Probability Of Recurrence-free Survival Research Articles

Validated Prognostic Nomograms for Patients With Parotid Carcinoma Predicting 2- and 5-Year Tumor Recurrence-Free Interval Probability.

Introduction: Salivary gland malignancies are rare tumors with a heterogenous histological and clinical appearance. Previously, we identified multiple prognostic factors in patients with parotid cancer and developed prognostic indices which have repeatedly been validated internationally, demonstrating their general applicability and lasting relevance. Recently, nomograms gained popularity as a prognostic tool. Thus, in this research we aimed to construct nomograms based on our previous validated prognostic models.Material and Methods: Nomograms were constructed using the previously reported dataset of 168 patients with parotid cancer which was used to develop pre- and postoperative prognostic scores, PS1 and PS2, respectively. Concordance indices for PS1 and PS2 were previously estimated at 0.74 and 0.71, respectively, and are in line with other, widely accepted oncological nomograms.Results: Pre- and postoperative nomograms predicting 2- and 5-year tumor recurrence-free survival probability are presented. All previously multivariately identified and validated prognostic factors, are incorporated (T size, N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins). Examples of clinical application and interpretation are given.Conclusions: The presented prognostic nomograms for predicting 2- and 5-year tumor recurrence-free probability in patients with parotid cancer are powerful, user-friendly, visual tools and are based on internationally validated prognostic indices. They allow for a reliable prognostic assessment and result in a more individualized estimate of the risk for recurrence than the prognostic grouping based on PS1 and PS2. This facilitates assigning trial-patients to risk groups, and may assist in therapeutic decision making and determining appropriate follow-up intervals in clinical practice.

Factors Associated With Long-Term Risk of Recurrence After Percutaneous Radiofrequency Thermocoagulation of the Gasserian Ganglion for Patients With Trigeminal Neuralgia Involving the Ophthalmic Division: A Retrospective Study.

To evaluate risk factors associated with recurrence after radiofrequency thermocoagulation (RFT) of the gasserian ganglion among patients with ophthalmic trigeminal neuralgia (TN) and prognostic factors in terms of recurrence-free survival (RFS) during a long-term follow-up. From January 2005 to December 2017, 300 patients with ophthalmic TN underwent RFT. A retrospective analysis of 14-year outcomes was performed. Kaplan-Meier analysis was used for RFS after the procedure. Univariate and multivariate Cox regression analyses were performed to identify risk factors for pain recurrence. The initial effective rate of RFT for ophthalmic TN was 92%. The mean follow-up time was 77.38±43.24months. The cumulative probability of RFS was 86.94% at 1year, 80.03% at 2 years, 77.27% at 3 years, 74.01% at 5 years, and 59.92% at 10 years after RFT. The mean duration of RFS was 114.67 months (95% confidence interval [CI] 106.27 to 123.06 months). In multivariate analysis, atypical pain (hazard ratio [HR]=2.831, 95% CI 1.759 to 4.554, P<0.001) and mild facial hypesthesia (HR=2.540, 95% CI 1.309 to 4.931, P=0.006) before RFT were independently associated with pain recurrence. Patients with a prognostic index (PI) >1.27 were at high risk for pain recurrence. Major complications included troublesome dysesthesia (0.7%), keratitis (10.9%), diplopia (0.4%), facial paresthesia (6.2%), and masseter weakness (12.7%). Masseter weakness was more common in patients with V3 branch involvement. Three patients lost their sight due to keratitis. Our study investigated long-term outcomes and complications of RFT for ophthalmic TN. Patients at high risk for pain recurrence were identified, which might provide a basis for clinical decision making before RFT.

Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID.

