bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic cancer: Cutaneous metastases, clinical descriptors and outcomes.
Authors: Gu Lilly , Paras Mehta , Rao Devika , Rotemberg Veronica , Capanu Marinela , Chou Joanne F. , Sigel Carlie S. , Busam Klaus J. , Boyce Lindsay , Gordon Allison , O'Reilly Eileen Mary
Published: January 2022

615

Background: The occurrence of cutaneous metastasis from pancreatic cancer (PC) is rare, and the exact incidence is unknown. The literature to date is primarily limited to isolated case reports. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. Methods: Institutional databases were queried using search terms “pancreas cancer” and “cutaneous mets”. Clinical history, demographics, PC cutaneous metastasis details, and survival outcomes were abstracted. Results were described using descriptive statistics, and overall survival (OS) from the diagnosis of cutaneous metastasis was estimated using Kaplan-Meier methods. Results: Of 140 on initial search, 40 patients met inclusion criteria of PC and cutaneous metastases and were analyzed. The median age (Q1-Q3, IQR) of pancreatic cancer diagnosis was 66.0 (59.3-72.3, 12.9) years. Most common histologic subtype was adenocarcinoma (n= 39, 98%), and one patient had a neuroendocrine malignancy. Most patients had stage IV disease at diagnosis (n=26, 65%). The most common location of the primary tumor was tail of the pancreas (n=17, 43%). Forty-eight percent (n= 19) had cutaneous metastasis at/within one month of cancer diagnosis. Most patients received chemotherapy (n=37, 93%), with 14 patients (35%) patients also receiving local therapy in the form of local excision or radiation. The most common cutaneous metastasis site was the abdomen (n=40, 66%), with umbilical lesions occurring in 58% (n=23) of abdominal lesions. The median interval (Q1-Q3, IQR) between diagnosis of pancreatic cancer and development of cutaneous metastasis was 1.4 (0-14.5, 14.5) months. The median OS (95% CI) from cutaneous metastasis diagnosis was 11 months (7.0, 20). Table details the observed differences between umbilical vs. non-umbilical metastases. Sixteen of 40 (40%) patients underwent somatic testing. The most frequently mutated genes were KRAS (n= 16, 100%), TP53 (n=7, 44%), CDKN2Ap14ARF (n=5, 31%), CDKN2Ap16INK4A (n=5, 31%), and CDKN2B (n=3, 19%). Germline testing was undertaken in 12 (30%) patients, and pathogenic variants were observed in 3: CHEK2 (n=1, 8%), BRCA1 (n=1, 8%), and ATM (n= 1, 8%). Summary of cutaneous metastasis characteristics. Conclusions: Cutaneous metastases from PC are rare and can be present at the time of diagnosis of stage IV disease, occurring most frequently in the umbilicus. Cutaneous metastases can be classified into umbilical and non-umbilical metastases, which may be due to a different biology.[Table: see text]
Retrospective study of survival outcomes in patients with hereditary pathogenic and variants of unknown significance mutations in pancreatic adenocarcinoma.
Authors: Lin Ching Ying , Moshayedi Natalie , Thomassian Shant , Gong Jun , Osipov Arsen , Hendifar Andrew Eugene
Published: January 2022

616

Background: Since 2019, all patients with pancreatic adenocarcinoma (PDAC) are recommended to undergo germline testing per the National Comprehensive Cancer Network guidelines. Outside of PARP inhibitors in germline BRCA mutated PDAC, the predictive and prognostic implications of these genetic alterations are unclear. Many hereditable mutations are continually discovered, but the majority are considered Variants of Unknown Significance (VUS). The purpose of this retrospective study is to characterize the clinical characteristics of multiple pathogenic and VUS germline mutations in PDAC. Methods: An IRB approved institutional database of PDAC patients (n=442) was queried for patients diagnosed between 2007 and 2021. Only patients who tested positive for hereditary mutations (n=35) or VUS (n=41) were included. Patients with both pathogenic mutation and VUS were considered in the pathogenic mutation group. Results: 76 patients (35 pathogenic, 41 VUS) were included in the analysis. Pathogenic mutations were divided into subcategories including DNA repair (n=21), polyposis (n=2), pancreatitis-associated (n=11), and other (n=2). With a mean follow-up period of 636 days, the overall survival (OS) for pathogenic mutations at 90 days, 180 days, 1 year, and 2 years was 100%, 97.1%, 88.6%, and 74.3% respectively. The cumulative recurrence was 2.9%, 11.4%, 22.9%, and 37.1%. For VUS, the OS was 97.6%, 95.1%, 75.6%, and 56.1% and cumulative recurrence was 0%, 14.6%, 31.7%, and 43.9% in the same time intervals. Conclusions: This data suggests that patients with germline mutations may have favorable outcomes when compared to the general population. Overall germline alterations in our intuitional cohort had a 2-year survival of nearly 75%. Notably, pancreatitis-associated hereditable mutations consisted a sizeable portion of our overall cohort. Although current therapy is most focused on DNA repair mechanisms, these results show that other novel germline genetic alterations may be prognostic and warrant further investigation.[Table: see text]
Clinical characteristics, treatment, and oncological outcomes in patients with ampullary cancer at a reference center in Mexico.
Authors: Torres Valdiviezo Lucero Itzel , Rodríguez Flores Karla Lucero , Rosas Camargo Vanessa Rosas , Noguez-Ramos Alejandro , Meneses Medina Mónica Isabel , Rosas Flota Ximena , Gamboa Dominguez Armando , Huitzil Melendez Fidel David
Published: January 2022

