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Background Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. Methods We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). Results Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. Conclusions This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

High rates of cell proliferation and protein synthesis in pancreatic cancer are among many factors leading to endoplasmic reticulum (ER) stress. To restore cellular homeostasis, the unfolded protein response (UPR) activates as an adaptive mechanism through either the IRE1α, PERK, or ATF6 pathways to reduce the translational load and process unfolded proteins, thus enabling tumor cells to proliferate. Under severe and prolonged ER stress, however, the UPR may promote adaptation, senescence, or apoptosis under these same pathways if homeostasis is not restored. In this review, we present evidence that high levels of ER stress and UPR activation are present in pancreatic cancer. We detail the mechanisms by which compounds activate one or many of the three arms of the UPR and effectuate downstream apoptosis and examine available data on the pre-clinical and clinical-phase ER stress inducers with the potential for anti-tumor efficacy in pancreatic cancer. Finally, we hypothesize a potential new approach to targeting pancreatic cancer by increasing levels of ER stress and UPR activation to incite apoptotic cell death.

The fibroblast growth factor receptor (FGFR) pathway is essential in cell proliferation, differentiation, migration, and survival. Cancers such as intrahepatic cholangiocarcinoma (IHCA) have demonstrated alterations of FGFR allowing unregulated growth. Infigratinib (BGJ398) is a potent ATP-competitive inhibitor of all four FGFR receptors as demonstrated by the consistently high prevalence of hyperphosphatemia, indicating disruption of FGFR-related phosphate homeostasis.In this article, the authors discuss preclinical studies and the biological characterization of BGJ398 that inspired its investigation for cancer treatment. They summarize results from phase I and II studies and comment on ongoing phase III clinical trials primarily focusing on its role in treating IHCA.Infigratinib exhibits high potency FGFR1-3 inhibition in preclinical studies. Clinically, agents targeting FGFR including infigratinib show promising anti-tumor activity in targeted trials. Pemigatinib, an FGFR inhibitor, has recently been approved by the FDA for use in refractory IHCA. We believe infigratinib represents a promising agent in the treatment of refractory IHCA with FGFR2 fusions and is uniquely positioned to be a potential option in chemonaive patient populations. An ongoing phase III trial (PROOF-301) compares the efficacy and safety of infigratinib versus standard gemcitabine and cisplatin in untreated patients with IHCA and FGFR2 fusions.

While the associations of common metabolic conditions with ethnicity have been previously described, disparity among Hispanic individuals based on country of origin is understudied. This multi-institutional analysis explored the prevalence of metabolic conditions and their association with cancer subtypes among Mexican and non-Mexican Hispanics. After IRB approval, we conducted a cross-sectional study at two academic medical centers with a significant Hispanic patient population (Texas Tech University Health Sciences Center, El Paso, TX (TTUHSC-EP) and Cleveland Clinic Florida in Weston, FL (CCF)). A total of n = 1020 self-identified Hispanic patients with breast cancer consecutively diagnosed between 2005 and 2014 were selected from the two institutional databases. Comparisons between Mexican and Non-Mexican Hispanics revealed variations in tumor types and metabolic conditions. Mexican Hispanics were found to have a higher prevalence of diabetes mellitus (27.8% vs. 14.2%, p < 0.001), obesity (51.0% vs. 32.5%, p < 0.001), and ductal carcinoma type (86.6 vs. 73.4%, p < 0.001). On the other hand, hormone-receptor-positive breast cancer was more common in non-Mexicans, while Mexicans had more triple-negative breast cancer, especially in premenopausal women. In addition to highlighting these variations among Hispanic patients with breast cancer, this study supports a more focused approach to addressing obesity and other metabolic conditions prevalent in the Hispanic population with breast cancer. Moreover, Hispanic individuals with breast cancer are diverse and should not be lumped under one category without reference to their country of origin regarding the impact of race and ethnicity.

