Low-stage Disease Research Articles

Trends and appropriateness of perioperative chemotherapy for muscle-invasive bladder cancer

IntroductionContemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use. MethodsUsing Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment. ResultsWe identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05). ConclusionFrom 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Upper Endoscopy up to 3 Years Prior to a Diagnosis of Gastric Cancer Is Associated With Lower Stage of Disease in a USA Multiethnic Urban Population, a Retrospective Study

Objectives:In the USA, certain races and ethnicities have a disproportionately higher gastric cancer burden. Selective screening might allow for earlier detection and curative resection. Among a USA-based multiracial and ethnic cohort diagnosed with non-cardia gastric cancer (NCGC), we aimed to identify factors associated with curable stage disease at diagnosis.Methods:We retrospectively identified endoscopically diagnosed and histologically confirmed cases of NCGC at Mount Sinai Hospital in New York City. Demographic, clinical, endoscopic and histologic factors, as well as grade/stage of NCGC at diagnosis were documented. The primary outcome was the frequency of curable-stage NCGC (stage 0-1a) at diagnosis in patients with versus without an endoscopy negative for malignancy prior to their index exam diagnosing NCGC. Additional factors associated with curable-stage disease at diagnosis were determined.Results:A total of 103 racially and ethnically diverse patients were included. Nearly 38% of NCGC were stage 0-Ia, 34% stage Ib-III, and 20.3% stage IV at diagnosis. A significantly higher frequency of NCGC was diagnosed in curable stages among patients who had undergone an endoscopy that was negative for malignancy prior to their index endoscopy that diagnosed NCGC, compared to patients without a negative endoscopy prior to their index exam (69.6% vs. 28.6%, p=0.003). A prior negative endoscopy was associated with 94.0% higher likelihood of diagnosing curable-stage NCGC (p=0.003). No other factors analyzed were associated with curable-stage NCGC at diagnosis.Conclusions:Endoscopic screening and surveillance in select high-risk populations might increase diagnoses of curable-stage NCGC. These findings warrant confirmation in larger, prospective studies.

Rising Serum Uric Acid Level Is Negatively Associated with Survival in Renal Cell Carcinoma.

Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005–8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.

The association of rising serum uric acid levels with survival in renal cell carcinoma.

608 Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative and postoperative SUA levels between 8/2005-8/2014. Increased SUA was defined as &gt; 7mg/dL for males and &gt; 5.7 mg/dL for females. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. Results: 905 patients were analyzed. Decreased/stable SUA levels were noted in 675(74.6%) and increased SUA levels were noted in 230(25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs 18.3%, p = 0.004). Increased SUA had significantly greater de novo CKD (38.7% vs. 18.4%, p &lt; 0.001) and proteinuria (30.9% vs. 20.7%, p = 0.002). KMA demonstrated improved 5-year OS for patients with decreased/stable SUA compared to increased SUA for stage I, (93% vs. 60%), stage II (87% vs. 50%), and stage III (88% vs. 62%) RCC (all p &lt; 0.001). MVA revealed that increasing BMI (OR 1.05, p = 0.009), statin use (OR 0.11, p &lt; 0.001), dyslipidemia (OR 2.66, p = 0.004), stage III/IV cancer (OR 1.89, p = 0.015 and OR = 10.78, p &lt; 0.001), and postoperative de novo CKD stage 3 (OR 5.95, p &lt; 0.001) were predictors for increased postoperative SUA levels. MVA revealed increasing BMI (OR 1.09, p = 0.002), increasing SUA (OR = 4.70, p &lt; 0.001), stage IV RCC (OR = 7.7, p &lt; 0.001, and de novo CKD stage 3 (OR 7.07, p &lt; 0.001) to be independent risk factors for worsened all-cause mortality. Conclusions: Increasing SUA post operatively was associated with worsened outcomes in RCC patients. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.