617

Background: Ampullary cancer (AC) represents 0.2% of gastrointestinal cancers. Given the rarity of the disease, information regarding treatment strategies and outcomes derives from studies that include the different types of periampullary cancers, which constitute a heterogeneous group. Our aim was to describe the clinical characteristics, treatment modalities and outcomes in patients (pts) with true AC treated at our institution. Methods: A retrospective review of medical records of all consecutive pts with histological diagnosis of AC evaluated at our institution from Jan 2009-Dec 2019. Clinical, pathological and laboratory variables at diagnosis were recorded. Overall survival (OS) was estimated by Kaplan-Meier and compared with the Log-rank test. Statistical significance was determined at P<0.05. Results: 133 pts with AC were included. Median age was 62 yo (IQR 53-70), 51.9% were women. 25% had ampullary adenoma history. Symptoms at diagnosis: 89% jaundice, 63% weight loss and 56% abdominal pain. Median laboratory values were total bilirubin 1.7 mg/dL (0.7-5.1), albumin 3.7 g/dL (3.1-4.2), hemoglobin 12.6 g/dL (10.9-14.2), carbohydrate antigen (CA) 19-9 34.7 U/mL (6.4-113.9) and carcinoembryonic antigen (CEA) 2.6 ng/mL (1.2-4.2). Most tumors were moderately differentiated (59%). Histologic subtypes of adenocarcinoma were available in 84 pts: intestinal 46.4%, pancreaticobiliary 39.3% and mixed 14.3%. Stage at diagnosis was localized (46%), locally advanced N+ (29%) and advanced (25%). For those with localized/locally advanced disease, 91% (91/100) underwent surgical resection, 25.3% (23/91) received adjuvant chemotherapy (ChT), 69.6% (16/23) received single agent and 30.4% (7/23) duplet. Pts who received adjuvant Cht presented N+ in 69.6%, moderate differentiation in 73.9%, intestinal 47.8% and pancreaticobiliary subtype 43.5%. In advanced setting, 63.6% (21/33) received palliative Cht, 66.7% received a duplet regimen. Median OS was 32.8 (22.9-42.8) months (mos). Median OS according to stage was 152.1, 28.1 and 10.2 mos for localized, locally advanced, and advanced, respectively (P<0.001). OS univariate analysis is shown in table. Conclusions: Most of pts presented with localized/locally advanced disease, were eligible to surgical resection and had a better survival. For those with N+ disease it is required to evaluate the role of adjuvant Cht. In the advanced setting, Cht improves prognosis.[Table: see text]
Genomic landscape in small intestine cancer from real-world data (RWD) of clinical genomic testing.
Authors: Takeda Hiroyuki , Yamamoto Hiroyuki , Oikawa Ritsuko , Umemoto Kumiko , Doi Ayako , Horie Yoshiki , Mizukami Takuro , Ogura Takashi , Izawa Naoki , Moore Jay A. , Sokol Ethan , Sunakawa Yu
Published: January 2022

642

Background: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide, however, large aggregated RWD of patients with advanced small intestine cancer have not been characterized. In particular, there has been limited data regarding examining CGP in pediatric/ Adolescent and Young Adult (AYA) small intestine cancer. For patient subgroups, it is unclear what clinically relevant alterations co-occur. Here, we investigated the genomic landscape of small intestine cancer patients, stratified by sub-group to help refine and discover new targets for improved cancer therapies in advanced small intestine cancer. Methods: This is a collaborative biomarker study using RWD paired with CGP testing (Foundation Medicine, Inc.). Hybrid capture was carried out on up to 395 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. One thousand three hundred sixty-four patients were available for analyses and were stratified by age (≥40/ < 40), MSI status, tumor mutational burden (TMB) status (High ≥10/Low < 10Muts/Mb), and select gene alterations. Using a chi-square test with Yate’s correction, frequencies of alterations were analyzed according to clinical or genomic background. Results: Genes with frequent alterations including mutation, amplification, and rearrangement/fusion were TP53 (59.8%), KRAS (54.8%), APC (27.7%), CDKN2A (22.4%), and SMAD4 (20.2%). Genomic profiling according to age, MSI, and TMB status is shown in the following table. In pediatric/AYA patients, frequency of APC alterations was significantly low ( P< 0.001). In KRAS mutated tumors, codon 12 most abundant mutations were G12D (31.1%) followed by G12V (22.3%), G12C (6.2%), and G12R (5.1%), while G13D (13.8%) was the predominant mutation in codon 13. In TMB-High tumors, which were detected in 12% of patients, the mutation rate of KRAS was modestly lower compared to TMB-Low tumors (42.3% vs. 53.3%). Frequent genes with amplification were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), CCND1 (3.4%), FGF19 (3.3%), and ERBB2 (2.3%). The number of any gene amplification was lower in MSI-High compared to TMB-High population. Conclusions: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer and differences in CGP according to clinical or genomic background. These findings would provide insight on the direction of the future development of the treatment in advanced small intestine cancer.[Table: see text]
Lower COVID-19 vaccination rates amongst Australians with gastrointestinal (GI) compared to other cancers.
Authors: Nguyen Mike , Bain Nathan , Grech Lisa , Hamad Nada , Chan Bryan Anthony , Blennerhassett Richard , Nott Louise M. , Harris Samuel J. , Chau Nguyen Minh Hieu , Underhill Craig , Williams Janne , Kwok Alastair , McCartney Amelia , Webber Kate , Day Daphne , Segelov Eva
Published: January 2022

