Median Disease-specific Survival Research Articles

Laser Interstitial Thermal Therapy in the Treatment of Thalamic Brain Tumors: A Case Series.

Surgical options for patients with thalamic brain tumors are limited. Traditional surgical resection is associated with a high degree of morbidity and mortality. Laser interstitial thermal therapy (LITT) utilizes a stereotactically placed laser probe to induce thermal damage to tumor tissue. LITT provides a surgical cytoreduction option for this challenging patient population. We present our experience treating thalamic brain tumors with LITT. To describe our experience and outcomes using LITT on patients with thalamic tumors. We analyzed 13 consecutive patients treated with LITT for thalamic tumors from 2012 to 2017. Radiographic, clinical characteristics, and outcome data were collected via review of electronic medical records. Thirteen patients with thalamic tumors were treated with LITT. Most had high-grade gliomas, including glioblastoma (n=9) and anaplastic astrocytoma (n=2). The average tumor volume was 12.0 cc and shrank by 42.9% at 3 mo. The average hospital stay was 3.0 d. Median ablation coverage as calculated by thermal damage threshold (TDT) lines was 98% and 95% for yellow (>43°C for >2 min) or blue (>10 min), respectively. Median disease-specific progression-free survival calculated for 8 patients in our cohort was 6.1 mo (range: 1.1-15.1 mo). There were 6 patients with perioperative morbidity and 2 perioperative deaths because of intracerebral hematoma. LITT is a feasible treatment for patients with thalamic tumors. LITT offers a cytoreduction option in this challenging population. Patient selection is key. Close attention should be paid to lesion size to minimize morbidity. More studies comparing treatment modalities of thalamic tumors need to be performed.

Abstract A11: Prognostic model for disease-specific survival in anorectal melanoma

Abstract Background: Anorectal melanoma (AM) is generally staged using criteria developed and validated for cutaneous melanoma (CM), primarily due to its rarity and the lack of a specific staging system, despite limited evidence to support this. In an attempt to risk-stratify AM patients (pts), we analyzed the performance of the AJCC 8th edition CM staging system and a system recently developed for vulvar melanoma (VM) in a retrospective cohort. Methods: Demographics, clinicopathologic factors, and follow-up information were collected for 160 AM pts treated at our institution. The pts were grouped based on their clinical stage at presentation (localized to anorectum [L], regional metastases [R], distant metastases [D]). For further risk stratification, L pts were grouped according to the following systems: (i) AJCC 8th edition CM T-categories (T1a to T4b, 8 tiers); (ii) AJCC 8th edition CM stage (I vs. II, 2 tiers); (iii) the tumor thickness (TT) system (thin [T1], intermediate [T2-T3], thick [T4], 3 tiers); and TM system previously derived for VM (T1: TT≤ 2.0mm and mitotic rate (MR) <2/mm2 and T2: TT >2.0mm and MR <2/mm2). Univariate (UV) and multivariable (MV) Cox proportional hazards regression modeling determined associations with disease specific survival (DSS). The Kaplan-Meier method estimated overall survival (OS) and DSS. Results: The cohort (n=160) included 67 L, 55 R and 38 D pts. With median follow-up of 1.63 years (y), the median DSS was 1.75y for all pts. DSS progressively decreased according to stage at presentation (L: 2.39y; R: 1.81y and D: 1.25y). By UV analysis, clinical stage at presentation correlated with DSS (R: p=0.05, HR=1.52; D: p<0.001, HR=3.24, compared to L). By MV analysis (including clinical stage, tumor thickness, regression [REG], lymphovascular invasion [LVI], perineural invasion and resection margin status), the presence of distant metastasis correlated with DSS (p<0.001, HR=2.71), in addition to tumor thickness, REG, and LVI. To further optimize risk modeling and clinical management, we analyzed L pts using 4 distinct T-categorization systems. The 3-tier TT system robustly stratified DSS (p=0.03; HR- intermediate=2.36, thick=4.98, compared to thin). AJCC stage also classified 2 groups of pts according to DSS, with a trend towards significance (p=0.1; HR=3.37). In contrast, only OS models could be derived for the AJCC 8th edition T-categories (p=0.14) and TM system (p=0.1), with the latter yielding clear differences in outcomes, compared to the former. Analysis was also performed on a combined cohort of L pts with VM and AM, to determine if there are unifying themes among anogenital mucosal melanomas, and all the 4 systems stratified the pts (p<0.001), with stage, TT, and TM systems yielding clear differences in outcomes, compared to the 8 AJCC T-categories. Conclusion: Clinical stage at presentation and T-categorization of L pts based on modifications of the 8th edition AJCC CM staging criteria (stage and TT system) appear to be potentially informative tools to stratify risk in AM pts. Citation Format: Priyadharsini Nagarajan, JIn Piao, Jing Ning, Laura E. Noordenbos, Jonathan L. Curry, Carlos A. Torres-Cabala, A. Hafeez Diwan, Phyu P. Aung, Doina Ivan, Merrick I. Ross, Richard E. Royal, Jennifer A. Wargo, Wei-Lien Wang, Rashmi Samdani, Alexander J. Lazar, Asif Rashid, Michael A. Davies, Victor G. Prieto, Jeffrey E. Gershenwald, Michael T. Tetzlaff. Prognostic model for disease-specific survival in anorectal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A11.

