Clinical Staging System Research Articles

Single Center Real World Data That Compares Autologous Stem Cell Transplant in the Era of Anti-CD38 Monoclonal Antibody Based Treatments for AL Amyloidosis

Introduction: Systemic AL amyloidosis is a plasma cell disease characterized by the deposition of insoluble amyloid fibrils causing organ dysfunction and death. Results from the ANDROMEDA study showed that the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone (VCD) was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. In our single-center retrospective real-life case series, we aimed to evaluate the role of AHCT in the era of Anti-CD38 monoclonal antibody based treatments for AL amyloidosis Patients and Methods: One hundred and two consecutive patients newly diagnosed with AL amyloidosis at our center between 2007-2022 were included retrospectively. The F/M ratio was 50/52 The median age was 61 years (range:31-85), and the median follow-up was 11.8 months (range: 1-100 months). There were 68 (66%) patients with cardiac involvement and 79 (76.7%) patients with renal involvement at the time of diagnosis. Among all patients, 33% had stage 0-1, 60.2% ≥ stage 2 cardiac involvement. At the time of diagnosis, 61.2% of the patients had renal stage 2-3 disease. Fourthy-six patients (44.7%) patients had stages III and IV according to the Revised Mayo Clinic Staging System. Induction treatments that were used in our center were melphalan-dexamethasone(2007-2014), bortezomib-dexamethasone (2007-2022), VCD (2007-2022), Daratumumab-VCD (2018-2022) and up-front AHCT for transplant-eligible patients (2007-2022). Results: Eighty of 102 patients (78.4%) underwent AHCT and post-transplant 41 patients achieved ≥VGPR but 43 patients deceased during post-transplant follow-up. Among patients who received daratumumab-based induction treatment without AHCT consolidation, 11/20 patients achieved ≥VGPR and none of these patients relapsed. In patients who received daratumumab-based induction treatment renal and cardiac responses were observed in 50% and 60%, respectively. Death was significantly lower among patients with Mayo Clinic Risk Stage 3-4 who received daratumumab (20% (3/15) vs 71% (22/31); p=0.002). Median overall survival was 56.8 months (95% CI 22.7-90.9) and the probability of 2-years OS was 56.2%. There were significant differences in median OS according to daratumumab administration (NR vs 23.3 mos; p=0.015) (Figure-1). Patients who had received daratumumab as an induction treatment without AHCT consolidation (n=20) have displayed prolonged OS compared to others (n=80) (NR vs 32.6 mos (95% CI 0-71.5); p=0.1) (Figure-2). There were no significant differences in 2-years PFS between the two groups but it's important to note that no progression was seen in the daratumumab group (Figure-3). If Cox proportional hazards model including Revised Mayo Clinic Stage, w/wo AHCT, and w/wo Daratumumab was used, only Daratumumab administration was associated with better PFS (HR: 18.8 (95% CI: 3.3-108.8); p=0.001). Conclusion: From the prognostic point of view, our results based on real-world AL amyloidosis experience showed the improvement in OS with daratumumab-based treatments even in advanced stages of the disease. In addition, all patients rapidly achieved hematological response that deepened over time, and also cardiac and the renal response was also observed in a substantial proportion of our cohort. The data presented here add to the growing body of literature supporting the delayed use of AHCT in patients with AL amyloidosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Invasive and Real-Time Monitoring of the Breast Cancer Metastasis Degree via Metabolomics.

Breast cancer (BC) is a serious threat to women's health and metastasis is the major cause of BC-associated mortality. Various techniques are currently used to preoperatively describe the metastatic status of tumors, based on which a comprehensive treatment protocol was determined. However, accurately staging a tumor before surgery remains a challenge, which may lead to the miss of optimal treatment options. More severely, the failure to detect and remove occult micrometastases often causes tumor recurrences. There is an urgent need to develop a more precise and non-invasive strategy for the detection of the tumor metastasis in lymph nodes and distant organs. Based on the facts that tumor metastasis is closely related to the primary tumor microenvironment (TME) evolutions and that metabolomics profiling of the circulatory system can precisely reflect subtle changes within TME, we suppose whether metabolomic technology can be used to achieve non-invasive and real-time monitoring of BC metastatic status. In this study, the metastasis status of BC mouse models with different tumor-bearing times was firstly depicted to mimic clinical anatomic TNM staging system. Metabolomic profiling together with metastasis-related changes in TME among tumor-bearing mice with different metastatic status was conducted. A range of differential metabolites reflecting tumor metastatic states were screened and in vivo experiments proved that two main metastasis-driving factors in TME, TGF-β and hypoxia, were closely related to the regular changes of these metabolites. The differential metabolites level changes were also preliminarily confirmed in a limited number of clinical BC samples. Metabolite lysoPC (16:0) was found to be useful for clinical N stage diagnosis and the possible cause of its changes was analyzed by bioinformatics techniques.

