High Risk Of Disease Recurrence Research Articles

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p<0.01). Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Recurrence of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Systematic Review of the Literature.

Background: This study aimed to systematically review the existing literature on uterine smooth muscle tumor of uncertain malignant potential (STUMP) to provide information about characteristics and outcomes of patients and the risk factors for recurrence over a period of 60 years (1960-2021). Methods: According to PRISMA guidelines, we searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed (all fields) and Scopus (Title/Abstract/Keywords) databases (accessed on 1 January 2022). Relevant articles were obtained in full-text format and screened for additional references. The only filter used was the English language. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: Thirty-four studies, including 189 cases, were included. The median age was 43 years, and in 21.5% of cases there was a recurrence of the disease. Bivariate analysis showed a significant association between use of morcellation without bag and risk of recurrence (p = 0.001). Unprotected morcellation during demolitive or conservative surgery was independently associated with a higher risk of disease recurrence with a relative risk of 2.94 (p &lt; 0.001). A significant progressive decrease in the recurrence rate was observed over time (r = -0.671, p = 0.008). The percentage of patients who underwent surgery followed by in-bag protected morcellation significantly increased after the publication of the U.S. Food and Drug Administration alert about the risk linked to this procedure (p = 0.01). Conclusions: Unprotected morcellation of the lesion is associated with the relapse of the disease. However, this clinical condition showed a drastic decrease over time. This could likely be due to the increased awareness by surgeons of the importance of customizing surgical treatment.

FC 115: Long-Term Outcomes in Eculizumab-Treated Kidney Transplant Patients Enrolled in the Global Atypical Haemolytic Uraemic Syndrome Registry

Abstract BACKGROUND AND AIMS The global atypical haemolytic uraemic syndrome (aHUS) registry (NCT01522183), the largest repository of real-world data on patients with aHUS, provides key insights into disease course, natural history, and patient (pt) outcomes with and without complement inhibitor therapy. Prior to eculizumab availability, pts with aHUS had a reportedly high risk of disease recurrence and graft loss following a kidney transplant (KTx). We report the long-term clinical outcomes of eculizumab-treated pts who received a KTx. METHOD This analysis included pts enrolled from April 2012–November 2021. Pts were included in a long-term treatment outcomes study if they had ever been treated with eculizumab and were excluded if they had DGKE mutations or their diagnosis was later revised to any condition other than aHUS. The current analysis set included pts who had received a KTx no more than 30 days prior to eculizumab start or up to 60 days post eculizumab start date, had ≥3 years of follow-up (FU) post-transplant and had serum creatinine (SCr) measurements at baseline (BL) and post 3 years FU. Changes in kidney function, haematological parameters and clinical characteristics at last follow-up (LFU) were assessed. RESULTS A total of 329/1970 adult and paediatric registry pts met the inclusion criteria and received a KTx; 78 pts from 12 countries met sub-group inclusion criteria. BL demographics are shown in Table 1. Mean (SD) treatment duration was 5.7 (2.4) years and 47 (60%) pts had pathogenic genetic variants. Lab parameters at BL (closest measurement at or following KTx) and LFU are reported in Table 2. Despite large ranges, median SCr levels remained stable at LFU. Median eGFR and platelet levels were similar at BL and LFU, while lower median lactose dehydrogenase levels were seen at LFU. At LFU: four pts (5%)—three adult—had subsequent KTx(s); eight (10%)—seven adults—had received dialysis by last observation; and two (3%) had received plasma exchange/infusion. Two pts (3%) died during the observation period. CONCLUSION This study assessed a large, real-world population of pts at high risk of KTx failure. Lab parameters suggest most pts benefitted from eculizumab treatment, with few TMA-related complications and stable kidney function and haematological parameters for ≥3 years. Overall, the proportions of female pts and of pts with pathogenic genetic variants were consistent with previous studies. A potential study limitation was the relatively stringent sub-population-specific inclusion criteria. However, these data further demonstrate the beneficial impact of eculizumab treatment in the long-term management of aHUS in pts requiring KTx.

