Disease Recurrence In Patients Research Articles

Value of serum platelet/albumin and C-reactive protein/albumin ratios in evaluating mucosal healing and disease recurrence in patients with Crohn’s disease

Value of serum platelet/albumin and C-reactive protein/albumin ratios in evaluating mucosal healing and disease recurrence in patients with Crohn’s disease

Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003)

ObjectiveTo identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). MethodsA total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. ResultsOf 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152–8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507–7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031–9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. ConclusionDuring MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.

Postoperative Early Body Weight Loss Is a Risk Factor for Recurrence in Patients with pStage III Gastric Cancer

Introduction: The goal of this study was to determine whether postoperative early body weight loss (EWL) after radical gastrectomy is a risk factor for recurrence in patients with pathological stage III (pStage III) gastric cancer who received postoperative adjuvant chemotherapy, which included tegafur/gimeracil/oteracil (S-1). Methods: Patients who underwent gastrectomy for gastric cancer were identified from a prospectively managed gastric cancer database. We analyzed 58 consecutive patients who underwent radical gastrectomy with D2 lymph node dissection for confirmed pStage III gastric cancer treated postoperatively with adjuvant chemotherapy including S-1 between 2010 and 2019. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Weight changes were evaluated from the preoperative period to the start of adjuvant chemotherapy. EWL was defined as % BMI change = (preoperative BMI – postoperative BMI at the start of adjuvant chemotherapy) × 100/preoperative BMI. Results: Of the 58 consecutive patients who underwent radical resection for gastric cancer, 72.4% were male, with a mean age of 65.5 years, and a mean preoperative BMI of 21.2 (range: 15.4–29.1) kg/m². The degree of EWL was found to be closely correlated to compliance with adjuvant chemotherapy. Multivariate analysis by Cox proportional hazard analysis revealed that EWL was an independent factor for relapse-free survival (RFS), and patients with an EWL of 15.9% or more severe had poorer RFS. Conclusion: EWL above a certain rate at the start of adjuvant chemotherapy was a predictor of poor compliance with adjuvant chemotherapy and a high risk of disease recurrence in patients with pStage III gastric cancer.

Dynamics of Serum CA19-9 in Patients Undergoing Pancreatic Cancer Resection.

Carbohydrate antigen (CA) 19-9 is an established perioperative prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). However, it is unclear how CA19-9 monitoring should be used during postoperative surveillance to detect recurrence and to guide the initiation of recurrence-focused therapy. This study aimed to elucidate the value of CA19-9 as a diagnostic biomarker for disease recurrence in patients who underwent PDAC resection. Serum CA19-9 levels at diagnosis, after surgery, and during postoperative follow-up were analyzed in patients who underwent PDAC resection. All patients with at least two postoperative follow-up CA19-9 measurements before recurrence were included. Patients deemed to be nonsecretors of CA19-9 were excluded. The relative increase in postoperative CA19-9 was calculated for each patient by dividing the maximum postoperative CA19-9 value by the first postoperative value. Receiver operating characteristic analysis was performed to identify the optimal threshold for the relative increase in CA19-9 levels to identify recurrence in the training set using Youden's index. The performance of this cutoff was validated in a test set by calculating the area under the curve (AUC) and was compared to the performance of the optimal cutoff for postoperative CA19-9 measurements as a continuous value. In addition, sensitivity, specificity, and predictive values were assessed. In total, 271 patients were included, of whom 208 (77%) developed recurrence. Receiver operating characteristic analysis demonstrated that a relative increase in postoperative serum CA19-9 of 2.6× was predictive of recurrence, with 58% sensitivity, 83% specificity, 95% positive predictive value, and 28% negative predictive value. The AUC for a 2.6× relative increase in the CA19-9 level was 0.719 in the training set and 0.663 in the test set. The AUC of postoperative CA19-9 as a continuous value (optimal threshold, 52) was 0.671 in the training set. In the training set, the detection of a 2.6-fold increase in CA19-9 preceded the detection of recurrence by a mean difference of 7 months ( P <0.001) and in the test set by 10 months ( P <0.001). A relative increase in the postoperative serum CA19-9 level of 2.6-fold is a stronger predictive marker for recurrence than a continuous CA19-9 cutoff. A relative CA19-9 increase can precede the detection of recurrence on imaging for up to 7 to 10 months. Therefore, CA19-9 dynamics can be used as a biomarker to guide the initiation of recurrence-focused treatment.

