bluuebunny/crossref_metadata_2025 huggingface dataset:
A subclass of meromorphic Janowski-type multivalent q-starlike functions involving a q-differential operator
Authors: Ahmad Bakhtiar , Mashwani Wali Khan , Araci Serkan , Mustafa Saima , Khan Muhammad Ghaffar , Khan Bilal
Published: January 2022

Keeping in view the latest trends toward quantum calculus, due to its various applications in physics and applied mathematics, we introduce a new subclass of meromorphic multivalent functions in Janowski domain with the help of the q-differential operator. Furthermore, we investigate some useful geometric and algebraic properties of these functions. We discuss sufficiency criteria, distortion bounds, coefficient estimates, radius of starlikeness, radius of convexity, inclusion property, and convex combinations via some examples and, for some particular cases of the parameters defined, show the credibility of these results.
Couple’s Satisfaction among Lebanese adults: validation of the Toronto Alexithymia Scale and Couple Satisfaction Index-4 scales, association with attachment styles and mediating role of alexithymia
Authors: El Frenn Yara , Akel Marwan , Hallit Souheil , Obeid Sahar
Published: January 2022

Background

Lebanon is passing through an economic crisis leading to a decreased monthly income within a couple and more couple’s dissatisfaction. Furthermore, many studies postulate that the different types of attachment styles affect the romantic relationship experienced between adults. The main objectives of our study were to (1) validate the Toronto Alexithymia Scale (TAS) and Couple Satisfaction Index-4 (CSI-4) scales, and (2) assess the association between attachment styles and couple satisfaction and evaluate the mediating role of alexithymia in these associations.

Methods

This cross-sectional study involved 445 Lebanese participants (April–May 2021). A confirmatory factor analysis (CFA) was carried out using SPSS AMOS v.24 on the couple satisfaction index and Toronto alexithymia scales’ items. A linear regression was conducted, taking the couple satisfaction index as the dependent variable.

Results

The CFA results of the CSI-4 scale indicated an excellent fit (χ2/df = 3.845/2 = 1.92, TLI = 0.992, RMSEA = 0.046 [95% CI 0.001–0.115] (pclose = 0.436) and CFI = 0.998). The CFA of the TAS indicated a good/acceptable fit (χ2/df = 422.31/132 = 3.2, TLI = 0.89, RMSEA = 0.07 [95% CI 0.063–0.078] (pclose < 0.001) and CFI = 0.91) (items 4 and 8 were removed due to low factor loading (< 0.4)). Being married and higher secure attachment style were significantly associated with more couple satisfaction, whereas older age, higher household crowding index, more alexithymia and mode depression were significantly associated with less couple satisfaction. In addition, alexithymia mediated the association between secure attachment style and couple satisfaction, between preoccupied attachment style and couple satisfaction and between dismissing attachment style and couple satisfaction.

Conclusion

Couple’s satisfaction is positively associated with secure attachment style. In addition, alexithymia plays a mediating role between couple’s satisfaction and attachment styles. Upcoming studies should determine if other mental illnesses play a mediating role between attachment style and couple satisfaction.
Carbon nanotubes in the holding solution stimulate flower opening and prolong vase life in carnation
Authors: Ahmadi-Majd Masoumeh , Mousavi-Fard Sadegh , Rezaei Nejad Abdolhossein , Fanourakis Dimitrios
Published: January 2022

Background

Cut flower longevity is often limited by adverse water relations or oxidative stress. The potential of single- and multi-walled carbon nanotubes (SWCNTs and MWCNTs, respectively) on prolonging vase life was addressed. Dose–response curves were obtained by applying five concentrations (0–80 mg L−1) of SWCNTs or MWCNTs either once as a foliar spray or continuously in the holding solution of three carnation cultivars. Next, the optimal concentration of either SWCNTs or MWCNTs was employed to evaluate several parameters critical for vase life.

Results

Foliar spray application exerted minor effects on water relations, flower opening and keeping quality. By contrast, including CNTs in the holding solution sustained a positive water balance for a longer period, improved flower opening and prolonged vase life. These effects were similar between SWCNTs and MWCNTs, and were concentration-dependent. The optimal concentration for vase life was higher for MWCNTs as compared to SWCNTs, and for two cultivars as compared to the third one. At optimal concentration, SWCNTs or MWCNTs in the holding solution generally maintained turgidity, and alleviated chlorophyll degradation, electrolyte leakage and lipid peroxidation. These effects were related to increased activation of enzymatic (ascorbate peroxidase, catalase, peroxidase and superoxide dismutase) and non-enzymatic (carotenoids, polyphenols, and flavonoids) antioxidants.

Conclusion

CNTs in the holding solution were very effective in stimulating vase life through improved water relations and enhanced antioxidant machinery stimulation.

