Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Challenges in Recruitment and Retention: Leveraging Health-Related Antecedents and Information Carrier Factors to Improve Patient Participation in Pancreatic Cancer Research-A Review Article.

ABSTRACT: Advancements in pancreatic ductal adenocarcinoma (PDAC) prevention, diagnosis, and treatment rely on representative and robust clinical trial participation. Given the severity of PDAC, along with the lack of effective early detection approaches, the need for accessible screening tools and new treatments is dire. Unfortunately, enrollment barriers often result in low participant accrual rates for PDAC studies and illustrate the challenging terrain researchers are facing. Research participation along with access to preventative care has been further impacted by the coronavirus disease 2019 pandemic. In this review, we use the Comprehensive Model for Information Seeking to discuss underexplored factors that influence patient participation in clinical studies. Adequate staffing, flexible scheduling, effective patient and physician communication, and culturally responsive messaging, along with the use of telehealth, can support enrollment objectives. Clinical research studies are a key component of health care, informing medical advancements, and improving outcomes. By leveraging health-related antecedents and information carrier factors, researchers can more effectively address barriers to participation and implement potential evidence-based mitigating strategies. While this work focuses on the PDAC research context, the lessons delineated here are applicable to the wider cancer research setting.

The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

INTRODUCTION: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up. RESULTS: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093). CONCLUSION: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

Telemedicine and intraductal papillary mucinous neoplasms: Analysis of a new follow-up strategy during COVID-19 outbreak.

BACKGROUND: The Coronavirus pandemic outbreak in 2019 and the saturation of healthcare system led to an increased use of digital tools for surveillance. In this study we described our experience using telemedicine to follow-up on patients with intraductal papillary mucinous neoplasms during the COVID-19 era and analyze those factors associated to patients' satisfaction. METHODS: This 1-year retrospective observational study enrolled patients with intraductal papillary mucinous neoplasms followed-up by telemedicine during COVID-19 outbreak. Patients with high-risk features needing on-site physical examination or declining remote follow-up were excluded. A 13-question survey was conducted; demographic, geographic, and employment information was collected. Univariate and multivariate analyses were performed to evaluate those factors associated to patients' satisfaction. RESULTS: Out of 287, a total of 177 patients with intraductal papillary mucinous neoplasms were included: the mean age was 69 (44-87) years and the male/female ratio was 0.78. A total of 80 (45.2%) patients had previously experienced abdominal pain. Most patients (85.3%) were satisfied with telemedicine: at univariate analysis, age ≥70 years (P = .007), retirement (P = .001), and absence of previous abdominal pain (P = .05) were significantly associated with patient satisfaction. At multivariate analysis, the absence of previous abdominal pain was the only factor independently associated with patient satisfaction (odds ratio 5.964, 95% confidence interval 2.21-16.11, P < .001). CONCLUSION: Telemedicine allows a new follow-up strategy that can be used in selected patients with intraductal papillary mucinous neoplasms. The absence of previous abdominal pain is associated with patient satisfaction during follow-up. Further studies are needed to evaluate safety of remote follow-up in patients with intraductal papillary mucinous neoplasms.

[Patient- and Family-Centered Physical and Psychological Distress Care Model for Adult Patients With Cancer].

Patient- and family-centered care (PFCC) has become more important due to advances in medical treatment and the impact of the COVID-19 pandemic. The evidence in the literature has proven the ability of PFCC to accomplish win-win results for the three principal parties (patients, family, and healthcare providers). In Taiwan, pancreatic cancer has risen to the 7th largest cause of cancer mortality, with increasing numbers of pancreatic-cancer-related deaths over the past ten years. Pancreatic cancer is difficult to diagnose early, and diagnoses are nearly always made during the late stage, resulting in high levels of physical and psychological distress for patients. This article was developed to introduce the core concept of PFCC and its evidence in the context of adult patients with cancer. Furthermore, the rehabilitation care model, based on PFCC, includes the 6 aspects of Family involvement, Optimistic attitude, Coping effectiveness, Uncertainty reduction, Symptom management, and Physical enhancement (FOCUS+P). A PFCC-based example of pancreatic cancer care is proposed that may be expanded to the care of patients with other types of cancer to improve the quality of life of patients and their families.

The Impact of the COVID-19 Pandemic on Multidisciplinary Clinics: A High-Volume Pancreatic Cancer Center Experience.

The unprecedented impact of the Sars-CoV-2 pandemic (COVID-19) has strained the healthcare system worldwide. The impact is even more profound on diseases requiring timely complex multidisciplinary care such as pancreatic cancer. Multidisciplinary care teams have been affected significantly in multiple ways as healthcare teams collectively acclimate to significant space limitations and shortages of personnel and supplies. As a result, many patients are now receiving suboptimal remote imaging for diagnosis, staging, and surgical planning for pancreatic cancer. In addition, the lack of face-to-face interactions between the physician and patient and between multidisciplinary teams has challenged patient safety, research investigations, and house staff education. In this study, we discuss how the COVID-19 pandemic has transformed our high-volume pancreatic multidisciplinary clinic, the unique challenges faced, as well as the potential benefits that have arisen out of this situation. We also reflect on its implications for the future during and beyond the pandemic as we anticipate a hybrid model that includes a component of virtual multidisciplinary clinics as a means to provide accessible world-class healthcare for patients who require complex oncologic management.