648

Background: People with cancer are at higher risk of serious illness and death from COVID-19 infection. We investigated the differences in COVID-19 vaccine uptake and attitudes in people with various solid organ and hematological malignancies. Methods: An online survey of adult patients with cancer attending eight health services across four states in Australia, was conducted from June to September 2021. Demographics, cancer history and vaccination status were recorded. Only completed surveys were analysed. Variables were compared with chi-squared and multivariable analysis using logistic regression. Vaccine hesitancy was assessed using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford Vaccine Confidence and Complacency Scale, and the Monash Disease Vaccine Acceptance Scale. T-test analysis was used to examine relationships between the scales and groups. Results: There were 2997 evaluable responses; 53.2% female, 61.8% from metropolitan areas, 27.5% with metastatic solid organ disease and 50.6% on current anti-cancer treatment. Patients with GI cancers comprised 13.5% (n = 405), compared with hematological 28.4%, breast 24.6%, genitourinary 14.1% and other cancer types 19.4%. Vaccination rates were significantly lower for respondents with GI cancers compared to other cancer types (71.6% v 79.3%; p< 0.001). Significant differences in the GI cancer population compared to all others were: more males ( p < 0.001), lower level of education ( p= 0.001), fewer reporting English as first language ( p = 0.02) and shorter time since cancer diagnosis ( p < 0.001). These remained significant after logistic regression. Among GI cancer respondents, factors associated with being vaccinated compared to unvaccinated included: older age ( p < 0.001), higher education level ( p = 0.03) and English as first language ( p = 0.01). There was no significant difference in the scales measuring vaccine hesitancy, confidence and complacency, for the GI cancer population compared to other cancers. As expected, there were significant differences in all scales comparing vaccinated to unvaccinated respondents with GI cancers. Conclusions: In our large, contemporary survey, Australians with GI cancers report lower COVID-19 vaccine uptake compared with patients with other cancer types. We identified demographic and disease related characteristics that contribute to these differences. Interventions and targeted communication are required for people with GI cancers to maximise vaccination uptake in this medically vulnerable group.
HGCSG1902: Multicenter, prospective, observational study for patients with dysgeusia caused by chemotherapy for gastrointestinal cancer.
Authors: Ito Ken , Yuki Satoshi , Nakatsumi Hiroshi , Ando Takayuki , Sawada Kentaro , Yagisawa Masataka , Ishiguro Atsushi , Dazai Masayoshi , Iwanaga Ichiro , Hatanaka Kazuteru , Sato Atsushi , Matsumoto Ryusuke , Shindo Yoshiaki , Tateyama Miki , Muranaka Tetsuhito , Katagiri Masaki , Yokota Isao , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito
Published: January 2022

649

Background: Dysgeusia is the one of important adverse events in patients treated with chemotherapy because it could reduce daily oral intake and worsen patient’s nutritional status. It is said that the lack of zinc is often observed in patients with chemotherapy because taste buds cells injured by chemotherapy require large amounts of zinc for their regeneration and cytotoxic agents have the possibility of working as a chelator for zinc. Some retrospective studies showed that zinc administration may improve dysgeusia in patients treated with chemotherapy, however, there is no prospective study. Therefore, we planned this study to clarify the effect of zinc therapy on dysgeusia in patients with gastrointestinal cancer. Methods: This was a multicenter, prospective observational study. From February 2020 to June 2021, patients with dysgeusia during chemotherapy for gastrointestinal cancer were enrolled from 17 institutes in Japan. The investigator selected one of the following treatment: no intervention (N), polaprezinc administration (P: contains 34.1mg of zinc par daily normal dose), or zinc acetate hydrate administration (Z: contains 50-100mg of zinc par daily normal dose). Serum zinc levels were measured at baseline, after 6 and 12 weeks, respectively. Dysgeusia was assessed by questionnaires according to four criteria, CTCAE v5.0, Subjective Total Taste Acuity (STTA), Visual Analogue Scale (VAS), and Chemotherapy-induced Taste Alteration Scale (CiTAS) at the time of enrollment and after 12 weeks. Results: A total of 180 patients, 60 in each group, were enrolled in the study. The mean serum zinc levels in each group at baseline were similar (67.3, 66.6, and 67.5μg/dl in N, P, Z group, respectively) and lower than lower limit of normal. The mean alterations of serum zinc level from baseline to after 12 weeks were -3.8, +14.3, and +46.6μg/dl in N, P, Z group, respectively. The STTA score was significantly improved in the P group compared to the N group at 12 weeks (p = 0.045), whereas it was not improved in the Z group (p = 0.945). The association between the alteration values of serum zinc level and improvement of dysgeusia was not observed. Conclusions: In this study, administration of polarezinc or zinc acetate hydrate increased serum zinc levels, but there was no significant correlation between the degree of serum zinc elevation and the improvement of dysgeusia. The STTA score was improved only in P group, thus our results suggest there are any factors for improvement of dysgeusia by polaprezinc administration other than serum zinc levels. Clinical trial information: UMIN000039653.
Making cancer care accessible: The practicality and value of a virtual gastrointestinal tumor board (VTB).
Authors: Agarwal Mohit Shiv , Ogden John R , Chiec Lauren , Shonkwiler Erin , Chaby Michael , Dempsey Naomi , Pishvaian Michael J. , Klempner Samuel J , Benson Al Bowen , Lieu Christopher Hanyoung , Jahanzeb Mohammad
Published: January 2022