Outcome Comparison of Functional Laryngectomy for the Dysfunctional Larynx to Salvage Laryngectomy.

To compare functional outcomes of total laryngectomy (TL) with microvascular free tissue transfer (MVFTT) reconstruction in the treatment of dysfunctional larynx (DL) versus salvage therapy for locally recurrent disease in patients with a history of laryngeal squamous cell carcinoma (SCC). Retrospective review from a tertiary medical center between August 2015 and August 2022. Sixty-nine patients underwent TL with MVFTT following primary laryngeal radiation or chemoradiation; 15 (22%) patients underwent functional laryngectomy (FL) and 54 (78%) underwent a salvage laryngectomy (SL). There were no total flap failures. Four (6%) patients developed a pharyngocutaneous fistula; one (7%) FL patient and 3 (6%) in the SL cohort. There was no significant difference in average hospital length of stay (LOS) between the cohorts (8.6 ± 3.0 days vs. 12.8 ± 10.1 days, p = 0.12). All patients (100%) in the FL cohort achieved a total oral diet compared to 41 (76%) in the SL cohort (p = 0.03). Two (13%) and 10 (19%) patients developed pharyngoesophageal stenosis in the FL and SL cohorts, respectively (p = 1.0). Nine (60%) and 23 (43%) patients in the FL and SL cohorts underwent tracheoesophageal puncture (TEP) placement, with 89% and 91% achieving fluency, respectively (p = 0.23). Although the role of TL for the definitive treatment of laryngeal SCC has decreased over the past 30 years, organ-preservation protocols can impact speech, swallowing, and airway protection with life-threatening consequences. The use of elective FL with MVFTT for the treatment of DL results in similar or better functional outcomes compared to SL for recurrent disease. 3 Laryngoscope, 134:222-227, 2024.

Early Post-operative Stimulated Serum Thyroglobulin: Role in Preventing Unnecessary Radioactive Iodine Treatment in Low to Intermediate Risk Papillary Thyroid Cancer.

The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC). This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included. The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1ng/mL for those with recurrent disease. This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1ng/mL was identified with a high negative predictive value.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. To analyze postoperative serum cortisol and recurrence rates in Cushing disease. Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Association of circulating tumor DNA kinetics with disease recurrence in patients with stage IIIB/C/IV melanoma treated with adjuvant immunotherapy in Checkmate 238.

9577 Background: In patients (pts) with resected, stage III/IV melanoma receiving adjuvant immunotherapy, pre-treatment (pre-Tx) and on-treatment (on-Tx) circulating tumor DNA (ctDNA) combined with tumor features were evaluated to predict recurrence risk. Methods: We used analytically validated, mutation-specific droplet digital PCR (ddPCR) assays to measure ctDNA in pre- and on-Tx plasma samples from pts with resected stage IIIB/C/IV melanoma enrolled in CheckMate 238 (NCT02388906) receiving either adjuvant Nivolumab (NIVO) or Ipilimumab (IPI). Assay choice was based on detection of one of the 7 melanoma hot-spot mutations in pt tumors: BRAF V600E/K, NRAS Q61R/L/K, or TERT C228T/C250T. We evaluated associations between ctDNA detection, recurrence free survival (RFS), distant metastasis free survival (DMFS), and known immunotherapy tumor biomarkers including PD-L1, IFNg gene signature, CD8, and tumor mutational burden. Associations between ctDNA kinetics and RFS/DMFS were analyzed using Kaplan-Meier and Cox regression models. Results: Mutations were identified in 87% of tumors. ctDNA was detected in pre-Tx samples from 94/753 (12.5%) pts. Pre-Tx ctDNA was significantly associated with higher stage of disease, LDH ≥ ULN, PD-L1 &lt; 5%, and tumor IFNg-RNA signature expression below the median. Detection of pre-Tx ctDNA was associated with shorter RFS and DMFS in both NIVO and IPI arms compared to undetectable ctDNA (Table). ctDNA detection on-Tx (week (w) 3, 7, 13, 25, 37, 49) was also associated with shorter RFS. Refined subgroup predictions that potentially impact therapy were achieved by incorporating pre- and on-Tx time points. Of those with baseline and w7 ctDNA results, pts in the NIVO arm with undetectable pre-Tx ctDNA (n=308) that became positive at w7 (n=22) had shorter RFS (median RFS 20.68 mos [95% CI, 2.79, NR]) than pts in whom on-Tx ctDNA remained undetectable (n=286) (median RFS, NR [95% CI, 61.1, NR]). Pts with positive pre-Tx ctDNA (n=42) that remained positive at w7 (n=23) had markedly shorter RFS (median RFS, 3.35 mos [95% CI, 2.73, 20.44]) vs pts in whom on-Tx ctDNA became undetectable (n=19) (median RFS, NR [95% CI, 14, NR]). Similar results were observed in the IPI arm. Conclusions: Pre- and on-Tx ctDNA measurements are associated with melanoma recurrence risk during adjuvant checkpoint inhibitor therapy. Incorporation of ctDNA with other tumor molecular features may improve prediction of RFS and DMFS in this setting. Clinical trial information: NCT02388906 . [Table: see text]