New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

Head to Head Impact of Margin, Ischemia, Complications, Score Versus a Novel Trifecta Score on Oncologic and Functional Outcomes After Robotic-assisted Partial Nephrectomy: Results of a Multicenter Series

BackgroundThere is a paucity of data describing the ability of margin, ischemia, complications, score (MIC) and trifecta in predicting long-term outcomes of robotic-assisted partial nephrectomy (RAPN). ObjectiveTo compare a novel trifecta (negative margins, no significant complications, and perioperative estimated glomerular filtration rate [eGFR] decrease ≤30%) versus standard MIC as predictors of oncologic and functional results in a large series of RAPNs. Design, setting, and participants: Between 2009 and 2019, a multicenter dataset was queried for patients with nonmetastatic renal masses who underwent RAPN at eight participating institutions. InterventionRAPN. Outcome measurements and statistical analysisMIC and trifecta achievement were determined for the overall cohort and a subgroup undergoing off-clamp RAPN (ocRAPN), respectively. The overall survival (OS), recurrence-free survival (RFS), and new onset of end-stage renal disease (ESRD; defined as eGFR <30 ml/min) probabilities were assessed by the Kaplan-Meier method. Cox regression analyses were used to identify predictors of OS, RFS, and ESRD. For all analyses, two-sided p < 0.05 was considered significant. Results and limitationsOut of 1807 patients, MIC and trifecta were achieved in 71.1% (n = 1285) and 82.6% (n = 1492), respectively, and once restricted to the ocRAPN cohort, in 95.6% (n = 625) and 81.6% (n = 534), respectively. On Kaplan-Meier analysis, both MIC and trifecta achievement predicted higher OS and lower ESRD probabilities (all p < 0.014), while only trifecta achievement was a predictor of RFS probabilities (p = 0.009). On multivariable Cox regression, MIC did not predict any of the endpoints independently, while trifecta achievement was an independent predictor of higher OS (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.18–0.86; p = 0.019) and lower ESRD development probabilities (HR 0.32, 95% CI 0.15–0.72; p = 0.005). ConclusionsTrifecta, initially described as comprehensive measures of perioperative outcomes, needs to stand the test of time. Compared with MIC, the recent trifecta was an independent predictor of clinically significant endpoints, namely, survival and ESRD development probabilities. Patient summaryOur novel trifecta represents a reliable method for estimating survival and development of end-stage renal disease after robotic-assisted partial nephrectomy.

Clinical features and prognosis of pediatric infradiaphragmatic craniopharyngioma relative to the tumor inflammatory response.

The relationship between clinical responses in pediatric infradiaphragmatic craniopharyngioma (Q-CP) and inflammatory response is still unclear. The objective of this study was to investigate the clinical significance of tumor inflammatory response in pediatric Q-CPs. The inflammatory response was evaluated by measuring the number of inflammatory cells in the tumor near adenohypophysis junction. The specimens were classified as mild, moderate, or severe based on the number of inflammatory cells. In addition, the levels of pro-inflammatory cytokines and chemokines in the specimens were measured using a cytokine antibody array. Clinical outcomes were analyzed and compared to the markers of inflammatory response. IL-6 and IL-8 were highly expressed in pediatric Q-CPs, and the transcription level of IL-6 was the highest in the severe group. Most patients (87.3%) had hypopituitarism; the severe inflammation group had an increased incidence of hypopituitarism, which correlated with significantly lower probability of recurrence-free survival and worsened functional status. Inflammatory response is common in craniopharyngiomas and is closely related to their biological behavior and the patients' clinical prognosis. Further studies of the relationship between craniopharyngiomas and the inflammatory response will enable the discovery of potential therapeutic targets, which will reduce morbidity and result in better outcomes for pediatric Q-CP patients. Pediatric infradiaphragmatic craniopharyngiomas are histologically benign brain tumors that often follow an aggressive clinical course. The inflammatory response in craniopharyngioma is common, which is closely related to the biological behavior and clinical prognosis. Several inflammatory and immune markers have been identified in CP; inflammation is an important role in the pathogenesis of hypopituitarism. The aim was to study the relationship between craniopharyngioma and inflammatory response and find potential therapeutic targets can reduce morbidity and result in better outcomes.