Nuclear β‐catenin and CDX2 expression in ovarian endometrioid carcinoma identify patients with favourable outcome

Ovarian endometrioid carcinoma (EC) generally has a good prognosis. Adjuvant chemotherapy can be spared in low-stage disease, but prognostic biomarkers are needed to refine the treatment threshold. Wnt/β-catenin signalling is commonly altered in EC. We examined immunohistochemical expression of nuclear β-catenin and CDX2 as prognostic biomarkers for EC; both are mediators of the Wnt pathway. We evaluated two ovarian EC cohorts, discovery set (n=183) and validation set (n=174), with ovarian cancer-specific survival (OCSS) as the primary end-point. In univariable analysis, nuclear β-catenin expression was significantly associated with longer OCSS in the discovery set [hazard ratio (HR)=0.36, 95% confidence interval (CI)=0.16-0.74, P=0.004] and the validation set (HR=0.35, 95% CI=0.11-0.89, P=0.006). Similar significant associations were observed with CDX2 expression in the discovery set (HR=0.25, 95% CI=0.11-0.50, P<0.001) and validation set (HR=0.27, 95% CI=0.07-0.75, P=0.020). In multivariable analysis, combined positivity of both markers was significantly associated with longer OCSS in the discovery set (HR=0.20, 95% CI=0.06-0.49, P<0.001) and in the validation set (HR=0.33 95% CI=0.07-0.1.06, P=0.047). In a stratified analysis for stage IC/II EC, combined positivity identified a subset of patients with a significantly longer OCSS in the discovery cohort but only a non-significant trend in the validation cohort. Nuclear β-catenin and CDX2 expression individually or in combination are validated prognostic markers for ovarian EC. However, their full potential to stratify low risk patients at adjuvant threshold awaits further multimarker study.

Care Pathways Deliver Improved Survival in Populations with Colon Cancer

Background - Causes of variations in outcomes from cancer care in developed countries are often unclear and multifactorial. The pathways by which a patient travels to access health care services and the impact of health as a system on outcomes is not well understood. In this study, we sought to understand what factors within health system pathways influenced outcomes by measuring clinical care compliance with an evidenced-based pathway - the Optimal Care Pathway (OCP). The OCP is a framework outlining standards of care from pre-diagnosis to end-of-life care. Methods - Colon patients diagnosed from 2008-14 were identified from the Australian State of Victoria Cancer Registry (VCR) and cases linked with State and Federal health datasets. The impact of pathway deviations on outcomes was estimated. Findings- Compliance with the prevention phase of the OCP occurred for 88% of 13,539 individuals and was associated with lower disease stage at diagnosis (OR = 0.33 [95% CI = 0.24 - 0.42]), improved three year survival (69.2% vs 62.2%; p<0.001) and reduced likelihood of emergency surgery (17.7% versus 25.6%, p<0.001). For patients treated first with surgery (n=10,807), compliance with the diagnosis and treatment phase indicators (44% of patients) conferred a (risk-adjusted) survival benefit (HR=1.49 [95% CI = 1.28-1.73]), better perioperative outcomes, comparable costs and higher compliance to follow-up and end-of-life care. Interpretation - This high-income population-based study provides new evidence that adherence to evidence-based pathways within a whole systems approach is crucial for improving cancer outcomes. Funding Statement - The authors declare: None. Declaration of Interests - All authors declare no competing interests. Ethics Approval Statement - The Australian Institute of Health and Welfare Ethics Committee approved (Approval EO2015/4/219) the use of linked, routinely collected State and Federal datasets for the study of Victorians diagnosed with colon cancer (ICD-10-AM diagnosis codes C18) between 2008 and 2014 through the Victorian Cancer Registry (VCR).

Predictors of loss to follow-up among children attending HIV clinic in a hospital in rural Kenya.