652

Background: Patients with cancer benefit from coordination with multiple subspecialties, often facilitated by discussion at a multidisciplinary tumor board. This enables collaboration on individualized patient plans and offers an opportunity for education. Regrettably, not all physicians have access to a multidisciplinary team, particularly those practicing outside of an academic setting or in underserved areas. Additionally, patients may want a second opinion but are limited by resources to travel to an academic center. A virtual tumor board could be a solution for these patients and physicians. Methods: Expert gastrointestinal (GI) oncology faculty in the US gathered via a virtual tumor board panel to discuss complex cases submitted by oncology providers and trainees. Panels consisted of a moderator and GI specialists from radiology, medical, surgical, and radiation oncology. The purposes of these panels were to test the feasibility of a virtual tumor board, provide expert opinions on complex cases, and create educational content. The panel’s recommendations were shared with the submitting providers within 48 hours and the recordings made available. Afterward, submitting physicians were surveyed to assess their satisfaction with the panel’s discussion and recommendations. Results: From March to June 2021, 4 GI virtual panels were conducted with 5 expert faculty discussing 44 patient scenarios from 14 providers; 12 providers (86%) submitted multiple cases. Surveys were sent to providers with a 50% response rate. Conclusions: Virtual tumor boards are feasible and lead to a high degree of satisfaction among the users. In this small cohort of responders, management of patients changed based on the panel’s recommendations, there was a perception that learning was improved, and the providers’ internal tumor boards’ recommendations were mostly included in the VTB discussion and expanded upon. Respondents felt that the service improved the care of patients and that they would submit future cases to this forum. Additional data from a larger cohort will be more helpful in understanding the impact of this endeavor.[Table: see text]
Validation of GIST nomogram performance from a statewide community cancer center.
Authors: Hitscherich Kyle Joseph , Garg Meera , Lozano Alicia J. , Hanlon Alexandra L. , Petrelli Nicholas J. , Bennett Joseph
Published: January 2022

654

Background: Malignant behavior of Gastrointestinal Stromal Tumors (GISTs) can be predicted based on characteristics (size, location, etc.) which have been used to create risk calculators to anticipate recurrence. The most utilized nomogram (Gold et al 2009) was applied to a patient population from a statewide academic community-based cancer center to evaluate performance compared to that of Memorial Sloan Kettering (MSK), Mayo Clinic and National Spanish Registry (GEIS) populations. Methods: A retrospective review of all operative pathology reports for the past 14 years (January 2005 – May 2019) identified all patients diagnosed with GISTs. Patient demographics, pathology characteristics and recurrence free survival (RFS) was compiled. Those without recurrence or death were censored at the date of their last follow-up within hospital system. The nomogram prediction of RFS was estimated using methods described in the original text. Concordance probabilities for risk stratified quartiles were calculated based on nomogram scores to test performance of the nomogram against our Kaplan-Meier curve. Results: A total of 195 patients were treated for GISTs at our institution within the study timeline. The small majority were female (54%) with an average age of 64 years at presentation (21-90). Only one patient did not follow up within our system (n=194). The most prevalent tumor location was in the stomach (68%) and overall mitotic index was preferentially less than 5 mitosis per high power field (77%). Surgical margins negative of microscopic disease were obtained in 93% of resections. The average tumor size on final pathology was 3.4cm (0.2-29). Within our patient population, 16 (8%) developed recurrences with 1 patient deceased. Kaplan-Meier estimated RFS rates were 91% at 2 years and 88% at 5 years with a mean disease-free survival of 8.8 years (SE=0.2). Concordance probability of the nomogram with our data was found to be 0.82 (95% CI: 0.71-0.92), compared to concordance within the MSK (0.78), GEIS (0.76) and the Mayo Clinic (0.80) populations. Overall, the nomogram predicts a worse 2- and 5-year RFS particularly for the highest risk malignant GISTs (0.82 vs 0.38 and 0.76 vs. 0.21). Conclusions: The concordance of the predictive nomogram was similar in our population to other published series. However, the nomogram overpredicts recurrence rates for the highest risk quartile of GIST patients. Our patient population fared better than the nomogram predicted, in particular for the patients at highest risk of recurrence.[Table: see text]
Exploration of drug resistance in advanced gastrointestinal stromal tumor.
Authors: Xu Hao , Xu Zekuan , Xu Jianghao , Shao Yang
Published: January 2022