PURPOSE This investigation sought to evaluate the prognostic value of pretreatment of circulating tumor DNA (ctDNA) in metastatic biliary tract cancers (BTCs) treated with platinum-based first-line chemotherapy treatment. MATERIALS AND METHODS We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis, we considered the detected gene with highest variant allele frequency as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients' demographics, progression-free survival (PFS), and overall survival (OS). RESULTS The median age of patients was 67 (27-90) years. Fifty-four (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma, and six gallbladder cancers. Forty-six (68.6%) of the patients were treated with cisplatin plus gemcitabine, and 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations, whereas 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20, or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11, and IDH1 were the genes with highest frequency as DCAF. The median DCAF was 3% (0%-97%). DCAF > 3% was associated with worse OS (median OS: 10.8 v 18.8 months, P = .032). Stratifying DCAF in quartiles, DCAF > 10% was significantly related to worse PFS (median PFS: 3 months, P = .014) and worse OS (median OS: 7.0 months, P = .001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9. CONCLUSION DCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities.

Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients. In this review, we will address the biology and clinical results of FGFR inhibition in intrahepatic cholangiocarcinoma, highlighting limitations associated with treatment and discussing the use of circulating tumor DNA to detect mechanisms of resistance.

Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.

PURPOSEThis investigation sough to evaluate the prognostic value of pre-treatment ctDNA in metastatic biliary tract cancers (BTC) treated with platinum based first-line chemotherapy treatment.METHODSWe performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis we considered the detected gene with highest variant allele frequency (VAF) as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients’ demographics, progression-free survival (PFS) and overall survival (OS).RESULTSThe median age of patients was 67 years (27-90). 54 (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma and six gallbladder cancers. 46 (68.6%) of the patients were treated with cisplatin plus gemcitabine, 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations while 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20 or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11 and IDH1 were the genes with highest frequency as DCAF. Median DCAF was 3% (0-97%). DCAF >3% was associated with worse OS (median OS: 10.8 vs. 18.8 months, p=0.032). Stratifying DCAF in quartiles, DCAF>10% was significantly related to worse PFS (median PFS: 3 months, p=0.014) and worse OS (median OS: 7.0 months, p=0.001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9.CONCLUSIONDCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decrease survival probabilities.

Background: Sarcopenia is one of the early pathological features of cancer cachexia, yet the effect of sarcopenia on clinical outcomes in patients with advanced HCC is unclear. Our objective was to determine the effect of Sarcopenia on response to systemic therapy with advanced HCC. Methods: Patients with unresectable and advanced liver cancer were retrospectively evaluated between 2010 to 2019. Skeletal muscle area (SMA) was computed with a previously validated computed tomography (CT) body composition AI algorithm. The skeletal muscle index (SMI) was derived from the skeletal muscle area (SMA) (cm2) divided by patient height (m2) calculated from images at the level of L3 on pretreatment CT. Sarcopenia cutoffs for females was less than 39 cm2/m2 SMI or less than 50 cm2/m2 SMI for males. Patients’ demographics, systemic treatment response, toxicity, progression-free survival (PFS) and overall survival (OS) were compared between first-line therapy groups. Kaplan-Meier and Cox proportional hazards regression were used for survival analysis comparisons. Results: A total of 146 patients with advanced HCC were assessed from Mayo Clinic Arizona and Emory University. Seventy-six patients received immunotherapy as first-line treatment and seventy patients received TKI as first-line therapy. Sarcopenia at baseline was assessed in a total of 91 patients at first-line systemic treatment: n=48 with immunotherapy (IO) and n=43 with tyrosine kinase inhibitor (TKI). Sarcopenia was more prevalent in male patients (p=0.009), and in patients with low BMI (p=0.02). When comparing those with sarcopenia at baseline, higher response rate was observed in patients treated with IO without sarcopenia (47% versus 15%, p=0.019), this was not observed in TKI group. Interestingly, median PFS and OS was not significantly changed in patients with or without sarcopenia treated with IO or TKI on first-line therapy. Conclusions: Sarcopenia was associated with reduced response rate (RR) in patients treated with IO, but not in TKI groups. Both didn’t translate into deleterious effect in PFS and or OS. Further research with sufficient adjustments for confounding factors is warranted to better elucidate the prognostic value of sarcopenia in these patients. Citation Format: Gehan Botrus, Pedro Luiz Serrano Uson Junior, Heidi Kosiorek, Mehmet Akce, Isabela Chang, Zhubene Mesbah, Eric Yancey, Daniel Blezek, Jason Klug, Lana Khalil, Puneet Raman, Mohamad Sonbol, Mitesh Borad, Daniel Ahn, Tanios Bekaii-Saab. Prognostic impact of Sarcopenia on clinical outcomes in advanced hepatocellular carcinoma (HCC) treated with systemic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6274.