Construction and evaluation of a polygenic hazard score for prognostic assessment in localized gastric cancer

To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer (GC), we performed two genome-wide association studies (GWASs) of GC survival in the Jiangsu (N = 1049) and Shanghai (N = 1405) cohorts. By using a TCGA dataset, we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci. Then, we constructed a weighted polygenic hazard score (PHS) and developed a nomogram in combination with clinical variables. We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic (ROC) curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We identified a single nucleotide polymorphism (SNP) of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12 × 10−8, and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort. The PHS derived from these 26 SNPs (PHS-26) was an independent prognostic factor for GC survival (all P < 0.001). The 5-year AUC of PHS-26 was 0.68, 0.66 and 0.67 for Jiangsu, Shanghai and their pooled cohorts, respectively, which increased to 0.80, 0.82 and 0.81, correspondingly, after being integrated into a nomogram together with variables of the clinical model. The PHS-26 could improve the NRIs by 16.20%, 4.90% and 8.70%, respectively, and the IDIs by 11.90%, 8.00% and 9.70%, respectively. The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.

Exploitation and Verification of a Stroma- and Metastasis-Associated Risk Prognostic Signature in Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD), one of the most malignant tumors, not only has abundant mesenchymal components, but is also characterized by an extremely high metastatic risk. The purpose of this study was to construct a model of stroma- and metastasis-associated prognostic signature, aiming to benefit the existing clinical staging system and predict the prognosis of patients. First, stroma-associated genes were screened from the TCGA database with the ESTIMATE algorithm. Subsequently, transcriptomic data from clinical tissues in the RenJi cohort were screened for metastasis-associated genes. Integrating the two sets of genes, we constructed a risk prognostic signature by Cox and LASSO regression analysis. We then obtained a risk score by a quantitative formula and divided all samples into high- and low-risk groups based on the scores. The results demonstrated that patients with high-risk scores have a worse prognosis than those with low-risk scores, both in the TCGA database and in the RenJi cohort. In addition, tumor mutation burden, chemotherapeutic drug sensitivity and immune infiltration analysis also exhibited significant differences between the two groups. In exploring the potential mechanisms of how stromal components affect tumor metastasis, we simulated different matrix stiffness in vitro to explore its effect on EMT key genes in PAAD cells. We found that cancer cells stimulated by high matrix stiffness may trigger EMT and promote PAAD metastasis.

Developing and validating nomograms for predicting the survival in patients with clinical local-advanced gastric cancer.

Many patients with gastric cancer are at a locally advanced stage during initial diagnosis. TNM staging is inaccurate in predicting survival. This study aims to develop two more accurate survival prediction models for patients with locally advanced gastric cancer (LAGC) and guide clinical decision-making. We recruited 2794 patients diagnosed with LAGC (2010-2015) from the Surveillance, Epidemiology, and End Results (SEER) database and performed external validation using data from 115 patients with LAGC at Yantai Affiliated Hospital of Binzhou Medical University. Univariate and multifactorial survival analyses were screened for meaningful independent prognostic factors and were used to build survival prediction models. Concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were evaluated for nomograms. Finally, the differences and relationships of survival and prognosis between the three different risk groups were described using the Kaplan-Meier method. Cox proportional risk regression model analysis identified independent prognostic factors for patients with LAGC, and variables associated with overall survival (OS) included age, race, marital status, T-stage, N-stage, grade, histologic type, surgery, and chemotherapy. Variables associated with cancer-specific survival (CSS) included age, race, T-stage, N-stage, grade, histological type, surgery, and chemotherapy. In the training cohort, C-index of nomogram for predicting OS was 0.722 (95% confidence interval [95% CI]: 0.708-0.736] and CSS was 0.728 (95% CI: 0.713-0.743). In the external validation cohort, C-index of nomogram for predicted OS was 0.728 (95% CI:0.672-0.784) and CSS was 0.727 (95% CI:0.668-0.786). The calibration curves showed good concordance between the predicted and actual results. C-index, ROC, and DCA results indicated that our nomograms could more accurately predict OS and CSS than TNM staging and had a higher clinical benefit. Finally, to facilitate clinical use, we set up two web servers based on nomograms. The nomograms established in this study have better risk assessment ability than the clinical staging system, which can help clinicians predict the individual survival of LAGC patients more accurately and thus develop appropriate treatment strategies.