Graphical Abstract
Evidence-based uncertainty estimates for the International Geomagnetic Reference Field
Authors: Beggan Ciarán D.
Published: January 2022

The International Geomagnetic Reference Field (IGRF) is a multi-institute model of the Earth’s magnetic field, compactly described by sets of up to 195 spherical harmonic (Gauss) coefficients to degree and order 13, which allows the continuous evaluation of the field at any location and time on or above the surface. It is developed from satellite and ground-based magnetometer data and describes the large-scale variation of the magnetic field in space and time under quiet conditions. While much effort has been made on improving the forecast of the secular variation of the field over the 5-year intervals between release and renewal, less emphasis has been placed on understanding the spatial errors from a user point of view. In this study, we estimate the large-scale time-invariant spatial uncertainty of the IGRF based on the globally averaged misfit of the model to ground-based measurements at repeat stations and observatories between 1980 and 2021. As the ground measurements are reduced to quiet-time values, the external field is minimized for the purposes of this study. We find the 68.3% confidence interval is 87 nT in the North (X) component, 73 nT in the East (Y) component and 114 nT in vertical (Z) component. Due to the Laplacian distribution of the residuals, the standard deviations are larger at 144, 136 and 293 nT, respectively.

Graphical Abstract
Impact of COVID-19 pandemic on psychological health of a sample of the health care workers in the western region of Kingdom of Saudi Arabia
Authors: Sultan Sadia , Bashar Abu , Nomani Ibtesam , Tabassum Aisha , Iqbal Mohammad Shahid , Fallata Ebtihaj O. , Sindi Ramya Ahmad , Almasoudi Nouf M. , Rheem Seeqa
Published: January 2022

Background

The coronavirus disease 2019 pandemic has shown a significant impact on the psychological well-being of health care workers. The aim of the study was to evaluate the impact of the COVID-19 pandemic on the psychological health of health care workers in the Kingdom of Saudi Arabia. During the months of November and December, 283 health care workers completed a survey containing measures of depression, anxiety and stress (using Depression Anxiety and Stress-21 scale [DASS-21]) and questions regarding potential predictors such as the role of COVID-19 perception, availability of mental health support and work-related factors. Pearson X2 test revealed factors associated with the presence of significant psychiatric symptoms.

Result

Among the participants, 17.3% screened positive for depression, 26.2% for anxiety and 17.3% for stress. Nurses reported significantly more depression, anxiety and stress than doctors. Those who received mental health support reported significantly lesser depression, anxiety and stress. Those who felt that quality of life was heavily impacted due to COVID-19 reported significantly high depression, anxiety and stress.

Conclusions

Poor psychological well-being was prevalent in health care workers; however, mental health measures have been shown to significantly reduce the mental health burden in health care workers.
Competencies for Nurses Regarding Psychosocial Care of Patients With Cancer in Africa: An Imperative for Action
Authors: Uwayezu Marie Goretti , Nikuze Bellancille , Maree Johanna E. , Buswell Lori , Fitch Margaret I.
Published: January 2022

Psychosocial care is considered an important component of quality cancer care. Individuals treated for cancer can experience biologic or physical, emotional, spiritual, and practical consequences (eg, financial), which have an impact on their quality of living. With the establishment of cancer centers in Africa, there is growing advocacy regarding the need for psychosocial care, given the level of unmet supportive care needs and high emotional distress reported for patients. Nurses are in an ideal position to provide psychosocial care to patients with cancer and their families but must possess relevant knowledge and skills to do so. Across Africa, nurses are challenged in gaining the necessary education for psychosocial cancer care as programs vary in the amount of psychosocial content offered. This perspective article presents competencies regarding psychosocial care for nurses caring for patients with cancer in Africa. The competencies were adapted by expert consensus from existing evidenced-based competencies for oncology nurses. They are offered as a potential basis for educational program planning and curriculum development for cancer nursing in Africa. Recommendations are offered regarding use of these competencies by nursing and cancer program leaders to enhance the quality of care for African patients with cancer and their family members. The strategies emphasize building capacity of nurses to engage in effective delivery of psychosocial care for individuals with cancer and their family members.
Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8.
Authors: Lenz Heinz-Josef , Parikh Aparna Raj , Spigel David R. , Cohn Allen Lee , Yoshino Takayuki , Kochenderfer Mark D. , Elez Elena , Shao Spencer H. , Deming Dustin A. , Holdridge Regan C. , Larson Timothy , Chen Eric , Mahipal Amit , Ucar Antonio , Cullen Dana , Baskin-Bey Edwina S , Ledeine Jean-Marie , Hammell Amy , Tabernero Josep
Published: January 2022