How Would You Manage This Patient With Recurrent Diverticulitis? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Acute diverticulitis, which refers to inflammation or infection, or both, of a colonic diverticulum, is a common medical condition that may occur repeatedly in some persons. It most often manifests with left-sided abdominal pain, which may be associated with low-grade fever and other gastrointestinal symptoms. Complications may include abscess, fistula formation, perforation, and bowel obstruction. The American College of Physicians recently published practice guidelines on the diagnosis and management of acute diverticulitis, the role of colonoscopy after resolution, and interventions to prevent recurrence of this condition. Among the recommendations were the use of abdominal computed tomography (CT) scanning in cases where there was diagnostic uncertainty, initial management of uncomplicated cases in the outpatient setting without antibiotics, referral for colonoscopy after an initial episode if not performed recently, and discussion of elective surgery to prevent recurrent disease in patients with complicated diverticulitis or frequent episodes of uncomplicated disease. Here, 2 gastroenterologists with expertise in acute diverticulitis debate CT scanning for diagnosis, antibiotics for treatment, colonoscopy to screen for underlying malignancy, and elective surgery to prevent recurrent disease.

SA5 Defining Colorectal Cancer Recurrence with Structured-Health Data Algorithms: A Targeted Literature Review

Roughly 50% of patients with colorectal cancer (CRC) experience recurrence within 2 years of surgical resection. Population-level real-world data often lacks recurrence status, making it difficult to adequately classify patients. Several algorithms have been developed to detect progression, metastasis, and recurrence in structured-health data, but methods and validation vary, thus potentially misclassifying patients and leading to inconsistent results dependent on the algorithm used for outcomes research. This review aimed to identify current approaches to developing and validating structured-health data algorithms used to define disease recurrence in patients with CRC.

Circulating tumor DNA–based detection of molecular residual disease as a biomarker for recurrence monitoring predict disease recurrence in patients with ovarian cancer.