Updated Clinical Nodal Staging System for p16+ Oropharyngeal Squamous Cell Carcinoma Associated with Loss of Prognostic Data

<h3>Purpose/Objective(s)</h3> Due to human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) having significantly improved prognosis, the American Joint Committee on Cancer (AJCC) introduced a distinct staging system for p16+ OPSCC in its 8^th edition. The clinical nodal staging system removed multiple pathologic factors present in the 7^th edition, including nodal quantity and extracapsular extension (ECE). This study aimed to characterize whether the simplification of the staging system resulted in the loss of prognostic value by using the National Cancer Database (NCDB). <h3>Materials/Methods</h3> The NCDB was queried for patients diagnosed with p16+ OPSCC. Patients with no staging information, metastatic disease, who did not receive definitive surgery or radiation, or had unknown follow-up were excluded. The prognostic impact of nodal size, nodal quantity, nodal laterality, and ECE on overall survival (OS) were assessed using survival analysis with the Kaplan Meier method, univariable, and multivariable Cox proportional hazards regression. <h3>Results</h3> A total of 21,868 patients met inclusion criteria. On Kaplan Meier analysis, patients with more than one positive lymph node had significantly inferior OS (p<0.001; 5-yr OS: 82% vs 86%). Patients with ECE also had inferior outcomes (p<0.001; 5-yr OS: 82% vs 75%). Patients with contralateral or bilateral nodal involvement also had inferior OS (p<0.001; 5-yr OS: 71% vs 84%). Lastly, a largest nodal size of >6 cm was also associated with inferior OS (p<0.001; 5-yr OS: 66% vs 82%). Interestingly, a nodal size of ≤3 cm was also associated with inferior OS compared to 3-6 cm (p<0.001; 5-yr OS: 81% vs 84%). On multivariable Cox regression, having more than one positive node (p<0.001; HR [95% CI]: 1.17 [1.07-1.28]), ECE (p<0.001; HR [95% CI]: 1.20 [1.04-1.38]), and a node >6 cm (p<0.001; HR [95% CI]: 1.52 [1.30-1.79]) remained associated with inferior OS. Node laterality was no longer significant (p=0.99). There was no longer a significant difference between ≤3 cm nodes and 3-6 cm nodes (p=0.63), but only when the model included T stage. Other factors associated with OS included age, Charlson Deyo score, insurance type, T stage, and lymphovascular invasion (LVSI). <h3>Conclusion</h3> Although incorporation of p16 status in OPSCC staging was an important addition to the AJCC 8^th edition, the associated simplifications in the current staging system result in loss of valuable prognostic information in nodal staging, including nodal quantity and ECE, which could limit risk stratification of patients with node-positive OPSCC. Although all of these factors needn't necessarily be included in the staging system, and could instead be used as additional prognostic and predicative considerations, further work evaluating the impact of the updated clinical nodal staging for p16+ OPSCC prognostication and treatment selection is warranted, and should be considered for future iterations of the AJCC staging system.