8

Background: Standard 1L therapies for mCRC include a fluoropyrimidine with oxaliplatin and/or irinotecan, and a biologic agent. NIVO may enhance antitumor activity in combination with 1L standard therapies within a subset of patients (pts) with mCRC. CheckMate 9X8 evaluated NIVO + mFOLFOX6/BEV vs mFOLFOX6/BEV in 1L mCRC (NCT03414983). Methods: Adults with previously untreated, unresectable, mCRC were randomized 2:1 to NIVO 240 mg + mFOLFOX6/BEV Q2W (NIVO + standard-of-care [SOC]) or mFOLFOX6/BEV Q2W (SOC). Primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1. Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), overall survival (OS), and safety. Results: 195 pts were randomized to NIVO + SOC (n = 127) or SOC (n = 68). Median (range) follow-up was 23.7 (0–33.2) months (mo; NIVO + SOC) vs 23.2 (0–32.3) mo (SOC). Median (range) duration of therapy was 9.9 (0.1–31.8+) mo (NIVO + SOC) and 7.7 (0.1–26.7+) mo (SOC). The HR (95% CI) for PFS was 0.81 (0.53–1.23; P = 0.30), which did not meet the prespecified threshold for statistical significance (median PFS, 11.9 mo in both arms; Table). PFS rates after 12 mo were higher with NIVO + SOC vs SOC (Table). ORR was 60% (NIVO + SOC) and 46% (SOC; odds ratio 1.72 [95% CI 0.96–3.10]) and median (95% CI) DOR was 12.9 (9.0–13.1) mo (NIVO + SOC) and 9.3 (7.5–11.3) mo (SOC; Table). Rates of grade 3−4 treatment-related adverse events (TRAEs) were higher with NIVO + SOC; however, no new safety signals were identified (Table). Biomarker analyses, including tumor mutational burden and baseline CD8 levels, will be presented. Conclusions: The primary endpoint of PFS was not met; however, NIVO + SOC showed higher PFS rates after 12 mo, a higher response rate, and more durable responses compared with SOC, along with acceptable safety, in 1L mCRC. Clinical trial information: NCT03414983. [Table: see text]
Medicaid expansion to reduce racial disparity in the incidence of early onset colorectal cancer.
Authors: Rahman Shafia , Patel Riya Jayesh , Liu Jianyou , Acuna-Villaorduna Ana , Kim Mimi , Goel Sanjay
Published: January 2022

24

Background: Early onset colorectal cancer (EO-CRC, age < 50 years) is an emerging public health crisis, especially in minorities. We evaluated and compared the effects of Medicaid expansion on the incidence of EO-CRC among Hispanics, Blacks, and Whites across the United States. Methods: The National Cancer Data Base was used to collect data on newly diagnosed cases of EO-CRC (40-49 years) among the three races, across all stages, from 2010-2017. Data for 21 expansion states (ES) that expanded Medicaid in 2014, and 16 non-expansion (NES) states was analyzed, excluding the states which expanded after 2014.The yearly state-wise population of all three races was collected from the U.S Census Bureau for 2010-17. A segmented Poisson regression model with generalized estimating equations was used for statistical analysis. Results: Annual incidence (AI) of EO-CRC pre and post expansion, in ES was 6/100,000 and 9/100,000 in Hispanics; 17/100,000 and 21/100,000 in Blacks and 14/100,000 and 18/100,000 for Whites. In NES the AI, pre and post 2014 was 8/100,000 and 10/100,000 among Hispanics, 19/100,00 and 24/100,000 among Blacks and 16/100,000 and 20/100,000 among Whites. Rate of change in AI of EO-CRC among Hispanics was 4.3% per year (2010-14), and 9.8% (2014-17) for ES states; and 6.4% (2010-14), and 1% (2014-17) in NES; among blacks was 3.8 % per year (2010-14), and 1.3% (2014-17) for ES states; and 1.6% (2010-14), and 3.2% (2014-17) in NES. Among Whites, increase in AI was 4.3% per year (2010-14), and 6.3% (2014-17) for ES states; and 4.0% (2010-14), and 5.7% (2014-17) in NES. ES showed greater change in incidence after expansion compared to pre-expansion in the incidence of EO-CRC as compared to NES (p=0.03) in Hispanics, however no significant difference was noted among Blacks (p=0.33) and Whites(p=0.94). Racial groups did significantly differ with respect to the degree of change in pre and post expansion (2014) rates of incidence of EO- CRC in the ES, however, in the NES, there were significant difference between the Hispanics and Whites (p=0.01), but not between Blacks versus Whites. Conclusions: Medicaid expansion reduces racial disparities in detection of EOCRC.[Table: see text]
Correlation of circulating tumor DNA (ctDNA) with clinical outcomes in appendiceal cancers (AC).
Authors: Kothary Vishesh , Eng Oliver , Polite Blase N. , Liao Chih-Yi , Catenacci Daniel V.T. , Dhiman Ankit , Turaga Kiran , Shergill Ardaman
Published: January 2022