Prognostic factors of metastatic myxoid liposarcoma

BackgroundMyxoid liposarcoma (MLS) has the tendency to metastasize extrapulmonary. Although prognostic factors at the initial diagnosis of MLS have been reported, those at diagnosis of metastasis remain unclear. The purpose of this study was to investigate the prognostic factors for disease-specific survival at the initial diagnosis of metastasis.MethodsThis retrospective observational study was conducted at three cancer centers and two university hospitals in Japan. Of 274 MLS patients pathologically diagnosed between 2001 and 2015, 48 metastatic patients were examined.ResultsLung metastases were detected in nine patients (18.8%) and extrapulmonary metastases in 45 (93.8%). Interval from primary diagnosis to the first metastasis was significantly shorter in patients with lung metastases than without (p = 0.007). Median disease-specific survival after diagnosis of metastases was 52.5 months in all patients. In multivariable analysis, liver metastasis (hazard ratio (HR), 2.71 [95% confidence interval (CI), 1.00–7.09]) and no evidence of disease (NED) achieved by radical treatment (resection with or without radiation therapy, or radiation therapy ≥60 Gy) or semi-radical (radiation therapy ≥40 Gy) treatment were significantly related to survival (HR, 0.36; 95%CI [0.13–0.95]). The number of metastases (odds ratio (OR), 0.44; 95%CI [0.25–0.78]) and abdominal/retroperitoneal metastases (OR, 0.09; 95%CI [0.008–0.95]) were the significant inhibitory factors of achieving NED.ConclusionsThis is the first study to statistically demonstrate the importance of achieving NED with surgical resection or radiation therapy for longer survival in metastatic MLS patients. As number of metastases was a significant factor for achieving NED, early detection of metastases might be important.

Chemopreventive Agents After Pancreatic Resection for Ductal Adenocarcinoma: Legend or Scientific Evidence?

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection. All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially "chemopreventive agents" considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6months before diagnosis and regularly after surgery along the follow-up period. A total of 430 patients were enrolled in this study, with median DFS and DSS of 21months (IQR 13-30) months and 34 (IQR 26-52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3. The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.

Recurrent retroperitoneal sarcomas: Clinical outcomes of surgical treatment and prognostic factors

Background and purposeLocoregional recurrence after resection of primary retroperitoneal sarcoma (RPS) is a challenging therapeutic issue. The objective of this study was to identify clinicopathological factors predictive of overall survival (OS) and disease specific survival (DSS) after reoperation for recurrent RPS. Patients and methodsWe retrospectively collected data from the medical records of 800 patients who underwent resection for sarcoma at our Institution, from 1983 to 2015. Among these patients, 120 were treated for retroperitoneal sarcoma and 55 had a locoregional recurrence (LR). Four of them did not undergo surgery and thus were excluded from this study leaving 51 cases available for data analysis. Univariate and multivariate survival analyses were performed to identify prognostic factors. ResultsMedian overall survival was 33 months. The 1-year, 3-year and 5-year OS rates were 75.5%, 47.1% and 31.6% respectively. Multivariate Cox regression analysis suggested that extension of surgery (P = 0.026), surgical margin status (P = 0.015) and histological grade of recurrent tumor (P = 0.047) were independent prognostic factors for OS. Median DSS was 48 months. The 1-year, 3-year and 5-year DSS rates were 79.2%, 53.1% and 40.9%, respectively. At multivariate analysis, predictors of DSS were extension of surgery (P = 0.004), margin status (P = 0.011), histological grade of recurrent tumor (P = 0.008), and disease free interval (DFI) (P = 0.020). As regards histological subtype of recurrent RPS, at univariate analysis, well-differentiated liposarcoma (WDLS) was associated with better OS and DSS (P = 0.052 and P = 0.016 respectively) compared to dedifferentiated liposarcoma (DDLS). ConclusionsAccording to our findings, surgery is more beneficial in patients with low-grade sarcoma, WDLS and long DFI. The achievement of clear resection margins, rather than performing a multivisceral resection, appears to be a key factor to improve OS and DSS.

Integrative assessment of clinicopathological parameters and the expression of PD-L1, PD-L2 and PD-1 in tumor cells of retroperitoneal sarcoma.

