Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma.

A woman in her 60s was diagnosed with a metastatic, unresectable rare histological type of liver cancer; combined hepatocellular cholangiocarcinoma. She had palliative chemotherapy, initially with gemcitabine and cisplatin, and then with oxaliplatin, L-folinic acid and fluorouracil. Both treatment strategies demonstrated disease progression, and somatic mutation profiling revealed no actionable mutations. The patient was started on immuno-oncology (IO) with nivolumab and ipilimumab, followed by maintenance nivolumab. She has achieved a sustained ongoing partial response since the start of this therapy for at least 12 months. The outcome in this patient is in keeping with the growing evidence of the role that IO agents have in metastatic biliary tract cancer and also serves to highlight their importance in mixed histology liver tumours.

Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations.

PURPOSE: We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease. METHODS: We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including BRCA1 and BRCA2, PALB2, ATM, Lynch syndrome, TP53, CDKN2A, and STK11. For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained. RESULTS: For men with relative risk (RR) 12.33 (CDKN2A) and RR 28 (STK11), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (STK11), with annual screening starting at age 45 years. CONCLUSION: Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR >12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level.

OBJECTIVE: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to <10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level. METHODS: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis. RESULTS: Projected LE gains from surveillance were <3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality. DISCUSSION: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.

Updated COVID-19 clearance time among patients with cancer in the Delta and Omicron waves.

BACKGROUND: COVID-19 infection delays therapy and in-person evaluation for oncology patients, but clinic clearance criteria are not clearly defined. METHODS: We conducted a retrospective review of oncology patients with COVID-19 at a tertiary care center during the Delta and Omicron waves and compared clearance strategies. RESULTS: Median clearance by two consecutive negative tests was 32.0 days (Interquartile Range [IQR] 22.0-42.5, n = 153) and was prolonged in hematologic malignancy versus solid tumors (35.0 days for hematologic malignancy, 27.5 days for solid tumors, p = 0.01) and in patients receiving B-cell depletion versus other therapies. Median clearance by single negative test was reduced to 23.0 days (IQR 16.0-33.0), with recurrent positive rate 25.4% in hematologic malignancy versus 10.6% in solid tumors (p = 0.02). Clearance by a predefined waiting period required 41 days until an 80% negative rate. CONCLUSIONS: COVID-19 clearance remains prolonged in oncology patients. Single-negative test clearance can balance delays in care with risk of infection in patients with solid tumors.

Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. METHODS: This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided. RESULTS: Among 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P < .00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver-directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%) (all P < .001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months; P < .001). CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

Partial response in non-resectable adenosquamous carcinoma of the pancreas with high tumour mutation burden treated with gemcitabine, nab-paclitaxel and pembrolizumab.

A previously healthy man in his 60s was diagnosed with a rare histological subtype of pancreatic cancer, adenosquamous carcinoma. After somatic mutation profiling, it was found that the tumour had microsatellite instability status high and a high tumour mutational burden. The patient was started on combination therapy with gemcitabine, nab-paclitaxel and pembrolizumab. Tumour size and biomarkers showed a dramatic response eventually leading to the patient being transitioned to maintenance therapy with pembrolizumab. The patient has demonstrated continued response since the start of the treatment. This is the first report in the literature showing a sustained response in this type of neoplasm that was treated with a checkpoint inhibitor, and thus adds to the evidence supporting universal somatic testing in all pancreatic cancers for a tailored approach to therapy.

Primary Undifferentiated Neoplasm of the Left Arm with Characteristics of Extragonadal Germ Cell Tumor and High-Grade Sarcoma.

A previously healthy man in his late 20s was diagnosed with a primary undifferentiated non- metastatic tumor of the left arm. After a biopsy, a clear pathological diagnosis could not be established. The tumor had positive immunohistological markers for both an extragonadal germ cell tumor and a high-grade sarcoma. Given the presumed germ cell etiology, he was started on empiric chemotherapy with etoposide and cisplatin. After a few cycles, the tumor showed dramatic response. However, due to poor patient follow- up, it progressed to massive size with severe compromise of the joint and critical neurovascular structures, which led to the decision for limb amputation. Post-surgical checkups showed no recurrence of the primary tumor or metastasis. This is the first report in the literature showing a tumor with these histological characteristics that responded to platinum-based therapy. It provides evidence for the need of more specific markers for the pathological evaluation of undifferentiated neoplasms.

Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model.

BACKGROUND: First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. METHODS: We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. RESULTS: For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days). CONCLUSIONS: Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. EXPERIMENTAL DESIGN: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes. RESULTS: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients. CONCLUSIONS: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

Burden of illness for patients with cholangiocarcinoma in the United States: a retrospective claims analysis.

BACKGROUND: Advanced cholangiocarcinoma (CCA) is associated with considerable morbidity and mortality. Novel second-line treatments for advanced CCA underscore the need to understand treatment patterns and economic burden of illness in clinical practice. METHODS: This retrospective, claims-based study using Optum's de-identified Clinformatics® Data Mart Database [2007-2019] selected patients with CCA who experienced failure of a line of therapy containing either gemcitabine or fluorouracil. The index date was defined based on evidence of treatment failure: date of last administration of the gemcitabine- or fluorouracil-based regimen plus 28 days, or initiation date of the next-line systemic therapy. Treatment patterns, healthcare resource use (HRU), costs, and survival were assessed during the follow-up period (index until death or end of eligibility). RESULTS: A total of 1,298 patients met inclusion criteria and had a mean age of 69.1 years. There were 958 patients (73.8%) with intrahepatic and 275 patients (21.2%) with extrahepatic CCA. Average follow-up was 7.5 months. Almost 40% of patients did not receive another line of therapy after the index date. Among the 784 patients who received another line of therapy, 40.3% used fluorouracil-based therapy, 30.7% used gemcitabine-based therapy, and 29.3% used capecitabine-based therapy. Total mean per patient per month CCA-related healthcare costs were $7,743, with medical services ($6,685) a larger driver of monthly costs relative to treatment costs ($1,058). Median overall survival (OS) was 5.3 months among all patients. CONCLUSIONS: Many patients with advanced CCA do not initiate additional therapy after failure of gemcitabine or fluorouracil treatment, and there is considerable variation in treatments among those who do. This study highlights the high costs and unmet need for a standard of care in this patient population.