29

Background: Appendiceal Cancers are a heterogenous group of rare tumors with distinct histopathologic and genomic alterations. These often have peritoneal spread that might not be easily detected on current imaging modalities, and conventional tumor markers may not lend diagnostic support. Hence, novel diagnostic techniques are needed. Measurement of ctDNA for recurrence risk prediction, response to therapy and and early diagnosis is a promising technique. However, limited published data exist in AC to validate the role and utility of ctDNA in clinical practice. Here we present a single institution experience of ctDNA analysis in patients with AC. Methods: ctDNA measurements of 37 pts with stage II-IV AC treated between 1/1/2019 and 9/15/2021 were reviewed retrospectively. ctDNA analysis was done using Signatera bespoke mPCR NGS assay. ctDNA results were compared to crossectional imaging, CEA levels, and clinical evaluation. Results: 19/37 patients (51%) had at least one positive ctDNA test result. Of those, 8 had testing done during the surveillance setting (two with grade 3, one with grade 2, two with grade 1, and three with unknown grade). Of those, 5 pts (62.5%) had positive ctDNA detected, while 33.33% had elevated CEA level, 25% had radiographic and 42.9% had clinical evidence of recurrence (Table). 7/14 (50%) pts had high-grade pathology and positive ct-DNA, 3/6 (50%) patients had low-grade (grade 1) pathology and positive ct-DNA findings. 4 patients had longitudinal ct-DNA measurements available which correlated well with their disease course. Median duration to recurrence (radiographic or laparoscopic) was 376 days. Median duration to the first positive ctDNA test was 370 days. Median duration to positive CEA after initial treatment was 475 days. Conclusions: Measurement of ctDNA can be a useful tool to follow disease course and to guide management decision-making in patients with AC. Prospective studies with serial measurements of ctDNA are planned. [Table: see text]
COVID-19 vaccination in gastrointestinal cancer patients receiving chemotherapy: A single institute experience.
Authors: Suenaga Mitsukuni , Yamauchi Shinichi , Masuda Taiki , Hanaoka Marie , Iwata Noriko , Sato Yuya , Tomii Chiharu , Tokunaga Masanori , Kinugasa Yusuke
Published: January 2022

30

Background: Early approval of COVID-19 vaccine has significant benefits for cancer patients treated under the COVID-19 pandemic worldwide. However, there has been limited reports that investigated the safety and efficacy of vaccination in cancer patients and the optimal timing of vaccination during chemotherapy. We therefore investigated the effects of vaccination on treatment in cancer patients receiving chemotherapy. Methods: Our retrospective observational study included 52 patients with gastrointestinal (GI) cancer receiving chemotherapy at the medical hospital of Tokyo Medical and Dental University in Tokyo who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and September 2021. All patients had no history of COVID-19 infection. Treatment- and vaccination-related adverse events were recorded by outpatient interviews and self-reports. All adverse events were evaluated using CTCAE v5.0. Results: Characteristics of patients were as follows (N = 52): median age, 70y (range, 49–89); male/female, 30/22; ECOG PS 0, 75%; local/metastatic, 12/40; mean BMI, 23.4±4.1; comorbidities in 36 (cardiovascular in 24, diabetes in 8, kidney disease in 8, liver disease in 6, lung disease in 1); treatment (cytotoxic in 45, biologics in 23, immune checkpoint inhibitor in 4). Of the 52 patients, 45 received chemotherapy prior to vaccination; days from last dose to first vaccination, median 11 (range, 1–70); days from first to second vaccinations, median 21 (range, 21–41); days from first vaccination to chemotherapy, median 10 (range, 2–34). 11 patients (24.4%) changed treatment schedule: 3 for safety reasons, 4 for myelosuppression and 4 for convenience. 4 patients stopped treatment due to disease progression. Following the first vaccination, 37 patients (82.2%) had adverse events (AEs): injection site pain (n = 35), fatigue (n = 6), fever (n = 3), headache (n = 2), gastrointestinal symptoms (n = 2), redness (n = 1), insomnia (n = 1). There was no treatment- and vaccine-related deaths. Conclusions: Our findings suggest that vaccine-related AEs in GI cancer patients receiving chemotherapy are tolerable, and treatment schedule changes could be minimized. Although careful monitoring is required, COVID-19 vaccination is also recommended for cancer patients toward the convergence of the COVID-19 pandemic.
Patient care satisfaction and emergency room utilization among young adult colorectal cancer survivors during the SARS-CoV-2 pandemic.
Authors: Kagramanov Dalia , Miller Kimberly Ann , Gallagher Phuong , Freyer David R. , Milam Joel , Lenz Heinz-Josef , Barzi Afsaneh
Published: January 2022