MP59-02 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR THE PREDICTION OF INTRAVESICAL BCG TREATMENT RESPONSE: A PILOT STUDY

You have accessJournal of UrologyCME1 May 2022MP59-02 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR THE PREDICTION OF INTRAVESICAL BCG TREATMENT RESPONSE: A PILOT STUDY Kaoru Murakami, Ashish M. Kamat, Yunfeng Dai, Ian Pagano, Runpu Chen, Yijun Sun, Amit Gupta, Nari Kim, Steve Goodison, Charles J. Rosser, and Hideki Furuya Kaoru MurakamiKaoru Murakami More articles by this author , Ashish M. KamatAshish M. Kamat More articles by this author , Yunfeng DaiYunfeng Dai More articles by this author , Ian PaganoIan Pagano More articles by this author , Runpu ChenRunpu Chen More articles by this author , Yijun SunYijun Sun More articles by this author , Amit GuptaAmit Gupta More articles by this author , Nari KimNari Kim More articles by this author , Steve GoodisonSteve Goodison More articles by this author , Charles J. RosserCharles J. Rosser More articles by this author , and Hideki FuruyaHideki Furuya More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002642.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical Bacillus Calmette-Guerin (BCG), a live attenuated tuberculosis vaccine that acts as a non-specific immune system stimulant, is the most effective adjuvant treatment for patients with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC). However, to date, there are no reliable tests that are predictive of BCG treatment response. In this study, we evaluated the performance of OncuriaTM, a bladder cancer detection test, to predict response to intravesical BCG. METHODS: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 64 subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. The ability of the test to identify those patients in whom BCG is ineffective against tumor recurrence was tested. Predictive models were derived using supervised learning and cross-validation analyses. Model performance was assessed using ROC curves. RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved an AUROC 0.89 [95% CI: 0.80–0.99], outperforming any single biomarker, with a test sensitivity of 81.8% and a specificity of 84.9%. Hazard ratio analysis revealed that patients with higher urinary levels of ANG, CA9 and MMP10 had a significantly higher risk of disease recurrence. CONCLUSIONS: Monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients considering intravesical BCG treatment. We are currently performing a validation study with a larger retrospective cohort of ∼120 subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The results will be presented in the AUA 2022. Source of Funding: NIH/NCI R01CA198887 (CJR) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1001 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kaoru Murakami More articles by this author Ashish M. Kamat More articles by this author Yunfeng Dai More articles by this author Ian Pagano More articles by this author Runpu Chen More articles by this author Yijun Sun More articles by this author Amit Gupta More articles by this author Nari Kim More articles by this author Steve Goodison More articles by this author Charles J. Rosser More articles by this author Hideki Furuya More articles by this author Expand All Advertisement PDF DownloadLoading ...

Exploring the Feasibility of Utilizing Limited Gene Panel Circulating Tumor DNA Clearance as a Biomarker in Patients With Locally Advanced Non-Small Cell Lung Cancer.

IntroductionCirculating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC.MethodsPlasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst®-Lung to detect mutations in 36 cancer-related genes. ctDNA clearance was defined as absence of pre-CRT variants at post-CRT1. Patients without detectable pre-CRT variants or no post-CRT1 samples were excluded.ResultsTwenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01).ConclusionsAlthough it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer.

N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease

BackgroundNormal human tissues do not express glycans terminating with the sialic acid N-glycolylneuraminic acid (Neu5Gc), yet Neu5Gc-containing glycans have been consistently found in human tumor tissues, cells and secretions and have been proposed as a cancer biomarker. We engineered a Neu5Gc-specific lectin called SubB2M, and previously reported elevated Neu5Gc biomarkers in serum from ovarian cancer patients using a Surface Plasmon Resonance (SPR)-based assay. Here we report an optimized SubB2M SPR-based assay and use this new assay to analyse sera from breast cancer patients for Neu5Gc levels.MethodsTo enhance specificity of our SPR-based assay, we included a non-sialic acid binding version of SubB, SubBA12, to control for any non-specific binding to SubB2M, which improved discrimination of cancer-free controls from early-stage ovarian cancer. We analysed 96 serum samples from breast cancer patients at all stages of disease compared to 22 cancer-free controls using our optimized SubB2M-A12-SPR assay. We also analysed a collection of serum samples collected at 6 monthly intervals from breast cancer patients at high risk for disease recurrence or spread.ResultsAnalysis of sera from breast cancer cases revealed significantly elevated levels of Neu5Gc biomarkers at all stages of breast cancer. We show that Neu5Gc serum biomarker levels can discriminate breast cancer patients from cancer-free individuals with 98.96% sensitivity and 100% specificity. Analysis of serum collected prospectively, post-diagnosis, from breast cancer patients at high risk for disease recurrence showed a trend for a decrease in Neu5Gc levels immediately following treatment for those in remission.ConclusionsNeu5Gc serum biomarkers are a promising new tool for early detection and disease monitoring for breast cancer that may complement current imaging- and biopsy-based approaches.