e17542 Background: Despite recent advances in cancer diagnostics and treatments, nearly 75% ovarian cancer patients relapse within two years of primary therapy and become candidates for treatment of recurrent diseases. A novel approach to post-surgical risk stratification for molecular residual disease (MRD) detection and treatment monitoring is needed to improve patient outcomes. Methods: We analyzed a cohort of 22 stage Ⅰ-Ⅳ ovarian cancer patients which were followed up at median 6 (range,3-15) times between July 2017 and December 2020. Among the 22 patients, stage I, II, III and Ⅳ comprised 9%, 5%, 50% and 36%, respectively. Tumor tissue and blood samples of all subjects were collected at Ruijin Hospital, Shanghai Jiao Tong University.Somatic mutations were identified by whole exome sequencing and assessed from plasma collected during treatment using personalized tumor-informed MRDtect assays with a median of 25（range,17-30） amplicons/assay targeting tumor-specific variants unique to each patient, sequenced at mean 200,000X depth. Plasma samples with ≥2 variants detected were considered MRD-positive and ctDNA levels were reported in mean tumor molecules per mL (MTM/mL) of plasma. Sequencing data were analyzed using PiVAT secondary analysis software and MRD positive was concluded when at least two variants were detected in plasma. Results: CtDNA was preoperatively detectable in 18 (85.7%) patients, and the positive rate became 38.8% (7/18) after surgery. Serial ctDNA analysis during surveillance after definitive treatment of the 22 patients with longitudinal collected plasma samples identified relapse with 100% sensitivity and 100% specificity. The median lead time from ctDNA detection in plasma to relapse detection by standard-of-care computed tomography was 135 days (range,45-387days). Variants from a total of 526 genes were selected from the WES results of these 22 patients. Among these 526 genes, 96% (505 genes) were selected for only one patient, 3.4% (18 genes) were selected for two patients and 0.2% (one gene) were selected for three patients. Compared with tumor-agnostic assay, tumor-informed assay is a more accurate route that is more consistent with the heterogeneity of tumor and can maximize the ability to reflect the real situation of each patient. Conclusions: Sensitive methods for risk stratification, therapeutic efficacy monitoring, and early relapse detection may have a major impact on treatment decisions and patient management for ovarian cancer patients. MRD can be used as an effective biomarker to prompt prognosis and recurrence risk, providing powerful assistance for accurate diagnosis and treatment for patients.

Predictive Role of Serum Thyroglobulin after Surgery and before Radioactive Iodine Therapy in Patients with Thyroid Carcinoma.

Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg-30), on the day of RAI (Tg0), and seven days after RAI (Tg+7). One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with 131I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, 131I-whole body scan (WBS) after Thyrogen® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients' groups. A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg-30 (with suppressed TSH) has the same sensitivity and specificity than Tg0 (with stimulated TSH), and it is slightly better than Tg+7, which can be influenced by the size of the residual thyroid tissue. Serum Tg-30 value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up.

Application of Machine Learning Analyses Using Clinical and [18F]-FDG-PET/CT Radiomic Characteristics to Predict Recurrence in Patients with Breast Cancer.

To develop and identify machine learning (ML) models using pretreatment clinical and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]-FDG-PET)-based radiomic characteristics to predict disease recurrences in patients with breast cancers who underwent surgery. This retrospective study included 112 patients with 118 breast cancer lesions who underwent [18F]-FDG-PET/ X-ray computed tomography (CT) preoperatively, and these lesions were assigned to training (n=95) and testing (n=23) cohorts. A total of 12 clinical and 40 [18F]-FDG-PET-based radiomic characteristics were used to predict recurrences using 7 different ML algorithms, namely, decision tree, random forest (RF), neural network, k-nearest neighbors, naive Bayes, logistic regression, and support vector machine (SVM) with a 10-fold cross-validation and synthetic minority over-sampling technique. Three different ML models were created using clinical characteristics (clinical ML models), radiomic characteristics (radiomic ML models), and both clinical and radiomic characteristics (combined ML models). Each ML model was constructed using the top ten characteristics ranked by the decrease in Gini impurity. The areas under ROC curves (AUCs) and accuracies were used to compare predictive performances. In training cohorts, all 7 ML algorithms except for logistic regression algorithm in the radiomics ML model (AUC = 0.760) achieved AUC values of >0.80 for predicting recurrences with clinical (range, 0.892-0.999), radiomic (range, 0.809-0.984), and combined (range, 0.897-0.999) ML models. In testing cohorts, the RF algorithm of combined ML model achieved the highest AUC and accuracy (95.7% (22/23)) with similar classification performance between training and testing cohorts (AUC: training cohort, 0.999; testing cohort, 0.992). The important characteristics for modeling process of this RF algorithm were radiomic GLZLM_ZLNU and AJCC stage. ML analyses using both clinical and [18F]-FDG-PET-based radiomic characteristics may be useful for predicting recurrence in patients with breast cancers who underwent surgery.