34

Background: Survivors of colorectal cancer (CRC) are at risk for late effects of therapy and recurrence of cancer. With recurrence rates ranging between 30-40% (Siegal et al., 2020), consistent, survivor-focused follow-up care is needed for early detection of late effects and recurrence (Jeffery et al., 2019). CRC-related care delivery has been significantly disrupted by the SARS-CoV-2 pandemic, with decreases of 40% in CRC services in the United States between April 2020 and 2019 (Jammu, 2020). Consequentially, survivors may be left with fewer options for care, potentially causing increases in emergency room (ER) utilization. Methods: This cross-sectional study examined the patterns of ER utilization during the SARS-CoV-2 pandemic among young adult CRC survivors and assessed the relationship between self-reported care satisfaction and ER use. Eligible participants were diagnosed with colon or rectal cancer between 18-39 years, between 6-36 months from diagnosis/relapse, English speaking, and based in the United States. Questions on care satisfaction were Consumer Assessment of Healthcare Providers and Systems (CAHPS) questions. A multivariable logistic regression was conducted to assess the association between patient satisfaction and ER utilization, adjusting for factors related to the pandemic. Covariates for this analysis were chosen based on a significance of p < 0.1 at the univariate level, as well as general clinical significance. Results: The overall sample was N = 196, mean age (SD) was 32.1 years (4.5), and 116 survivors (59%) were male. Tumor location was colon or rectal in 42% and 57%, respectively, and the majority (56%) were diagnosed with stage 2 disease; 42.6% reported relapsed disease, and 20% had an ostomy. The majority of survivors (72.5%) had between 1-4 visits to an emergency room in the last 12 months and were categorized as normal users. Approximately 24.7% of the sample had greater than 4 visits to the ER in the last 12 months and were categorized as super-utilizers (Johnson et al., 2015). Colorectal cancer survivors that reported a delay in their follow-up cancer care as a result of the pandemic were two times (OR: 2.05, 95% CI 0.99, 4.24) more likely to be super-utilizers of the ER. Higher self-reported satisfaction with overall care was associated with a 13.7% (OR: 0.86, 95%CI: -0.68, 1.09) lower likelihood of being a super-utilizer. Conclusions: This study found strong associations between delays in care, self-reported care satisfaction, and being a super-utilizer of the ER during the pandemic among young adult CRC survivors off treatment. Increasing patient satisfaction and minimizing care interruptions amongst this vulnerable population may aid in mitigating over-utilization in the ER during an ongoing pandemic.
A real-world comparison of trifluridine/tipiracil and regorafenib in refractory metastatic colorectal cancer in the United States.
Authors: Nevala-Plagemann Christopher Duane , Ying Jian , Sama Shashank , Florou Vaia , Haaland Benjamin , Garrido-Laguna Ignacio
Published: January 2022

39

Background: For patients with refractory metastatic colorectal cancer (mCRC), both trifluridine/tipiracil (TAS-102) and regorafenib have received approval for use in the United States. The approvals of these agents were based on modest improvements in overall survival (OS) when compared to best supportive care plus a placebo in the RECOURSE and CORRECT trials, respectively. However, TAS-102 and regorafenib have never been directly compared in a prospective clinical trial. This study utilized a large real-world database to compare clinical outcomes with use of these agents. Methods: The nationwide de-identified Flatiron Health EHR-derived database was reviewed for patients diagnosed with mCRC between 2015 and 2020. Patients who received at least two lines of guideline recommended therapy for advanced disease followed by treatment with TAS-102 and/or regorafenib in the third line or greater were included for analysis. Patients who did not have a visit or medication order within 90 days of metastatic diagnosis were excluded to ensure patients were engaged with care at the data-providing institution. Kaplan-Meier and propensity score weighted models were used to compare survival outcomes between groups. Results: The records of 22,078 patients with mCRC were reviewed. Of the 4,407 patients that received at least two lines of standard therapy, 2,072 subsequently received regorafenib and/or TAS-102. Of these, 813 (39.2%) received TAS-102 alone, 275 (13.3%) TAS-102 followed by regorafenib, 736 (35.5%) regorafenib alone, and 248 (12.0%) regorafenib followed by TAS-102. Median OS for patients treated with TAS-102 alone or prior to receiving regorafenib was 6.66 months (95% CI 6.16-7.18) compared to 6.30 months (95% CI 5.80-6.79) for those treated with regorafenib alone or prior to receiving TAS-102 (p = 0.36). A propensity score weighted analysis controlling for age, race, stage at initial diagnosis, performance status at start of therapy, MSI/MMR status, RAS/RAF status, and line in which TAS-102 or regorafenib was received did not demonstrate a significant difference in survival between groups (HR 0.99, 95% CI: 0.90 -1.09, p = 0.82). A subgroup analysis did not identify any significant differences in outcomes stratified by age, performance status, MSI status, or RAS/RAF status. Conclusions: This analysis of real-world data did not identify a significant difference in survival outcomes in mCRC patients who were treated with TAS-102 or regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. This data should be considered when discussing the risks and benefits of TAS-102 and regorafenib with mCRC patients who are eligible for third line or greater treatment.
Integrated approach to collecting patient reported toxicities in a colorectal cancer trial.
Authors: Gaddy Jacquelyne Janean , Sanoff Hanna Kelly , Deal Allison Mary , Basch Ethan , Wood William Allen
Published: January 2022