TPS4181 Background: The mainstay of treatment (TX) for pts with advanced or mPDAC consists of CT, with FOLFIRINOX and gemcitabine (gem)/nab-paclitaxel currently representing the front-line standards of care. TX is generally continued until either dis progression (progr) or cumulative toxicity, with pts often reaching a plateau in response after 4-6 mos. For those who have achieved dis control (stable dis or better) on front-line CT, a maint TX strategy that can effectively delay dis progr while preserving quality of life with minimal cumulative toxicity is highly desirable. However, aside from PARP inhibition in the subset of PDAC pts with gBRCA mutated dis, there is no current standard of care in this maint setting. Ival is a pan-HDAC (histone deacetylation) inhibitor that increases histone acetylation (HA), suppresses PDAC cell proliferation, and promotes apoptosis in PDAC cell lines in a dose-dependent manner. It has demonstrated synergy with 5-FU in cholangiocarcinoma cell lines and shows promising antitumor activity when combined with cap in syngeneic PDAC mouse models. On these bases, we are conducting a ph1b/randomized ph2 trial of ival plus cap vs cap alone in the maint setting for pts with mPDAC who have not progressed on front-line FOLFIRINOX. Methods: Key eligibility criteria include pts with mPDAC; no evidence of dis progr following at least 16 wks of front-line FOLFIRINOX at full or modified doses; ECOG PS 0-1; and no known gBRCA1/2 mutation. The study includes an initial dose-esc ph1b evaluating 3 dose levels of ival, (60, 125, and 250mg/m2 iv weekly on days 1 and 8) in combination (comb) with cap (1000mg/m2 po BID on days 1-14) of a 21-day cycle, using a standard 3 + 3 dose-esc design. Of note, ival 250 mg/m2 represents the RP2D identified in prior clinical studies of this agent both as monotherapy in solid tumors and in comb with gem/erlotinib in advanced PDAC pts. In the ph2 portion, pts will be randomized 1:1 to receive either ival plus cap or cap alone, in 21-day cycles, until dis progr, with tumor assessments occurring at 6-wk intervals. Blood will be collected at pre-specified serial timepoints for pharmacodynamic assessments, including HA of PBMCs. Primary endpoint for ph2 is investigator-adjudicated PFS. The primary analysis will compare PFS distributions in the ival/cap and cap alone arms using a one-sided log rank test with an alpha = 0.10. The assumed true 6-mo PFS rates are 35% (cap), based on historic data, and 60% (ival/cap), which corresponds to an HR of 0.487. Assuming an accrual duration of 18 mos and a dropout/lost to follow-up rate of 10%, the estimated total number of pts in the randomized ph2 portion is 52 (26 per arm). Enrollment is expected to being in spring 2022 across 25 U.S. sites.

Purpose Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. Materials and Methods From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. Results All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. Conclusion Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. Implications for Practice Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.

Background: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latina women nationwide. Hispanic women are more likely to be presented with advanced disease and might have adverse prognosis. Further, the Hispanics of Mexican-American origin might reflect different clinico-pathological characteristics as opposed to other Hispanics and ethnic groups. No previous largest studies comprised with Hispanics of Mexican-American origin explored tumor characteristics and compared to other ethnic groups. Thus, the aim of this study was to describe the clinico- pathological characteristics and disparities in breast cancer in this minority group at two tertiary care University- based medical centers in 2 states with a large Hispanic presence. Methods: After IRB approval, cancer registry was used to analyze the variables of 3,441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical centers in El Paso, TX and Loma Linda, CA between 2005-2015. Unadjusted and adjusted associations of race/ethnicity with cancer stage, hormone receptor status and treatment option were investigated, as well as comparison to other ethnic groups. Results: Overall 45.5% of the patients were Hispanic (n= 1566). Hispanics were more likely to be diagnosed at a younger age (57 years) compared to in non-Hispanic (NH) whites, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have HR+ & HER2- as opposed to 71% in NH whites. In addition, Hispanic individuals presented with advanced stages (III and IV) of BC (25.3%, 95% CI: 23% to 28%) similar to African Americans (25.4%), and had a lower proportion of lumpectomy versus mastectomy compared to NH whites (50%) but similar to African Americans (50%). Hispanic patients had the highest prevalence of triple negative BC (17.1% in Hispanics Versus 13.9 % in African Americans, versus 8.5% in NH whites). Hispanics also had significantly higher relative risk of HER2+/HR - disease (RRR=1.77, p Conclusions: This large multi-institutional study shows that Hispanics are diagnosed with breast cancer at a younger age, have a higher prevalence of triple negative and HER2 positive/HR- breast cancer, are diagnosed at more advanced stages of disease and undergo less lumpectomies compared to NH whites. Increased efforts geared toward early detection, improving awareness and access to health care is desperately needed in this rapidly increasing minority in the U.S. Citation Format: Otoukesh S, Nahleh Z, Mirshahidi HR, Nguyen AL, Botrus G, Badri N, Diab N, Alvarado A, Sanchez LA, Dwivedi A. “Disparities in breast cancer: A multi-institutional comparative analysis focusing on American Hispanics” [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-04.