Evidence is limited regarding the immunologic profile and immune microenvironment of soft tissue sarcoma subtypes. The aim of the present study was to describe the clinical significance and prognostic implications of PD-L1, PD-L2, and PD-1 in patients with retroperitoneal sarcoma (RSar). In this retrospective, multicenter, collaborative study, medical charts were reviewed and the immunohistochemical staining results of resected tissue specimens from 51 patients with RSar were examined. Immunohistochemical staining was performed with primary antibodies against PD-L1, PD-L2, PD-1, and Ki-67. The correlations between the baseline clinical parameters and expression levels of the four molecules in sarcoma cells were evaluated, and their prognostic values after tumor resection were assessed. Dedifferentiated liposarcoma (41%), leiomyosarcoma (20%), and undifferentiated pleomorphic sarcoma (16%) were the three major types identified. Dedifferentiated liposarcoma and leiomyosarcoma showed higher levels of PD-L1 expression than did other sarcomas. The Spearman correlation analysis revealed that baseline serum lactate dehydrogenase levels were moderately and positively correlated with PD-L1 (P=0.02, r=0.41) and PD-L2 (P=0.006, r=0.47) expression. The median recurrence-free and disease-specific survival was 58 and 16 months, respectively, during the 29-month median follow-up after surgery. On univariate analysis, a higher expression level of PD-1 was associated with a higher risk of recurrence, whereas multivariate analyses revealed that independent predictors of recurrence-free and disease-specific survival indicated a high expression of Ki-67 (P=0.03; hazard ratio, 2.29 vs. low expression) and prognostic stage IIIB (P=0.04; hazard ratio, 5.11 vs. stage I–II), respectively. Findings of the current study provide novel insights about the prognostic value of PD-L1, PD-L2, and PD-1 expression in RSar. Serum lactate dehydrogenase levels constitute a potential predictor of PD-L1 and PD-L2 expression levels in RSar. Further investigations are needed to determine the immunologic landscape of RSar and provide a foundation for therapeutic intervention using immune checkpoint inhibitors.

1317P Survival, quality of life (QoL) and geriatric outcomes of elderly patients (pt) with advanced non-small cell lung cancer (NSCLC), treated with pembrolizumab (P) in the first-line setting

NSCLC has a median onset at 70 years (y). Median overall survival (OS) of elderly pt (EP) with advanced NSCLC is near 8 months (m) in the 1st line setting. Many trials have established the role of immunotherapy in metastatic NSCLC, but EP have been underrepresented in them. So, we conducted this trial to evaluate safety and efficacy of 1st line P in EP with advanced NSCLC, along with QoL and geriatric issues. Our main objective was OS at one y. Secondary Objectives were outcomes in QoL and geriatric parameters, Objective Response Rate (ORR) and Progression-free Survival (PFS) according to RECIST 1.1, median Disease-specific survival (DSS), OS at 2 y, and safety profile. This was a non-randomized, open label phase II trial led in 12 Spanish sites. Eligibility criteria required pt >70 y, PS 0-1, stage IIIB-IIIC-IV untreated NSCLC, PD-L1 >1% and wild-type EGFR/ALK. All pt had basal QoL and Comprehensive Geriatric Assessments. They received P 200 mg Q3W for a maximum of 2 y. Radiologic, geriatric, and QoL follow-up were done every 9 weeks for one y. Our statistical plan set that 74 pt accrued over 12 m, with 12 m of follow-up, could test with an alpha and beta errors of 0.05 and 0.10 whether P could improve median OS to 12 m. We accrued 75 pt from Feb 2018 to Nov 2019, and 74 of them received P. Mean age was 78.0 (70-91). Mean Charlson Index was 2.53 and mean Edmonton Frail Score was 4.23. Other cognitive, functional and nutritional features will be reported. Treatment-related toxicity has been seen in 55 pt (74,3%). Grade 1, 2 and 3 adverse events have been identified in 24, 26, and 5 pt. Grade 3 toxicities were diarrhea (1 pt), thrombocytopenia (1 pt), renal disorder (1 pt), and pneumonitis (2 pt). No grade 4-5 adverse event has been detected until now. ORR was Partial Response, Stable Disease and Progression Disease in 18 (29%), 30 (48.3%), and 14 (22.5%) pt. At the time of this analysis, we had no data for response in 12 pt. Outcomes in QoL and Geriatric tests, as well as preliminary PFS, DSS and OS data will be presented in the meeting. Single P seems safe and effective in EP with untreated, PD-L1 positive, advanced NSCLC.

Long-Term Follow-Up of Yearly Replaced Double Internal Stents for Extrinsic Malignant Ureteral Obstruction.