51

Background: Understanding the toxicities experienced by patients treated with advanced CRC is critical when considering appropriate dose modifications, standard drug dosing, and quality of life. A workflow that makes available Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) to clinicians to inform overall toxicity assessment should be easy to use and focus on clinically relevant issues. The value of a system that not only collects PRO-CTCAE but integrates it with clinician grading to inform overall symptomatic adverse event assessment during clinical trials is unclear. Methods: Patients were simultaneously enrolled in a phase II multi-center clinical trial that evaluated a genotype-guided dosing strategy for irinotecan by prospectively analyzing efficacy in 100 mCRC patients receiving FOLFIRI (5-fluorouracil, leucovorin, irinotecan) and bevacizumab. On day 1 and day 15 of each cycle patients provided PRO-CTCAE responses on 13 symptoms (26 questions) which were made available to clinicians at the time of their toxicity assessment. Descriptive statistics were used to summarize patient demographic and clinical characteristics. Concordance was defined as both patient and clinician giving the same response (both positive or both negative). Results: 100 patients participated in the study, of which 48% were female and 83% White. Overall, 96% of both patients and providers completed at least 80% of PRO-CTCAE forms available to them, demonstrating the feasibility of an integrated workflow for patient-clinician toxicity grading. Across all symptoms, concordance was high (73%) for the patient and provider reporting severe symptoms. 39% of patient-provider pairs reported at least 1 severe symptom and 34% of pairs never reported a severe symptom. In 23% of pairs the patient reported a severe symptom and the provider never did, and in 3% of pairs, the provider reported a severe symptom, but the patient never did. On the symptom level, the concordance was highest (>90%) for dysphagia and vomiting, and lowest (74-82%) for abdominal pain, fatigue, and pain. 52 patients required dose decreases, with the first decrease most often due to hematologic toxicity (80%). In 46% of cases the patient reported at least one severe toxicity prior to or on the same day as the dose decrease, compared to 19% of cases where the provider reported at least severe toxicity prior to or on the same day as the dose decrease. Conclusions: A workflow that brings patient-reported toxicity to clinicians at the time of clinical toxicity rating is feasible. Nevertheless, discordance continues to exist between patient-reported and clinician-reported toxicity ratings, consistent with prior research. Further research could formally compare concordance when using an integrated vs a non-integrated toxicity rating workflow and could ascertain the reasons for continued discordance within an integrated workflow.
Can second-generation multitarget stool DNA panels reliably detect colorectal cancer and advanced precancerous lesions?
Authors: Kisiel John B. , Gagrat Zubin D , Krockenberger Martin , Bhattacharya Abhik , Bourne Bridget L , Leduc Christine M , Matter Michael B , Fourrier Keith D , Edwards David , Limburg Paul J. , Domanico Michael J.
Published: January 2022

63

Background: Population-based colorectal cancer (CRC) screening can reduce mortality by detecting and removing advanced precancerous lesions (APL) and early-stage invasive disease. One guideline-included strategy is the multi-target stool DNA test (mt-sDNA), which combines detection of methylation DNA markers (MDMs), KRAS mutations, and fecal hemoglobin. Since the mt-sDNA pivotal study was conducted, novel biomarkers have been discovered. A panel of highly discriminant MDMs ( LASS4, LRRC4, PPP2R5C, and reference marker ZDHHC1) was identified through a blinded, case-control study of archival specimens. Here, we evaluated the performance of this novel mt-sDNA panel, combined with fecal hemoglobin, in archival stool samples weighted to early-stage CRC and prospectively collected APL, simulating a screening population. Methods: The verification study featured 777 samples—210 cases (112 CRC [49 stage I, 38 stage II, 17 stage III, and 8 stage IV] and 98 APL) and 567 controls (176 non-APL and 391 colonoscopy-negative)—from three trials (NCT01397747, NCT01260168, and NCT02503631). Median APL size was 12 mm (interquartile range: 10 mm to 15 mm), with 86.7% adenomas (n = 85) and 13.3% sessile serrated polyps (SSPs; n = 13). The average age was 65.5 years for cases (57% men) and 63.2 for controls (47% men). Samples were processed through homogenization, targeted MDM capture, bisulfite conversion, and MDM quantitation using Long‐probe Quantitative Amplified Signal (LQAS). Fecal hemoglobin was quantified using enzyme-linked immunosorbent assay (ELISA). Samples were split into stratified 75%/25% training-testing sets and model outcomes were cross-validated 1,000 times. Results: Mean performance from the cross-validation analysis is summarized in the table below. Overall sensitivity was 95.2% for CRC and 57.2% for APL, with specificities of 89.8% (no CRC/APL) and 92.4% (no neoplasia). Subgroup analyses showed high sensitivity for early-stage CRC, with 93.4% at stage I and 94.2% at stage II. By APL subtype, sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSPs. Conclusions: These data support high sensitivity and specificity for a second-generation mt-sDNA panel. A multicenter pivotal trial evaluating the panel is underway (NCT04144738). [Table: see text]
Colorectal cancer caregivers demonstrate need for a one-stop comprehensive resource.
Authors: Newcomer Kim , Fathi Negeen , George Manju , Shoeb Abdullah , Goodman Andrea
Published: January 2022