132 Background: Enhancing equitable oncologic care is an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage. Methods: We performed a retrospective, case control study, (from 2014-2020); 39 Hispanic ethnicity uninsured patients (UP) from underserved communities with newly diagnosed BC and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, estrogen receptors and HER-2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients were treated at MCA. Results: Similar treatment patterns with radiotherapy, chemotherapy and surgery were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p < 0.001, percent of high school or lower (53.0 % v 23.2 %, p < 0.001), and lower income for UP (33733.5 v 64728.0 p values < 0.001).BMI was significantly higher for UP (30.6 V 24.7, p = 0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p < 0.001), hypertension (35.9 % v 20.2%, p = 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p = 0.013), and tobacco use (17.9% v 2.5%, p < 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p = 0.004), lower acceptance of nutrition consultation for UP (29.4% vs 7.4%, p = 0.024). Median time from mammogram to biopsy (25.5 days vs. 14 days, p = 0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p = 0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP and IP with newly diagnosed BC, we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling, nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations allowed development of tailored interventions to achieve greater equity in delivery of BC care at Mayo Clinic.

e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.

423 Background: Advanced PDAC remains a deadly disease with a 5-year survival rate of less than 10%. cfDNA - based next generation sequencing (NGS) may identify actionable alterations in patients with PDAC. In this study, we aim to determine the feasibility of utilizing serial cfDNA NGS testing and its potential relevance in predicting therapeutics outcomes. Methods: A total of 23 PDAC patients with PDAC cfDNA isolated from plasma collected at diagnosis and upon disease progression to first line SOC therapy and were analyzed on a 73-74 gene NGS panel (Guardant Health). Changes in molecular profiles from baseline to progression were analyzed for overall survival, progression free survival (PFS), and treatment response. PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test was used to compare the survival of different groups of patients. All p-values were two-sided. Analyses were performed using R (version 3.5.1, R Foundation, Vienna, Austria). Results: In this retrospective study, the 1-year probability of survival was 71% (median 473 days) and the 1-year PFS was 14% (median 212 days). TP53 and KRAS were the most frequently mutated genes identified in baseline samples, with 78% prevalence for each. Patients with clearance of TP53 17% (3/18) patients and/or KRAS 33% (6/18) patients clones after first line therapy significantly increases PFS (p=0.0056 and p=0.037, with HR of 0.087 and 0.32, respectively). However, appearance of TP53 or KRAS alterations upon progression does not significantly affect overall survival or PFS. Conclusions: The preliminary results from this study suggest that cfDNA clearance of TP53 and/or KRAS alterations may predict for improved PFS in PDAC. Confirmation of these findings in larger studies is warranted.

Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in a substantial group of patients and carries a significant mortality risk. With adequate risk stratification, catheter-directed techniques could be used as a therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter-directed thrombolysis (UCDT) represents a novel endovascular technique with good clinical and safety outcomes. Ultrasound-assisted catheter-directed thrombolysis can achieve reduction in the thrombus burden and improvement of pulmonary hemodynamics and right ventricular (RV) dysfunction and/or dilatation, without major procedure-related complications, major bleeding, or hemorrhagic strokes. This narrative review will focus on the major studies involving the efficacy and safety of UCDT in the intermediate-risk PE population. Prospective, randomized clinical trials with long-term follow-up and a large sample size are needed for further evaluation of mortality benefit and to further define which subgroup of patients may benefit from this novel endovascular technique.