Detection of 13q deletion in patients with chronic lymphocytic leukemia and its correlation to hematopathological parameters

Background: Chronic lymphocytic leukemia(CLL) is a monoclonal malignancy characterized by an accumulation of small and mature looking B lymphocytes in the blood, bone marrow and other tissues, and is typically characterized by expression CD5+, CD23+, CD22 -, CD79b-, with weak expression of surface immunoglobulin (sIg). Two major clinical staging systems (Rai and Binet staging), that developed to estimate prognosis in CLL. However both these systems are unable to prospectively distinguish the rapidly developing patients from those appreciated to remain with a stable disease for decades. Several publications reported the prognostic important of 13q deletion in patients with chronic lymphocytic leukemia. 13q deletion is the most important cytogenetic abnormalities detected by Fluorescence In situ Hybridization in CLL patients and represent a good prognostic marker with 60% of patients alive after 5 years as compared with 27% for patients with a normal FISH analysis. Aims of the study: To investigate 13q deletion in patients with chronic lymphocytic leukemia by using FISH technique. To correlate the presence of 13q deletion with hematological and clinical prognostic markers including complete blood picture, absolute lymphocyte count, and modified Rai staging.

Clinical practice guidelines for endometriosis in Japan (The 3rd edition).

Clinical practice guidelines for endometriosis in Japan (The 3rd edition).

Construction of a new clinical staging system for colorectal cancer based on the lymph node ratio: A validation study.

AimThis study aims to construct a new staging system for colorectal cancer (CRC) based on the lymph node ratio (LNR) as a supplement to the American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system for predicting the prognosis of CRC patients with <12 lymph nodes.MethodsThe data of 26,695 CRC patients with <12 lymph nodes were extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. A total of 635 CRC patients were also enrolled from Northern Jiangsu People's Hospital affiliated with Yangzhou University as an independent validation set. Classification and regression tree analysis was used to obtain the LNR cutoff value. Survival curves were estimated using the Kaplan–Meier method, and the log-rank test was used for comparisons of differences among the survival curves. The monotonic decreasing trend of the overall survival curve in the staging system was expressed by the linear correlation degree R.ResultsThe 5-year survival rates of patients in the training set based on the AJCC staging system from stage I to stage IV were 75.6% (95%CI: 74.4–76.8), 59.8% (95%CI: 58.6–61.0), 42.1% (95%CI: 34.5–49.7), 33.2% (95%CI: 24.6–41.8), 72.0% (95%CI: 69.1–74.9), 48.8% (95%CI: 47.4–50.2), 26.5% (95%CI: 23.0–30.0), and 11.3% (95%CI: 10.3–12.3). The 5-year survival rates of patients in the training set from stage I to stage IIIC were 80.4%, 72.9%, 59.8%, 48.4%, 32.5%, and 15.0%, according to the TNM + LNR (TNRM) staging system. According to the AJCC staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 91.3%, 90.8%, 72.6%, 61.3%, 72.4%, 58.1%, and 32.8%. Based on the TNRM staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 99.2%, 90.5%, 81.4%, 78.6%, 60.2%, and 35.8%.ConclusionThe TNRM staging system successfully eliminated “survival paradox” in the AJCC staging system, which might be superior to the AJCC staging system.

Prognostic implications of CT/MRI LI-RADS in hepatocellular carcinoma: State of the art and future directions.

Hepatocellular carcinoma (HCC) is the fourth most lethal malignancy with an increasing incidence worldwide. Management of HCC has followed several clinical staging systems that rely on tumour morphologic characteristics and clinical variables. However, these algorithms are unlikely to profile the full landscape of tumour aggressiveness and allow accurate prognosis stratification. Noninvasive imaging biomarkers on computed tomography (CT) or magnetic resonance imaging (MRI) exhibit a promising prospect to refine the prognostication of HCC. The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology, techniques, interpretation, reporting and data collection of liver imaging. At present, it has been widely accepted as an effective diagnostic system for HCC in at-risk patients. Emerging data have provided new insights into the potential of CT/MRI LI-RADS in HCC prognostication, which may help refine the prognostic paradigm of HCC that promisesto direct individualized management and improve patient outcomes. Therefore, this review aims to summarize several prognostic imaging features at CT/MRI for patients with HCC; the available evidence regarding the use of LI-RDAS for evaluation of tumour biology and clinical outcomes, pitfalls of current literature, and future directions for LI-RADS in the management of HCC.

Amygdala abnormalities across disease stages in patients with sporadic amyotrophic lateral sclerosis.