74

Background: Patients with colorectal cancer often require a caregiver’s assistance with daily activities, medical care, social needs, and navigating treatment options. In providing this assistance, caregivers may be at an increased risk for psychological distress. Direct support to manage a caregiver’s stress and maintain their well-being is essential. More research is needed to fully understand the challenges caregivers face and to provide solutions. Previous studies have found that caregivers experience high levels of depression and anxiety, and many lack access to resources despite the evidenced need for support. Methods: A survey was disseminated via the Colorectal Cancer Alliance’s Blue Hope Nation community for two weeks and by email. Forty caregivers of colorectal cancer patients of varying stages and diverse demographic backgrounds completed the survey. Results: Half of the respondents have been providing care for 1-3 years, and 63% indicated they were a patient’s spouse or partner. Most caregivers were in the 35-40 age group, and 30% were full-time caregivers. A majority reported experiencing anxiety/stress (97.5%), fatigue (80%), poor sleep (77.5%), depression (75%), and feelings of isolation (72.5%). Primary caregiver activities included providing moral support, completing household chores, and researching treatment options. Only 32.5% of caregivers received help or advice from their patient’s doctors or medical team on the tasks listed. The survey results suggest the need for a comprehensive resource with information on medications, side effects and treatments; a guide for medical discussions; organization for medical forms and documents; and a tool to connect with peer caregivers. Conclusions: Survey themes indicate that caregivers often feel unprepared to provide care, have inadequate knowledge, and receive little guidance from health care providers, so there is continued need to place both the patient and caregiver at the center of care. A comprehensive centralized resource given at diagnosis with vital information and a method for document organization would help reduce caregivers’ stress and allow them to share information easily. Such patient and caregiver-directed resources would enable a better quality of care experience, and potentially better mental health outcomes, for patients and their caregivers.
Association between environmental quality index and young onset colorectal cancer.
Authors: Goksu Suleyman Yasin , Khatib Jude , Reddy Sarah , Ozer Muhammet , Maxwell Mary Claire , Khosama Leticia , Kainthla Radhika , Sanford Nina Niu , Pogacnik Javier Salgado , Chilakamarry Sitaram , Huang Emina , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali
Published: January 2022

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Background: The factors associated with the rise of young-onset colorectal cancer (YOCRC) remain unclear. In addition to hereditary factors, environmental exposures are believed to be associated with YOCRC. Therefore, we aimed to study the association between the national level Environmental Quality Index (EQI) and YOCRC in the US. Methods: We used the SEER database to select the CRC patients diagnosed between 2010-2016. YOCRC was defined based on age at diagnosis < 50 years. EQI (2005-2010) is a measure of county-level cumulative environmental exposures that includes 5 domains: sociodemographic, built, air, land, and water. A higher value represents a lower environmental quality. We distributed the total EQI and each EQI domain into five quintiles. Multivariable logistic regression analysis was used to assess the relationship between YOCRC and quintiles (upper-most vs. lowest) of EQI after adjusting by race (White, Black, and Others), gender, and stage at diagnosis. The age-adjusted incidence rate was also calculated using the SEER*Stat, and correlation efficiency was estimated between EQI domains and incidence rate. Results: A total of 261,417 CRC patients were included; 11% were YOCRC. In the adjusted multivariable analysis, poor built EQI (OR 1.15 [1.11-1.20]) and water EQI (OR 1.08 [1.03-1.12]) were more likely to be associated with YOCRC. Poor built EQI was more strongly associated with Black YOCRC (OR 1.21 [1.09-1.35]) as compared to White YOCRC (OR 1.14 [1.09-1.19]). Poor sociodemographic EQI was more strongly associated with Others (OR 1.47 [1.25-1.72]) compared to Black YOCRC (OR 1.14 [1.03-1.25]). In addition, poor built EQI (OR 1.19 [1.12-1.27]) and water EQI (OR 1.12 [1.05-1.19]) were more strongly associated with the metastatic disease among YOCRC patients. However, the total poor EQI was not associated with YOCRC (OR 0.99 [0.95-1.03]). On incidence analysis, there was a positive correlation between the incidence rate of YOCRC and sociodemographic EQI (rho=0.49, p<0.001), air EQI (rho=0.30, p<0.001), and land EQI (rho=0.18, p<0.001). Conclusions: This study evaluated a population-based ecological approach and showed that YOCRC was associated with lower environmental quality, including built and water domains. EQI domains were also associated with different racial groups among YOCRC. [Table: see text]
A survey study of prevention and treatment patterns by academic and community oncologists for cancer therapy-associated diarrhea.
Authors: Marathe Omkar Subhash , Tang Lina , Tyler Robert C , Webb Mark L , Chen Liping , Wu Chengguang , Li Wenxi , Ju Juegang , Luo Jie , Tang Hong , Vogelzang Nicholas J.
Published: January 2022

