bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pylori infection in patients with metabolic syndrome, with or without nonalcoholic fatty liver disease
Authors: Rakha Mohamed , Saleh Omayma , Abdelgawad Mohamed S. , El Baiomy Azza
Published: January 2021

Background

Helicobacter pylori (HP) infection is considered a risk factor of GIT diseases, e.g., gastric and duodenal ulcers and gastric carcinomas. It is transmitted through feco/oral route and can be diagnosed by many methods, e.g., stool antigen test (SAT). Metabolic syndrome (MET S) is considered a circle of metabolic derangements that can cause some complications as ischemic changes and heart diseases. Metabolic syndrome may also cause nonalcoholic fatty liver disease (NAFLD) resulting in liver fibrosis, cirrhosis, and HCC.

Results

The study included 300 subjects recruited from Obesity Clinic and Diabetes & Endocrinology Unit, Specialized Medical Hospital, Mansoura University. Two hundred of metabolic syndrome patients were subdivided into two groups according to the presence or absence of NAFLD, in addition to 100 subjects not having metabolic syndrome and served as control group. We found that HP infection is more frequent in MET S with NAFLD patients (73%) than in MET S without NAFLD (47%) with (P value < 0.001) emphasizing that HP infection increases the risk of NAFLD development in patients with MET S.

The study proved that HP infection is associated with increased degree of fibrosis significantly (P value < 0.001) with progression to marked fibrosis which may complicate with NASH with over all predictive value of 75% especially in patients with hyperglycemia.

Conclusions

Our findings show that a circle of metabolic abnormalities seems to be attributed to HP infection in MET S patients increasing the risk of fatty liver and progression to marked fibrosis especially with coexistent hyperglycemia, dyslipidemia, and upper body obesity.

Diagnosis and early eradication of HP infection will help in decreasing metabolic disturbances and possibility of NAFLD, and protect against marked fibrosis progression.
Exploration of 1, 2-naphthoquinone-4-sulfonate derivatizing reagent for determination of chlorthalidone in tablets: a spectrophotometric investigation
Authors: Chaudhari Suraj R. , Shirkhedkar Atul A.
Published: January 2021

Background

Chlorthalidone is a diuretic medicinal agent used to treat hypertension. Lowering hypertension results in the prevention of strokes, heart attacks and kidney-related problems.

Results

In this work, the spectrophotometric investigation was employed to examine the reaction between chlorthalidone and 1, 2-naphthoquinone-4-sulfonate. A reaction is performed at the alkaline environment (pH 9.2) and heated at a moderate temperature of 60 ± 1 °C using a water bath. The red colour product was produced, and it displayed a maximum absorbance at 440.50 nm. Further, the advancement of response conditions was explored by UV/visible spectrophotometer. The stoichiometric of the reaction was considered by using Job’s plot and the reaction mechanism of the proposed work was drawn. The established approach obeyed the calibration curve in the concentration range of 2–12 μg/mL with a regression coefficient superior to 0.994. The accuracy of the method, assessed by employing the % recovery, was in the range of 99.06–99.60% with the % relative standard deviation being less than 2%. The limit of detection and limit of quantification were 0.58 μg/mL and 1.72 μg/mL, respectively.

Conclusion

A UV/visible spectrophotometric investigation for the analysis of the chlorthalidone in the tablet matrix was successfully established and validated. The established investigation was found to be simple and accurate, and because of its ease of use, the proposed strategy could be applied for quality control investigation of chlorthalidone in pharmaceutical matrices.
Impact and utility of COLONTOWN, an online CRC patient and caregiver support group in clinical trial design.
Authors: George Manju , Smith Jesse Joshua , Miller Eric David , Romesser Paul Bernard , Seybold Nancy
Published: January 2021

140

Background: Online cancer patient and caregiver support groups have burgeoned in the recent years; many provide critical emotional support and experiential wisdom to newly diagnosed patients. We outline below our experience engaging patients in clinical trial design working with COLONTOWN, a 5000+ member, online colorectal cancer (CRC) patient and caregiver support and educational community. Effective trial design is a complicated and lengthy process that requires input from multiple sources. Complex trial design can be particularly challenging, where opinions are mixed and a clear path forward may not be visible. Informed patient perspectives from support groups can be invaluable in such situations. Methods: Principal Investigators (PIs) for the oligometastatic CRC ERASure trial and the Janus rectal cancer trial worked with the lead author, a patient who is the Scientific Director of COLONTOWN. An interactive survey strategy was adopted and followed to solicit group feedback. COLONTOWN members (n = 70-120) were enthusiastic to participate and share the logic behind poll choices, and their personal experiences. Poll participation led to additional scientific discussion and improved community engagement around the survey questions. Poll data and highlights of the discussion were collected and passed on to study PIs in a de-identified manner. Results: Feedback from COLONTOWN helped PIs gauge patient enthusiasm for trial concepts and provide patient perspective and clarity to controversial questions in study design. This was particularly useful where data to support more than one option was available and the guidance from the NCI Task Force or cooperative group was split. The perspective from COLONTOWN was invaluable and used alongside NCI Task Force and cooperative group feedback to make decisions to move the trial concept forward. Conclusions: Support groups such as COLONTOWN are a versatile, valuable, underutilized and available resource that can be used to tap into patient perspectives during any clinical trial design process. Ideally, when utilized early, structured patient input can provide unique insights to PIs developing clinical trial concepts that could eliminate barriers and shorten the inception part of trial design. Increased awareness and knowledge of trial design support provided by such cancer communities could facilitate the development of patient-friendly trials to promote better accrual.
Checkmate 577:Health-related quality of life (HRQoL) in a randomized, double-blind phase III study of nivolumab (NIVO) versus placebo (PBO) as adjuvant treatment in patients (pts) with resected esophageal or gastroesophageal junction cancer (EC/GEJC).
Authors: Van Cutsem Eric , Singh Prianka , Cleary James M. , Kelly Ronan Joseph , Moehler Markus H. , Kuzdzal Jaroslaw , Mendez Guillermo , Motoyama Satoru , Elimova Elena , Grootscholten Cecile , Sun Xiaowu , Taylor Fiona , Lawrance Rachael , Padilla Brad , Moreno-Koehler Alejandro , Zhang Jenny , Blum Steven I. , Ajani Jaffer A.
Published: January 2021