Outcomes for endoscopic submucosal dissection of pathologically staged T1b esophageal cancer: a multicenter study

The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC. We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n= 6) and Brazil (n= 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates. Sixty-six patients with pathologically staged T1b EC after ESD were included in the study. A preprocedure staging EUS was available in 54 patients and was Tis/T1a in 27 patients (50%) and T1b in 27 patients (50%). En-bloc resection rate was 92.4% (61/66) and R0 resection rate was 54.5% (36/66). Forty-nine of 66 patients (74.2%) did not undergo surgery immediately after resection and went on to surveillance. Ten patients had ESD resection within the curative criteria, and no recurrences were seen in a 13-month (range, 3-18.5) follow-up period in these patients. Ten of 39 patients (25.6%) with noncurative resections had residual/recurrent disease. Of the 10 patients with noncurative resection, local recurrence alone was seen in 5 patients (12.8%) and metastatic recurrence in 5 patients (12.8%). On univariate analysis, R1 resection had a higher risk of recurrent disease (hazard ratio, 6.25; 95% confidence interval, 1.29-30.36; P= .023). EUS staging of T1b EC has poor accuracy, and a staging ESD should be considered in these patients. ESD R0 resection rates were low in T1b EC, and R1 resection was associated with recurrent disease. Patients with noncurative ESD resection of T1b EC who cannot undergo surgery should be surveyed closely, because recurrent disease was seen in 25% of these patients.

Effectiveness of Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy in the Treatment of Primary Spontaneous Pneumothorax-A Retrospective Long-Term Single-Center Analysis.

Background: Video-assisted thoracoscopic surgery (VATS) with bullectomy and partial pleurectomy (VBPP) is an increasingly used and well-established surgical treatment for primary spontaneous pneumothorax (PSP). However, reports on its effectiveness and long-term outcomes are limited. The aim of this study was to assess and compare long-term recurrence rates following VBPP and chest tube (CT) treatment and to identify potential risk factors for disease recurrence in patients with PSP. Methods: A total of 116 patients treated either by VBPP or CT were included in this study. Long-term recurrence rates and associations between clinical parameters and recurrence of pneumothorax were analyzed. Results: Sixty-two patients (53.4%) underwent VBPP, whereas 54 (46.6%) patients underwent CT treatment only. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly lower recurrence rate compared to CT patients (6/62 vs. 35/54; p < 0.0001). CT treatment (VBPP vs. CT; p < 0.001) and a large initial pneumothorax size (Collins < 4 vs. Collins ≥ 4; p = 0.018) were independent risk factors for pneumothorax recurrence. Conclusion: VBPP is an effective and safe surgical treatment for PSP. Therefore, patients with a large pneumothorax size might benefit from VBPP, as they are at high risk for disease recurrence.

Machine learning methods to predict presence of residual cancer following hysterectomy

Surgical management for gynecologic malignancies often involves hysterectomy, often constituting the most common gynecologic surgery worldwide. Despite maximal surgical and medical care, gynecologic malignancies have a high rate of recurrence following surgery. Current machine learning models use advanced pathology data that is often inaccessible within low-resource settings and are specific to singular cancer types. There is currently a need for machine learning models to predict non-clinically evident residual disease using only clinically available health data. Here we developed and tested multiple machine learning models to assess the risk of residual disease post-hysterectomy based on clinical and operative parameters. Data from 3656 hysterectomy patients from the NSQIP dataset over 14 years were used to develop models with a training set of 2925 patients and a validation set of 731 patients. Our models revealed the top postoperative predictors of residual disease were the initial presence of gross abdominal disease on the diaphragm, disease located on the bowel mesentery, located on the bowel serosa, and disease located within the adjacent pelvis prior to resection. There were no statistically significant differences in performances of the top three models. Extreme gradient Boosting, Random Forest, and Logistic Regression models had comparable AUC ROC (0.90) and accuracy metrics (87–88%). Using these models, physicians can identify gynecologic cancer patients post-hysterectomy that may benefit from additional treatment. For patients at high risk for disease recurrence despite adequate surgical intervention, machine learning models may lay the basis for potential prospective trials with prophylactic/adjuvant therapy for non-clinically evident residual disease, particularly in under-resourced settings.