MP72-03 ASSESSING THE IMPACT OF ABSENCE OF DETRUSOR MUSCLE IN TA-LG UROTHELIAL CARCINOMA OF THE BLADDER ON RECURRENCE FREE SURVIVAL

You have accessJournal of UrologyBladder Cancer: Non-invasive III (MP72)1 Apr 2020MP72-03 ASSESSING THE IMPACT OF ABSENCE OF DETRUSOR MUSCLE IN TA-LG UROTHELIAL CARCINOMA OF THE BLADDER ON RECURRENCE FREE SURVIVAL Riccardo Mastroianni*, Aldo Brassetti, Yazan Al Salhi, Umberto Anceschi, Alfredo Bove, Antonio Carbone, Cosimo De Nunzio, Andrea Fuschi, Mariaconsiglia Ferriero, Antonio Nacchia, Antonio Pastore, Giorgia Tema, Gabriele Tuderti, and Giuseppe Simone Riccardo Mastroianni*Riccardo Mastroianni* More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , Yazan Al SalhiYazan Al Salhi More articles by this author , Umberto AnceschiUmberto Anceschi More articles by this author , Alfredo BoveAlfredo Bove More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Cosimo De NunzioCosimo De Nunzio More articles by this author , Andrea FuschiAndrea Fuschi More articles by this author , Mariaconsiglia FerrieroMariaconsiglia Ferriero More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Antonio PastoreAntonio Pastore More articles by this author , Giorgia TemaGiorgia Tema More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , and Giuseppe SimoneGiuseppe Simone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000952.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Obtaining detrusor muscle in TURBt specimen is recommended by European Association of Urology guidelines. Few studies assessed this specific topic in the setting of Ta low-grade (LG) urothelial carcinoma (UC) of the bladder. The aim of this study was to assess if the absence of detrusor muscle at pathologic report has a negative impact on recurrence free probability in patients with a Ta LG UC of the bladder. METHODS: A multicenter TURBt database was queried for: “low-grade Ta, UC of the bladder”. All patients treated between 2008 and 2018 with tumor grade assessed according to both ISUP and WHO grading systems and with a minimum follow-up of 1-yr were included. Patients with previous history of high-grade UC were excluded. Baseline demographic, clinical and pathologic data were analyzed. EORTC risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data on Recurrence-Free Survival (RFS) probability, computed at 12, 36, 60 months after TURBt. RESULTS: Overall, 203 consecutive patients were included. Most of them were men (84%), median age was 69 yrs (IQR: 61-77). Patients and tumors characteristics were reported in Table1. At Kaplan-Meier analysis low-risk EORTC cohort displayed a significantly higher RFS probability compared with intermediate-risk cohort (5-yr probability 89.5% vs 72.4%, respectively; log-rank p=0.011. Figure 1a). At univariable Cox regression multiple tumors (HR 1.36, 95%CI 1.02-1.82; p=0.037), tumor diameter ≥3cm (HR 2.8, 95%CI 1.01-7.9; p=0.049), previous history of UC ≤1 yr (HR 1.96, 95%CI 1.02-3.75; p=0.043) and combined EORTC risk group (HR 3.15, 95%CI 1.23-8; p=0.017) were significant predictors of recurrence. Absence of detrusor muscle at pathologic report (HR 1.45, 0.61-3.45; p=0.4. Figure 1b) and adjuvant intravesical treatments (HR 0.95, 95%CI 0.5-1.78; p=0.87) had negligible impacts on RFS probabilities (Table 2). CONCLUSIONS: EORTC risk group is a strong predictive tool to assess the risk of recurrences in patients with Ta-LG UC of the bladder. Absence of detrusor muscle in the TURBt specimen has negligible role on recurrence of patients with Ta-LG tumors, therefore it should no longer be considered as a mandatory data to assess prognosis or treatment schedule. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1073-e1074 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Riccardo Mastroianni* More articles by this author Aldo Brassetti More articles by this author Yazan Al Salhi More articles by this author Umberto Anceschi More articles by this author Alfredo Bove More articles by this author Antonio Carbone More articles by this author Cosimo De Nunzio More articles by this author Andrea Fuschi More articles by this author Mariaconsiglia Ferriero More articles by this author Antonio Nacchia More articles by this author Antonio Pastore More articles by this author Giorgia Tema More articles by this author Gabriele Tuderti More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...