167

Background: NIVO is the first adjuvant therapy to provide a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus PBO in resected EC/GEJC following neoadjuvant chemoradiotherapy as demonstrated by CheckMate 577. NIVO was well tolerated with an acceptable safety profile. This analysis provides additional information on the exploratory HRQoL endpoints in this clinical trial. Methods: The effect of NIVO versus PBO on HRQoL, including general and disease-related symptoms, functioning, disease burden, and overall QoL, was assessed using FACT-E and EQ-5D-3L patient-reported outcome (PRO) questionnaires administered at baseline (BL), every 4 weeks during the 12-month treatment period, and at post-treatment follow-up visits (up to 2 years after last dose). Longitudinal change from BL in PRO scores over 12 months was assessed using descriptive statistics. Additionally, mixed model for repeated measures and time to deterioration analyses evaluated the difference between treatment with NIVO and PBO (data not shown). Results: 794 pts with EC/GEJC were randomized 2:1 to NIVO (n = 532) or PBO (n = 262). PRO completion rates were ≥ 95% at BL and ~ 90% at 12 months on treatment. Mean (SD) BL HRQoL scores were similar between treatment arms for the FACT-E total score (NIVO: 133.40 [20.97]; PBO: 134.03 [20.40]); esophageal cancer subscale (ECS; NIVO: 50.2 [9.3]; PBO: 50.1 [8.9]); EQ-5D Visual Analogue Scale (NIVO: 70.4 [22.3]; PBO: 69.1 [24.1]); and EQ-5D Utility Index (NIVO: 0.820 [0.179]; PBO: 0.831 [0.163]) based on the UK value set. Descriptive analyses showed a trend for increases from baseline at most time points through week 49 for both NIVO and PBO treatment groups for FACT-E total score, ECS, and EQ-5D Visual Analogue Scale and Utility Index. Conclusions: Preliminary results from CheckMate 577 demonstrated that pts on NIVO treatment showed trends of improvement in both esophageal-specific and general HRQoL. Similar trends were also observed in pts treated with PBO over 1 year. Pts treated with NIVO did not experience a reduction in HRQoL, further supporting clinical data to demonstrate treatment benefit and tolerability for adjuvant NIVO in pts with resected EC/GEJC. Clinical trial information: NCT02743494.
Update results of paclitaxel and cisplatin in combination with anlotinib as first-line regimen for advanced esophageal squamous cell carcinoma (ESCC): A multicenter, single-arm, open-label phase Ⅱ clinical trial.
Authors: Wang Junsheng , Luo Suxia , Li Ning , Wu Tao , Hong Yonggui , Guo Yanzhen , Cheng Yufeng , Li Baosheng , Tan Bingxu
Published: January 2021

181

Background: The prognosis of pts with advanced ESCC remains dismal clinically. Paclitaxel and cisplatin were used as the standard first-line regimen in ESCC for almost two decades. As a novel multitarget tyrosine kinase inhibitor mainly targeting antiangiogenic single pathway, anlotinib was demonstrated to be an effective second-line monotherapy for pts with advanced or recurrent ESCC in China. Consequently, the aim of this study was to investigate the efficacy and toxicity of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC. Methods: Pts with previously untreated metastatic or unresectable, locally advanced ESCC, who had not received (neo) adjuvant therapy/radical surgery within 6 months were recruited in this study. Eligible subjects were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 4~6 cycles during initial therapy. For those without progressive disease, maintenance treatment was administrated with anlotinib monotherapy (10mg, po, d1~14, q3w) until progression or unacceptable toxicity. The tumor response was assessed by investigator according to RECIST version 1.1 using CT scans every two cycles. And the calculated sample size of this study was 47. The primary endpoint was PFS, secondary endpoints were safety, objective response rate (ORR), disease control rate (DCR) and duration of response (DOR). Results: From Oct 2019 to Aug 2020, 27 pts were available for efficacy and safety evaluation. In best overall response assessment, there were 7.4% CR (2/27), 66.7% PR (18/27) and 25.9% SD (7/27). ORR was 74.1% (95%CI: 53.7. ~ 88.9), and DCR was 100.0% (95%CI: 87.2~100.0). The median PFS of the 27 pts was not yet available. The safety profile indicated that the most common drug-related adverse events were myelosuppression, gastrointestinal reaction, fatigue, hypertension, constipation, hypokalemia and hepatotoxicity. The common grade 3-4 treatment-related adverse events were myelosuppression (18.5%), hypertension (7.4%). Conclusions: The current results indicated that paclitaxel and cisplatin combined with anlotinib as first line therapy for advanced ESCC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more pts consecutively. Clinical trial information: NCT04063683. [Table: see text]
Racial ethnic disparities in clinical/pathological features, treatment, and survival among patients with early-onset colorectal cancer.
Authors: Lyudmer Michael , Patel Riya Jayesh , Chergui Adel , Tolu Seda Serra , Rao Devika , Kaubisch Andreas , Chuy Jennifer W. , Elrafei Tarek N. , Acuna-Villaorduna Ana , Goel Sanjay
Published: January 2021