Abstract P3-12-20: Outcomes of patients with pathologic complete response following neoadjuvant HER2-targeted therapy in patients with HER2+ early stage breast cancer

Abstract BACKGROUND: Contemporary clinical trials of HER2-targeted therapies have shown benefits regarding recurrence and survival in patients (pts) with HER2+ early stage breast cancer. The outcomes of pts treated in community practice settings who had a pathologic complete response (pCR) to neoadjuvant therapy or who had residual disease at definitive surgery (non-pCR) have not been well characterized. This preliminary study aimed to describe the patient characteristics, disease-free survival (DFS) and overall survival (OS) in patients with and without pCR following neaoadjuvant HER2-targeted therapy in The US Oncology Network. METHODS: This retrospective cohort study identified pts diagnosed with stage I-III HER2+ breast cancer who initiated neoadjuvant HER2-targeted therapy in the community setting between April 1, 2014 - March 31, 2019. Pts were followed through the date of last visit, death, or study end (March 31, 2021), whichever occurred first. Data were collected from the US Oncology Network’s electronic medical record database, iKnowMed. Natural language processing/artificial intelligence was used to identify pts with pCR status and pts with disease recurrence during the study period. Patient profiles, risk of recurrence (RR), and time to recurrence (TTR) were assessed descriptively. Kaplan-Meier methods were used to evaluate DFS and OS from the start of neoadjuvant therapy. Results were stratified by pCR status. RESULTS: The study included 641 pts (median age, 55 years), 71% had non-pCR and 29% had pCR. The majority of pts were Caucasian (79%) or black (8%). At diagnosis, 78% of pts had stage I/II disease, and 21% stage III. Nearly 74% were HR+. With a median follow-up of 33 months, pts who had non-pCR had a higher risk of disease recurrence (10.3% vs 8.1%) and a shorter median TTR (18.6 vs 21.1 months) compared to pts with pCR. Three-year DFS (87.5% vs 92.2%) and OS (96.0% vs 98.8%) were lower in pts with non-pCR than with pCR. CONCLUSIONS:Findings from this real-world study of HER2+ early stage breast cancer pts who received neoadjuvant HER2-targeted therapy in the community setting suggested that pts with non-pCR had shorter DFS and OS outcomes than pts with pCR. Pts with non-pCR had a risk of recurrence of nearly 10% over approximately a 3-year time period . This residual risk of recurrence among non-pCR pts suggested a potential opportunity to improve long-term outcomes in this group. Future analyses, including HR subgroups, are planned as data mature and longer follow-up time is available. Results on additional pts with known pCR/non-pCR data, with longer follow-up, and outcomes by HR+ vs HR- status will be presented. Disclosure DeclarationThis study was funded by Puma Biotechnology, Inc. Outcomes of pts with pCR or non-pCR following neoadjuvant HER2-targeted therapyNon-pCRpCROverall CohortN=429N=185N=641Follow-up time, months, median (range)30.8 (0.0,81.6)38.4 (2.8,83.3)33.0 (0.0,83.3)Patients with recurrence, n (%)44 (10.3%)15 (8.1%)59 (9.6%)Time to recurrence, median (range)18.6 (0.0,42.4)21.1 (0.0,60.3)18.8 (0.0,60.3)Disease-free survival at 36 months87.5% (83.4,90.7)%92.2% (86.8,95.4)%89.0% (85.9,91.5)%Overall survival at 36 months96.0% (92.8,97.8)%98.8% (95.2,99.7)%97.0% (94.9,98.3)% Citation Format: Joyce O'Shaughnessy, Nina Oestreicher, Nicole Fulcher, Wan-Yu Tseng, April Beeks, Julia Moore, Deepa Lalla. Outcomes of patients with pathologic complete response following neoadjuvant HER2-targeted therapy in patients with HER2+ early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-20.

