting BCRL excess arm volume, fat mass, and lean mass. However, there was a high degree of variance in excess arm volume, fat mass, and lean mass within each staging system, and neither the ICG-L nor clinical staging forecasted perfectly.

Predict Early Recurrence of Resectable Hepatocellular Carcinoma Using Multi-Dimensional Artificial Intelligence Analysis of Liver Fibrosis.

Simple SummaryHepatocellular carcinoma (HCC) is the third most commonly diagnosed cancer in the world, and surgical resection is the commonly used curative management of early-stage disease. However, the recurrence rate is high after resection, and liver fibrosis has been thought to increase the risk of recurrence. Conventional histological staging of fibrosis is highly subjective to observer variations. To overcome this limitation, we used a fully quantitative fibrosis assessment tool, qFibrosis (utilizing second harmonic generation and two-photon excitation fluorescence microscopy), with multi-dimensional artificial intelligence analysis to establish a fully-quantitative, accurate fibrotic score called a “combined index”, which can predict early recurrence of HCC after curative intent resection. Therefore, we can pay more attention on the patients with high risk of early recurrence.Background: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. Methods: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model “combined index” according to the morphological collagen features of each patient’s non-tumor hepatic tissues. Results: Our results showed that the “combined index” can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher “combined index” is also a poor prognostic factor of disease-free survival and overall survival. Conclusions: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed.

Predictors of Undergoing Surgical Resection after Neoadjuvant Chemoradiotherapy for Borderline Resectable and Resectable Pancreatic Adenocarcinoma

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemoradiotherapy (CRT) serves to downstage and increase the rate of surgical resection for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). Although conventional staging provides prognostic information, it remains a challenge to predict which patients will proceed with resection. We hypothesize that the severity of vessel involvement and the trajectory of CA19-9 levels after neoadjuvant treatment would associate with proceeding to resection. <h3>Materials/Methods</h3> Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC and treated with neoadjuvant CRT between 1/2005 and 12/2020. Progress notes were evaluated to determine if a patient proceeded to surgery and the trajectory of CA 19-9 levels in response to treatment. Radiologist notes were evaluated to determine the extent of mesenteric vessel (superior mesenteric artery, celiac axis, portal vein, hepatic artery, and superior mesenteric vein) involvement. A vessel involvement score was calculated as the sum of all vessels in contact with tumor: 1 point for each vessel, with partial (< 180 degrees) encasement of artery counting as 2 points. Odds ratios (OR) of proceeding to resection were computed with 95% confidence intervals (CI) for CA19-9 response to treatment. Ordinal logistic regression models were fit to estimate the impact of greater vessel involvement on the odds of NOT proceeding with surgery. <h3>Results</h3> Forty-two (n = 42) patients were included in the analysis. The median age was 65 years (IQR: 61 to 71). 73% of patients were treated with 3600 cGy in 15 fractions (fx), 24% of patients were treated with 4500-5040 cGy in 25-28 fx, and 3% of patients were treated with 3300 cGy in 5 fx. 55% of patients were treated with neoadjuvant FOLFIRINOX and 45% of patients were treated with other regimens. 88% of patients were considered borderline resectable and 12% were resectable at the time of diagnosis. Patients with any decrease in CA19-9 levels after CRT had higher odds of proceeding with resection (OR = 21.0, 95% CI: 3.2 to 139.2). However, decrease in CA19-9 levels after upfront chemotherapy was not significantly associated with proceeding with resection (<i>P</i> = 0.91). The odds of NOT proceeding with resection after neoadjuvant CRT were 1.81 times higher (95% CI: 0.97 to 3.39) for each increase in vessel involvement score, however these findings were not statistically significant (<i>P</i> = 0.062). <h3>Conclusion</h3> Patients diagnosed with (B)RPC proceeding with CRT have different odds of proceeding to surgery based on their response to CRT and extent of vessel involvement. Post-CRT CA19-9 can help predict which patients may proceed to resection. Future investigations will develop nomograms for estimating odds of proceeding to surgery in larger datasets to help aid in patient counseling and multidisciplinary discussion.