21

Background: Globally, the incidence of early-onset colorectal cancer has risen. Racial disparities in colorectal cancer (CRC) are well-described, however data in EO by race/ethnicity is lacking. We aim to compare the presenting features, treatment, and survival features of patients with metastatic early-onset CRC (EO). Methods: Patients with metastatic CRC diagnosed between 2010-2019 at two NYC hospitals were identified by tumor registry (n = 646). Clinical/pathological features, treatment and survival data was collected by chart review and compared between Non-Hispanic Whites (NHW), Non-Hispanic Blacks (NHB) and Hispanics (H) using Chi-square or Fisher’s exact test. Kaplan Meier curves were plotted to compare overall survival (OS) among groups. Stata v15 was used for statistical analysis. Results: Of 646 CRC patients, 126 (21.5%) were NHW, NHB or H diagnosed with EO with a frequency ranging from 16.6% in NHW to 26.1% in H. Non statistically significant lower frequencies of male gender, low/moderate grade, left-sided tumors,and higher frequency of KRAS mutations were seen in NHB (Table). Metastectomy was performed in 20 patients (13.9%) and did not differ between groups. There was no difference in the use of chemotherapy or biologics in general (Table), but NHW were more likely to get cetuximab than NHB (OR:4.5, p = 0.02) and H (OR:4.7, p = 0.02).There were no differences in median OS (1.8 vs. 2.2 vs. 2 years, p = 0.9)or 1-year OS (72% vs 72.3% vs 70.8%) in NHW, NHB and H, respectively. A lower 5-year OS was seen in NBH (14.5%) and Hispanics (24.4%) compared to NHW (44%). Conclusions: EO-CRC is more frequently seen in minority racial/ethnic groups. Despite no differences in the use of chemotherapy or biologic treatment in general, NHB have a lower 5-year survival rate compared to NHW and H. [Table: see text]
Sintilimab plus oxaliplatin/capecitabine (CapeOx) as neoadjuvant therapy in patients with locally advanced, resectable gastric (G)/esophagogastric junction (GEJ) adenocarcinoma.
Authors: Jiang Haiping , Yu Xiongfei , Kong Mei , Ma Zhiming , Zhou Donghui , Wang Weibing , Wang Haohao , Li Ning , Wang Haiyong , He Kuifeng , Li Zhongqi , Lu Yiming , Zhang Jing , Zhao Kui , Zhang Yafei , Xu Nong , Teng Lisong
Published: January 2021

211

Background: The application of anti-programmed death 1 (PD-1) antibodies in neoadjuvant setting has not been well established. This phase 2 study (NCT04065282) was conducted to evaluate the efficacy and safety of sintilimab plus CapeOx as neoadjuvant therapy for resectable G/GEJ adenocarcinoma. Methods: Patients with histologically confirmed resectable G/GEJ adenocarcinoma (stage cT3-4NxM0) were enrolled to receive neoadjuvant therapy with sintilimab (3mg/kg for wt < 60kg, 200mg for wt ≥60kg, Q3W) plus CapeOx (oxaliplatin 130mg/m2 iv D1, capecitabine 1000mg/m2 bid po D1-14, Q3W) for 3 cycles. Gastrectomy was scheduled within 4 weeks after last dose of neoadjuvant treatment. Tumor imaging evaluation was performed at baseline and within 1 week before gastrectomy. The primary endpoint was pathological complete response (pCR) per Becker criteria. Results: As of August 4, 2020, 36 pts were enrolled. Patients who had received gastrectomy after neoadjuvant treatment (n = 26) were included in this analysis. 25 (96.2%) pts completed 3 cycles of neoadjuvant treatment, except one completed 2 cycles due to grade 3 AST increased. All pts received complete resection (R0). 6 (23.1%) pts achieved pCR (TRG1a) and 14 (53.8%) pts achieved major pathologic response (MPR, TRG1a/b). 3 pts had partial response (ORR was 3/5 among pts with target lesions) and no patients progressed per RECIST 1.1 before surgery. Among 18 pts who received PET-CT evaluation per PERCIST, 11 (61.1%) achieved partial metabolic response (PMR). Neoadjuvant treatment-related AEs (neoTRAEs) to any drug were reported in 25 (96.2%) pts. Mostly TRAEs were grade 1-2, and only 6 (23.1%) pts experienced grade 3 TRAEs (Neutropenia in 4 pts, Leukopenia, Thrombocytopenia, AST increased, and GGT increased in 1 pt each). One patient experienced grade 1 hypothyroidism which is considered to be immune-related AE. There is no serious peri-operative complication and mortality. Conclusions: Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with high pCR and MPR rate and well-tolerated safety profile in neoadjuvant settings. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Clinical trial information: NCT04065282.
Exploring the diagnostic journey and life impact of patients with cholangiocarcinoma (CCA): Results from a large patient survey in the United States.
Authors: Bibeau Kristen , Bachini Melinda , Lindley Anouk , Barkey Natalie Marie , Lindsey Stacie
Published: January 2021