Impact of the SARS-CoV-2 pandemic on pancreatic cancer: diagnosis and short-term survival.

INTRODUCTION: The COVID-19 pandemic has delayed medical consultation, possibly leading to the diagnosis of gastrointestinal cancer. The aim of the study was to analyze the impact of SARS-Cov-2 pandemic on new diagnosis and short-term survival of patients with pancreatic cancer (PC). METHODS: All consecutive patients who had a suspected diagnosis of pancreatic lesion before (from March to September 2019) and during COVID 19 pandemic (from March to September 2020). Demographics, clinical and treatment were collected and compared. Short-term survival was assessed. RESULTS: A total of 25 patients (n=13 men) with diagnosis of adenocarcinoma of the pancreas and a median age of 70 years (IQR 62-74) were included. An increase was observed in the number of patients with newly diagnosed PC (n= 12 [19.1%] versus n=13 [20.9%]; P= 0.603). The subgroup analysis revealed a tendency toward a longer diagnosis (11 versus 12 days; P= 0.219) and treatment (28 versus 44; P= 0.375) delay for patients with PC during COVID-19 pandemic. A significant increase was observed for number of cases of advanced stage III and IV (n=4 [30.8%] versus n=7 [53.8%]; P= 0.006). Palliative treatment was the most frequent approach during COVID-19 period. During 1-year follow-up, 6 (50%) and 7 (61.5%) deaths were observed among patients diagnosed before and after COVID-19 (P= 0.449), respectively. CONCLUSIONS: The COVID-19 pandemic has led to delays in diagnosis and treatment in PC, which translates into an advanced staging and a worse prognosis. These data should stimulate health care provider to facilitate procedures for detection pancreatic cancer.

Impact of the COVID-19 Pandemic on Management of Patients with Metastatic Pancreatic Ductal Adenocarcinoma in the United States.

BACKGROUND: The purpose of this study was to understand how the COVID-19 pandemic has affected health care patterns and outcomes for patients diagnosed with metastatic pancreatic ductal adenocarcinoma (mPDAC) in 2020 compared with those diagnosed with mPDAC in 2019. PATIENTS AND METHODS: We used the Flatiron Health database to identify adults diagnosed with mPDAC from March 1 to September 30, 2019 (pre-COVID-19 cohort) and March 1 to September 30, 2020 (post-COVID-19 cohort). Between-cohort comparisons included demographic and clinical characteristics and year-over-year data for diagnosis of mPDAC, newly treated patients, time to and types of first-line therapy, and adverse events (AEs) during first-line therapy. Overall survival (OS) and milestone survival rates were evaluated. Kaplan-Meier methods were used to assess OS. RESULTS: Pre-COVID-19 (n = 923) and post-COVID-19 (n = 796) cohorts had similar baseline demographic characteristics. A smaller proportion of patients in the pre-COVID-19 cohort were initially diagnosed with stage IV disease versus the post-COVID-19 cohort (62.2% vs 69.7%). Between 2019 and 2020, there was a 13.8% decrease in diagnosis of mPDAC and a 13.0% decrease in newly treated patients. Median (interquartile range) times to first-line treatment were similar (21 [13-40] and 19 [12-32] days). Median OS (months) was significantly longer in the pre-COVID-19 cohort (8·4 [95% CI: 7·5, 9·0]) versus the post-COVID-19 cohort (6·1 [95% CI: 5·4, 6·9]; P < .001). Survival rates were higher in the pre-COVID-19 versus post-COVID-19 cohorts. CONCLUSIONS: During the pandemic, patients were initially diagnosed with PDAC at more advanced stages. While patients in both cohorts appeared to receive similar care, survival outcomes were adversely affected.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

Case presentation and panel discussion: Nutrition issues in cancer.

Advances in treatment of malignancy including novel pharmacologic therapies and surgical interventions has led to significant improvement in survival. As cancer becomes a chronic disease, nutrition interventions play an increasingly important role in short- and long-term outcomes. The current manuscript presents a case of a 66-year-old male with new diagnosis of pancreatic cancer diagnosed incidentally in the setting of COVID-19. Expert panelists in the field of nutrition discuss optimal strategies for diagnosis of malnutrition along with preoperative, perioperative, and postoperative optimization of nutrition. This discussion focuses on the use of probiotics, immune-modulating nutrition, fish oil, specialized proresolving mediators, and use of enteral and parenteral nutrition support.

New Insights Into Pancreatic Cancer: Notes from a Virtual Meeting.

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.

Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Novel Models of Genetic Education and Testing for Pancreatic Cancer Interception: Preliminary Results from the GENERATE Study.

Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (https://GENERATEstudy.org) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in BRCA2 (N = 15, 17%), ATM (N = 11, 12%), and CDKN2A (N = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches. PREVENTION RELEVANCE: Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.

Practical recommendations for the management of patients with gastroenteropancreatic and thoracic (carcinoid) neuroendocrine neoplasms in the COVID-19 era.

Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges.