Probability Of Recurrence-free Survival Research Articles

Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes. Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method. We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%. The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk. This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Development and validation of a nomogram to predict recurrence for clinical T1/2 clear cell renal cell carcinoma patients after nephrectomy

ObjectiveTo develop and validate a nomogram for predicting recurrence-free survival (RFS) for clinical T1/2 (cT1/2) clear cell renal cell carcinoma (ccRCC) patients after nephrectomy.MethodsClinicopathological and survival data from 1289 cT1/2 ccRCC patients treated at the Second Hospital of Tianjin Medical University between 2017 and 2020 were included. Cox regression analysis was used to identify independent risk factors in 902 and 387 ccRCC patients in the training and validation cohorts, respectively, and construct the nomogram. The performance of the nomogram was assessed through calibration plots, time-dependent receiver operating characteristic (ROC) curves, C-index (concordance-index), and decision curve analysis (DCA). Kaplan-Meier curves were used to evaluate the probability of RFS in patients with different recurrence risks.ResultsAge, tumor size, surgical approach, Fuhrman grade, and pT3a upstage were identified as independent predictors of RFS. The area under the curve (AUC) for the 3-year and 5-year RFS ROC curves were 0.791 and 0.835 in the training cohort, and 0.860 and 0.880 in the validation cohort. The DCA and calibration plots demonstrated the optimal application and excellent accuracy of the nomogram for predicting 3-year and 5-year RFS. Kaplan-Meier curves revealed significant differences in RFS among the three risk groups in both the training and validation cohorts. Clinically, the developed nomogram provides a more precise tool for risk stratification, enabling tailored postoperative management and surveillance strategies, ultimately aiming to improve patient outcomes.ConclusionsWe developed a nomogram for predicting RFS in cT1/2 ccRCC patients after nephrectomy with high accuracy. The clinical implementation of this nomogram can significantly enhance clinical decision-making, leading to improved patient outcomes and optimized resource utilization in the management of ccRCC.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination

BackgroundKRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions.MethodsCell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model.ResultsOur research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression.ConclusionsWe posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.

Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes. The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAFV600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p=0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p=0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p=0.017). Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

Abstract PO2-02-03: Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country

Abstract INTRODUCTION: Oncotype DX® recurrence score (ODX RS) is a 21-gene assay warranted to determine the the prognosis in patients with hormone receptor positive, HER-2 negative early stage breast cancer. In this context, the test is also predictive of benefit of adjuvant chemotherapy.1,2,3 OBJECTIVES: We aimed to correlate the clinical and pathological factors associated with Oncotype DX® 21-Gene in patients diagnosed with early stage Breast Cancer. Additionally, description of adjuvant treatment patterns and survival outcomes were described according to the Oncotype DX® 21-Gene result. METHODS: Data from medical records from a single center in Brazil were collected retrospectively from women over 18 years diagnosed with early breast cancer between 2012 and 2022. Included patients were diagnosed with stage T1-T2 breast cancer, hormone receptor positive, HER-2 negative, with up to three positive lymph nodes. All included patients had an Oncotype DX® test performed after definitive breast surgery. The ODX RS has been categorized into two levels according to menopausal status. Correlation between breast cancer recurrence and clinicopathological characteristics was done. The software SPSS was used for statistical analyzes with the significance of 0.05. RESULTS: From 197 patients, 20 have had breast cancer recurrence (10.15%) whom 10 were premenopausal and 10 were postmenopausal. The median ODX RS in these 20 patients was 15 (ranged from 9 to 31). The most common site of recurrence was breast and regional recurrence in 18 patients (90%). Adjuvant chemotherapy was omitted in 16 patients (80%) who have had breast cancer recurrence. Among premenopausal patients whose ODX RS was &amp;gt;20, 33 patients (91.66%) received adjuvant chemotherapy. Among postmenopausal patients whose ODX RS was &amp;gt;25, 19 (86.36%) received adjuvant chemotherapy. The probability of recurrence free survival was worse in premenopausal patients &amp;gt; 44-years-old compared to those with &amp;lt; =44 years-old (p = 0.036) and also worse in histological grade 3 tumors compared to grade 1 (p=0.0048). Tumor size &amp;gt;14 millimeters (mm) was correlated to worse recurrence free survival in premenopausal patients (p=0.017). Low estrogen and progesterone receptor was associated with a higher ODX RS (p=0.0035 and p&amp;lt; 0.0001, respectively) in premenopausal patients, but not associated with recurrence free survival. Clinicopathological characteristics and recurrence free survival correlation in postmenopausal patients were not significant. CONCLUSION: This retrospective analysis suggests that factors other than the Oncotype DX® score, such as age and grade contributed to worse survival outcomes among our patients population. Of note, age older than 44 years-old, histological grade 3 and tumor size &amp;gt;14 mm were associated with a higher probability of recurrence in premenopausal patients, despite the Oncotype DX® score. REFERENCES: 1. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med [Internet]. 2004;351(27):2817–26. Available from: http://dx.doi.org/10.1056/NEJMoa041588. 2. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med [Internet]. 2018;379(2):111–21. Available from: http://dx.doi.org/10.1056/NEJMoa1804710. 3. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med [Internet]. 2021;385(25):2336–47. Available from: http://dx.doi.org/10.1056/NEJMoa2108873. Table 1 – Clinical and pathological characteristics of 197 hormone receptor positive, HER-2 negative early breast cancer patients who did the Oncotype DX® 21-Gene Recurrence Score assay. Data from medical records collected retrospectively of women diagnosed with early breast cancer between 2012 and 2022 from a single center in Brazil. Figure 1 – Probability of recurrence free survival in premenopausal patients according to age &amp;lt;=44 (blue line) or &amp;gt; 44-years-old (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Figure 2 – Probability of recurrence free survival in premenopausal patients according to histological grade. Tumor with histological grade 1 (blue line) or histological grade 3 (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Citation Format: Carolina Cavalcanti Gonçalves Ferreira, Julio Araujo, Shermann Brandão Rodrigues Moreira, Antônio Buzaid, Débora Gagliato. Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-03.