IntroductionAfrican studies have reported high rates of loss to follow up (LTFU) among children in HIV care and treatment centres. Factors associated with LTFU may vary across populations. Few studies have been conducted among HIV infected children in care in rural areas of Kenya.Methodsthis involved children aged less than 15 years on follow up at Kangundo Level 4 Hospital HIV clinic from January 2010 to December 2015. We obtained sociodemographic and clinical information from patient files and electronic databases. Univariate and multivariate regression analyses were conducted to identify factors predictive of LTFU.Resultsa total of 261 HIV-infected children were followed up. The mean age was 10.0 years (IQR, 7-13) and median CD4 count of 582cells/ul (IQR 314-984). By December 2015, 171 children (65.5%) remained in active care, 32 (12.3%) transferred out, 13 (5%) died, while 45 (17.2%) were classified as LTFU. Out of the 45 children presumed as LTFU, we traced 44 out of the 45 children (98%) and found that their actual current status was as follows: 33 of the 44 children (75.0%) had dropped out of care (true LTFU). Factors strongly predictive of LTFU included low caregiver level of education (HR 2.3, 1.9-3.9, P = 0.001), WHO stage I and II at enrolment (HR 1.6, 1.4-2.1, P = 0.05).ConclusionLTFU of HIV infected children was common with an incidence of 32.9 per 1000 child years and occurred early in treatment and risk factors included poverty, low caregiver education, male child and early HIV disease stage.

Racial Disparities in the Presentation, Early Definitive Surgical Treatment, and Mortality Among Men Diagnosed with Poorly Differentiated/Undifferentiated Non-metastatic Prostate Cancer in the USA.

To assess the influence of race on presentation of poorly differentiated/undifferentiated prostate cancer, use of radical prostatectomy (RP) as primary treatment and survival outcomes. Using the 2004-2014 files of the Surveillance, Epidemiology, and End Results (SEER) data, we identified 244,167 black and white men diagnosed with poorly differentiated/undifferentiated prostate cancer. Demographic and tumor characteristics of study patients were compared by race. Logistic regression was used to evaluate the influence of race on receipt of RP. Cox proportional hazard models were fitted to determine the impact of RP and race on cancer-specific mortality (CSM) and all-cause mortality (ACM). Compared to white men, black men were diagnosed of prostate cancer at a younger age (64.2years versus (vs) 67.5years, p < 0.0001) and presented with higher median prostate-specific antigen, PSA (24.4ng/ml vs 22.1ng/ml, p < 0.0001) but lower disease stage. Lower proportion of black men received RP compared to white men (33.9% vs 42.6%; p < 0.0001). The odds of receipt of RP were 2 times higher in white men relative to black men. The risks of CSM and ACM were over 2 times and 3 times respectively higher in patients who did not receive RP vs patients who received RP in the study population and in each race. Despite the younger age at diagnosis of poorly differentiated/undifferentiated prostate cancer and higher PSA at diagnosis in black men, white men had significantly higher odds of receipt of RP relative to black men.

Idelalisib Plus Anti-CD20 Used Second Line Shows Improved PFS and Comparable Safety Compared to Later Line Therapy of Relapsed CLL