277

Background: Patients (pts) with CCA typically present with advanced disease and face a poor prognosis and impaired quality of life (QoL). Despite improvements in therapies, the impact of CCA on pts’ daily lives has been rarely studied. This pt-focused survey explored the diagnostic journey, life impact including work status, QoL and psychosocial impacts of CCA. Methods: Pts with CCA were recruited in partnership with the Cholangiocarcinoma Foundation from Aug 23 through Sept 20, 2019, and were categorized by AJCC stage. Pts participated in a 30-min online survey to assess disease staging, symptoms, demographics, diagnosis journey, daily life impact, mental health, and sexual function. The survey included the validated disease specific European Organization for Research and Treatment of Cancer (EORTC) QLQ-BIL21, the Patient Health Questionnaire-9 (PHQ-9), and the Work Productivity and Activity Impairment (WPAI) questionnaire. Results: Of 1,286 pts invited, 707 (55%) completed the survey (male, 77%; age ≥55 y, 13%; currently employed, 78%; perihilar CCA, 47%; intrahepatic CCA, 41%; distal CCA, 12%; stage 1–2, 22%, stage 3a, 51%, stage 3b–4, 20%, in remission, 4%, unknown stage, 2%). Median duration from symptom onset to CCA diagnosis was 19 months (range, 1–241), and median duration from diagnosis to completing survey was 24 months (0–744). Initial misdiagnosis occurred in 35% of pts (n=247); among whom the most common misdiagnosis was gall bladder cancer (52% [n=129]); misdiagnosis of cancer of unknown origin occurred in 9% of pts (n=21). CCA was most frequently first suspected and diagnosed by oncologists (38% [n=269] and 70% [n=492]); among non-specialty physicians, more first suspected than diagnosed CCA (eg, primary care physicians, 22% [n=156] vs 3% [n=22]). Pts’ primary considerations in treatment decisions were physician judgment (38% [n=272]), QoL (16% [n=111]), time spent in hospital (11% [n=75]), laboratory results (11% [n=79]), other pt experiences (6% [n=42]). On the EORTC QLQ-BIL21, pts reported negative life impact from anxiety (mean [SD], 52.9 [19.2]), tiredness (52.3 [19.3]), and treatment (51.3 [28.8]). On the WPAI, 61% of pts (n=429) reported some, and 28% (n=200) reported considerable impact on work status. On the PHQ-9, 58% (n=408) of pts reported significant impact of depression on daily life, with 72% (n=506) and 25% (n=177) reporting that depression makes daily life somewhat, or very difficult, respectively. Pts also reported considerable or some impact on sexual desire (51% [n=362]; 36% [n=255]) and intimacy (47% [n=332]; 39% [n=273]). Conclusions: Pts with CCA who participated in this survey were mostly <55 y of age and had experienced CCA symptoms for an extended time (2 y) before diagnosis, at which time CCA was often initially misdiagnosed. The burden of CCA symptoms on daily lives, work productivity, and mental health is immense.
The impact of changes in service delivery in patients with colorectal cancer during the first peak of the COVID-19 pandemic.
Authors: Kamposioras Konstantinos , Lim Kok Haw Jonathan , Saunders Mark P. , Marti Kalena , Anderson Daniel , Cutting Mark , McCool Danielle , Connell Jacqueline , Simpson Lilly , Hasan Jurjees , Braun Michael , Lavin Victoria , Mullamitha Saifee , Barriuso Jorge
Published: January 2021

28

Background: Increased levels of anxiety and distress in both patients and physicians have been reported in response to the significant impact COVID-19 has on cancer service delivery globally. We aimed to investigate how these changes have been perceived by patients diagnosed with colorectal cancer and identify determinants of increased anxiety. Methods: Survey (32-item) of consecutive patients diagnosed with colorectal cancer attending a large tertiary comprehensive cancer centre in the United Kingdom (18 May to 1 July 2020). Self-reported GAD-7 (both paper/electronic forms) was used as a screening tool for anxiety. Statistical analyses of associations:Chi-square, Fisher’s exact, and uni- and multi-variable analyses were performed using SPSS v19 and R. Results: A total of 143 patients (response rate 67%), 82% male, and median age of 61-70 years were included. Majority of patients had telephone consultation (78%), including 40% who had scan results discussed over the phone; with favourable feedback received with both respectively. Twenty-three patients (18%) were considered to have anxiety, with 7 (6%) scoring for moderate or severe anxiety. Three items asked patients if they had concerns about getting COVID-19, were worried that COVID-19 would have effect on mental health, and affect their experience of cancer care. Patients answering positively to any of these items were most likely to have anxiety; multivariate analysis – OR 2.361 (95% CI 1.187-4.694, p=0.014), 3.219 (95% CI 1.401-7.395, p=0.006) and 3.206 (95% CI 1.036-9.920, p=0.043), respectively. Majority of the patients did not feel that they needed support during the pandemic period and hence the available well-being services were not used. Patients felt that friends and family had been very supportive but less so the primary care services (p<0.05). However, they felt they were supported by the clinical team. Conclusions: At our centre, during the first-peak of COVID-19 pandemic in the UK, patients with colorectal cancer did not display increased rates of significant anxiety. The findings of this survey suggests that some service changes implemented, including increased telephone follow-up, may have already improved the overall experience of cancer care. Importantly, patients were much more concerned about their cancer treatment than COVID-19, emphasising the need to continue to provide comprehensive cancer care even if we get a “2nd wave” of COVID-19.
Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.
Authors: De Baere Thierry , Veloso Gomes Filipe , Verset Gontran , Tovar-Felice Gerardo , Malagari Katerina , Coimbra Elia , Bruix Jordi
Published: January 2021