Hashimoto’s Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma

A recent work analyzing the concomitant factors BRAF mutation (risk factor) and Hashimoto's thyroiditis (HT) (protective factor) found that the presence of HT reduced lymph node metastasis in BRAF-mutated papillary thyroid carcinoma. Whether this notion is upheld with respect to disease recurrence and differentiated thyroid carcinoma (DTC), however, is unknown. We aimed to investigate the effect of underlying HT in DTC patients and its influence on recurrence with a specific emphasis in BRAF-mutated tumors. A total of 469 patients were included. Patients were stratified according to BRAF and HT status. Multivariate regression analysis was conducted to determine protective and risk factors of disease recurrence in patients with DTC. HT was associated with less-aggressive carcinomas including more frequent microcarcinomas (HT: 45.0% vs. no-HT: 34.0%, p = 0.02), less lymph node involvement (HT: 16.4% vs. no-HT: 26.1%, p = 0.02), and less disease recurrence (HT: 2.9% vs. no-HT: 11.9%, p = 0.002). BRAF mutation was also significantly associated with higher rates of lymph node involvement (BRAF-mutant: 41.9% vs. BRAF-wild type: 14.6%, p < 0.001) and almost two times the rate of recurrence (BRAF-mutant: 14.9% vs. BRAF-wild type: 6.5%, p = 0.004). Underlying HT was the only protective factor determined, reducing the odds of developing recurrence by 70% (HR: 0.30, 95%CI: 0.11-0.88). In the BRAF-wild type cohort, regression analysis continued to determine HT as a protective factor (p = 0.03). However, in the BRAF-mutant cohort, HT was no longer an independent protective factor (p = 0.20) against recurrence. Sub-group regression analysis, including PTC patients, similarly found HT as a protective factor only in BRAF-wild type patients (p = 0.039) and not BRAF-mutant (p = 0.627). The presence of underlying HT is associated with less aggressive tumors and is an independent protective factor against DTC recurrence, reducing the risk by 70%. HT remains a protective factor in BRAF-wild type carcinoma, but not in patients with BRAF-mutant carcinoma. HT may potentially be considered as a parameter which enhances American Thyroid Association patient risk stratification.

PD36-05 ASSESSMENT OF CIRCULATING TUMOR DNA STATUS AS A PROGNOSTIC MARKER FOR RECURRENCE DETECTION IN PATIENTS WITH MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD36-05 ASSESSMENT OF CIRCULATING TUMOR DNA STATUS AS A PROGNOSTIC MARKER FOR RECURRENCE DETECTION IN PATIENTS WITH MUSCLE INVASIVE BLADDER CANCER Shivaram Cumarasamy, George Laliotis, Elshaddai White, Jordan Rich, Punashi Dutta, Shruti Sharma, Mark Calhoun, Adam Elnaggar, Minetta Liu, Kyrollis Attalla, Reza Mehrazin, Peter Wiklund, and John Sfakianos Shivaram CumarasamyShivaram Cumarasamy More articles by this author , George LaliotisGeorge Laliotis More articles by this author , Elshaddai WhiteElshaddai White More articles by this author , Jordan RichJordan Rich More articles by this author , Punashi DuttaPunashi Dutta More articles by this author , Shruti SharmaShruti Sharma More articles by this author , Mark CalhounMark Calhoun More articles by this author , Adam ElnaggarAdam Elnaggar More articles by this author , Minetta LiuMinetta Liu More articles by this author , Kyrollis AttallaKyrollis Attalla More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , Peter WiklundPeter Wiklund More articles by this author , and John SfakianosJohn Sfakianos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Though radical cystectomy (RC) is the gold standard treatment for patients with muscle invasive bladder cancer (MIBC), ∼50% of patients recur. Here, we aimed to elucidate the ability of circulating tumor DNA (ctDNA) as a prognostic biomarker to predict disease recurrence in patients who underwent RC. METHODS: ctDNA analysis was retrospectively performed in a cohort of 49 MIBC patients with a median age of 70 years (range: 46-88 years) and 81.63% (40/49) male. In this cohort, patients were subjected to RC alone (RC group, N=38) or neoadjuvant chemotherapy (NAC) followed by RC (NAC+RC group, N=11). A total of 62 blood samples were collected from 11/18/21 to 09/21/22 for a median follow-up of 8.01 months (range: 2.23 - 63.76 months). ctDNA was analyzed prior to (N=26) and after RC (N=36) using a personalized, tumor-informed ctDNA assay (SignateraTM, mPCR - NGS assay); its association with clinical outcomes was assessed. RESULTS: In this cohort, presurgical (baseline) mean MTM levels were significantly associated with advanced stage (III/IV) compared to early stage (I/II) disease, p=0.033 (Figure 1A). Among 26 and 36 patients with baseline and post-RC blood samples available, ctDNA detection rate was 34.6% (9/26) and 22.2% (8/36), respectively. ctDNA-positive patients were only observed in the RC group at both baseline (N=9) and post-RC (N=8). Clinical recurrence was observed in 22.2% (2/9) and 25% (2/8) of patients at the baseline and post-RC time points, respectively. Conversely, no recurrences were seen among the RC group who were ctDNA negative at both time points (NPV: 100%). Our data suggest that patients with ctDNA-positivity had a higher probability of recurrence (chi-square, p<0.001) (Figure 1B). On analyzing the association of ctDNA status post-RC with the survival benefit, ctDNA-positivity was associated with poorer recurrence free survival (RFS) (HR=13.13; 95%CI: 0.73 - 234, p=0.08) (Figure 1C). CONCLUSIONS: We report early results of presurgical (baseline) and post-RC ctDNA testing in patients with MIBC. ctDNA-negativity at both time points correlated with absence of disease recurrence. Further clinical evaluation with a longer follow-up is warranted to fully validate the role of baseline ctDNA in upfront clinical disease management. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e981 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shivaram Cumarasamy More articles by this author George Laliotis More articles by this author Elshaddai White More articles by this author Jordan Rich More articles by this author Punashi Dutta More articles by this author Shruti Sharma More articles by this author Mark Calhoun More articles by this author Adam Elnaggar More articles by this author Minetta Liu More articles by this author Kyrollis Attalla More articles by this author Reza Mehrazin More articles by this author Peter Wiklund More articles by this author John Sfakianos More articles by this author Expand All Advertisement PDF downloadLoading ...