Introduction: To assess long-term outcomes of double internal stents (DIS) for the relief of external malignant ureteral obstruction (MUO). Materials and Methods: DIS (7F each; 12-month indwelling time) were inserted under general anesthesia in 62 consecutive patients (75 renal units) with MUO during 2007-2018. Surveillance was performed every 3 months, and stents were exchanged routinely every year. The need for permanent stent retrieval was considered stent failure. Maintenance of stent patency and disease-specific survival (DSS) were estimated (Kaplan-Meier). Risk factors were also assessed (univariate and multivariable Cox regression analyses). Results: The median follow-up was 27 months (interquartile range [IQR] 20-27). The most frequent tumors causing obstruction were colorectal and ovarian cancers. Six patients (10%) had stent failure caused by sepsis, creatinine elevation, or hematuria. The average time to failure was 15 months (range 1-27). A history of radiation and an estimated glomerular filtration rate (eGFR) ≤45 mL/(min/1.73 m2) were associated with stent failure (p = 0.038 and p = 0.001, respectively). Thirty-nine patients died with a median DSS of 21 months (IQR 8.6-not reached). Multivariate analysis identified eGFR ≤60 mL/(min/1.73 m2) (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1-4.2, p = 0.02) and need for balloon dilation (HR 2.1, 95% CI 1.1-4.1, p = 0.02) as independent predictors for disease-related mortality. Twenty-six patients (42%) had stent-related complications, for example, irritative symptoms, hematuria, and infections, of whom only two failed. Conclusions: One-year indwelling DIS provide effective long-term relief of MUO and represent a simple and effective alternative to other methods of urinary diversion. They avoid the need for external tubes and contribute to improved patient satisfaction.

Role of Serum Carcinoma Embryonic Antigen (CEA) Level in Localized Pancreatic Adenocarcinoma: CEA Level Before Operation is a Significant Prognostic Indicator in Patients With Locally Advanced Pancreatic Cancer Treated With Neoadjuvant Therapy Followed by Surgical Resection: A Retrospective Analysis.

The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer.

Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tumor microenvironment (TME) may contribute to GR expression in bulk tumor and influence prognosis. To test this, mRNA expression data was accessed from METABRIC and TCGA. “High” and “low” expression was based on highest and lowest quartiles of NR3C1 gene expression, respectively. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. Computer algorithms CIBERSORT, Gene Set Enrichment Analysis and TIMER were used. GR-high BC has better median disease-free and disease-specific survival. Single cell sequencing data showed higher GR expression on immune cells compared to cancer and stromal cells. Positive correlation between GR-high BC and CD8+ T-cells was noted. In GR-high tumors, higher cytolytic activity (CYT) with decreased T-regulatory and T-follicular helper cells was observed. High GR expression was associated with lower proliferation index Ki67, enriched in IL-2_STAT5, apoptosis, KRAS, TGF-β signaling, and epithelial-to-mesenchymal transition. Immune cells significantly contribute to GR expression of bulk BC. GR-high BC has a favorable TME with higher CYT with favorable outcomes.

Predicting survival in non-functional pancreatic neuroendocrine tumours.

Owing to the limited prevalence and heterogeneity, it is difficult to predict long-term survival of non-functional pancreatic neuroendocrine tumours (NF-PNETs).This study aimed to evaluate the factors predicting disease-specific survival (DSS) for well-differentiated NF-PNETs. Data were collected retrospectively from 256 patients with pancreatic neuroendocrine tumours who underwent surgical resection between January 2009 and December at our institution. Of these, 103 NF-PNETs (40%) were identified for analysis. Of the 103 patients, 54 were male (52%) and the mean age was 52 years (range 21-75 years). Most patients (60/103, 58%) in our series were symptomatic. Seventeen patients (16%) died during follow-up, with a median period of 47 months. There were 88 patients with well-differentiated tumours and 10 of them (10/88, 11%) died of tumour progression. Median DSS after primary resection was 58.8 months (range 16-122 months). Multivariate analysis identified age >52 years (P = 0.038) and tumour grade G2 (P = 0.001) as statistically significant predictors of DSS. There was no association between gender, tumour size, symptoms, surgical procedure, severe complications, tumour location, tumour size, resection margin, positive lymph nodes and vascular invasion with DSS. Tumour grade, age, presence of symptoms and distant metastasis were related to poor DSS of NF-PNETs. Age >52 years and tumour grade G2 might be independent predictors of poor DSS for patients with well-differentiated NF-PNETs.

Surgical management of carcinomas of the infratemporal fossa and skull base: patterns of failure and predictors of long-term outcomes.

Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma. All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors' institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes. Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence. The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

Survival times are similar among patients with peritoneal, hematogenous, and nodal recurrences after curative resections for gastric cancer.

BackgroundThe three dominant recurrence patterns of gastric cancer are peritoneal, hematogenous, and nodal recurrence. Correlation between initial recurrence site and prognosis is poorly understood, particularly after standardization of postoperative S‐1 adjuvant chemotherapy.MethodsWe analyzed a multi‐institutional database of 3484 patients who underwent gastrectomy for gastric cancer between 2010 and 2014. Patients who experienced recurrences after curative gastrectomy classified into peritoneal, hematogenous, or nodal recurrence groups, according to their initial recurrence sites, and their prognoses were compared.ResultsWe included 313 patients in the analysis, of whom 190 patients (63%) were treated with postoperative adjuvant chemotherapy. Pathological disease states were stage I: n = 20 (6%), stage II: n = 62 (20%), and stage III: n = 231 (74%). Patients were categorized into groups by peritoneal (n = 127), hematogenous (n = 123), and nodal (n = 63) recurrence. The peritoneal recurrence group tended to have longer recurrence‐free survival, but shorter post‐recurrence survival, than the other two groups. Median disease‐specific survival after curative resection by group were peritoneal: 25.8 months, hematogenous: 29.0 months, and nodal: 27.8 months (peritoneal vs hematogenous, P = .152; hematogenous vs nodal, P = .955; peritoneal vs nodal, P = .213).ConclusionsPrognoses after curative resection for gastric cancer were similar among patients with peritoneal, hematogenous, or nodal recurrences.