To examine selective atrophy patterns and resting-state functional connectivity (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to explore any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King's clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We explored the pattern of selective amygdala subnucleus atrophy and amygdala-based whole-brain FC alteration in these patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between ALS patients at King's stage 1 and HCs for any amygdala subnucleus volumes. Compared with HCs, ALS patients at King's stage 2 had significantly lower left accessory basal nucleus and cortico-amygdaloid transition volumes. Furthermore, ALS patients at King's stage 3 demonstrated significant reductions in most amygdala subnucleus volumes and global amygdala volumes compared with HCs. Notably, amygdala-cuneus FC was increased in ALS patients at King's stage 3. Specific subnucleus volumes were significantly associated with Mini-Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed greatly across King's clinical disease stages, and amygdala abnormalities are an important feature of patients with ALS at relatively advanced stages. Moreover, our findings suggest that amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients.

Comparison Of King’s Clinical Staging In Multinational Amyotrophic Lateral Sclerosis Cohorts

Background: Amyotrophic lateral sclerosis (ALS) shows considerable clinical heterogeneity, which affects clinical trials. A clinical staging system has been proposed for ALS with potential applications in patient care, research, trial design and health economic analyses. The King’s system consists of five stages. We have previously shown that progressive clinical stages were reached at predictable proportions through the disease course, but this needs to be validated in other independent samples. Objectives: We aimed to compare King’s clinical staging in ALS in four patient groups, located in different regions and countries and using different health care systems from the original study population in South London. Methods: Clinical data were extracted from two European phase 3 randomized controlled trials (MitoTarget and LiCALS) and from two databases predominately from the United States: the PRO-ACT Consortium Database and a database of patients from the PatientsLikeMe website. Clinical stage was estimated using an algorithm, and standardized time to each clinical stage was calculated in deceased patients. Results: 8,796 patients were included, of whom 1,959 had died by the end of follow-up. Stages occurred in the same order as in the original study for all cohorts. Median standardized times to stages (interquartile range) were Stage 2: 0.61 (0.47–0.75), Stage 3: 0.68 (0.56–0.81), Stage 4A: 0.82 (0.71–0.91), Stage 4B: 0.82 (0.69–0.92) and Stage 4 0.80 (0.67–0.91). Discussion: Timings for all stages were similar to those reported in the original study, except Stage 2 which occurred later in the clinical trial databases due to recruitment occurring after diagnosis.

Comparison of a preoperative MR-based recurrence risk score versus the postoperative score and four clinical staging systems in hepatocellular carcinoma: a retrospective cohort study

ObjectivesTo establish a risk score integrating preoperative gadoxetic acid–enhanced magnetic resonance imaging (EOB-MRI) and clinical parameters to predict recurrence after hepatectomy for patients with hepatocellular carcinoma (HCC) and to compare its performance with that of a postoperative score and four clinical staging systems.MethodsConsecutive patients with surgically confirmed HCC who underwent preoperative EOB-MRI between July 2015 and November 2020 were retrospectively included. Two recurrence risk scores, one incorporating only preoperative variables and the other incorporating all preoperative and postoperative variables, were constructed via Cox regression models.ResultsA total of 214 patients (derivation set, n = 150; test set, n = 64) were included. Six preoperative variables, namely tumor number, infiltrative appearance, corona enhancement, alpha-fetoprotein (AFP) level, aspartate aminotransferase (AST) level, and sex, were independently associated with recurrence. After adding postoperative features, microvascular invasion and tumor differentiation were additional significant variables in lieu of corona enhancement and AFP level. Using the above variables, the preoperative score achieved a C-index of 0.741 on the test set, which was comparable with that of the postoperative score (0.729; p = 0.235). The preoperative score yielded a larger time-dependent area under the receiver operating characteristic curve at 1 year (0.844) than three existing systems (0.734–0.742; p < 0.05 for all). Furthermore, the preoperative score stratified patients into two prognostically distinct risk strata with low and high risks of recurrence (p < 0.001).ConclusionThe preoperative score integrating EOB-MRI features, AFP and AST levels, and sex improves recurrence risk estimation in HCC.Key Points• The preoperative risk score incorporating three EOB-MRI findings, AFP and AST levels, and sex achieved comparable performance with that of the postoperative score for predicting recurrence after hepatectomy in patients with HCC.• Two risk strata with low and high risks of recurrence were obtained based on the preoperative score.• The preoperative score may help tailor pretreatment decision-making and facilitate candidate selection for adjuvant clinical trials.

Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma.

BackgroundThe clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed.MethodsData were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy.ResultsThis retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively.ConclusionWe developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.