Adjuvant therapies in stages I-III epidermal growth factor receptor-mutated lung cancer: current and future perspectives.

Surgical resection followed by adjuvant cisplatin-based chemotherapy is the recommended treatment for patients with completely resected stage IB-IIIA non-small cell lung cancer (NSCLC). Even with the best management, recurrence is common and increases with disease stage (stage I: 26-45%; stage II: 42-62%; stage III: 70-77%). For patients with metastatic lung cancer and tumours that harbour epidermal growth factor receptor (EGFR) mutations, EGFR-tyrosine kinase inhibitors (TKIs) have improved survival. Their effectiveness in advanced stages of NSCLC raises the possibility that these agents may improve outcomes for patients with resectable EGFR-mutated lung cancer. In the ADAURA study, adjuvant osimertinib provided a significant improvement in disease-free survival (DFS) and reduced central nervous system (CNS) disease recurrence in patients with resected stage IB-IIIA EGFR-mutated NSCLC, with or without prior adjuvant chemotherapy. To reap the maximum benefits of EGFR-TKIs for patients with lung cancer, the early and rapid identification of EGFR mutations [and other oncogenic drivers, such as programmed cell death-ligand 1 (PD-L1), with matched targeted therapies] in diagnostic pathologic specimens has become essential. To ensure patients receive the most appropriate treatment, routine, comprehensive histological, immunohistochemical, and molecular analyses (with multiplex next generation sequencing) should be undertaken at the time of diagnosis. The potential for personalised treatments to cure more patients with early-stage lung cancer can only be realised if all therapies are considered when the care plan is formulated, by the multi-specialty experts managing patients. In this review, we discuss the progress and prospects for adjuvant treatments as part of a comprehensive plan of care for patients with resected stages I-III EGFR-mutated lung cancer, and explore how the field could go beyond DFS and overall survival to make cure a more frequent outcome of treatment in patients with resected EGFR-mutated lung cancer.

Incidence of Disease Recurrence in Patients With Colon and Upper Rectum Adenocarcinoma Stage II and III Receiving Adjuvant Capecitabine Monotherapy: Do Number of Chemotherapy Cycles and Relative Dose Intensity of the Drug Play a Role?