CA19-9 for detecting recurrence of pancreatic cancer

CA19-9 values are regularly measured in patients with pancreatic cancer. Certainly, its potential as a biomarker has been compromised by false negative results in CA19-9 negative patients and false positive results in benign pancreatico-biliary diseases. For detection of PDAC recurrence, however, CA19-9 might play an important role. The aim of this study is to analyze the accuracy of CA19-9 for detecting recurrence of pancreatic cancer. All included patients were treated either at the University Medical Center Goettingen, or at the Department of Interdisciplinary Oncology and Pneumonology, DRK-Kliniken Nordhessen, Kassel. We analyzed data of 93 patients with pancreatic cancer in the training set and 41 in the validation set, both retrospectively. Pre- and postoperative CA19-9 values and results of imaging techniques were compared. We performed ROC-analysis. The association between longitudinally measured CA19-9 values and relapse was studied with a joint model between a random effects model for the longitudinal CA19-9 measurements and a Cox proportional hazards models for the survival data. In the test set (n = 93 patients) the median follow-up time was 644 days (22 months). Overall, 71 patients (76.3%) developed recurrence during follow-up. Patients with CA19-9 values of <10kU/l were considered as CA19-9 negative patients (n = 11) and excluded from further analysis. Among the rest, approximately 60% of the patients showed significantly elevated CA19-9 prior to detection of recurrence by imaging techniques. Recurrence was shown by 2.45 times elevated CA19-9 values with 90% positive predictive value. In the validation set, 2.45 times elevated CA19-9 values showed recurrence with 90% sensitivity and 83,33% specificity, with an area under the curve of 95%. Based on measured CA19-9 values during follow-up care, the joint model estimates in recurrence-free patients the probability of recurrence-free survival. CA19-9 elevation is an early and reliable sign for PDAC recurrence. On the strength of a very high accuracy in CA19-9 positive patients, it should be considered to use CA19-9 for therapy decision even without a correlate of imaging technics. Using the joint model, follow-up care of PDAC patients after curative therapy can be stratified.

Twenty-five-Year Follow-up of a Prospective Randomized Trial Comparing Preoperative Versus Postoperative FLAC/Granulocyte Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer.

Preoperative chemotherapy is important in the management of women with breast cancer, with the ability to downstage the breast primary tumor and axillary lymph nodes. Long-term studies are needed to identify late toxicities, recurrence patterns, and equivalency with postoperative chemotherapy for recurrence-free survival (RFS) and overall survival (OS). We conducted a single-institution prospective randomized control trial comparing preoperative or postoperative fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor chemotherapy for women with untreated clinical stage II (T1N1, T2N0, and T2N1) breast cancer. Long-term follow-up was conducted to define toxicities, recurrence patterns and RFS and OS. Fifty-three women with clinical stage II breast cancer were randomized, 26 patients to receive preoperative chemotherapy and 27 to receive postoperative chemotherapy. Long-term follow-up, with a median of 25.3 years, was obtained. Local or systemic recurrence occurred in 8 women in the preoperative group and in 10 women in the postoperative group, and recurrences were predominantly within 10 years of treatment. Late toxicities included local upper extremity paresthesia's, upper extremity edema and congestive heart failure in 1 patient each. Analysis revealed no difference in RFS (20-year RFS probabilities; preoperative: 61.3%, postoperative: 54.7%, P=0.42), or in OS between the 2 treatment groups (20-year probabilities, preoperative: 64.6%, postoperative: 62.2%, P=0.44). Twenty-five of 53 patients (47%) were alive and without disease at this follow-up. Twenty-five-year follow-up for this prospective randomized trial confirms the equivalency of preoperative versus postoperative chemotherapy with fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor for stage II breast cancer for both RFS and OS.

Prediction of Postoperative Clinical Outcomes in Resected Stage I Non-Small Cell Lung Cancer Focusing on the Preoperative Glasgow Prognostic Score.