287

Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]
Understanding the impact of COVID-19 on the colorectal cancer community: Barriers and opportunities for care.
Authors: Garcia Reese , Dwyer Andrea , McDonnell Molly
Published: January 2021

29

Background: The novel coronavirus (COVID-19) has caused numerous disruptions across the cancer prevention and treatment landscape. Conservative modeling studies examining the effect of COVID-19 on cancer screening and treatment for breast and colorectal cancer (CRC) suggest that there will be 10,000 excess deaths from both cancers combined over the next decade. The goal of this analysis was to better understand the impact of COVID-19 on the CRC community, including gaps and opportunities for improving access to care and survivorship needs, and to advocate for the best possible care through policy, education and engagement of the entire cancer ecosystem. Methods: In April 2020, Fight Colorectal Cancer (Fight CRC) distributed an online survey to the colorectal cancer community. The survey was distributed through social media channels and targeted emails from April 24-May 5, 2020. Virtual focus groups were also conducted to gather rich qualitative data from cancer patients and caregivers about their experiences during the novel coronavirus pandemic. Results: In total, 222 individuals responded to the survey (survivors = 68%, caregiver = 12%, first degree family member = 8%, other = 8%), and 10 CRC survivors participated in focus groups (stage III = 30%, stage IV = 70%). Treatment disruptions and mental health were prevalent themes in both the survey and focus group. Over one-third of survey respondents indicated facing treatment disruptions (37%) and a majority (78%) of colorectal cancer patients reported feeling nervous and anxious. Another primary concern among respondents was access to care. Patients on Medicare were more likely than patients on private insurance to report having difficulties affording food and basic supplies. People living in rural areas were more likely to have greater concerns about maintaining a supportive network than those living in suburban areas. Conclusions: People with cancer face unique challenges as a result of the novel coronavirus, including treatment disruptions, increased feelings of anxiety, and financial concerns. Numerous health inequities also exist among low-income and rural patient groups. Identifying the barriers that patients face provides an opportunity to address the nuanced needs of the colorectal cancer community. Clinicians, supportive care providers, and advocacy organizations can tailor care delivery, increase access to care, and prepare patients for the future with reliable and accurate resources amidst a pandemic.
The use of cabozantinib in advanced hepatocellular carcinoma (HCC): Hong Kong multi-center experience.
Authors: Dong Yawen , Leung Thomas Wai-Tong , Kwok Gin Wai , Tang Vikki , Li Bryan , Leung Roland Ching-Yu , Chiu Joanne Wing Yan , Wong Jeffrey Sum Lung , Ma Ka Wing , She Wong Hoi , Tsang Wing Yan Josephine , Cheung Tan To , Yau Thomas
Published: January 2021

316

Background: In the phase III CELESTIAL trial, cabozantinib showed significant improvement in overall survival with good tolerability in advanced HCC population. We aimed to evaluate the efficacy, survival and tolerability of cabozatinib in advanced hepatocellular carcinoma (HCC) patients in a real life setting. Methods: Between February 2018 and October 2019, consecutive advanced HCC patients who received cabozatinib alone or in combination at University of Hong Kong Health System hospitals were analysed. Cabozantinib was administered at 60 mg continuously daily. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and tolerability were evaluated. Results: Overall, 22 patients were included. The median age was 57.1 years (range 48.5-58.6). All patients except one were hepatitis B carriers. More than 80% of the patients had underlying Child-Pugh A cirrhosis. Most patients had metastatic disease (95.5%). More than 70% of patients received cabozantinib beyond second-line, and most of the patients had prior exposure to tyrosine kinase inhibitor (TKI) and/or immunotherapy. The median time from the start of first-line systemic treatment to the start of cabozantinib was 11.2 months. Cabozantinib was administered to 11 patients (50%) as single agent, while the other half received cabozantinib in combination with mostly immune checkpoint inhibitors. The median follow-up was 7.6 months. The table below shows the ORR. The overall median TTP and OS were 4.2 and 8.90 months, respectively. Interestingly, among those who received single agent cabozantinib, the median OS was 5.36 months in contrast to 12.32 months in the patients received combination. Overall, 90.9% of patients experienced treatment related adverse events (TRAEs) with transient liver function occurred in nearly 50% patients. Nevertheless, Grade 3/4 TRAEs was only 12%. Conclusions: Our present study showed that the use of cabozatinib in advanced HCC patients had good anti-tumour activity and survival benefits with acceptable toxicity profile. [Table: see text]
Second-line chemotherapy (2L) in elderly patients with advanced biliary tract cancer (ABC): A multicenter real-world study.
Authors: Rizzo Alessandro , Salati Massimiliano , Frega Giorgio , Merz Valeria , Caputo Francesco , Ricci Angela Dalia , Palloni Andrea , Messina Carlo , Spallanzani Andrea , Saccoccio Gioconda , Mollica Veronica , Gelsomino Fabio , Benatti Stefania , Luppi Gabriele , Melisi Davide , Dominici Massimo , Brandi Giovanni
Published: January 2021