662

Background: Gastrointestinal stromal tumors (GISTs) are prone to multi-drug resistance after drug treatment, but tissue samples from advanced patients with drug resistance are hard to obtain, impeding the study of the mechanism of drug resistance. In this study, plasma samples from TKI-resistant GIST patients were collected for next generation sequencing (NGS) to detect circulating tumor DNA (ctDNA), which were then used to generate mutation profiles leading to TKI resistance. Methods: A total of 82 GIST patients who acquired TKI resistance were enrolled from Apr. 2016 to Jun. 2021. Plasma ctDNA samples after drug resistance were collected for NGS analysis of 425 genes. Results: Among 82 patients, 54 received monotherapy with imatinib, 24 with 2 TKIs (21 with imatinib and subsequent sunitinib, 2 with imatinib subsequent regorafenib, and 1 with imatinib subsequent anlotinib), and 4 with 3 TKIs (imatinib subsequent sunitinib and regorafenib). Fifty patients (61%) were ctDNA-positive and their mutation profiles were further analyzed. Detection rate of ctDNA in imatinib-resistant patients was 57% (31/54). Among these 31 patients, 12 (39%) showed KIT gene mutation (8 with the known drug-resistant KIT mutations, 6 of these patients exhibited single-drug resistance while 2 showed multi-drug resistance due to KIT mutations mainly in Exon 13 V654A, Exons 17 Y823D, D820Y, N822Y, and N822K). The remaining 19/31 cases (61%) could be attributed to other gene mutations, with 47% due to cancer-associated mutations or other downstream signaling pathways (such as, cell cycle, TP53, RAS and PI3K). Among patients resistant to imatinib followed by other TKIs, ctDNA detection rate was 68% (19/28). Among these 19 patients, 10 (53%) showed KIT gene mutation (including 5 with the known drug-resistant KIT mutations, 4 of these patients exhibited single-drug resistance, while 1 showed multi-drug resistance due to mutations mainly in Exon 13 V654A, Exons 17 D820A, and D820G). The remaining 9/19 cases (47%) could be attributed to other gene mutations, with 44% due to cancer-associated mutations or other in downstream signaling pathways (such as Wnt, cell cycle, TP53, RAS and PI3K). Results indicated a growing trend of mutations leading to resistance among GIST patients treated with multiple TKIs (baseline vs. imatinib resistance vs. multiple TKIs resistance, 3.95% vs. 25.81% vs. 26.32%). Conclusions: Advanced GIST patients who received one or more TKI(s) may be resistant to single or multiple drugs due to complex mutations. NGS can be used to detect ctDNA without the need to obtain tumor tissue samples. This approach facilitates the monitoring of drug resistance in patients with advanced tumors, especially those with multiple metastases. NGS allows detection of mutations at multiple secondary sites and helps to overcome tumor heterogeneity, ctDNA-based NGS analysis will play an increasingly important role in assessment of drug resistance in GIST patients.
A feasibility study of leveraging the electronic health record to measure social determinants of health in patients with gastrointestinal cancer.
Authors: Hao Scarlett , Popowicz Patrycja , Iasiello Jack , Mejia Christopher , Wercholuk Ashley , Parikh Alexander A. , Snyder Rebecca A
Published: January 2022

666

Background: Social determinants of health (SDOH) or circumstances influenced by a patient's neighborhood, social, political, and economic environment are not routinely assessed, and the prevalence and burden of individual SDOH needs among patients with cancer is not well-understood. The primary study aim was to evaluate feasibility of implementation of an electronic health record (EHR) instrument designed to measure SDOH into routine clinical practice. Methods: A prospective study was performed of all adult patients with gastrointestinal malignancy presenting to a regional cancer center for initial evaluation (11/2020-7/2021). An SDOH screening was administered by a nurse navigator or social worker or medical student using the EHR. Primary outcome measures included % eligible patients screened, median clinic visit time compared to historical control, and acceptability to the inter-professional care team. Secondary outcomes included the number of identified SDOH needs per patient and subsequent interventions. Results: Of 118 eligible patients, 113 (95.8%) were successfully screened for SDOH. Nearly half self-identified as Black (40.7%; n = 46) and the remainder White (58.4%; n = 66); 4.4% (n = 5) were uninsured and 17.7% (n = 20) Medicaid-insured. Median visit time was 97 minutes (95%CI 70-107) before implementation and 100 minutes after (95%CI 75-119; p = 0.95). Team members reported no significant clinic disruptions and were supportive of ongoing use. Most patients had 2-3 total needs with 1-2 moderate or 1-2 severe needs. In addition, 21 patients had 4 total needs and 13 patients had 5 or more needs. Most common severe needs included physical activity (n = 62), stress (n = 55), tobacco use (n = 23), and food insecurity (n = 9). Most common moderate needs included social connections (n = 76), tobacco use (n = 44), physical activity (n = 21), and financial strain (n = 12). Resources were offered to 20 patients (17.6%) to address SDOH needs. Conclusions: Routine collection of SDOH in an outpatient oncology setting using an EHR instrument is feasible and non-disruptive to workflow. Further investigation to determine if standardized SDOH assessment can improve cancer care delivery on an individual and population level is ongoing.
Evaluation of post-discharge deterioration following major gastrointestinal cancer surgery.
Authors: Joung Rachel H. , Li Ruojia D. , Chung Jeanette W. , Bentrem David J. , Yang Anthony D. , Bilimoria Karl Y. , Merkow Ryan P.
Published: January 2022

667

Background: Clinical deterioration, defined as end-organ dysfunction following surgery, is a devastating, yet potentially preventable set of complications, usually occurring after an inciting event. The extent to which deterioration occurs post-discharge after major gastrointestinal cancer surgeries is unknown. Our objectives were to (1) evaluate the incidence of post-discharge deterioration (PDD), (2) characterize the events surrounding PDD, and (3) identify factors associated with PDD. Methods: Patients who underwent gastrointestinal resection for cancer were identified from the American College of Surgeons National Surgical Quality Improvement Program Participant Use Data File (2016-2019). Clinical deterioration was measured as a composite event consisting of respiratory failure, acute renal failure, cardiac arrest, or septic shock. Factors associated with PDD were evaluated using multivariable logistic regression. Results: Of 121,458 patients, 3,947 (3.3%) experienced clinical deterioration, with 19.1% occurring post-discharge. The median time to PDD from discharge was 8 days (IQR 4-13 days). Among patients who developed PDD, 58.9% had a previously diagnosed post-discharge complication, most commonly surgical site infection (38.2%), pneumonia (9.9%), and venous thromboembolism (5.4%). PDD was associated with older age, male sex, medical comorbidities, dependent functional status, longer operative time, transfusion, and discharge to a facility (all p < 0.05). Patients who underwent esophagectomy (OR 2.08 [95%CI, 1.39-3.10]) or pancreatectomy (OR 1.36 [95%CI, 1.07-1.74]) had significantly higher odds of developing PDD compared to patients who underwent colectomy. Conclusions: Post-discharge deterioration after major cancer surgeries commonly occurred after other potentially treatable post-discharge complications. Efforts should focus on improving post-discharge monitoring and timely and effective management of post-discharge complications to arrest their progression to post-discharge deterioration and mortality.
GOBLET: A phase 1/2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal cancers exploring treatment combinations with pelareorep and atezolizumab.
Authors: Arnold Dirk , Collienne Maike , Wilkinson Grey A , Loghmani Houra , Heineman Thomas Charles
Published: January 2022