Several randomized clinical trials have suggested the effectiveness of bevacizumab (Bev) in early and advanced breast cancer; however, due to the increased toxicity and lack of a clear long-term survival benefit, there is currently no defined role for Bev in breast cancer in the USA, while it has been approved in Europe. We herein sought to conduct a meta-analysis of large randomized trials comparing the efficacy and long-term outcome of neoadjuvant chemotherapy with Bev compared with chemotherapy without Bev in human epidermal factor receptor 2 (HER2)-negative breast cancer. A search was conducted through PubMed and Ovid Medline databases. Among the 279 articles identified, 5 met the eligibility criteria and were included in the present analysis. A total of 2,268 patients treated with Bev and 2,278 treated without Bev were analyzed. Pathological complete response (pCR) was obtained in 35% of patients treated with Bev and in 26% of those treated without Bev. A statistically significant increase (26%) in the incidence of pCR was observed in the Bev-treated group. However, patients treated with Bev exhibited no significant difference in the risk of disease recurrence or death. To the best of our knowledge, this is the first meta-analysis addressing the long-term outcomes of Bev in combination with chemotherapy in the neoadjuvant treatment of HER2-negative breast cancer. The results confirmed the significant benefit of Bev combined with chemotherapy compared with chemotherapy alone on breast cancer response, in both triple-negative and hormone receptor-positive cases. However, this benefit does not translate into a long-term disease-free or definitive overall survival advantage. Optimizing patient selection is desirable for maximizing the long-term benefits of Bev, while reducing cost and treatment-related adverse effects. Future efforts directed toward the discovery of predictive markers would be crucial for identifying the subset(s) of breast cancer patients who are most likely to benefit from Bev therapy.

BACKGROUND Breast cancer is the leading cause of cancer death in Hispanic/Latina women nationwide. Limited cancer research has been conducted in this population. El Paso, Texas is a large border city with a population of around 900,000, of which 85% are Latinos and would provide a suitable setting for this study. The aim of this study is to evaluate ethnic differences and cancer characteristics in Hispanic/latina women with breast cancer. METHODS After IRB approval, we retrospectively analyzed the variables of patients with breast cancer treated consecutively at a large tertiary medical center in El Paso, TX between 2005-2015. Descriptive statistics, bivariate, and multivariable analyses were conducted. RESULTS 1,252 patients were identified. Mean age at diagnosis was 57 years. 1074 were Hispanics/Latinas (86%). When comparing Hispanics versus non-Hispanics, 31% of Hispanics compared to 24% Non-Hispanics were diagnosed at age

Joint hypermobility is a common, primarily benign finding in the general population. However, in a subset of individuals joint hypermobility causes a range of clinical problems mainly affecting the musculoskeletal system and, to a lesser extent, extra-articular disorders. Joint hypermobility often appears as a familial trait and is shared by several inherited connective tissue disorders, including the hypermobility subtype of Ehlers-Danlos syndrome (hEDS) and benign joint hypermobility syndrome (BJHS/JHS). Although joint hypermobility has primarily been thought of as a rheumatological disorder, increasing evidence shows significant associations between both hEDS and BJHS with specific extra-articular disorders. To date, the strongest associations of these 2 conditions are with anxiety disorders, orthostatic tachycardia, various functional gastrointestinal (GI) disorders and pelvic and bladder dysfunction. This review article focuses on GI disorders associated with both hEDS and BJHS. The aim of this review is to evaluate existing research and literature regarding associations between JHS (hEDS/BJHS) and GI disorders. Our goal is to raise awareness of BJHS/JHS and hEDS as an explanation for chronic unexplained symptoms and functional GI disorders as well as to review the current standard tests available for proper evaluation of GI symptoms in these patients.

Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico‐ pathological characteristics and disparities in breast cancer in this group at two tertiary care University‐based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ & HER2− as opposed to 71% in non‐Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American). Conclusion: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR) = 2.05, P

Background & Aims Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. Methods We performed a case–control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. Results The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32–0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = . 001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20–0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67–11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88–79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40–0.77; P = . 01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7–41.3 months) and 24.1 months for nonusers (95% CI, 19.02–29.30 months; P = . 008). Conclusion In a case–control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

e16143Background: Limited data are available about the prognostic significance of Periostin in hepatocellular carcinoma (HCC). Previous studies showed that Periostin is associated with the epitheli...