Introduction: Idelalisib (IDELA) is a first-in-class PI3Kδ inhibitor that is approved for use in combination with rituximab for patients with relapsed or refractory chronic lymphoid leukemia (R/R CLL) in the United States and in combination with rituximab or ofatumumab for the same indication in the European Union. Clinical trials evaluating IDELA in the first line setting for CLL were prematurely terminated due to an increased incidence of serious adverse events (AEs) and mortality; therefore, IDELA is not indicated as a first line therapy for CLL. The safety signal observed in the treatment naïve setting has produced a prevailing view that early line use of IDELA may also lead to inferior clinical outcomes. To address this question, we evaluated the clinical benefit:risk balance for IDELA in early vs. later lines of use in the relapsed setting.Objective: To investigate clinical outcomes across sub-populations of IDELA + anti-CD20-treated patients with R/R CLL based on number of prior chemo-immunotherapy treatment regimens.Methods: Using clinical outcomes data collected in Gilead-sponsored clinical trials of patients with R/R CLL treated with IDELA + anti-CD20 (312-0116/0117, N=110, Furman et al., N. Engl. J. Med. 2014; 370:997-1007, and 312-0119, N=173, Jones et al., Lancet Haematol. 2017; 4:e114-e126), we retrospectively compared the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and AE profile for patients previously treated with 1 prior regimen (IDELA given in the second line setting, 2L), 2 prior regimens (3L), or ≥3 prior regimens (≥4L). PFS and OS were estimated using the Kaplan-Meier method and groups were compared using a log-rank test. The incidence of AEs was compared using the Kruskal Wallis test.Results: Among 283 patients treated with IDELA + anti-CD20, 49 (17.3%) received IDELA 2L, 69 (24.4%) received it 3L, and 165 (58.3%) received it ≥4L. Patient characteristics were similar except that patients in the ≥4L group presented with Rai stage III/IV disease more frequently compared to the 2L and 3L groups (70.3% vs. 61.3% and 57.9%, respectively, Table 1). ORR was similar irrespective of the number of prior regimens (85.7% for the 2L group, 73.9% for the 3L group, and 80% for the ≥4L group, p=0.2866); however, PFS and OS were longer in the 2L group compared to the 3L and ≥4L groups (median PFS= 31.5 months, 16.6 months, and 17.3 months, respectively, [Figure 1] and median OS=47.4 months, not reached (NR), and 34.6 months, respectively). No statistically significant difference was observed across treatment setting groups in the incidence of grade 3/4 key treatment-emergent AEs, including cough, diarrhea, infection, transaminitis, and colitis (Figure 2).Conclusion: These analyses indicate that patients with R/R CLL experience comparable or improved efficacy and have a similar safety profile when IDELA + anti-CD20 regimens are used 2nd line as compared to later line, after chemo-immunotherapeutic regimens. The longer PFS and OS times for patients treated with IDELA in the 2L may reflect shorter time since diagnosis, lower stage disease, or less disease resistance in this group, but also suggest that the efficacy benefit of IDELA + anti-CD20 is greater and may therefore better offset the potential toxicity in this patient sub-group. These findings support the use of IDELA + anti-CD20 in the 2L+ setting for patients with R/R CLL following chemo-immunotherapy. DisclosuresBrown:Abbvie: Consultancy; TG Therapeutics: Consultancy; Sunesis: Consultancy; Gilead: Consultancy, Research Funding; Genentech: Consultancy; Boehringer: Consultancy; Pharmacyclics: Consultancy; Verastem: Consultancy, Research Funding; Loxo: Consultancy; Sun Pharmaceutical Industries: Research Funding; Invectys: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy; Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy. Ye:Gilead Sciences, Inc.: Employment, Equity Ownership. Xing:Gilead Sciences, Inc.: Employment. Roudet:Gilead Sciences, Inc.: Employment. Ruzicka:Gilead Sciences, Inc.: Employment. O'Brien:TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Alexion: Consultancy; Acerta: Research Funding; Astellas: Consultancy; GlaxoSmithKline: Consultancy; Aptose Biosciences Inc.: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy, Research Funding; Regeneron: Research Funding; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy; Kite Pharma: Research Funding; Amgen: Consultancy; Vaniam Group LLC: Consultancy.