Combining Pre- and Postoperative Lymphocyte-C-Reactive Protein Ratios Can Better Predict Hepatocellular Carcinoma Prognosis After Partial Hepatectomy.

BackgroundVarious preoperative inflammatory indicators have been identified as potential predictors of poor prognosis in patients with hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of the postoperative lymphocyte–C-reactive protein ratio (PostLCR) on its own and combined with preoperative LCR (PreLCR).MethodsA total of 290 patients with primary HCC were retrospectively enrolled in the study. Univariate analysis was used to identify factors significantly associated with poor disease-free survival (DFS) and overall survival (OS), then multivariate analysis was performed to identify independent prognostic indicators of poor survival. Prognostic models based on preoperative, postoperative, and both types of indicators were then constructed, and their predictive performance were evaluated using time-dependent receiver operating characteristic curves and the concordance index (C-index).ResultsPreLCR and PostLCR levels correlated with DFS and OS more strongly than other pre- and postoperative inflammatory indicators, respectively. Decreased PreLCR and PostLCR were independent prognostic factors for both DFS and OS, while HCC patients with decreased PreLCR and PostLCR had worse prognosis than patients with increased PreLCR and PostLCR. Patients into three groups based on their cut-off values of PreLCR and PostLCR, Kaplan–Meier survival analysis indicated that HCC patients with low PreLCR and PostLCR had the worst DFS and OS. The combined model showed better predictive performance at 1 and 3 years post-surgery than individual pre- and postoperative models, the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system and the Barcelona Clinic Liver Cancer system. The combine model demonstrated a markedly superior C-index compared with the other models in DFS and OS.ConclusionOur study showed PreLCR and PostLCR are independent predictors of DFS and OS in HCC patients after partial hepatectomy. Models that include both PreLCR and PostLCR can predict prognosis better than well-established clinical staging systems.

Implications of Satellitosis or In-transit Metastasis in Cutaneous Squamous Cell Carcinoma

Unlike Merkel cell carcinoma and melanoma, satellitosis or in-transit metastasis (S-ITM) is not incorporated into the current cutaneous squamous cell carcinoma (CSCC) staging systems. It is important to determine if the clinical outcomes of S-ITM are relevant to prognosis for patients with CSCC. To evaluate the association of S-ITM with clinical outcomes in patients with CSCC and to determine its prognostic implications. A dual-institution (Cleveland Clinic and Brigham and Women's Hospital) database was queried for patients who were treated for CSCC in 2010 to 2020. Patients who were node-negative and had S-ITM-the presence of dermal lesions between the primary tumor and first-echelon lymphatic nodal basins at any point in the disease course-were identified. Subcohorts of patients with T3N0 tumors, T4N0 tumors (bone invasive), N1 to 3, and M1 disease were identified for comparison. The American Joint Committee on Cancer staging system was used to define cancer stages. Data were analyzed from January 15 to March 31, 2021. Pairwise comparison of CSCC recurrence and disease-specific survival in patients with and without S-ITM was performed using Cox proportional hazard modeling. Kaplan-Meier and Fine-Gray competing risk methods were used to estimate disease-specific survival and CSCC recurrence, respectively. In a total of 518 patients with CSCC, S-ITM was present in 72 (13.9 %) patients (median age [range], 73.9 [31.6-95.8] years; 59 [82%] men; 69 [96%] White non-Hispanic individuals; 25 [35%] patients with immunosuppression) who were node-negative. The subcohorts were composed of 341 patients with T3N0 cancer, 36 with T4N0, 70 with N1 to 3, and 19 with M1 disease. Pairwise comparisons between disease levels using Cox proportional hazard model demonstrated lower cumulative incidence of CSCC recurrence rates in the T3N0 (HR, 0.21; 95% CI, 0.14-0.30; P < .001) and T4N0 (HR, 0.36; 95% CI, 0.19-0.68; P = .001) cohorts compared with the S-ITM cohort. No significant difference was observed between patients who were node-positive and those with S-ITM (HR, 0.74; 95% CI, 0.48-1.14; P = .16). The 5-year disease-specific survival rates were 76% for T3N0, 64% for T4N0, 41% for S-ITM, and 39% for N1 to 3. Compared with the S-ITM cohort, DSS was significantly higher in the T3N0 (HR, 0.23; 95% CI, 0.15-0.35; P < .0001) and T4N0 (HR, 0.37; 95% CI, 0.19-0.76; P = .01) cohorts, and not significantly different in the node-positive (HR, 0.77; 95% CI, 0.84-3.93; P = .30) and metastatic cohorts (HR, 1.81; 95% CI, 0.84-3.93; P = .13). This multi-institutional cohort study found that patients with CSCC and S-ITM appear to have clinical outcomes comparable to those of patients who are node-positive, and an increased risk of recurrence and worse survival compared with patients who have T3 and T4 disease. These outcomes are similar to those observed for Merkel cell carcinoma and melanoma. Given that S-ITM may be a powerful prognostic factor, it should be incorporated into clinical staging systems.