Effectiveness of adjuvant chemotherapy for patients who undergo radical cystectomy without neoadjuvant chemotherapy: A retrospective cohort study of 115 advanced bladder cancer patients with pathological lymph node classification.

We investigated the clinical outcomes of radical cystectomy without cisplatin-based neoadjuvant chemotherapy (NAC) and identified factors affecting the effectiveness of cisplatin-based adjuvant chemotherapy (AC). Between September 2002 and February 2020, 288 bladder cancer patients who did not receive NAC underwent radical cystectomy. We retrospectively analyzed the recurrence rates, primary recurrence sites, recurrence-free survival (RFS), and overall survival (OS) of 115 advanced bladder cancer patients (pT3-4 or pN1-3) who were divided into the AC and observation groups. Subgroup analysis was performed, focusing on pathological stage. In total, 51 patients received AC, and 64 patients were observed. The median follow-up duration was 95 months. The recurrence rate was lower in the AC group than in the observation group (35.3% vs. 54.7%, p = 0.041). The rate of recurrences in the lymph node area (dissection site and proximal lymph nodes) was lower in the AC group (9.8% vs. 26.6%; p = 0.031). In the subgroup analysis of patients with pN1, the probability of RFS and OS was higher in the AC group than in the observation group. The hazard ratio for RFS and OS was 0.243 (95% confidence interval [CI]: 0.077-0.768) and 0.259 (95% CI: 0.082-0.816), respectively. The 5-year RFS and OS were significantly higher in the AC group (80.0% and 79.4%) than in the observation group (35.7% and 42.9%; p < 0.008 and p < 0.012, respectively). AC improved RFS and OS in patients with pN1 disease who did not receive NAC and should be considered for this population.

Development of an Automatic Rule-Based Algorithm for the Detection of Ovarian Cancer Recurrence From Electronic Health Records.

As the onset of cancer recurrence is not explicitly recorded in the electronic health record (EHR), a high volume of manual chart review is required to detect the cancer recurrence. This study aims to develop an automatic rule-based algorithm for detecting ovarian cancer (OC) recurrence on the basis of minimally preprocessed EHR data. The automatic rule-based recurrence detection algorithm (Auto-Recur), using notes on image reading (positron emission tomography-computed tomography [PET-CT], CT, magnetic resonance imaging [MRI]), biomarker (CA125), and treatment information (surgery, chemotherapy, radiotherapy), was developed to detect the first OC recurrence. Auto-Recur contains three single algorithms (images, biomarkers, treatments) and hybrid algorithms (combinations of the single algorithms). The performance of Auto-Recur was assessed using sensitivity, specificity, and accuracy of the recurrence time detected. The recurrence-free survival probabilities were estimated and compared with the retrospective chart review results. The proposed Auto-Recur considerably reduced human resources and time; it saved approximately 1,340 days when scaled to 100,000 patients compared with the conventional retrospective chart review. The hybrid algorithm on the basis of a combination of image, biomarker, and treatment information was the most efficient (sensitivity: 93.4%, specificity: 97.4%) and precisely captured recurrence time (average time error: 8.5 days). The estimated 3-year recurrence-free survival probability (44%) was close to the estimates by the retrospective chart review (45%, log-rank P value = .894). Our rule-based algorithm effectively captured the first OC recurrence from large-scale EHR while closely approximating the recurrence-free survival estimates obtained by conventional retrospective chart reviews. The study findings facilitate large-scale EHR analysis, enhancing clinical research opportunities.