Impact of Ovarian Metastatectomy on Survival Outcome of Colorectal Cancer Patients with Ovarian Metastasis: A Retrospective Study.

BackgroundOvarian metastasis from colorectal cancer (CRC) is rare and lacks standard treatment. The benefit of metastatectomy remains to be elucidated. This study was conducted to assess the impact of metastatectomy on survival outcome and explore prognostic factors in ovarian metastatic CRC patients.MethodsInformation of ovarian metastatic CRC patients between January 2008 and December 2017 were collected retrospectively from database of West China Hospital, Sichuan University. Kaplan–Meier method was used to estimate disease-specific survival (DSS) after diagnosis of ovarian metastasis, and multivariate Cox regression analysis was applied to identify prognostic factors.ResultsTotally, 68 female patients from a cohort of 2170 cases were eligible. The median age at diagnosis was 46.5 years. The median DSS was 25.0 months (95% confidence interval (CI): 21.0–29.0 months). Kaplan–Meier analysis and Log rank test showed that complete resection of ovarian metastases (median DSS: 33.0 months) could significantly prolong patients’ survival time, compared with palliative and no resection (median DSS: 20.0 months and 22.0 months, respectively), regardless of systemic chemotherapy (P<0.05). Multivariate analysis demonstrated regional lymph nodes metastasis of primary tumor (hazard ratio (HR): 3.438, 95% CI: 1.094–10.810, P=0.035), primary tumor resection (HR: 6.436, 95% CI: 1.770–23.399, P=0.005), differentiation grade (HR: 0.272, 95% CI: 0.107–0.693, P=0.006), complete resection of ovarian metastases (vs palliative resection: HR: 17.091, 95% CI: 3.040–96.099, P=0.001; vs no resection: HR: 9.519, 95% CI: 1.581–57.320, P=0.014), and systemic chemotherapy (HR: 3.059, 95% CI: 1.089–8.595 P=0.034) were independent prognostic factors.ConclusionComplete resection of ovarian metastases could independently predict favorable survival in ovarian metastatic CRC, while palliative resection could not improve patients’ prognosis compared with no resection.

Trends in the incidence and survival outcomes in patients with lung neuroendocrine neoplasms in the United States.

e19120 Background: The incidence and prevalence of Neuroendocrine Neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs has been lacking. Methods: We conducted a retrospective population-based analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database, and studied lung NENs patients from 1988 to 2015. Associated population data was utilized to report the annual age-adjusted incidence and overall survival trends. Trends in the incidence and survival of large-cell lung cancer (LCLC) and atypical carcinoid (AC) were reported from 2000-2015, while that for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988-2015. Results: We examined a total of 115,995 lung NENs [103,980 – SCLC; 3,303 – LCLC; 8,146 – TC; 656 – AC]. The age-adjusted incidence rate revealed decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015 per 100,000, AC increased from 0.17 in 2001 to 0.22 in 2015 per 100,000, and lastly, LCLC increased from 0.35 in 2001 to 0.41 in 2015 per 100,000. On multivariable analyses, the median overall survival (OS) and disease-specific survival (DSS) rate varied significantly by stage, grade, age at diagnosis, histological type, insurance type, marital status, and race. The 5-year OS rate among SCLC and LCLC patients was 5% and 17%, respectively, consistent with their high-grade nature. On the other hand, TC and AC, representing low-grade neuroendocrine tumors, had good 5-year OS: 84% and 64%, respectively. Conclusions: The incidence of lung NENs is rising, possibly because of advanced radiological techniques. However, we have seen a downtrend in the incidence of SCLCs likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