Time to SARS-CoV-2 clearance among patients with cancer and COVID-19.

BACKGROUND: For cancer patients, coronavirus disease 19 (COVID-19) infection can lead to delays in cancer therapy both due to the infection itself and due to the need to minimize exposure to other patients and to staff. Clearance guidelines have been proposed, but expected time to clearance has not been established. METHODS: We identified all patients at a tertiary care hospital cancer center between 25 March 2020 and 6 June 2020 with a positive nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a cancer-related visit within 3 years, and at least one follow-up assay. We determined the time to clearance using American Society of Clinical Oncology (ASCO), the UK National Institute for Health and Care Excellence (UK-NICE), and Centers for Disease Control and Prevention (CDC) criteria. A matched non-cancer comparison cohort was also identified. RESULTS: Thirty-two cancer patients were identified. Nineteen were cleared by ASCO criteria, with estimated median time to clearance of 50 days. Fourteen patients resumed chemotherapy prior to clearance. Using UK-NICE criteria, median time to clearance would have been 31 days, and using CDC criteria, it would have been 13 days. The matched non-cancer cohort had similar clearance time, but with less frequent testing. CONCLUSION: SARS-CoV-2 clearance times differ substantially depending on the criteria used and may be prolonged in cancer patients. This could lead to a delay in cancer care, increased use of clearance testing, and extension of infection control precautions.

Time to SARS-CoV-2 Clearance Among Patients with Cancer and COVID-19.

QUESTION: What is the median time to clearance of SARS-CoV-2 among cancer patients according to currently used criteria? FINDINGS: In this single-institution retrospective cohort study, the median time to SARS-CoV-2 clearance was 50 days using the ASCO/CDC criteria of 2 negative RT-PCR assays >24 hours apart. Using alternative criteria of 1 negative RT-PCR assay (UK-NICE) or CDC clinical criteria (10 days after first positive RT-PCR and 3 days after last symptoms), median clearance times were 31 days and 13 days, respectively. Meaning: SARS-CoV-2 clearance times differ substantially depending on criteria used and may be prolonged in cancer patients.

Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study.

BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.

Pancreatic cancer treatment costs, including patient liability, by phase of care and treatment modality, 2000-2013.

OBJECTIVES: Our study provides phase-specific cost estimates for pancreatic cancer based on stage and treatment. We compare treatment costs between the different phases and within the stage and treatment modality subgroups. METHODS: Our cohort included 20,917 pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed between 2000 and 2011. We allocated costs into four phases of care-staging (or surgery), initial, continuing, and terminal- and calculated the total, cancer-attributable, and patient-liability costs in 2018 US dollars. We fit linear regression models using log transformation to determine whether costs were predicted by age and calendar year. RESULTS: Monthly cost estimates were high during the staging and surgery phases, decreased over the initial and continuing phases, and increased during the three-month terminal phase. Overall, the linear regression models showed that cancer-attributable costs either remained stable or increased by year, and either were unaffected by age or decreased with older age; continuing phase costs for stage II patients increased with age. CONCLUSIONS: Our estimates demonstrate that pancreatic cancer costs can vary widely by stage and treatment received. These cost estimates can serve as an important baseline foundation to guide resource allocation for cancer care and research in the future.

Family communication and patient distress after germline genetic testing in individuals with pancreatic ductal adenocarcinoma.

BACKGROUND: Germline genetic testing currently is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). In the current study, the authors assessed how often results are communicated to first-degree relatives within 3 months and the emotional impact of testing on patients. METHODS: A total of 148 patients who were newly diagnosed with PDAC and who had undergone testing of 32 cancer susceptibility genes at 3 academic centers were selected; 71% participated. Subjects completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) and a family communication survey. The results of both surveys were assessed at 3 months according to the genetic test result (positive, negative, or variant of unknown significance [VUS]) and whether a patient met criteria for genetic testing. RESULTS: A total of 99 patients completed the MICRA survey and 104 completed the family communication survey. The average age of the patients was 67 years, 47% were female, 29% had stage III/IV (AJCC 8th edition) disease, and 42% met genetic testing criteria. Approximately 80% of patients told at least 1 first-degree relative about their result. There was a trend toward greater disclosure among patients who tested positive (93% vs 77% for those with a VUS result [P = .149] and 74% for those who tested negative [P = .069]). Patients not meeting genetic testing criteria were less likely to disclose results (69% vs 93%; P = .003). MICRA scores did not differ by test result, age, stage of disease, or sex. CONCLUSIONS: The rate of result communication was high, although it was lower among patients who did not meet genetic testing criteria, those who tested negative, or those who had a VUS result. Testing-associated distress was similar across patient groups, and was comparable to that reported by other patients with cancer. Improved communication for all patients is crucial given the prognosis of PDAC, which limits time for disclosure.