Predictor Of RFS Research Articles

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus

BackgroundSurgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients.MethodsWe collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients.ResultsThere were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05).ConclusionsFor HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data

Background and AimThe role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. Patients and MethodsA total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. ResultsIn overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33–2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20–3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92–1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16–2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91–2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68–1.48]; P = 0.981) ConclusionsThis multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Development of an improved risk stratification scheme for stage II and III colorectal cancers through incorporation of the digital pathology biomarker QuantCRC.

162 Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10-5) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10-11) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10-7) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.

Clinicopathologic Features and Survival Outcomes of Primary Lung Mucinous Adenocarcinoma Based on Different Radiologic Subtypes.

Primary lung mucinous adenocarcinomas (LMAs) could be subclassified as the pure-solid, part-solid, and pneumonic types according to the findings of high-resolution computed tomography. This study aimed to expound on the clinicopathologic, radiologic, and prognostic characteristics of LMAs based on radiologic classification within a large set of patients. From November 2009 to December 2016, this study enrolled 294 resected LMAs, which were divided into the pure-solid (n = 169), part-solid (n = 87), and pneumonic (n = 38) types. The clinicopathologic and radiologic characteristics of the tumors were evaluated, and patient prognosis was determined through follow-up evaluation. Survival outcomes were calculated by Kaplan-Meier curves and compared using log-rank tests. The prognostic impact of clinicopathologic variables, including radiologic presentations, were evaluated by establishing a Cox proportional hazards model. The LMAs were infrequently associated with lymph node metastasis (5.4 %), lymphatic/vascular invasion (4.4 %), or visceral pleural invasion (5.1 %). During the median 71-month follow-up period, recurrence was observed in 62 patients and death in 44 patients. The patients with pneumonic-type LMAs had a poorer prognosis (5-year recurrence-free survival [RFS], 23.7 %; 5-year overall survival [OS], 44.7 %) than those with the pure-solid type (RFS, 83.2 %; OS, 100 %) or part-solid type (RFS, 93.7 %; OS, 100 %). Besides, lymph node metastasis, emphysema, and clinical T stage were independent predictors of RFS and OS. Solitary-type LMA patients had excellent prognoses, whereas the survival outcomes for pneumonic-type LMA patients were dismal. Furthermore, pneumonic-type LMA patients were prone to intrapulmonary metastasis by means of aerogenous dissemination rather than distant metastasis.

The Prognostic Impact of Substantial Lymphovascular Space Invasion in Women with FIGO Stage I Uterine Endometrioid Carcinoma with Pathologically Negative Nodal Evaluation

Substantiallymphovascular space invasion (LVSI) is an important predictor of lymph node involvement in women with endometrial carcinoma. However, its prognostic significance in women with stage I who had pathologic negative nodal evaluation (PNNE) was not fully evaluated. We aimed to evaluate the prognostic significance of substantial LVSI on recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) in women with FIGO stage I uterine endometrioid adenocarcinoma (EC). Our uterine cancer database was queried for women with stage I EC who had a hysterectomy and PNNE at our institution between 1/1990 and 11/2022. Postoperatively, patients were managed with observation or adjuvant radiation therapy (RT) with pelvic external beam RT or vaginal cuff brachytherapy (VB). Women with synchronous malignancies and those who received adjuvant chemotherapy were excluded. Pathologic specimens were retrieved and LVSI was quantified by Gynecology pathologists (none, focal or substantial). Patients' demographics, surgical and pathologic variables were analyzed. Predictors of RFS, DSS and OS using univariate (UVA) and multivariate analysis (MVA) were studied. One thousand fifty-two patients were identified with a median age of 63 years and median follow-up of 9.7 years. Median number of examined lymph node (LN) were 9 (range 4-18). 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal and 58 (5.5%) had substantial LVSI. In patients with focal LVSI, 32.2% received pelvic RT and 39.1% received VB. In patients with substantial LVSI, 20.7% received pelvic RT and 58.6% received VB.Recurrence was diagnosed in 86 patients (8.2%). While any LVSI was associated with tumor recurrence, there was no significant difference for the site of initial recurrence between patients with focal vs. substantial LVSI. 5-year RFS was 93.3% (95% CI 91.5-95.1), 76.8% (67.2-87.7) and 79.1% (67.6-95.3) for no, focal and substantial LVSI. The 5-year DSS was 97.6% (96.5-98.7), 83.5% (75-93.1), and 90% (81.8-99.9); and 5-year OS was 90.7% (88.7-92.8), 72.8% (62.9-84.2) and 86% (76.2-97.2), respectively. Independent predictors of worse 5-year RFS and DSS include any LVSI, age > 60 years, higher tumor grade. Independent predictors of worse 5- year OS include any LVSI, age > 60, high comorbidity burden, and higher tumor grade. Our large data suggest similar recurrence-free, disease specific and OS for women with stage I uterine endometrioid carcinoma who had pathologically negative nodal evaluation and substantial or focal LVSI. There was no significant difference for the site of initial recurrence between patients with focal or substantial LVSI. Multi-institutional pooled analyses may be needed to validate our results.

Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it can trigger the expression of critical genes, including glucose transporter protein type 1 (GLUT1). The aim of the present study was to evaluate the roles of HIF-1α and GLUT1 in ESCC and their usefulness as prognostic markers. HIF-1α and GLUT1 were measured in four ESCC cell lines, namely Eca109, KYSE150, TE-1 and TE-10, by western blotting following culture under normoxic and hypoxic conditions. In addition, xenograft tumors were established in mice using normoxic and hypoxic Eca109 cells and the chemosensitivity of the xenografts to 5-fluorouracil (5-FU) was evaluated. Furthermore, HIF-1α and GLUT1 were analysed by immunochemistry in the tumor tissues of patients with ESCC and the associations of their expression levels with clinicopathological parameters were investigated. The results revealed that HIF-1α and GLUT1 protein expression was weak in all four cell lines under a normoxic atmosphere but increased following culture in a hypoxic environment. In vivo, 5-FU inhibited tumor growth more strongly in normoxic Eca109 ×enografts than hypoxic Eca109 ×enografts. Higher levels of apoptosis were also detected in the normoxic Eca109 ×enografts via western blotting and TUNEL analysis. In patients with ESCC, HIF-1α expression was associated with advanced ESCC while GLUT1 expression was associated with the sex of the patients. Multivariate analysis demonstrated that HIF-1α and GLUT1 were negatively associated with progression-free survival (PFS) and overall survival (OS). Additionally, a combination of HIF-1α and GLUT1 expression was a predictor of RFS and OS in patients with ESCC without lymph node metastasis but not those with lymph node metastasis. The study demonstrated that HIF-1α and GLUT1 were strongly expressed in vitro and in xenograft models when cells were exposed to hypoxia. The simultaneous high expression of HIF-1α and GLUT1 was associated with poorer survival, and may play an important role in ESCC chemoresistance and the prognosis of ESCC.

162 Evaluating Risk of Recurrence in Patients With Meningioma: Analysis of 703 Cases

INTRODUCTION: Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. METHODS: This is a retrospective study of a consecutive series of patients with WHO grade 1–3 meningioma resected at UT Southwestern from 1994 to 2015. Time to meningioma recurrence (RFS) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. RESULTS: A total of 703 consecutive patients with meningioma underwent resection at UT Southwestern between the years 1994 and 2015. The median age of the cohort was 56 years (range 16-88 years) and was 68.7% (n = 483) female. Median follow-up was 45 months (range 0-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade 1 meningioma (p = .82). Adjuvant radiation to subtotally resected WHO grade 1 meningiomas did not prolong the time to recurrence. Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p &lt; .01) on univariate analysis. In patients with high grade (WHO grade 2 or 3) meningiomas, location was predictive of RFS (p = .03) with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. CONCLUSIONS: Our data suggests that brain invasion does not increase the risk of recurrence in otherwise WHO grade 1 meningioma. Adjuvant radiation to subtotally resected WHO grade 1 meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model.

Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma.

Cancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma. A retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed. The high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21-12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21-170; p = 0.03). CAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

Evaluating risk of recurrence in patients with meningioma.

Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. This is a retrospective study of a consecutive series of patients with WHO grade I-III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16-88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44-1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03-1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.

Utility of ctDNA in predicting outcome and pathological complete response in patients with bladder cancer as a guide for selective bladder preservation strategies.