TPS216

Background: Checkpoint blockade therapy only benefits a small subset of GI cancer patients (approximately 4%) with microsatellite instability-high (MSI-H) tumors, which are characterized as immunologically ‘hot’ (Bonneville et al., 2017). Most GI cancers, however, have microsatellite stable (MSS) tumors, which have an immunologically “cold” phenotype with fewer genetic mutations, reduced immune cell infiltration, and downregulated immune checkpoint proteins. These attributes make MSS tumors resistant to conventional immunotherapy including checkpoint blockade therapy (Ooki et al., 2021). Pelareorep is a naturally occurring, non-genetically modified reovirus. Upon intravenous administration, pelareorep selectively kills tumor cells and promotes several immunologic effects that prime tumors to respond to checkpoint blockade. These include the stimulation of tumor-directed innate and adaptive immune responses, increased T cell infiltration, expansion of new T cell clones, and increased PD-L1 expression in tumors (Samson et al., 2018, Manso et al. 2021 AACR). Given its expected synergy with checkpoint blockade, as well as its encouraging efficacy in prior GI cancer studies (Mahalingam et al. 2020), the GOBLET study is designed to evaluate pelareorep plus atezolizumab in multiple GI cancer indications. Methods: GOBLET is an open-label, non-randomized, multiple-cohort, phase 1/2 study in patients with advanced or metastatic GI cancers. This study employs a Simon two-stage design. Stage 1 comprises four treatment groups: Cohort 1 – First-line pancreatic cancer treated with pelareorep plus atezolizumab and chemotherapy (gemcitabine and nab-paclitaxel) (N = 12); Cohort 2 – First-line MSI-H colorectal cancer (CRC) treated with pelareorep plus atezolizumab (N = 19); Cohort 3 – Third-line CRC treated with pelareorep plus atezolizumab and chemotherapy (trifluridine/tipiracil) (N = 14); and Cohort 4 – Second-line or later squamous cell carcinoma of the anal canal treated with pelareorep plus atezolizumab (N = 10). The first 3-6 patients enrolled into the chemotherapy-containing cohorts (Cohorts 1 and 3) comprise a safety run-in that must be successfully concluded prior to enrolling additional patients into these cohorts. The primary objectives are safety and efficacy based on objective response rate (ORR) at week 16. Any cohort showing a promising ORR in Stage 1, based on pre-specified criteria, may be advanced to Stage 2 and enroll additional patients. Clinical trial information: 2020-003996-16.
A phase 1b/2 study of VS-6766 in combination cetuximab in patients (pts) with advanced KRAS mt colorectal cancer (CRC).
Authors: Shergill Ardaman , Liao Chih-Yi , Kindler Hedy L. , Polite Blase N. , Catenacci Daniel V.T.
Published: January 2022

TPS219

Background: KRAS mutations (mts) are present in about 45% of CRC and predict lack of response to anti-EGFR therapy like cetuximab. Limited therapy options exist for pts after prior 5-FU based regimens. Regorafenib or TAS-102 is commonly used however, the modest clinical benefit, and toxicity limit their use. Novel therapies are needed for pts at this point in their disease course. KRAS G12D and G12V mts occur in 11-12% and 9-10% of CRC, respectively, whereas G12C mts occur in 3-4% of CRCs . KRAS G12C mts occur in 3-4% of CRCs. Recently, results of phase 1/2 KRYSTAL-1 study were reported. Adagrasib (a KRAS G12C inhibitor) was used with/without cetuximab in heavily pretreated CRC pts harboring KRAS G12C mts. The objective response rate (ORR) and disease control rate (DCR) was 43% and 100% (resp.) in pts receiving cetuximab and adagrasib (28 evaluable pts), and 22% and 87%, resp., in those receiving adagrasib alone (42 evaluable pts). Phase 1b CodeBreaK101 study evaluating sotorasib ( KRAS G12C inhibitor) and panitumumab (anti-EGFR) combination in KRAS G12C mt CRC showed 15.4% confirmed ORR and 26.9% unconfirmed ORR. These data are encouraging, suggesting EGFR inhibition in combination with downstream KRAS inhibition may represent important therapeutic strategy for this disease. KRAS mts lead to constitutive activation of the MAPK pathway signaling and cell activation. VS-6766 is a novel dual RAF/MEK inhibitor which has shown activity in KRAS mutated tumors. Combination of EGFR inhibition and VS-6766 may overcome resistance of KRAS mt CRC cancers to EGFR inhibition alone. Preclinically, VS-6766 and EGFR inhibition showed synergy in KRAS mt CRC cell lines, including cell lines harboring KRAS G12D and G12V mts, and CRC PDX of KRAS G12V mt CRC showed tumor regression with this combination. These data support the development of VS-6766 with anti-EGFR therapy in KRAS mt CRC warranting this phase 1 study to evaluate safety and efficacy of this combination in clinical settings. Methods: This is an open label, single arm study evaluating VS-6766 with cetuximab in pts with KRAS mt advanced CRC. Phase 1b primary endpoints include safety and tolerability, and maximum tolerated dose and recommended phase 2 dose determination. ORR is the primary endpoint of the Phase 2 study. Secondary endpoints include OS and PFS. There will be upto 4 dose levels tested. Three de-escalation doses to find the optimal cetuximab dose, and one dose escalation of VS-6766, are planned. Eligible pts include those with metastatic CRC and progression after 5-FU, oxaliplatin, irinotecan and VEGFi therapy. Based on prior studies, dermatologic, gastrointestinal, ocular and CPK elevation have been the main toxicities noted with VS-6766. The study is funded by research grants from Verastem Oncology. Cetuximab will be supplied by Eli Lilly.
KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients.
Authors: Kim Richard D. , Prenen Hans , Rottey Sylvie , Kim Dae Won , Flament Anne , Lehmann Frederic , Van Cutsem Eric
Published: January 2022