Abstract P1-22-03: Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ

Abstract Background. Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). High variability in clinical outcomes and propensity for invasion among DCIS is reported, but identifying high-risk DCIS remains a major clinical challenge. Therefore, biomarkers to differentiate patients with indolent DCIS from those who would benefit from therapy are warranted. There are recent data on the role of the tumor immune microenvironment in the progression from DCIS to IBC and the risk of recurrences. However, no comprehensive information on the clinical actionability of DCIS immune-biology is available. We hypothesize that immune escape mechanisms might play a critical role in the transition from DCIS to IBC. Here, we sought to establish whether immune-related gene expression signatures of DCIS might identify women at high risk of disease recurrence and/or progression. Methods. We performed a retrospective nested case-control study including women with pure DCIS, diagnosed between 2009 and 2015 at European Institute Oncology (median follow-up 39,5 months) treated with conserving surgery +/- adjuvant therapy (endocrine therapy or radiotherapy). The study group (cases) was composed of women with DCIS and subsequent ipsilateral breast events (IBE, in situ or invasive). Controls were selected in a 1.1 ratio among DCIS without IBE, matched for age, tumor size, treatment, and hormone receptors (HR), and HER2 status. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. RNA extracted from formalin-fixed paraffin-embedded blocks was subjected to gene expression analysis using a next-generation sequencing assay (Oncomine™ Immune Response Research Assay) targeting 395 immune-related genes. Samples that achieve run quality parameters (mapped reads &amp;gt;1 million, valid reads &amp;gt;800.000) were further processed with the Affymetrix Transcriptome Analysis Console software to compare the gene expression between cases and controls (ANOVA, gene-level fold change &amp;lt;-2 or &amp;gt;2).Results. A total of 116 patients were included, 58 cases and 58 controls. High sTILs count was significantly associated with high-grade DCIS (p=&amp;lt;0,0001), the presence of necrosis (p=0,0210) and HER2 expression (p=&amp;lt;0,0001) in both groups. No significant association between sTILs count and the probability of relapse was observed. Gene expression data were available for 56 cases and 56 controls that achieved sequencing quality parameters. Overall, five genes were differentially expressed between cases and controls. In particular, cases showed upregulation of IFNA17 (p-value &amp;lt;0,0001; FDR p-value &amp;lt;0.0001), IFNB1 (p-value &amp;lt;0,0001; FDR p-value &amp;lt;0.0001), PECAM-1 (p-value &amp;lt;0,0001; FDR p-value &amp;lt;0.0001) and significant lower expression of CCL2 (p-value &amp;lt;0,0001; FDR p-value &amp;lt;0.0001) as compared to control group. Other genes that were upregulated in DCIS with IBE included FCGR2B, CD3D, CD40LG, while TCF7, CDKN3, ADORA2A were found to be downregulated (p-value &amp;lt;0.05).Conclusion. Quantitative TILs density assessment remains of modest significance in DCIS prognostication in terms of risk of IBE. We showed that pure DCIS displayed significant differences in the expression of immune-related genes between women with and without subsequent breast cancer recurrence regardless of HR and HER2 status. The activation of immune-related pathways might play a part in the development of IBE in patients with a diagnosis of DCIS. The evaluation of immune-related gene expression profiles might improve risk stratification in patients with DCIS. Citation Format: Elena Guerini Rocco, Caterina Fumagalli, Alberto Concardi, Sergio V. Taormina, Aliana Guerrieri-Gonzaga, Federica Corso, Sara Gandini, Bernardo Bonanni, Giuseppe Viale, Massimo Barberis, Nicola Fusco, Lazzeroni Matteo. Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-03.

Application of a multiplex urinalysis test for the prediction of intravesical BCG treatment response: A pilot study.

BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG), a live attenuated tuberculosis vaccine that acts as a non-specific immune system stimulant, is the most effective adjuvant treatment for patients with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC). However, to date, there are no reliable tests that are predictive of BCG treatment response. In this study, we evaluated the performance of Oncuria, a bladder cancer detection test, to predict response to intravesical BCG.METHODS: Oncuria data was evaluated in voided urine samples obtained from a prospectively collected cohort of 64 subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The Oncuria test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. The ability of the test to identify those patients in whom BCG is ineffective against tumor recurrence was tested. Predictive models were derived using supervised learning and cross-validation analyses. Model performance was assessed using ROC curves.RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved an AUROC 0.89 [95% CI: 0.80–0.99], outperforming any single biomarker, with a test sensitivity of 81.8% and a specificity of 84.9%. Hazard ratio analysis revealed that patients with higher urinary levels of ANG, CA9 and MMP10 had a significantly higher risk of disease recurrence.CONCLUSIONS: Monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. With further study, the multiplex Oncuria test may be applicable for the clinical evaluation of bladder cancer patients considering intravesical BCG treatment.