563 Background: Muscle-invasive bladder cancer (MIBC) accounts for ~25–30% of all bladder cancer diagnoses. With neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) as standard-of-care, the 5-year survival rate ranges from 40%–60%. Bladder-sparing protocols (BSP) have emerged as a feasible alternative to RC for MIBC treatment, however better tools are needed. In this study, we evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting recurrence in patients who achieved pathological complete response (pCR). Methods: We analyzed a previously described cohort of 68 patients (656 plasma samples; Christensen et al., JCO 2019) with MIBC who received NAC prior to cystectomy. Patients had an updated median follow-up of 58.94 months (range: 7.19-81.77) post-cystectomy. ctDNA was analyzed at baseline (before NAC; N=64), and prior to cystectomy (N=65) using a commercially available assay (Signatera, Natera, Inc.). Additionally, exploratory RNA-Seq was performed on tumors from 59 patients (samples with &gt;5M total counts were utilized). Pathway analysis was used to compare ctDNA-positive and ctDNA-negative patients who failed to achieve pCR. Results: Of the 64 patients with ctDNA results available at baseline, 59.4% (38/64) tested ctDNA-negative, and of these 84.2% (32/38) achieved pCR. Furthermore, 40.6% (26/64) tested ctDNA-positive, and only 34.6% (9/26) achieved pCR. Likewise, prior to cystectomy, 83.9% (52/62) of patients were ctDNA-negative, and 80.7% (42/52) achieved pCR, while none of the ctDNA-positive patients achieved pCR (positive predictive value 100%; negative predictive value 80.8%). Based on both ctDNA timepoints, the probability of ctDNA-negative patients to achieve pCR was significantly higher than ctDNA-positive patients ( p&lt;0.0001). Notably, ctDNA-positive patients without pCR demonstrated significantly poorer RFS and OS compared to the ctDNA-negative patients, at both timepoints (Baseline: RFS; HR=8.2, p=0.017, OS; HR=8.4, p=0.015, prior to cystectomy: RFS; HR=5.2, p=0.0078, OS; HR=4.8, p=0.012). Furthermore, ctDNA status at baseline and before cystectomy was a better predictor of RFS compared to pCR (HR=8.5, p&lt;0.0001, HR=14, p&lt;0.0001, respectively). Transcriptomic pathway analysis of patients who did not achieve pCR showed an enrichment of oncogenic pathways, namely EMT and angiogenesis, in tumors from ctDNA positive patients, whereas tumors from ctDNA negative patients showed an enrichment of anti-tumor immune signatures, including IFNα and IFNγ. Conclusions: Absence of ctDNA was significantly associated with pCR both at baseline and prior to cystectomy, identifying patients who may benefit from BSP. Larger cohorts are warranted to test the prognostic value of ctDNA combined with transcriptomic profiling in informing patient selection for avoiding cystectomy.

Low skeletal muscle mass in cholangiocarcinoma treated by surgical resection. A meta-analysis

To date, the role of low skeletal muscle mass (LSMM) in cholangiocarcinoma (CC) is unclear. Our purpose was to analyze the influence of LSMM on survival in patients with CC treated by surgical resection.MEDLINE, Cochrane, and SCOPUS databases were screened for associations between LSMM and survival in CC up to June 2021. Overall, 16 studies met the inclusion criteria. The methodological quality of the involved studies was analyzed using the QUADAS instrument. The meta-analysis was undertaken using RevMan 5.4 software.The prevalence of LSMM was 48.40%. LSMM was associated with lower overall survival (OS): HR = 2.44, 95%CI = (2.01-2.96) (simple regression); HR = 2.39, 95%CI = (1.83-3.13) (multiple regression). In extrahepatic CC, sarcopenic patients had lower OS, simple regression: HR = 2.11, 95%CI = (1.39-3.20); multiple regression: HR = 2.28, 95%CI = (1.41-3.70). In intrahepatic CC, LSMM predicted recurrence free survival: HR = 2.33, 95%CI = (1.93-2.81) (simple regression); HR = 2.23, 95%CI = (1.73-2.88) (multiple regression). LSMM predicted OS in intrahepatic CC, simple regression: HR = 2.69, 95%CI = (2.24-3.24); multiple regression: HR = 2.43, 95%CI = (1.73-3.41).LSMM is a risk factor for OS in patients with CC treated by surgical resection. LSMM is a predictor of RFS in patients with intrahepatic CC.