Introduction/BackgroundAdjuvant capecitabine monotherapy is an option for colon and upper rectum adenocarcinoma patients, providing they have stage II disease with an intermediate risk of recurrence, or stage III but they are above 70’s or they have comorbidities. We wanted to examine whether the number of chemotherapy cycles and the relative dose intensity (RDI) of capecitabine monotherapy in the adjuvant setting are affecting disease recurrence. Patients and MethodsWe included patients with completely resected stage II and III colon and upper rectum cancer who received adjuvant capecitabine monotherapy, from 2003 until May 2020. Patients with early relapse, i.e. during chemotherapy or within 6 months after the completion of adjuvant chemotherapy, and those with rectal cancer who received radiotherapy were excluded. Patients were divided into 3 groups based on the number of chemotherapy cycles received and the RDI. Group A included patients with ≤4 cycles of chemotherapy, group B patients with >4 cycles of chemotherapy and RDI ≤80%, and group C patients with >4 cycles of chemotherapy and RDI >80%. Study’s endpoint, was recurrence free survival (RFS). ResultsTwo hundred twenty six patients with stage II and III disease (164 and 62 respectively) were included. Sixteen, 166 and 44 were included in groups A, B and C respectively. After a median follow-up of 41 months, 21 patients (9,3%) had relapsed. Patients belonging to group C were found to have a trend for lower relapse rate compared to patients belonging to group A or group B. ConclusionNumber of adjuvant capecitabine cycles and RDI might play a role in RFS in patients with stage II and III colon and upper rectum adenocarcinoma.

A DNA methylation signature for the prediction of tumour recurrence in stage II colorectal cancer.

A major challenge in stage II colorectal carcinoma is to identify patients with increased risk of recurrence. Biomarkers that distinguish patients with poor prognosis from patients without recurrence are currently lacking. This study aims to develop a robust DNA methylation classifier that allows the prediction of recurrence and chemotherapy benefit in patients with stage II colorectal cancer. We performed a genome-wide DNA methylation capture sequencing in 243 stage II colorectal carcinoma samples and identified a relapse-specific DNA methylation signature consisting of eight CpG sites. Two hundred and forty-three patients with stage II CRC were enrolled in this study. In order to select differential methylation sites among recurrence and non-recurrence stage II CRC samples, DNA methylation profiles of 62 tumour samples including 31 recurrence and 31 nonrecurrence samples were analysed using the Agilent SureSelectXT Human Methyl-Seq, a comprehensive target enrichment system to analyse CpG methylation. Pyrosequencing was applied to quantify the methylation level of candidate DNA methylation sites in 243 patients. Least absolute shrinkage and selection operator (LASSO) method was employed to build the disease recurrence prediction classifier. We identified a relapse-related DNA methylation signature consisting of eight CpG sites in stage II CRC by DNA methylation capture sequencing. The classifier showed significantly higher prognostic accuracy than any clinicopathological risk factors. The Kaplan-Meier survival curve showed an association of high-risk score with poor prognosis. In multivariate analysis, the signature was the most significant prognosis factor, with an HR of 2.80 (95% CI, 1.71-4.58, P < 0.001). The signature could identify patients who are suitable candidates for adjuvant chemotherapy. An eight-CpG DNA methylation signature is a reliable prognostic and predictive tool for disease recurrence in patients with stage II CRC.

Preoperative controlling nutritional status score predicts systemic disease recurrence in patients with resectable biliary tract cancer.

This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC). A total of 224 BTC patients (gallbladder, n=69; intrahepatic bile ducts, n=26; perihilar bile ducts, n=72; distal bile duct, n=57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ2 scores. The sites of recurrence were subclassified as locoregional or distant. Patients were subdivided into the CONUT-low (score ≤ 3, n=156) and the CONUT-high (score > 3; n=68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p=0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p=0.001), worse disease-specific survival (HR 1.840, p=0.006), and worse recurrence-free survival (HR 1.680, p=0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p=0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p=0.001). The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC.

Salvage surgery in lung cancer following definitive therapies.

Salvage surgery refers to operative resection of persistent or recurrent disease in patients initially treated with intention-to-cure nonoperative management. In non-small-cell lung cancer, salvage surgery may be effective in treating selected patients with locally progressive tumors, recurrent local or locoregional disease, or local complications after nonoperative therapy. Importantly, those patients who may be candidates for salvage surgery are evolving, in terms of disease stage as well as the types of attempted definitive therapy received.