Background: The Glasgow Prognostic Score (GPS), which consists of albumin and C-reactive protein (CRP), may predict overall survival (OS) in cancer patients. The aim of this retrospective analysis was to evaluate the clinical impact of the preoperative GPS on patients with resected early stage non-small cell lung cancer (NSCLC). Methods: 300 patients with curatively resected stage I NSCLC were followed-up for OS, recurrence-free survival (RFS), cancer-specific survival (CSS), and death from other causes. Results: 229 patients (76%) had a preoperative GPS of 0, and 71 (24%) a GPS ≥ 1. The three-year probabilities of RFS, OS, CSS, and death from other causes were 81%, 84%, 88%, and 96% in patients with GPS = 0, and 79%, 74%, 91%, and 82% in patients with a GPS ≥ 1, respectively. GPS ≥ 1 was significantly associated with a higher risk of death from other causes (p = 0.022), serving as an independent predictor of death from other causes (p = 0.034). Pathologically elevated CRP levels (CRP > 5 mg/L) were found in 91 patients (30%). The mean CRP level was 7.88 ± 15.80 mg/L (0.5–135.6 mg/L). Pre-treatment CRP level was significantly associated with coronary heart disease (p < 0.0001), histology (p = 0.013), tumor size (p = 0.018), tumor stage (p = 0.002), and vascular invasion (p = 0.017). Conclusion: The preoperative GPS predicts adverse survival outcomes in patients with resected stage I NSCLC.

Surgical quality, cancer control and functional preservation: introducing a novel trifecta for robot-assisted partial nephrectomy.

In order to improve standard reporting of outcomes after partial nephrectomy, different "trifecta" systems have been conceived. The subjective assessment of the included parameters and the unreliability for off-clamp procedures limited their reproducibility; their role in predicting functional and oncologic outcomes has never been assessed. We propose a new trifecta, based on standardized parameters, that summarizes PN outcomes regardless the clamping technique used and predicts main clinical outcomes. A retrospective analysis of a multicenter, multi-national dataset of patients with non-metastatic cT1-2 renal masses undergoing Robot-assisted partial nephrectomy was performed. Baseline demographic, clinical, pathologic and perioperative data were collected. Trifecta was defined as the coexistence of negative margins, no Clavien-Dindo ≥3 complications and ≤30% postoperative estimated glomerular filtration rate reduction. Univariable and multivariable regression analyses identified predictors of trifecta achievement. Kaplan-Meier method assessed differences in oncological outcomes between patients achieving trifecta or not. Univariable and multivariable Cox regression analysis identified predictors of newly onset chronic kidney disease stage ≥IIIa, recurrence-free and overall survival. Overall, 1492 patients achieved trifecta. This cohort displayed significantly lower incidence of newly onset IIIa-V chronic kidney disease stages (all P<0.001), higher recurrence-free (P=0.009) and overall (P=0.014) survival probabilities. Patients achieving trifecta had a 65% reduced risk of developing newly onset stage IIIb-V Chronic Kidney Disease and a 55% reduced risk of overall mortality. Heterogeneity of surgical technique is a limitation. This novel reproducible trifecta is based on standardized parameters and is an independent predictor of severe chronic kidney disease development and mortality.

Analysis of factors related to recurrence of paediatric hepatoblastoma - a single Centre retrospective study

BackgroundThis study was performed to identify risk factors associated with recurrence of hepatoblastoma.MethodsA retrospective study was conducted on 56 patients with hepatoblastoma from 2012 to 2015 in Beijing Children’s Hospital. Pretreatment extension stage (PRETEXT), serum alpha fetoprotein (AFP) value, change trend of tumors after treatment and some other clinical characteristics were collected and analyzed. The comparison of independent variables that were not distributed normally was performed with the log-rank test.ResultsTwenty-eight patients with tumour recurrence and 28 patients without recurrence were included in this study, and the median age at presentation was 46.5 (26, 71.5) months. There was a significant difference in the 3-year recurrence-free survival (RFS) probability between patients aged over 54 months and those younger than 54 months (p = 0.007). After neoadjuvant chemotherapy, the chance of recurrence in partial response (PR) patients was significantly lower than that in stable disease (SD) patients (p = 0.004). The 3-year RFS rate of patients with a reduction in AFP of more than 60% after neoadjuvant chemotherapy was significantly higher than that of patients with a reduction of less than 60% (p = 0.005). The postoperative follow-up revealed that patients whose postoperative AFP fell to normal levels within 6 months of the start of treatment had a 3-year RFS rate of 68.6%, which is higher than that of patients whose AFP fell below the normal range after 6 months (p = 0.0005). Finally, the multivariate analysis by Cox regression showed that AFP decreased by less than 60% and tumour size decreased by less than 50% after neoadjuvant chemotherapy were significant independent prognostic risk factors for the 3-year RFS rate. The other clinical features were not significantly associated with tumour recurrence in this study.ConclusionsThrough this study, we concluded that the prognosis of childhood HB is related to the age at presentation and the response of chemotherapy. The results of the multivariate analysis showed that AFP decreased by less than 60% and tumour size decreased by less than 50% after neoadjuvant chemotherapy were significant independent prognostic risk factors. These findings can be helpful to evaluate therapeutic effects and predict prognosis.