Circulating tumor DNA (ctDNA) as a minimal residual disease (MRD) assessment and recurrence risk in patients undergoing curative intent resection with or without adjuvant chemotherapy in colorectal cancer: A systematic review and meta-analysis.

3623 Background: Minimal residual disease (MRD) assessment may effectively detect cure in patients with colorectal cancer (CRC). Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for MRD in patients. Recent studies have shown the ability to detect MRD using ctDNA assay to assess recurrence risk and patient selection for adjuvant chemotherapy. We performed a systematic review and metanalysis of post operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative intent resection with or without adjuvant chemotherapy. Methods: We searched PubMed/Medline, EMBASE, Web of Science, Cochrane Library, and Google from inception to February 3, 2022 using keywords related to colorectal cancer, ctDNA, and MRD. The search also includes paper and conference presentations. The search resulted in 427 studies after removing the duplicates. Data were extracted to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results: After the initial abstract screening, 48 studies were identified. The final review led to the inclusion of 27 studies representing 3459 patients with evaluable ctDNA, with 623 having +ve post-surgery ctDNA levels. Seven studies had analyses of patients specifically with oligometastatic disease, the rest 20 studies subdivided within stages I-III. The pooled HR for RFS in post-surgical ctDNA +ve vs -ve patients in all stages was 7.16 (95% CI 6.12-8.36) p &lt;0.00001. Subgroup analysis revealed pooled HR = 8.27 (95% CI 6.16-11.09) and 6.07 (95% CI 4.54-8.13) for stage I-III and IV CRC, respectively. Only 11 studies did analysis for post adjuvant chemotherapy patients based on ctDNA status. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA +ve versus -ve patients in all stages was 12.40 (95% CI 9.24-16.64) p &lt;0.00001. Subgroup analysis revealed pooled HR = 13.95 (95% CI 9.08-21.43) and 11.39 (95% CI 5.99-21.66) for stage I-III and IV CRC, respectively. Conclusions: This is the largest and most current meta-analysis done on ctDNA levels as MRD assessment in CRC. Our analysis emphasizes that post operative ctDNA is a strong prognostic marker of RFS. Based on our results ctDNA can be a significant and independent predictor of RFS. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer. [Table: see text]

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Microscopic Extrathyroidal Extension Results in Increased Rate of Tumor Recurrence and Is an Independent Predictor of Patient's Outcome in Middle Eastern Papillary Thyroid Carcinoma.

BackgroundPapillary Thyroid Cancer (PTC) is the most common endocrine malignancy, with recurrence rate as high as 30%. A great deal of controversy surrounds the significance of microscopic extrathyroidal extension (m-ETE) as a prognostic factor. The most recent edition (8th) of American Joint Committee on Cancer (AJCC) staging system has removed m-ETE from the definition of pT3, which suggests that m-ETE may lack prognostic impact in PTC patients. Moreover, data about m-ETE prevalence and clinical impact on Middle Eastern PTC remains unknown. We therefore investigate the prevalence of m-ETE and its clinico-pathological correlation and prognostic impact in Middle Eastern PTC. We also compared the AJCC 7th and 8th staging systems and their prognostic performance.MethodsPTCs from 1430 consecutive adult (> 18 years) patients from single tertiary care hospital were included in this study. A retrospective analysis of PTC patients’ survival and recurrence were compared between AJCC 8th and AJCC 7th staging systems using Proportion of Variation Explained (PVE) and Harrell’s C-index.ResultsMedian follow up of the study cohort was 9.3 years. 31.2% (446/1430) of patients had m-ETE. In the overall cohort, m-ETE was associated with multiple adverse features such as older age (p < 0.0001), male sex (p = 0.0245), tall cell variant (p < 0.0001), bilateral tumors (p < 0.0001), multifocality (p < 0.0001), lymphovascular invasion (p < 0.0001), lymph node metastasis (p < 0.0001), distant metastasis (p = 0.0166), tumor recurrence (p < 0.0001), radioactive iodine refractoriness (p < 0.0001), BRAF mutation (p < 0.0001) and reduced recurrence-free survival (RFS; HR = 1.75; 95% CI = 1.30 – 2.35; p < 0.0001) irrespective of tumor size. Of the 611 patients with T3 disease based on AJCC 7th edition, 359 (58.8%) were down-staged in AJCC 8th edition classification. Overall, the prognostic performance of AJCC 8th edition was inferior to AJCC 7th on the basis of lower PVE (3.04% vs. 3.73%) and lower C-index (0.40 vs. 0.48).ConclusionsIn Middle Eastern PTC, m-ETE is significantly associated with compromised survival and acts as an independent predictor of RFS. Given these findings, m-ETE should be included in the thyroid cancer treatment guidelines.