TPS227

Background: The allogeneic chimeric antigen receptor (CAR) T-cell treatment CYAD-101 utilizes the NKG2D receptor that targets eight ligands expressed on tumor cells and also on stromal and immunosuppressive immune cells of the tumor microenvironment. CYAD-101 co-expresses a T-cell receptor (TCR) inhibitory peptide with the aim to eliminate the potential of graft versus host disease (GvHD), the main safety risk associated with engineered cells of allogeneic origin. In the previous alloSHRINK trial (NCT03692429), CYAD-101 was administered post FOLFOX preconditioning chemotherapy to 15 patients with progressive metastatic colorectal cancer (mCRC) who were previously treated with FOLFOX. Overall, the treatment was well tolerated with no evidence of GvHD. The disease control rate was 73.3% with two patients presenting a confirmed partial response per RECIST’s criteria (4 months and 8 months of duration from first CYAD-101 infusion) and nine had stable disease with a median duration of 4.6 months. Evidence of increase in the TCR repertoire and modulation of the cytokine profile post-treatment with CYAD-101 were observed implying that CYAD-101 may also be modulating the immune suppressive environment in patients mirroring what was demonstrated in pre-clinical models. We considered that a sequential therapy with the anti-PD1 monoclonal antibody pembrolizumab to further release the anti-tumor potential of this expanded T-cell population may drive deeper, more durable and new clinical responses beyond that currently demonstrated with the CAR T-cells alone. Methods: The phase 1b KEYNOTE-B79 trial (NCT04991948) will evaluate, according to a Simon’s two stage study design, the safety and clinical activity of three consecutive infusions of CYAD-101 (1x109 cells per infusion) post FOLFOX preconditioning chemotherapy with two-week interval between cycles, followed by pembrolizumab treatment (200 mg administered every three weeks for up to two years) in microsatellite stable/mismatch-repair proficient mCRC patients with recurrent/progressing disease after at least one metastatic line of therapy, which must include FOLFOX chemotherapy. The pembrolizumab treatment will be initiated 3 weeks after the last CYAD-101 infusion to fall outside the classical time window of potential CAR T-cell toxicities (e.g., cytokine release syndrome). The co-primary endpoints of the trial are the occurrence of dose-limiting toxicities (DLTs) at any time from the first FOLFOX preconditioning treatment up to 3 weeks after the first pembrolizumab treatment and the objective response rate (ORR) at the tumor assessment planned 6 weeks after the first pembrolizumab treatment administration. The KEYNOTE-B79 study will be initiated in Q4-2021 in five sites in USA and Europe. Clinical trial information: NCT04991948.
A prospective observational study to determine the feasibility of tumor response assessment by circulating tumor DNA (ctDNA) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT).
Authors: Chakrabarti Sakti , McKenna Edward , Oxencis Carolyn , Peterson Carrie , Hall William A. , Ludwig Kirk A. , Ridolfi Timothy , Erickson Beth , Miller James , Banerjee Anjishnu , Thomas James P.
Published: January 2022

TPS234

Background: Total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) is one of the standard treatment options for patients with locally advanced rectal cancer (LARC). A commonly employed TNT protocol consists of 8 biweekly cycles of oxaliplatin-based chemotherapy (CT) followed by radiation concurrent with fluoropyrimidine-based chemotherapy (CRT) for about 6 weeks. During the TNT, patients undergo tumor response assessments periodically with standard modalities (SM) consisting of pelvic magnetic resonance imaging (MRI) and proctoscopic/endoscopic examination. The objective of the current protocol is to evaluate the feasibility of tumor response assessment by ctDNA in patients with LARC undergoing TNT. The present feasibility study is designed to collect preliminary data to evaluate if a subsequent larger validation study is justified. If ctDNA-based response assessment is validated, ctDNA can potentially replace at least some components of the SM (for example, MRI) as tumor response assessment by SM is often time-consuming, expensive, and poses logistical challenges. Methods: Patients with LARC undergoing TNT will be enrolled. After obtaining informed consent, venous blood samples will be obtained for ctDNA level measurements at the following time points: baseline (within 1 week before the CT begins), after 4 cycles of CT within +/- 5 days of the MRI study, after 8 cycles of CT within +/- 5 days of the MRI study, and 1 to 14 days before TME. ctDNA levels will be measured by a commercially available ctDNA assay (Signatera by Natera), and ctDNA response is defined as >90% drop in the ctDNA level after treatment compared to the baseline level. Tumor response will be evaluated after 4 and 8 cycles of CT by SM. Primary endpoint: correlation between the response rate (RR) assessed by ctDNA and by SM after 4 cycles of CT. Secondary endpoints: 1) correlation between the RR assessed by ctDNA and by SM after 8 cycles of CT, and 2) correlation between the ctDNA defined RR and the complete pathological response (pCR) rate. The trial will enroll 30 patients. To evaluate the primary endpoint, differences in ctDNA levels between the baseline and 4-cycles post-CT will be computed. The differences will then be expressed as a proportion of each patient’s baseline level, D. This relative change, D, will be compared between the responder and non-responder groups using a two-sample Welch’s t-test. Similar methods will be applied for the secondary endpoints. All analyses will use the nominal type I error level of 0.05 and two-sided tests. Clinical trial information: NCT04670588.
Minimal residual disease assessment in colorectal cancer (MiRDA-C).
Authors: Dasari Arvind , Abdelrahim Maen , Acoba Jared David , Alluri Krishna Chaitanya , Dragovich Tomislav , Kazmi Syed Mohammad Ali , Musher Benjamin Leon , Sun Ryan , Wong Lucas , You Y. Nancy , Zaiden Robert Anthony , Kopetz Scott
Published: January 2022