A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy

BackgroundPatients with hepatocellular carcinoma (HCC) undergoing surgical resection still have a high 5-year recurrence rate (~ 60%). With the development of laparoscopic hepatectomy (LH), few studies have compared the efficacy between LH and traditional surgical approach on HCC. The objective of this study was to establish a nomogram to evaluate the risk of recurrence in HCC patients who underwent LH.MethodsThe clinical data of 432 patients, pathologically diagnosed with HCC, underwent LH as initial treatment and had surgical margin > 1 cm were collected. The significance of their clinicopathological features to recurrence-free survival (RFS) was assessed, based on which a nomogram was constructed using a training cohort (n = 324) and was internally validated using a temporal validation cohort (n = 108).ResultsHepatitis B surface antigen (hazard ratio [HR], 1.838; P = 0.044), tumor number (HR, 1.774; P = 0.003), tumor thrombus (HR, 2.356; P = 0.003), cancer cell differentiation (HR, 0.745; P = 0.080), and microvascular tumor invasion (HR, 1.673; P =0.007) were found to be independent risk factors for RFS in the training cohort, and were used for constructing the nomogram. The C-index for RFS prediction in the training cohort using the nomogram was 0.786, which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification (C-index, 0.698) and the Barcelona Clinic Liver Cancer staging system (C-index, 0.632). A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve. An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis, which was also confirmed in the validation cohort compared to other systems.ConclusionsWe constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients, which can be clinically implemented in assisting the planification of individual postoperative surveillance protocols.

Mutant-allele tumor heterogeneity in malignant glioma effectively predicts neoplastic recurrence.

Intra-tumor heterogeneity (ITH) is one of the most important causes of therapy resistance, which eventually leads to the poor outcomes observed in patients with glioma. Mutant-allele tumor heterogeneity (MATH) values are based on whole-exon sequencing and precisely reflect genetic ITH. However, the significance of MATH values in predicting glioma recurrence remains unclear. Information of patients with glioma was obtained from The Cancer Genome Atlas database. The present study calculated the MATH value for each patient, analyzed the distributions of MATH values in different subtypes and investigated the rates of clinical recurrence in patients with different MATH values. Gene enrichment and Cox regression analyses were performed to determine which factors influenced recurrence. A nomogram table was established to predict 1-, 2- and 5-year recurrence probabilities. MATH values were increased in patients with glioma with the wild-type isocitrate dehydrogenase (NADP(+)) (IDH)1/2 (IDH-wt) gene (P=0.001) and glioblastoma (GBM; P=0.001). MATH values were negatively associated with the 2- and 5-year recurrence-free survival (RFS) rates in patients with glioma, particularly in the IDH1/2-wt and GBM cohorts (P=0.001 and P=0.017, respectively). Furthermore, glioma cases with different MATH levels had distinct patterns of gene mutation frequencies and gene expression enrichment. Finally, a nomogram table that contained MATH values could be used to accurately predict the probabilities of the 1-, 2- and 5-year RFS of patients with glioma. In conclusion, the MATH value of a patient may be an independent predictor that influences glioma recurrence. The nomogram model presented in the current study was an appropriate method to predict 1-, 2- and 5-year RFS probabilities in patients with glioma.

Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence After Curative Resection of Pancreatic Neuroendocrine Tumors.

To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/ American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = <0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% confidence interval 0.79-0.88). Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery.

Sorafenib Versus Observation Following Radical Metastasectomy for Clear-cell Renal Cell Carcinoma: Results from the Phase 2 Randomized Open-label RESORT Study

BackgroundIn selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy. ObjectiveTo assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients. Design, setting, and participantsThe RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile. Outcome measurements and statistical analysisRFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves. Results and limitationsAt a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20–not available [NA]) in the observation arm versus 21 mo (95% CI 11–NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm. ConclusionsThis prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy. Patient summaryThis article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.