MP02-10 LONG-TERM USE OF DOUBLE INTERNAL STENTS FOR EXTRINSIC MALIGNANT URETERAL OBSTRUCTION

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I (MP02)1 Apr 2020MP02-10 LONG-TERM USE OF DOUBLE INTERNAL STENTS FOR EXTRINSIC MALIGNANT URETERAL OBSTRUCTION Ziv Savin*, Haim Herzberg, Reuven Ben David, Snir Dekalo, Ishay Mintz, Yazeed Barghouthy, Ofer Yossepowitch, and Mario Sofer Ziv Savin*Ziv Savin* More articles by this author , Haim HerzbergHaim Herzberg More articles by this author , Reuven Ben DavidReuven Ben David More articles by this author , Snir DekaloSnir Dekalo More articles by this author , Ishay MintzIshay Mintz More articles by this author , Yazeed BarghouthyYazeed Barghouthy More articles by this author , Ofer YossepowitchOfer Yossepowitch More articles by this author , and Mario SoferMario Sofer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000816.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with secondary extrinsic malignant ureteral obstruction (EMUO) seek for durable, simple and low-cost solutions of drainage. We report on long-term outcomes with double internal stents (DIS) for relief of EMUO. METHODS: DIS of 75 renal units (62 patients) presenting with EMUO were performed in 2007-2019. The procedure was done using dwelling 7 FR stents. Surveillance was performed every 3 months and stents were routinely exchanged annually. Need for permanent stents' retrieval was considered failure. Univariate and multivariate analyses were used to assess risk factors for stent failure and mortality. Kaplan-Meier estimations provided maintenance of stent patency and disease specific survival (DSS). RESULTS: Demographics and by-entry clinical data are presented in table 1. Balloon dilation was needed in 30 cases (48%). The median follow-up was 35.2 months (IQR 26.8-46.7) and the median DSS was 21 months (Range 7.1-45.5) (Figure 1). Thirty-nine patients died during the study period, 37 of them (95%) with patent stents in place. Multivariate analysis identified estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 and balloon dilation as independent predictors for mortality (HR=2.1, 95%CI=1.1-4.2, p=0.02 and HR=2.1, 95%CI=1.1-4.1, p=0.02, respectively). Six patients (10%) had stent failure due to sepsis, creatinine elevation, or intractable hematuria. The mean time to failure was 15 months. Radiation and eGFR < 45 ml/min/1.73m2 at presentation were independent risk factors for stent failure (p=0.038 and p=0.001, respectively). Stent-related side effects including irritative symptoms and hematuria were reported by 40% of patients. CONCLUSIONS: DIS provides durable relief of EMUO for long term. It represents a simple and valuable alternative to other methods of urinary diversion, avoiding the need for external tubes and contributing to improved patients quality of life. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e15-e15 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ziv Savin* More articles by this author Haim Herzberg More articles by this author Reuven Ben David More articles by this author Snir Dekalo More articles by this author Ishay Mintz More articles by this author Yazeed Barghouthy More articles by this author Ofer Yossepowitch More articles by this author Mario Sofer More articles by this author Expand All Advertisement PDF downloadLoading ...

Positive neck margin at frozen section analysis is a significant predictor of tumour recurrence and poor survival after pancreatodudenectomy for pancreatic cancer

BackgroundThe possible benefit of frozen section (FS) analysis during (PD) for pancreatic ductal adenocarcinoma (PDAC) and of additional resection up to total pancreatectomy (TP) is debated. Aim of this work is to evaluate the prognostic role of positive FS analysis after PD for PDAC. MethodsMulticentric retrospective analysis on prospective databases of three institutions. Based on FS analysis patients were classified as FS negative/FS positive. All positive FS patients underwent extended PD (EPD) or TP. Postoperative outcomes, disease-free (DFS) and disease-specific survival (DSS) were evaluated. ResultsOf 371 patients, 58 (16%) had positive FS. This resulted in 313 (84%) SPD (standard pancreatoduodenectomy), 22 (6%) EPD and 36 (10%) TP. Postoperative mortality was higher in patients undergoing TP (11% compared to 4.5% in EPD and 1% in SPD; p = 0.01). 26% of patients underwent neoadjuvant therapy, and it did not decrease the rate of positive FS. Systemic/local relapse rates were 59% and 41% in negative FS group, and 78% and 22% in positive FS group (p = 0.031). Median DFS and DSS were 20 and 37 months in negative FS group, and 12 and 23 months in positive FS patients (p = 0.001). Independent predictors of recurrence were G3, N1/N2 status and positive FS. R1 resection, G3, N1/N2 status, perineural invasion and positive FS were independent predictors of DSS. ConclusionsPositive FS analysis is a poor prognostic factor after PD for PDAC. It is significantly associated with a high rate of R1 resection at final histology, PDAC recurrence and poor survival.

Abstract P4-05-16: Immune landscape of glucocorticoid receptor high breast cancer