We report a case of a 39-year-old woman with a recurrent aneurysmal fibrous histiocytoma of the right lower leg. Cytogenetic analysis of the tumor specimen disclosed a 46,XX,t(12;19)(p12;q13) karyotype. Multicolor fluorescence in situ hybridization (M-FISH), followed by conventional FISH analysis, confirmed the reciprocal translocation as the sole cytogenetic anomaly, and allowed for the positioning of chromosomes 12 and 19 breakpoints proximal to the BCL3 gene and between ETV6 and PIK3C2G gene loci, respectively. Our case highlights the importance of distinguishing this recurrent but benign lesion from similarly appearing malignant skin tumors. Cytogenetic analysis may contribute to the diagnosis of this uncommon but distinctive clinicopathological entity.

e15642Background: In the United States, the incidence of hepatocellular carcinoma (HCC) has been tripled over the last two decades. Despite the overwhelming effect of environmental risk factors of ...

577Background: There is currently no defined role of Bev in the treatment of BC, despite several studies suggesting activity in early and advanced BC. The achievement of PCR after neoadjuvant chemo...

e12052Background: Breast conserving therapy is one of the major advances in breast cancer over the past two decades. However, socioeconomic barriers and ethnic disparities still exist that preclude patients from receiving breast-conserving therapy. The current study aimed at determining the rate of mastectomy versus breast-conserving surgery in a low income Hispanic population at our institution and assesses factors that might affect disparity in surgical options. Methods: After obtaining IRB approval, we retrospectively used our Breast Cancer Database and reviewed consecutive cases between 2011-2013 and determined clinical characteristics. Unpaired and Fisher’s exact tests were used to compare the clinical and demographic characteristics between the two types of surgery. A multiple logistic regression was used to determine the factors associated with lumpectomy as compared with mastectomy. Results: A total of 265 patients were included a. The rate of lumpectomy was found to be 190(71.7%) while mastectomy...

416 Background: Prognostic modeling of hepatocellular carcinoma (HCC) is complex due to preexisting cirrhosis in most cases. Tumor features and factors related to functional hepatic reserve must be taken into account when considering treatment options or counseling patients about their survival. The key prognostic factors may vary at different stages of the disease especially for early stage. Methods: From 1992 to 2011 total of 397 HCC patients with T1N0M0 were referred to MD Anderson Cancer Center for treatment. Detailed clinical-pathologic information were retrieved from medical records. Univariate analysis was done using the c2or Fisher’s exact test for categorical variables. Kaplan-Meier used to estimate the median overall survival (OS). Multivariate cox regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: The male to female ratio was3:1. The mean age ± standard deviation was 65.04 ± 12.5, 57.2% were non-viral related, 59.7% had cirrhosis, and 9.3% had poorly differentiated tumor (PDT). Median OS (95% CI) was 28.5 months (23.6 – 33.4). First line therapy is summarized in table 1. Surgical intervention was similar to systemic therapy with 76% reduction in mortality compared to non-treated group. Restricted analysis among cirrhotic patients showed similar results. PDT was associated with significant poor prognosis compared to well-differentiated tumor, HR (95% CI) was 2.42 (1.36-4.28) after adjustment for demographic, epidemiological, and clinical factors. Conclusions: Our results indicate that T1N0M0 HCC patients have similar outcome with systemic therapy and surgery which could be beneficial for patients with underlying cirrhosis and high risk of postsurgical complications. [Table: see text]

e17506 Background: Missed outpatient appointments adversely impact medical outcomes and result in loss of revenue. We studied multiple variables for correlation with no shows (NSh) among IntlPts re...

4011 Background: Hep B virus (HBV) and hep C virus (HCV) are the main viral causes of hepatocellular carcinoma (HCC) development and are responsible for ~50% of USA cases. Because HBV is a DNA viru...

4019 Background: In the United States, the incidence of hepatocellular carcinoma (HCC) has been tripled over the last two decades. Despite the overwhelming effect of several environmental risk fact...

e15138 Background: Hepatocellular carcinoma (HCC) is a highly vascular tumors and angiogenesis play an important role in HCC prognosis and treatment response. Our study aim to evaluate the efficacy...