Nicotinic Acetylcholine Receptor Subunit Alpha-5 Promotes Radioresistance via Recruiting E2F Activity in Oral Squamous Cell Carcinoma.

Radiotherapy is commonly used to treat patients with oral squamous cell carcinoma (OSCC), but a subpopulation of OSCC patients shows a poor response to irradiation treatment. Therefore, identifying a biomarker to predict the effectiveness of radiotherapy in OSCC patients is urgently needed. In silico analysis of public databases revealed that upregulation of CHRNA5, the gene encoding nicotinic acetylcholine receptor subunit alpha-5, is extensively detected in primary tumors compared to normal tissues and predicts poor prognosis in OSCC patients. Moreover, CHRNA5 transcript level was causally associated with the effective dose of irradiation in a panel of OSCC cell lines. Artificial silencing of CHRNA5 expression enhanced, but nicotine reduced, the radiosensitivity of OSCC cells. Gene set enrichment analysis demonstrated that the E2F signaling pathway is highly activated in OSCC tissues with high levels of CHRNA5 and in those derived from patients with cancer recurrence after radiotherapy. CHRNA5 knockdown predominantly suppressed E2F activity and decreased the phosphorylation of the Rb protein; however, nicotine treatment dramatically promoted E2F activity and increased Rb phosphorylation, which was mitigated after CHRNA5 knockdown in OSCC cells. Notably, the signature combining increased mRNA levels of CHRNA5 and the E2F signaling gene set was associated with worse recurrence-free survival probability in OSCC patients recorded to be receiving radiotherapy. Our findings suggest that CHRNA5 is not only a useful biomarker for predicting the effectiveness of radiotherapy but also a druggable target to enhance the cancericidal effect of irradiation on OSCC.

Outcomes After Adjuvant Hyperthermic Intraperitoneal Chemotherapy for High-Risk Primary Appendiceal Neoplasms After Complete Resection.

Appendiceal neoplasms are uncommon tumors. Optimal treatment for patients with perforation or high-grade pathology after initial resection is unknown. This study evaluated patients with increased risk for peritoneal dissemination after primary resection, but no evidence of peritoneal disease, who underwent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). This multi-institutional cohort study evaluated 56 patients with high-risk (HR) appendiceal neoplasms with a peritoneal carcinomatosis index of 0 who underwent HIPEC. The patients were divided into two groups: perforated low-grade appendiceal (LGA) carcinoma and HR neoplasms, which included perforated high-grade appendiceal carcinoma, positive margins after initial resection, minimal macroscopic peritoneal disease that was previously resected or completely responded to systemic chemotherapy prior to HIPEC, goblet cell carcinoma, and adenocarcinoma with signet ring cell features. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier analysis. Thirty-eight percent of patients had perforated LGA and 68% had HR features. Five-year OS probability was 82.1% for the entire cohort, and 100% and 70.1% for patients with perforated LGA and HR features, respectively (p = 0.024). Five-year RFS probability was 79.3% for the entire cohort, and 90.0% and 72.4% for patients with perforated LGA and HR features, respectively (p = 0.025). Eight patients recurred after HIPEC and their OS was significantly worse (p < 0.001). While adjuvant HIPEC is both safe and feasible, there appears to be little benefit over close surveillance when outcomes are compared with historical and prospective studies, especially for perforated LGA carcinoma.

Development of nomograms for prognostication of patients with primary soft tissue sarcomas of the trunk and extremity: report from the Bone and Soft Tissue Tumor Registry in Japan