Indications and Parameters Around Postoperative Radiation Therapy for Lung Cancer

Patients with locally advanced resected non–small-cell lung cancer present a high risk of relapse. Although adjuvant platinum–based chemotherapy has become the standard of care, the role of postoperative radiation therapy (PORT) has been controversial for years. In patients with incomplete resection, PORT should be proposed, on the basis of a strong consensus, despite the absence of randomized evidence. In patients with completely resected (R0) non–small-cell lung cancer, a meta-analysis showed poorer outcomes after PORT in the absence of mediastinal involvement (pN0 and pN1). In patients with pN2, the role of PORT was less clear and required further research. The meta-analysis included trials using older radiation techniques and poorer quality of surgery according to today's standards, and selection of patients was not positron emission tomography–based. Newer retrospective and nonrandomized studies and subgroup analyses of randomized trials evaluating adjuvant chemotherapy suggested a survival benefit of PORT in patients with pN2 R0. Two recent randomized trials (Lung ART and PORT-C) evaluating conformal PORT versus no PORT retrieved no disease-free survival advantage for stage IIIA-N2 patients, even if mediastinal relapse was significantly decreased with PORT. PORT had no effect on survival, possibly given the high rate of distant relapse and risk of additional cardiopulmonary toxicity. Ongoing and future analyses are planned in Lung ART to identify patients for whom PORT could be recommended. Incorporation of newer systemic treatments (immune checkpoint inhibitors or targeted therapy in oncogene-addicted patients) is underway in the neoadjuvant and/or adjuvant setting. Better identification of patients at a high risk of disease recurrence, with analysis of circulating tumor DNA, on the basis of the detection of postsurgical minimal (or molecular) residual disease is warranted in future studies.

Prognostic Factors for Localized Clear Cell Renal Cell Carcinoma and Their Application in Adjuvant Therapy.

Simple SummaryApproximately one fifth of patients with newly diagnosed renal cell carcinoma (RCC) present with metastatic disease and over one third of the remaining patients with localized RCC will eventually have metastases spread to distant sites after complete resection of the primary tumor in the kidney. Usually, disease recurrence is observed within the first five years of follow-up, but late recurrences after five years are seen in up to 10% of patients. Despite novel biomarkers, simple histopathological factors, such as tumor size, tumor grade, and tumor extension into the blood vessels or beyond the kidney, are still valid features in predicting the risk of disease recurrence after surgery. The optimal set of prognostic factors remains unclear. The results from ongoing placebo-controlled adjuvant therapy trials may elucidate prognostic features that help to define high-risk patients for disease recurrence.Approximately 20% of patients with renal cell carcinoma (RCC) present with primarily metastatic disease and over 30% of patients with localized RCC will develop distant metastases later, after complete resection of the primary tumor. Accurate postoperative prognostic models are essential for designing personalized surveillance programs, as well as for designing adjuvant therapy and trials. Several clinical and histopathological prognostic factors have been identified and adopted into prognostic algorithms to assess the individual risk for disease recurrence after radical or partial nephrectomy. However, the prediction accuracy of current prognostic models has been studied in retrospective patient cohorts and the optimal set of prognostic features remains unclear. In addition to traditional histopathological prognostic factors, novel biomarkers, such as gene expression profiles and circulating tumor DNA, are extensively studied to supplement existing prognostic algorithms to improve their prediction accuracy. Here, we aim to give an overview of existing prognostic features and prediction models for localized postoperative clear cell RCC and discuss their role in the adjuvant therapy trials. The results of ongoing placebo-controlled adjuvant therapy trials may elucidate prognostic factors and biomarkers that help to define patients at high risk for disease recurrence.

Ovarian cancer recurrence: is the definition of platinum sensitivity modified by PARPi, bevacizumab or other intervening treatments? : a clinical perspective.