The Number of Radiographically Positive Lymph Nodes Further Stratifies Patient Survival Among Clinical N1 Patients With Human Papillomavirus–Associated Oropharyngeal Cancer

PurposeHuman papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) requires further study to optimize the existing clinical staging system and guide treatment selection. We hypothesize that incorporation of the number of radiographically positive lymph nodes will further stratify patients with clinical N1 (cN1) HPV(+)OPSCC. Methods and MaterialsA post hoc analysis from 2 prospective clinical trials at a high-volume referral center was conducted. Patients underwent primary tumor resection and lymphadenectomy, followed by either standard-of-care radiation therapy (60 Gy in 30 fractions) with or without cisplatin (40 mg/m2 weekly) or de-escalated radiation therapy (30 Gy in 20 twice-daily fractions) with concomitant 15 mg/m2 docetaxel once weekly. Imaging studies were independently reviewed by a blinded neuroradiologist classifying radiographic extranodal extension (rENE) and the number and maximal size of involved lymph nodes. Patients without pathologic data available for assessment were excluded. ResultsA total of 260 patients were included. Of these, 216 (83%) were cN1. Patients had a median of 2 radiographically positive lymph nodes (range, 0-12), and 107 (41%) had rENE. For cN1 patients, stratifying by radiographically positive lymph nodes (1-2 vs 3-4 vs >4) was predictive of progression-free survival (PFS) (P = .017), with 2-year PFS rates of 96%, 88%, and 81%, respectively. More than 2 radiographically positive lymph nodes was identified as a significant threshold for PFS (P = .0055) and overall survival (P = .029). Radiographic ENE and lymph node size were not predictive of PFS among cN1 patients. ConclusionsThe number of radiographically positive lymph nodes is predictive of PFS and overall survival and could be used to meaningfully subcategorize cN1 patients with HPV(+)OPSCC. We recommend further validation of our proposal that cN1 patients with 1 to 2 radiologically positive lymph nodes be categorized as cN1a, patients with 3 to 4 radiologically positive lymph nodes categorized as cN1b, and patients with >4 radiographically positive lymph nodes categorized as cN1c.

Pathological Features and Prognosis of Thymoma With or Without Myasthenia Gravis.

IntroductionTo evaluate the different pathological and clinical characters of thymoma with and without myasthenia gravis (MG) and to determine whether the presence of MG influences the prognosis in patients with thymoma.MethodsFour hundred and twenty-five consecutive patients operated was analyzed. A median sternotomy was used in 189 cases, and video-assisted thoracoscopic thymectomy was used in 236 cases. These patients with thymoma were subdivided into two groups: thymoma with myasthenia gravis MG (n = 220) and thymoma without MG (n = 205). All thymic epithelial tumors were classified according to the WHO histologic classification and the Masaoka clinical staging system. The result was evaluated according to the Myasthenia Gravis Foundation of America's criterion. The clinical features of the 2 test were compared between the two groups, and the survival analysis of Cox treatment effects was compared between the two groups.ResultsThere were no perioperative deaths. The proportions of type A and thymic carcinoma were 0% in the group with MG and 10.7% (22/205) and 11.2% (23/205), respectively, in the group without MG. Thymic hyperplasia around the thymoma was 29.1% (64/220) in patients with MG and only 6.3% (13/205) in patients without MG (χ2 = 23.63, P = 0.000). The overall survival curve showed that the 5- and 10-year survival rates in the group without MG were 89.2 and 77.4%, respectively, while those in the MG group were 91.1 and 80.5%.ConclusionsThe existence of MG has little influence on the prognosis of thymomas, but it is suitable for early diagnosis and treatment. Extended thymectomy should be performed on all patients with thymoma, whether they have MG or not.