Trends and outcomes of lymphadenectomy for nonmetastatic renal cell carcinoma: A propensity score-weighted analysis of the National Cancer Database

PurposeLymph node (LN) involvement in renal cell carcinoma (RCC) is associated with a poor prognosis. While lymph node dissection (LND) may provide diagnostic information, its therapeutic benefit remains controversial. Thus, the aim of our study is to analyze survival outcomes after LND for nonmetastatic RCC and to characterize contemporary practice patterns. Materials and methodsThe National Cancer Database was queried for patients with nonmetastatic RCC who underwent either partial or radical nephrectomy from 2010 to 2014. A total of 11,867 underwent surgery and LND. Chi-square tests were used to examine differences in patient demographics. To minimize selection bias, propensity score matching (PSM) was used to select one control for each LND case (n = 19,500). Cox regression analyses were conducted to examine overall survival (OS) in patients who received LND compared to those who did not. ResultsOf all patients undergoing LND for RCC (n = 11,867), 5%, 23%, 31%, 47% were performed for tumors of clinical T stage 1, 2, 3, and 4, respectively. Proportions of LND have not significantly changed from 2010 to 2014. No significant improvement in median OS for patients undergoing LND compared to no LND was shown (34.7 vs. 34.9 months, respectively; P = 0.98). Similarly, no significant improvement in median OS was found for clinically LN positive patients undergoing LND compared to no LND (P = 0.90). On Cox regression analysis, LND dissection was not associated with an OS benefit (hazard ratio: 1.00; 95% confidence interval 0.97 to 1.04). ConclusionsAmong all RCC patients, LNDs are often performed for low stage disease, suggesting a potential overutilization of LND. No OS benefit was seen in any subgroup of patients undergoing LND. Further investigation is needed to determine which patient populations may benefit most from LND.

Detection of lymph node metastases in penile cancer.

Penile cancer (PC) is a relatively rare malignancy in the United States (US) but a greater concern in developing nations. Lymph node imaging remains critical to the staging and treatment of this disease as metastases develop in a predictable, anatomic fashion. Early surgical intervention remains a mainstay in treatment and imaging often aids in decision making. This review highlights the indications for imaging in both low-stage and advanced disease. Furthermore, we discuss the benefits and limitations of currently available imaging for staging of inguinal and pelvic lymph nodes in PC and novel modalities in development.

Merkel cell carcinoma and the challenge in its approach: a review based on a clinical context of immunosuppression.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cancer with high rate to local relapse and metastasis. Its connection to immunosuppression is well known, with reported association to human immunodeficiency virus (HIV).The authors present an 87-year-old woman, infected by HIV type 2 at advanced stage of the disease, whom presented a painless papule on left cheek in 2011. After its total excision, the histopathology confirmed MCC “in situ,” with no regional or distant metastases. Simultaneously, she revealed a viral load of 2220 copies/mL and 224 CD4/mm3. Five months later, the patient presented a local and distance relapse with an aggressive behavior and positive regional lymph node. Stage IV disease was confirmed due to presence of liver metastases. Concurrently to the relapse, it was detected low CD4 levels.In our multidisciplinary team decision meeting, it has been decided conservative treatment due to low Karnofsky status, comorbidities, and stage of disease.

PO-489 TP53 mutations and focal genomic amplifications for ctDNA detection in high-grade serous ovarian carcinoma

IntroductionHigh-grade serous ovarian carcinoma (HGSOC) is characterised by ubiquitous TP53 mutations and significant copy-number alterations. Current ctDNA assays for HGSOC have focused on detection of TP53 mutations. In patients with low-stage disease or during therapy, the amount of ctDNA may be below the threshold of reliable detection. We tested whether sensitivity for ctDNA detection could be increased by combining TP53 mutations with focal genomic amplifications.Material and methodsTargeted TP53 sequencing was performed on 264 plasma samples of 137 patients from the BriTROC-1 study with relapsed HGSOC tissue samples. Four patients had no somatic TP53 mutation detected and were excluded from analysis. Shallow WGS (0.1x) was performed on 256 plasma samples and matched tumour samples. The length-adjusted Z-score was calculated for each genomic segment and was used to distinguish significant focal amplifications (FA).Results and discussionsTP53 mutations were detected in 180 plasma samples with median mutant allele fraction (MAF) of 5% (IQR 1.4%–16%). Twenty-five patients had at least one plasma sample with MAF >20%, which could be used for genomic profiling.Focal amplifications were observed in 151 plasma samples with a median of 4 amplifications per sample. The FA with the maximum observed Z-score per sample was significantly correlated with TP53 MAF.Both approaches detected ctDNA in about half of the samples. However, in some plasma samples ctDNA could be detected only by one of the used methods.ConclusionCombining targeted TP53 sequencing with shallow WGS may be a more sensitive approach for ctDNA detection.