Abstract BACKGROUND: Glucocorticoid receptor (GR) activation is pro-apoptotic in lymphoid malignancies, whereas in estrogen-receptor negative (ER-) breast cancer, GR activation is anti-apoptotic and associated with relapse through a direct transcriptional role in tumor cells. A meta-analysis of GEO dataset has shown that higher GR expression is associated with an improved relapse free survival (RFS) in ER+ breast cancer but a worse RFS in triple negative breast cancer (TNBC). The relative contributions of GR expression on tumor vs. immune cells which may influence outcomes have not been studied. We hypothesize that there is a difference in the immune landscape between GR-high and GR-low tumors. METHODS: mRNA expression data was accessed from The Cancer Genome Atlas (TCGA) and METABRIC. K-clustering classified GR gene (NR3C1) expression into “high” and “low”. Computer algorithms TIMER, CIBERSORT, Immune pathway gene score, and cytolytic activity score (CYT) were used. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. RESULTS: 1904 and 1087 pts with stage I-III breast cancer had clinical and genomic data available in METABRIC and TCGA respectively. GR-high tumors had better median overall survival (mOS) [15 vs. 12yrs {HR 0.8(0.71-0.9), p&amp;lt;0.001}] in METABRIC, however, no significant difference observed in TCGA. GR-high tumors also had better median disease-specific survival (mDSS) [25 vs. 23.5yrs {HR 0.79 (0.67-0.93), p=0.005}] in METABRIC and [NR vs. NR {HR 0.4 (0.23-0.81), p=0.004}] in TCGA. Hormone receptor (HR) + subtype had better mOS [15.2 vs. 12.8yrs {HR 0.98(0.75-1), p=0.021}] but no significant difference in mDSS in GR-high vs. -low tumors in METABRIC; however, TCGA showed better mDSS [NR vs. NR {HR 0.4(0.22-0.92), p=0.049}]. TNBC subtype was associated with better mOS [17 vs. 7.4yrs {HR 0.66(0.48-0.9)}, p=0.0094] and mDSS [NR vs. 20yrs {HR 0.67(0.46-0.98)}, p=0.038] in GR-high vs. -low tumors in METABRIC; however, no significant differences were observed in TCGA. GR-high tumors had significantly higher number of immunomodulatory cells [B-cells, dendritic cells and mast cells] (p&amp;lt;0.001) and lower number of immunosuppressive cells [T regulatory cells (Treg) and T follicular helper cells] (p&amp;lt;0.001). There was a moderate correlation between GR-high and high CD8+T-cells (r=0.49, p=0.001) and macrophages (r=0.35, p=0.02). GR-high tumors had increased macrophages, lymphocyte infiltration and TGF-β response (p&amp;lt;0.001). Significantly higher expression of T-cell exhaustion genes PD-1, PD-L1, CTLA-4, IDO1 and TIM3 was observed in GR-high tumors (p&amp;lt;0.001). Strikingly, single cell sequencing data showed higher GR expression on immune cells (T-cells, B-cells and myeloid cells) compared to stromal or tumor cells (p&amp;lt;0.001), with significantly higher GR expression on CD8+T-cells compared to other immune cell subsets including Treg, CD4+T-cells, neutrophils, monocytes, dendritic cells, mast cells and macrophages (p&amp;lt;0.001). These findings explain why CYT was consistently elevated in GR-high tumors (p=0.001) observed both in TCGA and METABRIC. CONCLUSIONS: This study demonstrates that there are significant differences in the immune cell landscape in GR-high vs. GR-low tumors, suggesting that a higher immune cell infiltration accounts for greater anti-tumor cytolytic activity in GR high tumors. Thus, in addition to a direct transcriptional role for GR on tumor cells, contribution to outcomes by immune cells should also be acknowledged. Further studies examining the important contribution of factors causing activation/inactivation of immune cells in tumor microenvironment and their effects on clinical outcomes are warranted. Citation Format: Shipra Gandhi, Ahmed Elkhanany, Mateusz Opyrchal, Elizabeth A Repasky, Kazuaki Takabe. Immune landscape of glucocorticoid receptor high breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-16.

Abstract P3-08-38: Primary cutaneous melanoma of the breast in women. A retrospective study of 82 patients