Survival outcomes of epithelial ovarian cancer treated at a tertiary-level hospital in India.

One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015table were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival.

A ubiquitin-proteasome system-related signature to predict prognosis, immune infiltration, and therapy efficacy for breast cancer.

The ubiquitin-proteasome system (UPS) is an essential regulatory system for maintaining homeostasis, and its dysfunction may cause various diseases. The activity of proteasome and ubiquitin-conjugating enzymes has been found to be greatly increased in breast cancer (BC), indicating that the heterogeneity of UPS may be related to the progression of BC. Gene data was obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases and performed in multiple algorithms to construct a UPS-related signature for BC. Patients in the UPS low-risk group had greater overall and recurrence-free survival probability than those in the UPS high-risk group. This signature was closely associated with functional enrichment. Some high metabolism-related pathways were more active in the UPS high-risk group. The UPS low-risk group had more abundant anti-tumor immune cells, while in the UPS high-risk group, immunosuppressive cells were dominant. More importantly, we found that the UPS low-risk group was more sensitive to immunotherapy, while the UPS high-risk group responded better to radiotherapy. Drug sensitivity analysis identified more effective chemotherapy drugs in different UPS-related risk groups. This UPS-related signature may serve as a novel biomarker and independent prognostic factor for BC. It can effectively predict prognosis, immune infiltration, and therapy efficacy, providing new strategies for individualized treatment.

Prognostic evaluation of stage I lung adenocarcinoma based on systematic inflammatory response.

This study aimed to construct an effective nomogram based on the clinical and laboratory characteristics to predict the prognosis of stage I lung adenocarcinoma with EGFR alteration. A retrospective study was performed of 913 eligible patients with EGFR alteration after surgery at Shanghai Pulmonary Hospital. The peripheral blood indicators were included in the nomogram. Calibration plots, concordance index, decision curve analysis, and X-tile software were used in this study. Recurrence-free survival (RFS) and overall survival were estimated by the Kaplan-Meier method and compared using the log-rank test. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were independent risk factors for RFS. The calibration curves for RFS probabilities showed good agreement between the nomogram prediction and actual observation. Furthermore, the nomogram, including neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had a higher concordance index (0.732, 95% confidence interval = 0.706 to 0.758) than that without neutrophil to lymphocyte ratio or platelet to lymphocyte ratio (0.713, 95% confidence interval = 0.686 to 0.740), and decision curve analysis plots showed that the nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had better clinical practicability. Additionally, the patients were divided into 2 groups according to cutoff values of risk points, and statistically significant differences in RFS and overall survival were observed between the high-risk and low-risk groups (P < .001). High pretreatment levels of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were strongly associated with a worse prognosis in stage I EGFR-altered lung adenocarcinomas. Besides, the proposed nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio presented a better prediction ability for the survival of those patients.

Effectiveness of perioperative chemotherapy and radical cystectomy in treating bladder cancer

BackgroundDespite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy. MethodsA retrospective review was conducted in 805 patients with muscle invasive bladder cancer undergoing radical cystectomy with no perioperative chemotherapy, 761 with presurgical chemotherapy followed by radical cystectomy, and 134 radical cystectomy followed by adjuvant chemotherapy. Relevant clinicopathologic features were reviewed. Recurrence-free survival and Overall Survival probability estimates were calculated using the Kaplan–Meier method and compared using the Log-rank or Gehan-Breslow tests. The prognostic effects of presurgical chemotherapy and adjuvant chemotherapy regimens were evaluated by estimating hazard ratio and 95% confidence interval from an adjusted Cox proportional hazards model. Statistical tests were 2-sided, and significance was defined as P-value < 0.05. ResultsIn this contemporary, real-world cohort, 5-yr RFS was found to be 65.6% in pT0, 59.1%in <pT2, 35.4% in pT2, 15.3% in >pT2, and 10.8% in pN+ patients. Presurgical chemotherapy increased pathologic downstaging rates from 27.5% to 41.1% in patients with ≥cT2 BCa. Stratified by clinical T-stage, only cT2 patients derived recurrence-free survival (Median 45.3 months vs. 29.0 months, P < 0.01) and overall survival (Median 62.3 months vs. 41.9 months, P < 0.001) benefits. In patients with adverse pathologic features (≥pT3 or pN+), adjuvant chemotherapy improved recurrence-free survival (Median 22.8 months vs. 10.0 months, P < 0.0001) and overall survival (Median OS 32.4 months vs. 16.3 months, P < 0.0001). ConclusionsWe report real-world outcomes from a large cohort of muscle-invasive bladder cancer patients undergoing surgical treatment with/out perioperative chemotherapy. Pathologic response rates to pre-surgical chemotherapy were modest and led to clinical benefit only in cT2 patients. Adjuvant chemotherapy provided survival benefit for pathologically advanced MIBC patients irrespective of pT/N staging.