Abstract 4485: VGLL3 is a novel outlier in African American prostate tumors and its expression is associated with a tumor suppressor phenotype in prostate cancer

Abstract Higher incidence, progression and mortality of prostate cancer (PCa) have been noted in African American (AA) men compared with Caucasian (CA) men. In fact AA race is an independent predictor of biochemical recurrence for all stage of PCa (Dr. Schaeffer's data analysis, n=1634 of AA patients). The etiology of PCa racial disparities is likely multi-factorial with increasing support of biologic contributors to these differences. By analyzing large cohort of PCa, we have demonstrated that AA PCa exhibits a unique spectrum of molecular subtypes. For example, AA men presented with PCa have a significant decrease in fusion proteins such as ERG, ETS and SPINK, with an enrichment of fusion unknown (FU; triple negative) cases. Given the increased mortality of PCa in AA populations and the enrichment of FU cases among AA tumors, there is an urgent need to define and explore individual outlier as race-based modifiers of disease aggressiveness. By utilizing a large multi-institutional cohort of prostate cancer cases of mixed racial composition, we have identified novel outliers enriched in AA among FU group by COPA outlier analysis.VGLL3 is one of the top outliers enriched in AA. VGLL3 positive cases are associated with low stage (less LNI, p=0.001; SVI, p&amp;lt;0.001; and EPE, p=0.009) and low grade disease (less Gleason &amp;gt;7, p=0.012) of higher protective phenotype of adverse cancer grade and stage. This preliminary work on VGLL3 expression suggests it may be associated with a tumor suppressor-like phenotype with reductions in expression with increasingly aggressive PCa. Studies of VGLL3 in cancer are limited and the role of VGLL3 in prostate has not been explored at all. The goal of this study is to investigate the role of VGLL3 as a novel outlier in AA prostate cancer that modulates disease aggressiveness. We found that mRNA expression levels of VGLL3 were lower in prostate cancer epithelial cells than in normal epithelial cells or stromal cells. By establishing and characterizing PCa models overexpressing VGLL3 in vitro and in vivo, our data demonstrate that VGLL3 significantly reduced migration and invasion of PCa cells and inhibited primary tumor cell growth. Our preliminary data also indicate VGLL3 inhibits PCa metastasis. Furthermore, VGLL3 seems to negatively affect both hippo and AR activity in PCa cells and these might be the mechanisms that VGLL3 inhibits tumor cell growth. These data is consistent with our clinical data suggesting tumor suppressive role of VGLL3 in advanced PCa. Citation Format: Hongjun Kang. VGLL3 is a novel outlier in African American prostate tumors and its expression is associated with a tumor suppressor phenotype in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4485.

Molecular features of adenoid cystic carcinoma with an emphasis on microRNA expression.

Molecular features of adenoid cystic carcinoma with an emphasis on microRNA expression.

Author Reply

The commentator underscores several important points. First, since the United States Preventive Services Task Force recommendation to eliminate PSA screening, there has been an increased incidence of more clinically aggressive prostate cancers. Second, although the current data shows that with PSA screening at 12-18 months intervals, prostate cancer morbidity can be substantially reduced, it is critically important to mitigate the impact of unnecessary treatment by utilizing active surveillance, and various newer methods for risk stratification of patients with low-grade, low-stage disease.

Childbirth after adolescent and young adult cancer: a population-based study.

Annually, > 45,000US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics. We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression. Among 17,564 AYA cancer survivors, 1989 had ≥ 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006. Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15years. Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis.

Thrombocytosis is a Prognostic Factor in Women Treated with Chemoradiation for Advanced Cervical Cancer [21A

INTRODUCTION: Prior to the addition of chemotherapy to radiation, thrombocytosis was seen as a poor prognostic factor for women with advanced cervical cancer. The objective of this study was to see in the chemoradiation era whether thrombocytosis was still a prognostic factor. METHODS: An IRB study was performed analyzing all patients with cervical cancer receiving primary chemoradiation as therapy with a diagnosis between January 1, 2001 and December 31, 2011. Minimum follow up was 30 months. Records were examined for initial platelet count at diagnosis, stage, grade, histology and survival. Only patients receiving chemoradiation with stage IIa-Vb cervical cancer were studied included in the final analysis. RESULTS: 209 women with cervical cancer were diagnosed with 173 women treated with primary chemoradiation. The most common stage was IIIb (88, 50.9%). The mean platelet counts of those receiving chemoradiation was significantly higher (396k/ml; 95%CI 376-416k) than those with lower stage disease (313k/ml; 292-334k)(p&lt;0.001). Of the 173 patients, 42 (24.3%) had a platelet count &gt; 450k/ml and 24 (13.9%) had a platelet count &gt;500k/ml. Patients who died of disease had significantly higher initial platelet counts (mean 433k/ml; 95%CI 407-458k) than those who were alive at the completion of follow-up (mean 326k/ml; 95%CI 303-350k). None of the patients with an initial platelet count &gt;500k/ml were alive at the time of follow-up. CONCLUSION: High platelet count at initial diagnosis is a poor prognostic factor in women with cervical cancer treated by chemoradiation.

A stage-dependent link between metabolic syndrome components and incident prostate cancer.

Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research.

Time to surgery in colon cancer: Predictors and association with survival—An analysis of the National Cancer Database (NCDB).

599 Background: Time-to-surgery (TTS) refers to the wait time from the diagnosis of cancer to surgical resection of the primary tumor. In breast and bladder cancers, longer TTS has been shown to be associated with lower long-term survival. Prior evidence in colon cancer, has shown that older age, urban residence, and comorbidity are independent predictors of TTS. However, evaluation of TTS with survival in colon cancer has been limited to mostly single-center studies. Using the NCDB, this study aimed to both evaluate patient and clinical factors associated with TTS, and determine if TTS was associated with overall survival in colon cancer. Methods: Patients with colon cancer who underwent partial or subtotal colectomy/hemicolectomy were included, excluding those receiving neoadjuvant therapy. With prior colon cancer studies showing a median TTS of 15-20 days, we dichotomized the number of days from diagnosis to definitive surgery (TTS) as ≤ 21 days or &gt; 21 days. A modified Poisson regression model was utilized to evaluate relative risk of TTS &gt; 21 days. Overall survival in association with TTS was estimated using both the Kaplan-Meier method and multivariable Cox regression model, adjusting for patient-, disease- and facility-level characteristics. All analyses were conducted with SAS version 9.4, p-values &lt; 0.05 were considered significant. Results: We identified 26,999 colon cancer patients from 2006-2012 from the NCDB. Approximately 25.7% of patients had a TTS &gt; 21 days. Patients with comorbidities, who were older, were African American, with lower disease stage, and treated in academic facilities located in the Northeast, had a significantly increased relative risk of a TTS &gt; 21 days. Considering survival, a TTS &gt; 21 days was associated with a 24.5% decreased adjusted risk of death (95% CI: 21.6% to 27.2%). Conclusions: A longer TTS with colon cancer is understandably associated with older age, greater comorbidity, and lower stage, but questionably so in African American patients. However, given that TTS &gt; 21 days was associated with a lower adjusted risk of death, it may indicate that a reasonable delay could be pursued for more accurate preoperative evaluation and staging in colon cancer.