322

Background: The ABC-06 trial recently established the role of 2L in ABC progressing after platinum/gemcitabine combination. However, older patients are often under-represented in clinical trials and no data are currently available regarding 2L in elderly ABC. The aim of this real-world study was to explore the treatment pattern, safety and efficacy of 2L in ABC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed and data of interest retrieved to identify ABC who had received 2L from October 2002 to July 2020. Patients older than 70 years were considered as elderly individuals. The Kaplan-Meier methods was used to estimate survival and the log-rank test to make comparison. The impact of variables on survival was assessed through univariate and multivariate analysis. Results: A total of 190 ABC patients treated with 2L were identified and included in the analysis. Among them, 27.3% (n = 52) were aged ≥ 70 years (range 70-87y), of whom 25 patients had iCCA (48%), 13 GBC (25%) and 15 eCCA (27%). 56% (n = 29) were female and 38 (73%) patients had an ECOG-PS 0-1. The most frequently administered 2L regimens were capecitabine monotherapy (n = 14, 27%), single-agent gemcitabine (n = 9, 17%) and gemcitabine/capecitabine combination (n = 9, 17%). No differences in terms of prior surgery (p = 0.64) and 2L treatment intensity (p = 0.34) were observed compared to patients aged < 70 years. The disease control rate of 2L was 28.8% and 29.7% in elderly and youngers, respectively. No statistically significant differences in both mOS (5.7 months in elderly vs 6.1 months in youngers, HR 0.97; p = 0.86) and mPFS (4.7 vs 4.8 months, HR 0.88; p = 0.44) were recorded. Regarding the safety profile of 2L, grade 3 or 4 treatment-related toxicities occurred more frequently in the older group (48.5% versus 8.2%; OR 6.31; p < 0.001). When looking at prognostic factors, absolute lymphocyte count < 1000/mmc (p < 0.001) and albumin level < 3 g/dL (p < 0.001) were independently associated with worse prognosis. Conclusions: The results of this real-world study, limited by its retrospective nature and small sample size, suggest that for patients aged ≥ 70 years, 2L could be equally effective as for youngers, with survival outcomes aligned to those from ABC-06 trial. Notably, based on the higher incidence of grade 3-4 adverse events, the delivery of 2L should be carefully evaluated and monitored in this patient subset.
Results of a phase Ib study of regorafenib (REG) 80 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC).
Authors: Kim Richard D. , Harris William P. , Sung Max W. , Waldschmidt Dirk Thomas , Cabrera Roniel , Mueller Udo , Menezes Flavia , Ishida Tatiane , Galle Peter R. , El-Khoueiry Anthony B.
Published: January 2021

323

Background: In a phase Ib study, REG 120 mg/day plus PEMBRO for first-line treatment of advanced HCC showed no unexpected safety signals and encouraging anti-tumor activity. At the maximum tolerated dose (MTD) of REG (120 mg/day), approximately three-quarters of patients (pts) had a REG dose reduction or interruption due to a treatment-emergent adverse event (TEAE). Here, we present preliminary data for the REG 80 mg/day cohort. Methods: This is an ongoing, dose-finding study in pts who had no prior systemic therapy. In the first cohort, pts received REG 120 mg/day orally for 3 weeks on/1 week off plus PEMBRO 200 mg intravenously q 3 weeks. In later cohorts, the REG dose could be escalated (160 mg/day) or reduced (80 mg/day); the PEMBRO dose is fixed. The primary objective is safety and tolerability. Secondary objectives are to define the MTD and recommended phase II dose and assess anti-tumor activity. Results: By July 24, 2020, 16 pts were treated with REG 80 mg/day. Median age was 67 years (range 56–79), 25%/75% were Barcelona Clinic Liver Cancer stage B/C, 100% Child–Pugh A, and 69%/31% had Eastern Cooperative Oncology Group performance status 0/1. Grade (Gr) 3 TEAEs occurred in 8/16 pts (50%) and there were no Gr 4 TEAEs (Table); one pt experienced Gr 5 pneumonitis (not drug related). There were no reports of Gr 3 hand–foot skin reaction or Gr 3 maculopapular rash, and one report (6%) of Gr 3 rash. TEAEs led to a REG dose reduction or interruption in 50% of pts and to a PEMBRO dose interruption in 25% of pts. Median treatment duration (range) including pts ongoing was 4.1 months (0.4–7.1) for REG and 3.8 months (0.03–7.2) for PEMBRO. Of 13 evaluable pts, 2 (15%) had a partial response and 9 (69%) had stable disease (Response Evaluation Criteria in Solid Tumors v1.1); disease control rate was 85%. Conclusions: These preliminary results for the combination of REG 80 mg/day plus PEMBRO for first-line treatment of advanced HCC were consistent with the REG 120 mg/day cohort. The combination showed no unexpected safety signals and encouraging anti-tumor activity. Assessment of REG 80 mg/day plus PEMBRO is ongoing. Clinical trial information: NCT03347292. [Table: see text]
Activity of tepotinib in hepatocellular carcinoma (HCC) with high-level MET amplification (METamp): Preclinical and clinical evidence.
Authors: Faivre Sandrine J. , Blanc Jean-frederic , Pan Hongming , Grando Véronique , Lim Ho Yeong , Cubillo Gracián Antonio , Isambert Nicolas , Johne Andreas , Schumacher Karl , Stroh Christopher , Friese-Hamim Manja , O'Brate Aurora , Zhou Dongli , Qin Shukui
Published: January 2021