FAPI-PET/CT Improves Diagnostic Staging and Radiotherapy Planning of Adenoid Cystic Carcinomas ― Imaging Analysis and Histological Validation

Adenoid cystic carcinomas (ACCs) are rare epithelial tumors mostly situated in the head and neck region and characterized by infiltrative growth. The tumor stroma of ACCs includes cancer-associated fibroblasts (CAFs) expressing Fibroblast Activation Protein (FAP), a new target for positron emission tomography (PET) imaging. Here we describe the value of PET/ computed tomography (PET/CT) imaging using 68Ga-labelled FAP-Inhibitors (68Ga-FAPI-PET/CT) and their clinical potential for staging and radiotherapy planning in 12 ACC patients (7 primary, 5 recurrent).Patients underwent contrast enhanced CT (ceCT) and magnetic resonance imaging (ceMRI) before 68Ga-FAPI - PET/CT. PET-scans were acquired 10, 60 and 180 minutes after administration of 150-250 MBq of 68Ga-labelled FAPI tracers. SUVmax and SUVmean values of ACCs and healthy organs were obtained using a 60% of maximum iso-contour. FAP and alpha smooth muscle actin (α-SMA) immunohistochemistry was performed in 13 cases (3 with and 10 without 68Ga FAPI-PET/CT). Staging and radiotherapy planning based on 68Ga-FAPI-PET/CT versus ceCT/MRI alone were compared.We observed elevated tracer uptake in all ACCs. Immunohistochemistry showed FAP-expressing CAFs in the tumor. Compared to conventional staging, 68Ga-FAPI-PET/CT led to upstaging in 2/12 patients and to detection of additional metastases in 3 patients, thus in total 42% of patients had their staging altered. Moreover, 68Ga-FAPI PET improved the accuracy of target volume delineation for radiotherapy, as compared to CT and MRI.68Ga-FAPI-PET/CT is a promising imaging modality for ACC, providing additional information for staging and leading to altered radiotherapy planning compared to CT and MRI.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

TP53 Mutation as Molecular Marker in the Assessment of Surgical Margin Status in Head and Neck Squamous Cell Carcinoma

Genetic alteration of tumor suppressor and oncogene plays important role in development and progression of cancer. Tumor suppressor gene, Tp53 also knows as ‘guardian of genome’ has very important role in head and neck squamous cell carcinoma (HNSCC). Mutation of Tp53 has been commonly observed in other carcinomas including HNSCC, comprising of 75-85% of head and neck cancer, with highest in larynx and hypopharynx followed by oral cavity. Tp53 mutation is more commonly seen in Human Papilloma Virus (HPV)-ve and wild type Tp53 in HPV+ve carcinomas. Role of Tp53 mutation help us to know about the prognostic state, molecular stage and chance of local recurrence. Different studies have highlighted the importance of assessing Tp53 mutation in the negative surgical margin, which showed mutation of Tp53 in the negative surgical margin resulted increase in chance of local recurrence. These studies provide significance of moving conventional method of histopathological assessment to molecular assessment, that gives advantage of proper management decision as well as prognosis of tumor. Regarding techniques of these assessments, molecular technique has been always superior to immunohistochemistry (IHC) but is somewhat tedious, so more clinical analysis on the alternatives of IHC combined with Next generation sequencing (NGS) gives the platform to perform more Tp53 mutation test in the surgical margin. This is the need of time to incorporate molecular staging in the conventional staging for proper treatment and outcome in the management of head and neck cancers.

Personalising cancer medicine with prognostic markers.

Personalising cancer medicine with prognostic markers.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma

Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

The Value of Sentinel Lymph Node Mapping for the Staging of Node-Negative Colon Cancer: Propensity Score and Mediation Analyses.