A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7th and 8th Editions.

Importance: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual incorporated new changes from its 7th edition for classifying retinoblastoma (RB).Objective: We assessed the comparative prognostic values of the 7th and 8th editions of the AJCC clinical (cTNM) staging manuals for RB and suggested modifications for future edition accordingly.Design: A retrospective, observational study.Setting: King Hussein Cancer Centre.Participants: A cohort of 478 patients and 565 eyes with RB.Main Outcomes and Measures: Main outcome measures included demographics; tumor features, AJCC cTNM stage, and eye salvage rates. The prognostic performance of the different staging systems was assessed with the concordance index (C-index) and likelihood ratio χ2 tests.Results: The overall eye salvage rate was 65%. Stage migration occurred for 330 (48%) eyes with the AJCC Staging Manual, 8th edition. Based on the 7th edition AJCC staging, the eye salvage rate was 94% (n=177) for T1 tumors (98% for T1a, 93%for T1b, and 90%for T1c), 69% (n=204) for T2 tumors (73% for T2a and 62%for T2b), and 51% (n=40) for T3 tumors. Based on the 8th edition AJCC staging, the eye salvage rate was 95% (n=139) for T1 tumors (98% for T1a and 93% for T1b), 68% (n=281) for T2 tumors (90%for T2a and 66%for T2b), and 12% (n=1) for T3 tumors. With our proposed cTNM modifications, the eye salvage rate was 94% (n=177) for T1 tumors (98%for T1a, 93%for T1b, and 90% for T1c), 66% (n=243) for T2 tumors (73% for T2a, 62% for T2b, and 55% for T2c), and 12% (n=1) for T3 tumors. As estimated by odds ratios, more advanced cTNM stage (regardless of the cTNM staging system) was significantly associated with an increased chance of treatment failure (P < .0001). The C-index for both the 8th edition and the proposed modifications were approximately equal, and both were higher than that of the 7th edition. However, the proposed modifications had the highest likelihood ratio χ2 value and the best bootstrap 95% confidence interval.Conclusions and Relevance: Our proposed modifications on the clinical TNM Staging System for RB harbor more detailed subgroup classification criteria that provides better prognostic value for eye globe salvage than the published similar (but not identical) AJCC Staging Manual, 7th and 8th editions, furthermore these modifications may resolve the discrepancies in the previously published different classification systems for RB.

The Fate of Periprosthetic Joint Infection With Corynebacterium striatum: A Rare but Catastrophic Causative Organism.

The virulence and antibiotic resistance profile of an infecting organism have been shown to impact the outcomes of periprosthetic joint infection (PJI). However, there are no existing data on the outcomes of PJI caused by Corynebacterium striatum, a rare organism. Thus, our objective is to ascertain: (1) the treatment success of PJI caused by this rare organism and (2) patient characteristics in the setting of C striatum PJI. A retrospective review was conducted on 741 consecutive PJIs managed at 2 hospital facilities by 8 surgeons (February 4, 2015 to October 30, 2019). The inclusion criteria represented the presence of minimum 1 positive culture of C.striatum. After excluding 1 patient with no follow-up, 15 patients were finally analyzed (9 hips/6 knees). Out of 15 patients, 9 underwent explantation with spacer insertion, 5 underwent irrigation and debridement with polyexchange (I&D), and 1 underwent Girdlestone. Out of 9 explanted patients, only 6 cleared infection and were reimplanted. The clinical staging system for PJI was determined using McPherson classification. The mean follow-ups for I&D and explantation were 35 and 23.5 months, respectively. Success of reimplantation was determined using Delphi criteria. Out of 5 I&D patients, 40% had to be reoperated because of persistent infection. Out of 6 explanted patients who were reimplanted, 67% failed. According to McPherson, 40% of I&D and 22.2% of explanted patients were significantly compromised hosts. C.striatum PJI has a high-treatment failure rate in patient undergoing I&D or 2-stage revision surgery. Surgeons should be aware of the difficulty controlling this PJI and advise patients accordingly.