329

Background: Tepotinib, a potent and highly selective MET inhibitor, showed promising activity in advanced HCC with MET overexpression in two Phase Ib/II trials, which both met their primary endpoints. One trial enrolled Asian patients (pts) without prior systemic therapy (first line [1L]; NCT01988493) and one enrolled US/European pts with prior sorafenib (second line [2L]; NCT02115373). By investigator assessment, objective response rates and disease control rates with tepotinib in Phase II were 15.8% and 60.5% in 1L (n = 38), and 8.2% and 57.1% in 2L (n = 49). Outcomes appeared better in pts with METamp. Thus, we further investigated the preclinical and clinical activity of tepotinib in HCC, focusing on high-level METamp, which could be an oncogenic driver in this tumor type. Methods: Preclinical activity was assessed in 37 HCC pt-derived xenografts (PDXs) in nude mice treated with tepotinib (100 mg/kg, Days 1–5, every 7 days for five cycles; 6–12 replicates per PDX). Clinical activity was assessed by analyzing pts with METamp or high-level METamp (defined as mean MET gene copy number [GCN] ≥5 and ≥10, respectively; by fluorescence in situ hybridization), who received tepotinib 500 mg in Phase Ib or II of the 1L and 2L trials (n = 121). In the Phase Ib part of the 1L trial, pts could have received prior treatment. Results: Molecular profiling revealed high-level METamp in two of 37 HCC PDXs: LIM612 ( MET GCN 47.1) and LIPF210 ( MET GCN 44). Tepotinib induced significant tumor regression in both of these high-level METamp HCC PDX models (mean tumor volume reduction: 97% and 96%, respectively). Across the two trials, 15 pts treated with tepotinib 500 mg had METamp, of whom five had an objective response (one complete response [CR] and four partial responses [PRs]) and six had stable disease (SD) as best overall response. Four pts had high-level METamp (mean MET GCN 14.3, 18.1, 30.2, and 36.2), with best overall response of CR in one pt, PR in two pts and SD in one pt (Table). One pt with high-level METamp (mean MET GCN 14.3) treated with 1L tepotinib was still receiving treatment as of Sept 2020 (total tepotinib treatment duration: > 45 months). Conclusions: High-level METamp may be an oncogenic driver in HCC that sensitizes tumors to MET inhibition with tepotinib. Compared with MET overexpression, high-level METamp could be a better predictive biomarker for MET inhibitors in this setting. Clinical trial information: NCT01988493, NCT02115373. [Table: see text]
Development of a pancreatic cancer prediction model using a multinational medical records database.
Authors: Appelbaum Limor , Berg Alexandra , Cambronero Jose Pablo , Dang Thurston Hou Yeen , Jin Charles Chuan , Zhang Lori , Kundrot Steven , Palchuk Matvey , Evans Laura A. , Kaplan Irving D. , Rinard Martin
Published: January 2021

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Background: Previous work by our group has demonstrated that leveraging Machine Learning on diagnostic codes from Electronic Health Records (EHRs), can identify individuals at high-risk for Pancreatic Duct Adenocarcinoma (PDAC), as early as 1 year before current cancer diagnosis. We aim to improve the performance of our existing PDAC risk stratification model, by using an independent, multi-center dataset, and adding lab test features. Methods: EHR data from TriNetX, a federated global health research network, was utilized to develop Logistic Regression (LR) models. Diagnoses and lab test data from 32 different Health Care Organizations in the United States from 2015-2020 was used. PDAC patients ages 60-80 years, were identified using ICD codes, and cross-checked with tumor registry and pathology data to decrease false positives. Only patients with one or more clinical encounter/s, at least 6 months prior to cancer diagnosis, were included. Prediction time cutoffs of 180, 270, and 360 days before PDAC diagnosis were used. Preliminary basic data analysis was initially performed to explore potential lab test features that could be used to improve model performance. The discriminatory capabilities of the LR models were compared using Area Under the Receiver Operating Characteristic Curve (AUC) and 95% Confidence Interval using empirical bootstrap over test data were computed. We used L2-regularized LR, and performed evaluation using cross-validation. We report cross-validation performance. In contrast to prior published work that used predefined feature sets for model development, we incorporated a wide range of indicators, and relied on regularization to address potential overfitting risk. Results: The LR models were trained and evaluated on diagnoses and labs for 25,644 patients (cases= 1352; age-sex paired controls). Lab test administration per patient (i.e., for a given patient, what lab tests were administered and how frequently), was found to be the most valuable feature for improving discrimination. For almost every type of lab test, the average number of administrations per patient was higher for PDAC patients than controls. The top lab tests with highest discriminatory coefficients included glucose, potassium, hematocrit, hemoglobin, sodium, chloride and creatinine. With a 365-day lead time, the diagnoses-based LR obtained a test AUC of 0.58, the lab-test based LR obtained a test AUC of 0.72. The combined diagnoses and lab-test model (“concatenated LR model”) outperformed both of these models, obtaining a test AUC of 0.73. Conclusions: Our findings demonstrate that LR models based on concatenated lab test and diagnoses feature sets (“concatenated LR models”), can outperform both diagnoses-based LR models and lab-test-based LR models, and can be utilized in early prediction of PDAC development.
Efficacy and safety of 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) for previously treated advanced pancreatic cancer (APC).
Authors: Shirasu Hiromichi , Kawakami Takeshi , Hamauchi Satoshi , Tsushima Takahiro , Todaka Akiko , Yokota Tomoya , Yamazaki Kentaro , Fukutomi Akira , Onozawa Yusuke , Yasui Hirofumi
Published: January 2021