Mediation analysis to assess the protective impact of sentinel lymph node (SLN) mapping on prognosis and survival of patients with colon cancer through a more precise evaluation of the lymph node (LN) status. Up to 20% of patients with node-negative colon cancer develop disease recurrence. Conventional histopathological LN examination may be limited in describing the real metastatic burden of LN. Data of 312 patients with stage I & II colon cancer was collected prospectively. Patients were either staged using intraoperative SLN mapping with multilevel sectioning and immunohistochemical staining of the SLN or conventional techniques. The value of the SLN mapping for the detection of truly node-negative patients was assessed using Cox regression and mediation analysis. SLN mapping was performed in 143 patients. Disease recurrence was observed in 13 (9.1%) patients staged with SLN mapping and in 27 (16%) staged conventionally. Five-year overall survival (OS) rate was 82.7% (95% confidence interval [CI], 76.5-89.4%) with SLN mapping compared with 65.8% (95% CI, 58.8-73.7%). Five-year cancer-specific survival (CSS) was 95.1% (95% CI, 91.3-99.0%) with SLN mapping compared with 92.5% (95% CI, 88.0-97.2%). Node-negative staging with SLN mapping was associated with significantly better OS (hazard ratio [HR], 0.64; 95% CI, 0.56-0.72; P < 0.001) and CSS (HR, 0.49; 95% CI, 0.39-0.61; P < 0.001) in multivariate analysis. Mediation analysis confirmed a direct protective effect of SLN mapping on OS (HR, 0.78; 95% CI, 0.52-0.96; P < 0.01) and disease-free survival (DFS) (HR, 0.75; 95% CI, 0.48-0.89; P < 0.01). Staging performed by SLN mapping with multilevel sectioning provides more accurate results than conventional staging. The observed clinically relevant and statistically significant benefit in OS and DFS is explained by a more accurate detection of positive LN by SLN mapping.

Automated assessment of CD8+ T-lymphocytes and stroma fractions complement conventional staging of colorectal cancer.

BackgroundTumor development is critically dependent on the supporting stroma consisting of inflammatory cells and fibroblasts. This study intended to improve prognostic prediction for early colorectal cancer (CRC) by combined estimation of T-lymphocyte and stroma fractions with conventional markers.MethodsIn total 509 and 1041 stage II/ΙΙΙ CRC from the VICTOR and QUASAR 2 trials were included as a training set and a validation set, respectively. Intratumoral CD8+ T-lymphocytes and stroma were identified and quantified by machine-based learning on digital sections. The primary endpoint was to evaluate the prognostic value of the combined marker for time to recurrence (TTR).FindingsFor low-risk patients (n = 598; stage Ⅱ, and stage ΙΙΙ pT1-3 pN1 with neither lymphatic (L−) nor vascular (V−) invasion), low stroma fraction (n = 511) identified a good prognostic subgroup with 5-year TTR of 86% (95% CI 83–89), versus the high stroma subgroup TTR of 78% (HR = 1.75, 95% CI 1.05–2.92; P = 0.029). For high-risk patients (n = 394; stage ΙΙΙ pT3 pN1 L+/V+, pT4, or pN2), combined low CD8+ and high stroma fraction identified a poor prognostic subgroup (n = 34) with 5-year TTR of 29% (95% CI 17-50), versus the high CD8+ fraction and low stroma fraction subgroup (n = 138) of 64% (HR = 2.86, 95% CI 1.75–4.69; P < 0.001).InterpretationQuantification of intratumoral CD8+ T-lymphocyte and stroma fractions can be combined with conventional prognostic markers to improve patient stratification.

Improved outcomes and staging in non-small-cell lung cancer guided by a molecular assay.

There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as ‘early stage.’ A 14-gene quantitative PCR-based expression profile has been extensively validated to better identify patients at high-risk of 5-year mortality after surgical resection than conventional staging – mortality that almost always results from previously undetectable metastases. Furthermore, prospective studies now suggest a predictive benefit in disease-free survival when the assay is used to guide adjuvant chemotherapy decisions in early-stage non-small-cell lung cancer patients.