In view of the high risk of recurrent disease in stage III and IV ovarian cancer following primary first-line chemotherapy, a variety of maintenance and consolidation treatment strategies have been developed. These have included: radiation, intravenous or intraperitoneal chemotherapy, targeted therapies, and immunotherapy. Popular at this time is the use of Poly-adenosine ribose polymerase (PARP) inhibitors and bevacizumab as maintenance therapy. What effect these maintenance or consolidation therapies have on subsequent response to therapy, specifically platinum-based chemotherapy, is only beginning to be studied. In this manuscript, we review the impact of PARP inhibitors and bevacizumab as well as radiation and maintenance chemotherapy on subsequent response to treatment. Prior use of bevacizumab does not appear to adversely affect subsequent response to platinum-based chemotherapy or platinum-based chemotherapy with bevacizumab. Prior therapy with PARP inhibitors induces platinum resistance to subsequent platinum-based therapy and negates classic predictors of response such as platinum-free interval and breast cancer susceptibility gene (BRCA) mutational status.

Radiomics in predicting recurrence for patients with locally advanced breast cancer using quantitative ultrasound.

Background: The purpose of the study was to investigate the role of pre-treatment quantitative ultrasound (QUS)-radiomics in predicting recurrence for patients with locally advanced breast cancer (LABC).Materials and Methods: A prospective study was conducted in patients with LABC (n = 83). Primary tumours were scanned using a clinical ultrasound device before starting treatment. Ninety-five imaging features were extracted-spectral features, texture, and texture-derivatives. Patients were determined to have recurrence or no recurrence based on clinical outcomes. Machine learning classifiers with k-nearest neighbour (KNN) and support vector machine (SVM) were evaluated for model development using a maximum of 3 features and leave-one-out cross-validation.Results: With a median follow up of 69 months (range 7–118 months), 28 patients had disease recurrence (local or distant). The best classification results were obtained using an SVM classifier with a sensitivity, specificity, accuracy and area under curve of 71%, 87%, 82%, and 0.76, respectively. Using the SVM model for the predicted non-recurrence and recurrence groups, the estimated 5-year recurrence-free survival was 83% and 54% (p = 0.003), and the predicted 5-year overall survival was 85% and 74% (p = 0.083), respectively.Conclusions: A QUS-radiomics model using higher-order texture derivatives can identify patients with LABC at higher risk of disease recurrence before starting treatment.

Distress, Health-Related Quality of Life (HQOL) and Confidence in Survivorship Information (CSI) in Older (≥60 Years) Hematopoietic Cell Transplant (HCT) Patients