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Background: 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) is one of the preferred regimens for patients (pts) with advanced pancreatic cancer (APC) who received prior gemcitabine-based therapy in the National Comprehensive Cancer Network Guidelines. However, its survival benefit or safety in clinical practice is unclear. Methods: We retrospectively assessed the data of consecutive pts with APC who received FOLFIRI as a second or later-line treatment after gemcitabine-based therapy at Shizuoka Cancer Center between May 2014 and March 2020. Results: The characteristics of 102 pts included in this analysis were as follows: median age (range), 67 (39-78) y; male/female, 55/47; ECOG PS0/1/2, 21/72/9; the number of metastatic sites 0/1/2/3/4, 7/48/35/8/4; unresectable/recurrent, 84/18; UGT1A1 status wild/*6 or*28 heterozygous/homo or double-heterozygous/unknown, 40/40/5/17; treatment line of FOLFIRI 2nd/3rd/4th, 64/32/6. Previous treatment history according to the treatment line of FOLFIRI was as follows: 2nd-line, all patients received GEM-based regimen, GEM plus nanoparticle albumin bound paclitaxel in 63 pts (98.4%) and GEM in 1 (1.6%); 3rd, GEM-based and S1 in 20 (62.5%), GEM-based and 5-FU/levofolinate/oxaliplatin (FOLFOX) in 12 (37.5%); 4th, GEM-based, FOLFOX and S-1 or other agent in 5 (83.3%), 2 GEM-based regimens and S1 in 1 (16.7%). The median treatment cycle was 5 (range 1-55). The median treatment cycle according to the treatment line was as follows: 2nd-line, 7(1-55); 3rd, 4(1-14); 4th, 3.5(1-10). The initial dosage for each cytotoxic agent was as follows: bolus 5-FU injected/omited 72/30; continuous 5-FU 2400/2000/1200 mg/m2, 88/13/1; irinotecan 180/150/120/less than or equal to 100mg/m2, 27/59/13/3. The overall response rate (ORR) and disease control rate (DCR) were 5.9% and 52.9%, respectively. ORR and DCR according to the treatment line were as follows: 2nd-line, 9.3/64.1%; 3rd, 0/68.8%; 4th, 0/50.0%. At the median follow up 6.5 M, the median overall survival (OS) and progression free survival (PFS) were 6.6M and 3.1M, respectively. The median OS and PFS according to the treatment line were as follows: 2nd-line, 8.1/3.6M; 3rd, 5.1/2.1M; 4th, 6.6/2.0M. Adverse events (AEs) were observed in 70.8% pts. Grade 3 or higher AEs occurred in 27.2% pts [neutropenia in 26 (25.2%) pts, febrile neutropenia in 4 (3.9%) pts, nausea in 4 (3.9%) pts, decreased appetite in 3 (2.9%) pts]. No treatment related deaths were observed. Conclusions: FOLFIRI is well tolerated and effective especially in the second-line treatment for pts with gemcitabine-refractory APC.
Phase II randomized, double-blind study of mFOLFIRINOX plus ramucirumab versus mFOLFIRINOX plus placebo in advanced pancreatic cancer patients (HCRN GI14-198).
Authors: Shaib Walid Labib , Rupji Manali , Khair Tina Ashley , Robin Erwin L. , El-Rayes Bassel F. , Huyck Timothy K. , Liu Yuan , Sonbol Mohamad Bassam , Bekaii-Saab Tanios S.
Published: January 2021

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Background: Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-mediated signaling and angiogenesis contribute to the pathogenesis and progression of pancreatic adenocarcinoma (PCA).VEGF is expressed in all PCA tumors. VEGF-A/VEGFR-2 signaling plays an important role in inducing invasion and migration of PCA cells. The pVEGFR-2 is significantly associated with invasion of the anterior capsule of pancreas and arteries. In preclinical studies, the anti-tumor activity of fluoropyrimidines, but not that of gemcitabine, caused the release of bone marrow derived circulating endothelial progenitor cells (CEPs) and Tie-2 expressing monocytes (TEMs) as well as the induction of pro-angiogenic growth factors. Methods: This phase II randomized, multi-center, and double-blinded trial was designed to compare the efficacy and safety of mFOLFIRINOX/ramucirumab (Arm A) versus mFOLFIRINOX/ placebo (Arm B) as front-line therapy in recurrent or metastatic PCA patients. The primary endpoint was progression free survival (PFS) at 9 months, and the secondary endpoints included overall survival (OS) and response rate. Results: A total of 86 subjects were enrolled, 82 were eligible (42 in Arm A v. 40 in Arm B). The mean age of the subjects in the two arms were comparable (61.7 v. 63.0, respectively); 43 male, 69 Caucasian. On the univariate analysis, there was no difference in distribution between the 2 arms for age, gender, race and ethnicity. The median PFS was 5.6 in Arm A compared to 6.7 months in Arm B (one-sided log-rank, p = 0.322). At 9 months, the progression free rates were 25.1% v. 35% for Arms A and B, respectively. The mFOLFIRINOX/ramucirumab combination was well tolerated. Patients in Arm A reported a slightly higher number of adverse events (AEs) encounters, most commonly diarrhea (29 vs 28), fatigue (25 v. 25), vomiting (24 v. 14), weight loss (23 v. 17), and abdominal pain (20 v. 15). Arm A had more SAEs than Arm B (43 v. 25), with sepsis most commonly reported in both arms (3 in each), vomiting (3 v. 2), diarrhea (3 v.1) and duodenal obstruction (3 v. 0). Arm B had a slightly higher response rate (22.58%) compared to Arm A (17.65%) that was not statistically significant. The median OS in Arm A was 10.3 compared to 9.7 months for Arm B (one-sided log-rank, p = 0.094). Conclusions: In this randomized phase 2 study, the addition of ramucirumab to mFOLFIRINOX did not improve PFS, response rate, or OS as initial therapy for metastatic pancreatic cancer. FOLFIRINOX/Ramucirumab combination was well tolerated in the treatment of PCA. Clinical trial information: NCT02581215.