MP42-20 SURVIVAL OUTCOMES OF PT3A PATHOLOGICAL UPSTAGING IN PARTIAL VS. RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy III (MP42)1 Sep 2021MP42-20 SURVIVAL OUTCOMES OF PT3A PATHOLOGICAL UPSTAGING IN PARTIAL VS. RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA Ahmed Elshabrawy, Hanzhang Wang, Furkan Dursun, Ashok Hemal, James Porter, Ronney Abaza, Daniel Eun, Michael Stifelman, Ahmed M. Mansour, and Ketan Badani Ahmed ElshabrawyAhmed Elshabrawy More articles by this author , Hanzhang WangHanzhang Wang More articles by this author , Furkan DursunFurkan Dursun More articles by this author , Ashok HemalAshok Hemal More articles by this author , James PorterJames Porter More articles by this author , Ronney AbazaRonney Abaza More articles by this author , Daniel EunDaniel Eun More articles by this author , Michael StifelmanMichael Stifelman More articles by this author , Ahmed M. MansourAhmed M. Mansour More articles by this author , and Ketan BadaniKetan Badani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002063.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial nephrectomy (PN) is the preferred surgical treatment of Kidney confined tumors, as it can preserve renal function without compromising oncologic control when compared to radical nephrectomy (RN) . However, a proportion of patients will be diagnosed with more aggressive pT3a disease at time of surgery, potentially negating the benefits of PN and compromising the oncologic and survival outcomes. Therefore, we aimed to identify predictors of pT3a upstaging, and compare recurrence-free (RFS) and overall survival (OS) between patients who upstaged after PN versus RN. METHODS: A multi-institutional database of 4,406 RCC patients was queried to identify patients who underwent PN or RN for cT1-cT2 tumors between 2007 and 2020. Patients were further stratified according to pT3a upstaging, and descriptive statistics were utilized to summarize baseline characteristics between the study groups. Multivariate logistic regression model was fitted to identify predictors of upstaging, and the Kaplan-Meier method was utilized to characterize OS and RFS in the study population. Cox proportional hazards model was used to identify predictors of survival. RESULTS: A total of 4,406 patients were investigated, of which 397 (8.9%) were post-operatively upstaged to pT3a. Of those, 146 (39%) underwent PN and 227 (61%) underwent RN. Multivariate analysis identified Fuhrmann grades 3 and 4 (OR 4, CI 1.5 - 10, p=0.005; and 13.6, CI 2.8 - 64.8; respectively, p=0.001), cT2 stage (OR 4.2, CI 1.8 - 9.6, p=0.001) as independent predictors of upstaging. In addition, black patients were less likely to upstage compared to white (OR 0.16, CI 0.05 - 0.53, p=0.003). 5-year RFS for upstaged patients after PN was 78% (CI 54% - 90%) and 30% (CI 15% - 48%) after RN (p=0.021). 5y-RFS in upstaged cT1 patients who underwent PN vs. RN was 84% (CI 58% - 95%) and 49% (CI 18% - 74%), respectively. In upstaged cT2 patients, 5y-RFS after RN was 21% (CI 5%-43%). Five-year OS for upstaged patients overall was 97% (CI 82% - 99%) after PN and 50% (CI 31% - 67%) after RN. 5y-OS in upstaged cT1 patients was 100% after PN vs. 45% (CI 19%-69%) after RN. Cox proportional hazards model identified cT2 stage as an independent predictor of RFS (HR 3.43, CI 1.05 - 11.2, p=0.041). CONCLUSIONS: No OS differences were noted in pT3a upstaged patients who underwent PN vs. RN. Moreover, PN conferred a RFS advantage in this population. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e780-e780 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmed Elshabrawy More articles by this author Hanzhang Wang More articles by this author Furkan Dursun More articles by this author Ashok Hemal More articles by this author James Porter More articles by this author Ronney Abaza More articles by this author Daniel Eun More articles by this author Michael Stifelman More articles by this author Ahmed M. Mansour More articles by this author Ketan Badani More articles by this author Expand All Advertisement Loading ...