Background: The use of HCT to treat older (≥60 years) patients with hematological malignancies has markedly increased in recent years, however, the long-term effects of HCT on distress, psychosocial functioning, and HQOL in older HCT survivors is largely unknown. Though older HCT survivors have a higher risk of disease recurrence, they may have less access to resources and subsequently experience more pronounced late effects of disease and treatment. Confidence in Survivorship Information (CSI) in this specific age group has not been reported.Methods: We conducted a secondary analysis on a subgroup of patients enrolled in INSPIRE (NCT01602211) and PCORI-SCP (NCT02200133) clinical trials. Eligibility criteria for inclusion include HCT patients who were ≥ 60 years at time of transplant performed in 2003-2014, survived ≥ 1 year post-transplant with no evidence of disease relapse or secondary cancers. Patients were eligible for inclusion irrespective of transplant type (autologous or allogeneic), diagnosis, donor source or conditioning regimen. Primary endpoint was distress level in older HCT survivors; secondary endpoints included CSI and HQOL outcomes. We collected baseline distress level as measured by Cancer and Treatment Distress (CTXD) score, HQOL (measured by SF-12 Mental and Physical Component Summaries (PCS/MCS) and CSI (measured by a 15-item CSI questionnaire). Sociodemographic, disease and transplant factors were extracted from medical databases. Nonparametric (Wilcoxon rank sum/Kruskal-Wallis) test was conducted for comparing 2 or 3 groups. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group.Results: A total of 567 patients satisfied the eligibility criteria and were included in this analysis. Median age at time of HCT was 69 years with 57% male; two-thirds were autologous HCT recipients. Table 1 details patient characteristics. The median CTXD score for older HCT survivors was 0.7 (range 0-2.7, SD 0.6) indicating low/insignificant level of distress post-HCT. 20-30% of HCT survivors reported moderate distress when asked about concerns regarding relapse risk, loss of energy and functional decline. Type of transplant (auto vs allo), age group (<65 years, 65-70 years, ≥70 years), and time from HCT (≤2 years vs > 2 years) showed no apparent effect on reported distress level. CSI median score was 1.4 (range 0-2) which remains consistent with the score reported previously by the original trial including all age groups, indicating that older HCT survivors may have similar level of confidence in their survivorship information as their younger counterparts. Of note, close to 20% of the older HCT survivors reported poor CSI when asked about strategies for prevention and treatment of long-term effects of HCT and when asked about their confidence in availability of community resources to deal with long-term HCT complications. No statistically significant correlation was identified between CSI in older survivors and transplant type, time from HCT, or age group. HQOL outcomes indicated a median PCS of 48.2 (range 21.1 - 62.9) and a median MCS of 54.7 (range of 14.9 - 67.2). Interestingly, even though not reflected on the overall median CTXD and CSI scores for this cohort, a significant individual association between CTXD/CSI and PCS/MCS measures of HQOL was found (Figure 1). A subgroup analysis conducted on older alloHCT recipients confirmed the same findings of clinically insignificant distress level (mean CTXD ≤1.1) while having a similar level of CSI when compared to all age groups. Interestingly, time from HCT (≤2 years vs > 2 years) showed no significant effect on distress level reported by older alloHCT survivors, and cGVHD status did not correlate with CTXD or CSI scores nor with PCS/MCS in older alloHCT survivors.Conclusion: This is the largest study to date to investigate patient-reported distress, CSI and HQOL in older HCT survivors. Our data indicate that older HCT survivors have low levels of stress after HCT and had confidence in survivorship information in most aspects of their care. However, targeted interventions should focus on improving strategies for prevention, treatment and availability of community resources to deal with late effects of HCT; aspects reported as points of low CSI by older HCT survivors. [Display omitted] DisclosuresFarhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Be the Match: Current Employment; Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.

Perioperative circulating tumor DNA as a potential prognostic marker for operable stage I to IIIA non-small cell lung cancer.

Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited. This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years. After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months. These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC. The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention.

Impact of Computed Tomography-Based, Artificial Intelligence-Driven Volumetric Sarcopenia on Survival Outcomes in Early Cervical Cancer.

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028–3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016–8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, −3.9%; p < 0.001) and total fat (median, −5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009–3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257–6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence.

Lymph Node Parameters Predict Adjuvant Chemoradiotherapy Efficacy and Disease-Free Survival in Pathologic N2 Non-Small Cell Lung Cancer.

Pathologic N2 non-small cell lung cancer (NSCLC) is prominently intrinsically heterogeneous. We aimed to identify homogeneous prognostic subgroups and evaluate the role of different adjuvant treatments. We retrospectively collected patients with resected pathologic T1-3N2M0 NSCLC from the Shanghai Chest Hospital as the primary cohort and randomly allocated them (3:1) to the training set and the validation set 1. We had patients from the Fudan University Shanghai Cancer Center as an external validation cohort (validation set 2) with the same inclusion and exclusion criteria. Variables significantly related to disease-free survival (DFS) were used to build an adaptive Elastic-Net Cox regression model. Nomogram was used to visualize the model. The discriminative and calibration abilities of the model were assessed by time-dependent area under the receiver operating characteristic curves (AUCs) and calibration curves. The primary cohort consisted of 1,312 patients. Tumor size, histology, grade, skip N2, involved N2 stations, lymph node ratio (LNR), and adjuvant treatment pattern were identified as significant variables associated with DFS and integrated into the adaptive Elastic-Net Cox regression model. A nomogram was developed to predict DFS. The model showed good discrimination (the median AUC in the validation set 1: 0.66, range 0.62 to 0.71; validation set 2: 0.66, range 0.61 to 0.73). We developed and validated a nomogram that contains multiple variables describing lymph node status (skip N2, involved N2 stations, and LNR) to predict the DFS of patients with resected pathologic N2 NSCLC. Through this model, we could identify a subtype of NSCLC with a more malignant clinical biological behavior and found that this subtype remained at high risk of disease recurrence after adjuvant chemoradiotherapy.