Multivisceral resection for retroperitoneal liposarcoma-is it worth it? A 20-year single-center experience.

Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. The overall survival rate at 5years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Development of nomograms to predict recurrence after conversion hepatectomy for hepatocellular carcinoma previously treated with transarterial interventional therapy

BackgroundLack of opportunity for radical surgery and postoperative tumor recurrence are challenges for surgeons and hepatocellular carcinoma (HCC) patients. This study aimed to develop nomograms to predict recurrence risk and recurrence-free survival (RFS) probability after conversion hepatectomy for patients previously receiving transarterial interventional therapy.MethodsIn total, 261 HCC patients who underwent conversion liver resection and previously received transarterial interventional therapy were retrospectively enrolled. Nomograms to predict recurrence risk and RFS were developed, with discriminative ability and calibration evaluated by C-statistics, calibration plots, and the Area under the Receiver Operator Characteristic (AUROC) curves.ResultsUnivariate/multivariable logistic regression and Cox regression analyses were used to identify predictive factors for recurrence risk and RFS, respectively. The following factors were selected as predictive of recurrence: age, tumor number, microvascular invasion (MVI) grade, preoperative alpha‐fetoprotein (AFP), preoperative carbohydrate antigen 19-9 (CA19-9), and Eastern Cooperative Oncology Group performance score (ECOG PS). Similarly, age, tumor number, postoperative AFP, postoperative protein induced by vitamin K absence or antagonist-II (PIVKA-II), and ECOG PS were incorporated for the prediction of RFS. The discriminative ability and calibration of the nomograms revealed good predictive ability. Calibration plots showed good agreement between the nomogram predictions of recurrence and RFS and the actual observations.ConclusionsA pair of reliable nomograms was developed to predict recurrence and RFS in HCC patients after conversion resection who previously received transarterial interventional therapy. These predictive models can be used as guidance for clinicians to help with treatment strategies.

Dynamics of recurrence after curative resection of nonsmall cell lung cancer.

This study examined the trend of hazards for postoperative recurrence of lung cancer according to pathologic stages. We reviewed the records of 1987 patients who underwent resection for lung cancer between 2007 and 2012. Postoperative recurrence and development of second primary lung cancer were analyzed to evaluate the trend of hazard rate. Recurrence-free survival (RFS) probabilities at 5 postoperative years in patients with stage I/II/III disease were 87.8%/54.7%,/33.4%, respectively. The hazard rate of RFS was consistently low (<0.005) for stage I patients for 5 years after surgery. The hazard rate of RFS for stage II patients showed a peak of 0.016 at 12.4 months after surgery, and that for stage III patients had a higher peak of 0.029 at 13.7 months after surgery, after which they showed a gradual decrease. The hazard rate for the development of second primary lung cancer exceeded that of recurrence of first primary lung cancer after 72 months postoperatively. Short-interval postoperative surveillance might be unnecessary for stage I patients but should be considered in stage II/III patients. Screening of second primary lung cancer rather than surveillance of recurrence might be beneficial after more than 6 years postoperatively.

Effectiveness of adjuvant trastuzumab in women with HER-2+ breast cancer in the SUS.

The aim of this study was to evaluate the effectiveness in a real-world study of adjuvant trastuzumab in women with HER-2+ initial breast cancer in overall survival and recurrence-free survival. A retrospective cohort study was conducted with women who had HER-2+ breast cancer treated with trastuzumab from July 2012 to May 2017 and followed up until July 2021. The death rate was 2.62 per 100 persons/year, and the incidence rate of recurrence was 7.52 per 100 persons/year. The probability of survival at 8.7 years was 85.9%, while the probability of recurrence-free survival in the same period was 62.8%. The use of trastuzumab proved to be effective in the adjuvant treatment of breast cancer in a public health service in southern Brazil. Prognostic factors associated with worse overall survival or relapse did not influence the natural history of the disease, except locally advanced disease at the beginning of treatment. The data presented may prove to be useful in helping to make decisions about whether to use trastuzumab in the treatment of initial or locally advanced breast cancer in the Brazilian SUS.