Transcriptomic Profiling Identifies an Exosomal microRNA Signature for Predicting Recurrence Following Surgery in Patients With Pancreatic Ductal Adenocarcinoma.

We performed genome-wide expression profiling to develop an exosomal miRNA panel for predicting recurrence following surgery in patients with PDAC. Pretreatment risk stratification is essential for offering individualized treatments to patients with PDAC, but predicting recurrence following surgery remains clinically challenging. We analyzed 210 plasma and serum specimens from 4 cohorts of PDAC patients. Using a discovery cohort (n = 25), we performed genome-wide sequencing to identify candidate exosomal miRNAs (exo-miRNAs). Subsequently, we trained and validated the predictive performance of the exo-miRNAs in two clinical cohorts (training cohort: n = 82, validation cohort: n = 57) without neoadjuvant therapy (NAT), followed by a post-NAT clinical cohort (n = 46) as additional validation. We performed exo-miRNA expression profiling in plasma specimens obtained before any treatment in a discovery cohort. Subsequently we optimized and trained a 6-exo-miRNA risk-prediction model, which robustly discriminated patients with recurrence [area under the curve (AUC): 0.81, 95% confidence interval (CI): 0.70-0.89] and relapse-free survival (RFS, P < 0.01) in the training cohort. The identified exo-miRNA panel was successfully validated in an independent validation cohort (AUC: 0.78, 95% CI: 0.65- 0.88, RFS: P < 0.01), where it exhibited comparable performance in the post-NAT cohort (AUC: 0.72, 95% CI: 0.57-0.85, RFS: P < 0.01) and emerged as an independent predictor for RFS (hazard ratio: 2.84, 95% CI: 1.30-6.20). We identified a novel, noninvasive exo-miRNA signature that robustly predicts recurrence following surgery in patients with PDAC; highlighting its potential clinical impact for optimized patient selection and improved individualized treatment strategies.

Intra-corporeal robot-assisted versus open radical cystectomy: a propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns.

To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal urinary diversion (iRARC) and open radical cystectomy (ORC). We retrospectively analyzed 177 bladder cancer patients who received iRARC or ORC at Fujita Health University between 2008 and 2020. Our primary endpoint was long-term oncological outcomes. As a secondary endpoint, we examined perioperative outcomes, complications, and recurrence patterns. These outcome measures were compared between the propensity score (PS)-matched cohorts. PS-matched analysis resulted in 60 matched pairs from iRARC and ORC groups. The iRARC cohort was associated with significantly longer operative time (p = 0.02), lower estimated blood loss (p < 0.001), lower blood transfusion rate (p < 0.001), shorter length of hospital stay (p < 0.001), fewer overall complications (p = 0.03), and lower rate of postoperative ileus (p = 0.02). There was no statistically significant difference between iRARC and ORC in 5-year RFS (p = 0.46), CSS (p = 0.63), and OS (p = 0.71). RFS and CSS were also comparable, even in locally advanced (≥ cT3) disease. Multivariate analysis identified lymphovascular invasion as a robust predictor of RFS, CSS, and OS. The number of recurrence was similar between the groups, while extra-pelvic lymph nodes were more frequent in iRARC than that in ORC (22.7% vs. 7.7%). iRARC has favorable perioperative outcomes, fewer complications, and comparable long-term survival outcomes, including locally advanced (≥ cT3) disease, compared to that in ORC. Our results need to be validated in prospective randomized clinical trials.

Body temperature predicts recurrent febrile seizures in the same febrile illness

BackgroundThe incidence of recurrent febrile seizures during the same febrile illness (RFS) is 14–24%. A pilot study found that body temperature and male sex were predictors of RFS. This study sought to validate body temperature as a predictor of RFS, calculate the optimal cut-off body temperature for predicting RFS, and identify the other predictors of RFS. MethodsThis prospective cohort study enrolled children with febrile seizures aged 6–60 months who visited the emergency department at Atsugi City Hospital, Japan, between March 1, 2019, and February 29, 2020. Children who had multiple seizures, diazepam administration before the emergency department visit, seizures lasting >15 min, underlying diseases, or who could not be followed up were excluded. The optimal cut-off body temperature was determined using a receiver-operating characteristic curve. ResultsA total of 109 children were enrolled, of whom 13 (11.9%) had RFS. A lower body temperature was significantly associated with RFS (P = 0.02). The optimal cut-off body temperature for predicting RFS was 39.2 °C. Children with RFS also had significantly lower C-reactive protein and blood glucose levels (P = 0.01 and 0.047, respectively), but none of the other factors considered were significantly associated with RFS. ConclusionsThis large prospective study confirmed that body temperature is a predictor of RFS. The optimal cut-off body temperature for predicting RFS was 39.2 °C. Low C-reactive protein level and blood glucose level might be predictors of RFS, but this needs to be confirmed in prospective multicenter studies.