BackgroundThe use of nomograms for prognostication of individual cancer patients has been recommended in order to facilitate precision medicine. However, models for patients with soft tissue sarcomas (STSs) are limited because of the rarity and heterogeneity of such cancers. In addition, no model has been developed on the basis of an Asian cohort. Here, we attempted to develop and internally validate nomograms for patients with localized STSs of the trunk and extremity.MethodsThis study retrospectively extracted 2827 patients with primary trunk and extremity STSs after definitive surgery using the Bone and Soft Tissue Tumor Registry, which is a nationwide sarcoma database in Japan. We developed three nomograms predicting the probability of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS) at 2 years after surgery, using the Cox multivariate model. The nomograms were internally validated for discrimination and calibration using bootstrap resampling and assessed for their clinical applicability by decision curve analysis (DCA).ResultsLocal recurrence, distant metastasis and disease-specific death occurred in 241 patients (8.5%), 554 patients (19.6%) and 230 patients (8.1%), respectively. Histological diagnosis, grade and tumor size strongly influenced all three endpoints. The nomograms predicted accurately the probability of LRFS, DMFS and DSS (concordance index: 0.73, 0.70 and 0.75, respectively). DCA demonstrated that our nomograms had clinical applicability.ConclusionWe have developed the first nomograms for STSs based on an Asian cohort. These nomograms allowed accurate prediction of LRFS, DMFS and DSS at 2 years after definitive surgery, and can be used as a guide by clinicians for appropriate follow-up and counseling of patients.

Conditional Recurrence-Free Survival after Resection of Colorectal Liver Metastases: Persistent Deleterious Association with RAS and TP53 Co-Mutation

Conditional recurrence-free survival (RFS) probability, that is, the probability of remaining recurrence-free after a given interval without recurrence, has not been reported after resection of colorectal liver metastases (CLMs). We aimed to estimate conditional RFS and identify factors affecting conditional RFS. Patients undergoing initial resection of CLMs during 2000-2016 with mutation data were identified. The RFS and risk factors for recurrence were evaluated at the time of resection for all patients and at 1 year and 2 years after resection for patients who remained recurrence-free. Of 2,118 patients, 485 met the inclusion criteria, of which 225 were recurrence-free at 1 year and 109 were recurrence-free at 2 years. The 5-year RFS rates were 17.3%, 36.8%, and 70.7% for all patients and the 1-year and 2-year recurrence-free groups, respectively, when assessed from the time of initial CLM resection. RAS/TP53 co-mutation was the only factor independently associated with increased risk of recurrence for all groups (all patients, hazard ratio 1.47; 95% CI 1.19 to 1.82; p < 0.001; 1-year recurrence-free, hazard ratio 1.69; 95% CI 1.17 to 2.43; p= 0.005; 2-year recurrence-free, hazard ratio 2.41; 95% CI 1.12 to 5.17; p= 0.024). T category, extrahepatic disease, multiple CLMs, largest CLM diameter, and surgical margin status were risk factors for recurrence in all patients and/or the 1-year recurrence-free group, but not the 2-year recurrence-free group. Median RFS was lower for patients with RAS/TP53 co-mutation than for those with RAS/TP53 wild-type in the 1-year (1.5 vs 2.8 years; p= 0.006) and 2-year recurrence-free groups (3.0 vs 5.9 years; p= 0.024). Conditional RFS is useful for updating prognosis after a given time interval without recurrence after CLM resection. Importantly, RAS/TP53 co-mutation has a persistent deleterious association with recurrence.

Incidence and timing of recurrence of optic neuritis.

To describe the incidence and timing of recurrence in patients with optic neuritis (ON). Medical documents of adult patients with ON were retrospectively reviewed. The incidence and timing of recurrence of an ON episode were analyzed. One hundred eleven patients with ON were included in this study. Their mean follow-up duration was 4.1 ± 3.1years. Seven relapses occurred after intravenous methylprednisolone treatment. The estimated cumulative incidence of recurrence in either eye was 26% at 1year, 33% at 3years, 37% at 5years, and 50% at 10years after the first episode of ON. If there was no recurrence until 6months after the first episode of ON, the next 5-year recurrence-free survival probability was 67%. If there was no recurrence until 1year, the next 5-year survival probability was 72%. If there was no recurrence until 2years, the next 5-year survival probability was 81%. Relapse within 1month and the presence of neuromyelitis optica-immunoglobulin G were factors that increased the recurrence rate over time. We evaluated the incidence and timing of the recurrence in patients with ON after the first episode. Lower probability of recurrence was observed in patients with longer recurrence-free follow-up period. However, monitoring for recurrence is needed even in patients with a single episode of ON due to the increasing tendency of the estimated cumulative incidence of recurrence over many years.