Discovery and validation of AMBLor as a prognostic biomarker for non-ulcerated cutaneous AJCC stage I/II melanoma.

9573 Background: Cutaneous melanoma incidence continue to increase, with a particular increase in the number of patients diagnosed with thin, &lt; 1mm tumours with reduced probability of recurrence-free survival. The inability of current AJCC staging criteria to identify genuinely low risk subsets of patients with AJCC stage I/II tumours thus emphasises the acute need for credible prognostic biomarkers to stratify patient follow-up based on personalised risk. The combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas has recently been identified as a prognostic biomarker and valuable pre SLNB test. The aim of the present study was to evaluate the potential for AMBLor as a prognostic biomarker for both AJCC stage I and II non-ulcerated melanoma. Methods: Prospective analysis of AMBLor was performed in two independent retrospective cohorts of non-ulcerated AJCC (8th edition) stage I and II cutaneous melanomas derived from the USA and Australia (discovery cohort) and Spain and the UK (Validation cohort) following validated automated immune-histological staining and binary scoring analysis to define at risk vs low risk subgroups. Each cohort was powered to represent rates of 10% or up to 20% metastasis for stage I or stage II disease respectively. Results: Data revealed retention of AMBLor in the discovery cohort of 541 melanomas correlated with significantly increased recurrence-free survival (RFS) of 96% compared to 87% for patients with stage I/II melanomas in which AMBLor was lost (P = 0.06; HR 3.6, 95% CI 1.99-6.84, NPV 96%). Subsequent AMBLor analysis in the validation cohort of 303 tumours, further confirmed retention of AMBLor was associated with increased RFS of 98% compared to 81% for patients with stage I/II tumours in which AMBLor was lost (P = 0.01; HR 8.16, 95% CI 3.68-18.07). Conclusions: Collectively data from this multi-international study confirm AMBLor as a prognostic biomarker marker able to identify genuinely low risk subsets of AJCC stage I/II melanomas. Inclusion of AMBLor into clinical melanoma management may therefore aid stratification of patient follow up, enable significant savings on healthcare resources and improve patient anxiety.

Risk Factors and Oncologic Outcomes for Clinical T1 Renal Cell Carcinoma Upstaging to Pathological T3a and The Construction of Predictive Model: A Retrospective Study.

The study is intended to identify the independent predictors of clinical T1 (cT1) renal cell carcinoma upstaging to pathological T3a (pT3a) and construct the predictive nomogram model. The data of cT1 renal cell carcinoma was collected from patients who were treated in the Second Hospital of Tianjin Medical University from January 2010 to December 2016. Mann-Whitney U and chi-square tests were performed to analyze continuous and categorical variables respectively. Univariate and multivariate logistic regression were used to identify the predictors of upstaging. Kaplan-Meier method, log-rank test and Cox regression were performed to analyze survival materials. Among 1,376 cT1 renal cell carcinoma patients, 75 patients were observed upstaging to pT3a, accounting for 5.5%. There were 6 potential predictors of upstaging, i.e age, clinical symptom, tumor size, Fuhrman grade, tumor necrosis and tumor edge regularity. The 5-year recurrence free survival probabilities of upstaging and non-upstaging patients were 73.3% and 91.1%, respectively and upstaging was an independent predictor of recurrence free survival. Two predictive nomograms were constructed and the C-index of them were 0.842 and 0.806, and the calibration curve and decision curve analysis showed highly clinical accuracy of the nomograms. Two nomogram models were built to predict the probability of cT1 renal cell carcinoma upstaging to pT3a with highly accuracy and specificity. Upstaging was an independent risk factor of recurrence free survival for cT1 renal cell carcinoma patients.

Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study

BackgroundImmune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration–approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited. ObjectiveTo evaluate the safety and outcomes of nephrectomy following an ICI. Design, setting, and participantsA retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021. Outcome measurements and statistical analysisClinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method. Results and limitationsA total of 113 patients with a median (interquartile range) age of 63 (56–69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13–15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received. ConclusionsNephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted. Patient summaryThis study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.