Nomograms for predicting overall and recurrence-free survival after trimodality therapy for esophageal adenocarcinoma.

Locally advanced esophageal carcinoma is treated with neoadjuvant chemoradiation and esophagectomy. Patients may still experience recurrence and death despite undergoing potentially curative trimodality therapy. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after the completion of trimodality therapy. A total of 215 patients with esophageal adenocarcinoma underwent trimodality therapy from September 2010 to April 2018. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts. On multivariate analysis, clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, body mass index, age, and number of lymph nodes removed were predictive variables for overall survival. Clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, age, and positive lymph nodes were significant predictors of RFS in a multivariate model. The nomogram for OS had good predictive ability (Harrell's Concordance index [C-index]: 0.71 [95% confidence interval {CI}: 0.66-0.76]). The nomogram for RFS also performed well (C-index: 0.70 [95% CI: 0.65-0.74]). Our nomograms can accurately predict OS and RFS after trimodality therapy and may provide guidance regarding adjuvant therapy and surveillance.

The Pattern of Serum Conversion between Pre-treatment and Post-treatment Levels of Squamous-cell Carcinoma Antigen (SCC-Ag) as a Predictor of Recurrence and Survival in Locally Advanced Cervical Cancer after Definitive Concurrent Chemoradiotherapy

Cervical cancer is the second most commonly diagnosed malignancy and the second leading cause of cancer death in the developing countries. Although the value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for disease surveillance is generally accepted, its role as a reliable predictor for recurrence and survival is still controversial. This study was conducted to investigate the predictive efficacy of serum conversion between baseline and post-treatment SCC-Ag levels in locally advanced cervical cancer. Patients with biopsy-proven, stage IB2-IVA squamous cell-carcinoma of the cervix who received definitive concurrent chemoradiotherapy (CRT) between 2008 and 2017 in five institutions were consecutively included. All were tested for serum SCC-Ag levels pre- and post-CRT. Serum positivity was determined by plotting cumulative recurrence rate against post-treatment SCC-Ag level. A serum SCC-Ag level ≥ 2 ng/mL was defined as seropositive. Negative conversion was defined as pre-treatment SCC-Ag level ≥ 2 ng/mL reduced to post-treatment SCC-Ag level < 2 ng/mL. Serum conversion between pre-treatment and post-treatment SCC-Ag levels was categorized into the following three groups: i) seronegative: pre-treatment SCC-Ag < 2 ng/mL and post-treatment SCC-Ag level < 2 ng/mL; ii) negative conversion: pre-treatment SCC-Ag ≥ 2 ng/mL and post-treatment SCC-Ag level < 2 ng/mL; and iii) seropositive: pre-treatment SCC-Ag ≥ 2 ng/mL and post-treatment SCC-Ag level ≥ 2 ng/mL. A total of 291 patients were included. 162 (55.7%) underwent negative conversion. For seronegative (N = 65), negative conversion (N = 162), and seropositive groups (N = 64), the 3-year RFS rates were 92.9%, 75.3%, and 59.7% (P < 0.001) and the 3-year OS rates were 87.8%, 81.7%, and 55.9% (P < 0.001), respectively. The serum conversion of SCC-Ag levels between pre- and post-treatment was the most potent predictor of RFS (P = 0.001) and OS (P = 0.002) in multivariate analysis. Our data suggests that simply checking whether the serum SCC-Ag is above or below 2 ng/mL at pre- and post-treatment can function as a simple rule-of-thumb for prediction of recurrence and survival. Although prospective validation in a larger cohort is warranted, this predictor may provide clinicians to consider adjuvant therapy in consistently seropositive patients with risk of poorer outcome.