TPS236

Background: Detection of circulating tumor DNA (ctDNA) in the bloodstream is emerging as a novel marker for identifying of radiographically occult microscopic or minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts) after curative intent treatments. Accumulating data suggest that ct-DNA defined MRD is a highly specific prognostic biomarker for future recurrences with a lead time of several months and prospective clinical trials are being conducted using ct-DNA defined MRD as an integral biomarker for improving risk stratification for adjuvant chemotherapy decision making. However, large scale, prospective data regarding kinetics of ctDNA-defined MRD with accurate pre-analytical methodology for plasma isolation and paired clinical data are limited. Methods: In this multi-center, prospective observational study, 1,000 pts with resectable CRC (stages II – IV) without other active malignancies undergoing therapy with curative intent will be enrolled any time from time of diagnosis up to start of adjuvant therapy (or ≤ 3 months post curative surgery, whichever is earlier). All therapeutic and surveillance visits decisions are at the discretion of the treating physicians. Serial biospecimens including blood (in Cell-Free DNA BCT tubes) to be processed to plasma and buffy coat in ≤ 2 days and formalin fixed tumor tissue will be collected at key time points until the time of radiographic recurrence or up to 5 years of surveillance. Blood draws will be at study entry, after each line of neoadjuvant therapy, post-surgery, during and after adjuvant therapy in addition to each surveillance visit. These blood draws will be coordinated with pts’ standard of care visits in order to minimize additional venipunctures. Relevant clinical data including demographics, cancer history, treatment details and outcomes, serum tumor markers and genomic data will be collected at each time point. Samples will be evaluated retrospectively with a primary objective of evaluating sensitivity and specificity of post-operative MRD for radiographic recurrences utilizing Guardant Health’s Reveal assay. Other key objectives include evaluating ctDNA kinetics with neoadjuvant and adjuvant therapies and to correlate with outcomes. The study is active, and enrollment is ongoing. Clinical trial information: NCT04739072.
PIONEER: A multicenter, open-label, randomized phase II trial of second-line apatinib plus chemotherapy versus chemotherapy alone in gastric and gastroesophageal junction adenocarcinoma (GA/GEA) refractory to or intolerant of prior anti-PD-1 therapy.
Authors: Yu Dandan , Liu Hongli , Hu Jianli , Ma Hong , Xue Jun , Liu Junli , Wang Jing , Lin Zhenyu , Jin Min , Yang Shengli , Zhao Lei , Zhang Tao
Published: January 2022

TPS361

Background: Immunotherapy has revolutionized landscape of cancer treatment. Anti-PD-1 therapy provides significant clinical benefit and durable response in various types of cancers. However, clinical response rate to anti-PD-1 therapy has been reported to vary from 10%-40% in different cancers. And, a substantial number of patients who initially responded to anti-PD-1 therapy developed acquired resistance over time. Few effective treatment options are available for such patients. Previous studies indicated that prior anti-PD-1 exposure might increase tumor response to anti-VEGFR2 (ramucirumab) plus chemotherapy in patients with advanced/metastatic GA/GEA. Apatinib, a highly selective VEGFR2 inhibitor, has been demonstrated to be efficacious and well-tolerated for the treatment of chemotherapy-refractory advanced GA/GEA. The PIONEER study is designed to evaluate the efficacy and safety of second-line apatinib plus chemotherapy in GA/GEA patients after prior anti-PD-1 therapy. Methods: PIONEER (NCT05029453) is a multicenter, open label, randomized phase II trial of second-line apatinib plus chemotherapy versus chemotherapy alone in patients with histologically confirmed advanced GA/GEA refractory to or intolerant of prior anti-PD-1 therapy for no less than 2 months. Patients must be ≥18 years of age, with ECOG PS of 0 or 1, and have measurable disease per RECIST v1.1, adequate organ function, and expected survival time of ≥12 weeks. Patients who previously received antiangiogenic agents (such as apatinib or ramucirumab), had concurrent or previous tumor history within past 3 years, or underwent anti-tumor therapy within 4-week of recruitment will be excluded. Approximately 60 patients will be randomized (1:1) to receive apatinib (500 mg orally qd) plus chemotherapy (docetaxel 60/75 mg/m2, d1 q3w, and nab-paclitaxel 125 mg/m2 d1 & d8 q3w or 260 mg/m2 d1 q3w) or chemotherapy alone until disease progression, unacceptable toxicity, or death. The primary endpoint is progression-free survival (PFS). The secondary endpoints are overall response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and adverse events (AEs) per NCI CTCAE v5.0. Patient enrollment has just started and is expected to be completed in June 2022. Clinical trial information: NCT05029453.