Abstract Background: Primary cutaneous melanoma of the breast (PCMB) is a relatively uncommon type of melanoma staged according to the AJCC system for other cutaneous melanomas. However, whether their outcome is different from primary cutaneous melanomas of other sun-exposed sites and the features that predict outcome specifically in PCMB are currently unclear. Moreover, histologically, the breast skin is considered to be a special site for melanocytic lesions. Therefore, we analyzed a retrospective cohort of female PCMB patients to determine the clinical and primary tumor features that correlate with time-to-event outcomes of overall survival (OS) and disease specific survival (DSS). Design: We identified women with PCMB diagnosed and/or treated at our institution between 2002 and 2015. The following data were collected: clinical/ demographic features (age at diagnosis, ethnicity, anatomic site [nipple-areolar complex, upper, lower, medial, lateral]); primary tumor pathologic features (Breslow thickness, Clark level, ulceration, mitotic rate, vertical growth phase (VGP), regression, lymphovascular invasion (LVI), perineural invasion (PNI), tumor infiltrating lymphocytes (TIL) and cytology); and metastatic disease features (satellitosis, date and metastasis to sentinel and/or regional lymph nodes, clinical detectability of nodal metastasis, and date and site of distant metastases). Kaplan Meier methods, univariate and multivariate Cox proportional hazards regression models determined associations with OS and DSS. Results: 82 cases, including 16 in-situ and 66 invasive PCMBs were identified. Most patients were white (98%), with a median age at diagnosis of 40.5 years (range: 15-77). With a median follow up of 7.6 years, the 1, 3, 5, 10-year OS rates were 97.4%, 94.7%, 91.9% and 81.3%, respectively; the 1, 3, 5, 10-year DSS rates were 98.7%, 95.9%, 93.1% and 86.9%, respectively; the median OS and DSS were not reached. Thirteen patients developed metastasis: 5 regional only, 1 distant only and 7 both; of which 6 had metastatic disease at presentation. Eleven patients died, and 8 was due to progression of PCMB. Most of the invasive PCMB were of superficial spreading type (84.8%), with median tumor thickness of 0.47 mm. Univariate analysis of patients with invasive melanoma revealed the following features to be associated with shorter survival (Table 1): age at presentation, Breslow thickness, Clark level, ulceration, mitotic rate and VGP; while histologic type, anatomic site, LVI, PNI, regression, associated nevus, cytology, and TIL were not significant. Adjusting covariate of features significant in univariate analysis, the multivariate analysis demonstrated only Breslow thickness and ulceration to be independently associated with OS and DSS. Conclusion: Primary cutaneous melanomas of the breast often affects white adult women and increasing tumor thickness and ulceration are associated with shorter survival, similar to primary melanomas of other cutaneous sites. Table 1: Clinical and Primary Tumor Features Associated with Overall (OS) and Disease Specific Survival (DSS) in Primary Cutaneous Melanomas of the BreastUnivariate Analysis (p-value)Clinical/ primary tumor featureOSDSSAge at presentation ≥ 41.5 years0.0020.018Breslow Thickness0.0020.001Clark Level0.0040.003Vertical Growth Phase0.0430.038Mitotic Rate0.001&amp;lt;0.001Ulceration&amp;lt;0.001&amp;lt;0.001Regression0.2870.195Tumor Infiltrating Lymphocytes0.1370.278Lymphovascular Invasion0.1980.147Associated Nevus0.830.41Predominant Cytology0.7280.874Multivariate Analysis (p-value)Breslow Thickness0.0140.006Ulceration0.0060.017 Citation Format: Madhuchhanda Roy, Junsheng Ma, Aysegul A Sahin, Senthilkumar Damodaran, Michael T Tetzlaff, Jonathan L Curry, Ana M Ciurea, Jing Ning, Carlos A Torres-Cabala, Doina Ivan, Phyu P Aung, Merrick I Ross, Jeffrey E Gershenwald, Michael A Davies, Victor G Prieto and Priyadharsini Nagarajan. Primary cutaneous melanoma of the breast in women. A retrospective study of 82 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-38.

A Risk-Adjusted Model for Ovarian Cancer Care and Disparities in Access to High-Performing Hospitals.

To validate the observed/expected ratio for adherence to ovarian cancer treatment guidelines as a risk-adjusted measure of hospital quality care, and to identify patient characteristics associated with disparities in access to high-performing hospitals. This was a retrospective population-based study of stage I-IV invasive epithelial ovarian cancer reported to the California Cancer Registry between 1996 and 2014. A fit logistic regression model, which was risk-adjusted for patient and disease characteristics, was used to calculate the observed/expected ratio for each hospital, stratified by hospital annual case volume. A Cox proportional hazards model was used for survival analyses, and a multivariable logistic regression model was used to identify independent predictors of access to high-performing hospitals. The study population included 30,051 patients who were treated at 426 hospitals: low observed/expected ratio (n=304) 23.5% of cases; intermediate observed/expected ratio (n=92) 57.8% of cases; and high observed/expected ratio (n=30) 18.7% of cases. Hospitals with high observed/expected ratios were significantly more likely to deliver guideline-adherent care (53.3%), compared with hospitals with intermediate (37.8%) and low (27.5%) observed/expected ratios (P<.001). Median disease-specific survival time ranged from 73.0 months for hospitals with high observed/expected ratios to 48.1 months for hospitals with low observed/expected ratios (P<.001). Treatment at a hospital with a high observed/expected ratio was an independent predictor of superior survival compared with hospitals with intermediate (hazard ratio [HR] 1.06, 95% CI 1.01-1.11, P<.05) and low (HR 1.10, 95% CI 1.04-1.16, P<.001) observed/expected ratios. Being of Hispanic ethnicity (odds ratio [OR] 0.85, 95% CI 0.78-0.93, P<.001, compared with white), having Medicare insurance (OR 0.74, 95% CI 0.68-0.81 P<.001, compared with managed care), having a Charlson Comorbidity Index score of 2 or greater (OR 0.91, 95% CI 0.83-0.99, P<.05), and being of lower socioeconomic status (lowest quintile OR 0.41, 95% CI 0.36-0.46, P<.001, compared with highest quintile) were independent negative predictors of access to a hospital with a high observed/expected ratio. Ovarian cancer care at a hospital with a high observed/expected ratio is an independent predictor of improved survival. Barriers to high-performing hospitals disproportionately affect patients according to sociodemographic characteristics. Triage of patients with suspected ovarian cancer according to a performance-based observed/expected ratio hospital classification is a potential mechanism for expanded access to expert care.