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Background: Chemotherapy and targeted therapies are associated with GI toxicities including diarrhea that affects 50% to 80% of patients. Severe complications include dehydration, malnutrition, fatigue, renal insufficiency, and systemic infection. There are no specific prevention strategies, and treatment options are limited. Dose reduction or interruption of anti-cancer medications may lead to decreased efficacy. This survey was conducted to assess current toxicity management patterns and gaps for cancer therapy-associated diarrhea. Methods: An online survey (MedSurvey) with 6 eligibility & 15 practice questions was conducted (April 27 to 30, 2021). Fifty (50) practicing oncologists completed the survey. Results: Among the 50 oncologists,82% have been practicing ≥ 11 years with 24% from an academic setting and 76% from a community setting. They (percent of respondents) prescribed the following anti-cancer medications more than 10 times per week: cytotoxic chemotherapy (86%), targeted agents (78%), and immuno-oncology therapies (80%). Prevention of chemotherapy-induced diarrhea (CID) with Imodium (loperamide) and Lomotil (diphenoxylate and atropine) were commonly administered (10% always, 60% sometimes) as prophylactic treatment prior to the start of chemotherapy. The majority (60%) would prophylactically use a novel agent for a patient with previous CID, and 38% would use this agent for selected anti-cancer therapies. Many oncologists (5% always, 60% sometimes) start chemotherapy at a lower dose and titrate up to prevent CID. Similar treatment patterns were observed for targeted therapy induced diarrhea (TTID). For Grade 1 CID (multiple choices allowed), 18% used observation only for management, whereas 72% prescribed Imodium, and 22% used Lomotil. For Grade 1 TTID (multiple choices allowed), 26% used observation only, 58% prescribed Imodium, and 26% used Lomotil. Dose reduction was implemented 10% and 6% of the time for CID and TTID, respectively. For Grade 2 CID (multiple choices allowed) 4% used observation only, most started either Imodium (82%) or Lomotil (72%), and 34% considered dose reduction as a treatment strategy. For Imodium or Lomotil non-responders, 50% would dose reduce, and 44% would use an alternate anti-diarrheal treatment (e.g., octreotide). TTID had similar treatment patterns. For immune-oncology agents (e.g., ipilimumab, nivolumab, pembrolizumab) 40% suggested induced GI toxicities (e.g., diarrhea/colitis) require an innovation for managing toxicity. Conclusions: Treating cancer therapy-associated diarrhea continues to be a significant challenge with Grade 2/3 often requiring a therapeutic dose reduction or interruption that may impact the efficacy of cancer treatment. Effective management (prevention and treatment) for GI toxicity remains an unmet need for many patients.
Pre‐emptive oral clarithromycin to reduce the skin toxicity of panitumumab treatment for metastatic colorectal cancer.
Authors: Kagawa Yoshinori , Komori Takamichi , Nakata Ken , Saso Kazuhiro , Ota Hirofumi , Morita Shunji , Noura Shingo , Hayashi Nobuyasu , Uemura Mamoru , Matsuda Chu , Satoh Taroh , Mizushima Tsunekazu , Murata Kohei , Doki Yuichiro , Eguchi Hidetoshi ,   Multicenter Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO)
Published: January 2022

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Background: Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities. Methods: We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with pani- tumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period. Results: Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17–0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths. Conclusions: Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab. Clinical trial information: UMIN000011485.
Associations of sarcopenia with hematologic toxicity, treatment intensity, and healthcare utilization in patients with metastatic colorectal cancer.
Authors: Lei Matthew , Nipp Ryan David , Tavares Erica , Lou Uvette , Grasso Erica , Mui Stephanie Y , Marquardt Jan Peter , Best Till D. , Van Seventer Emily E. , Saraf Anurag , Tahir Ismail , Horick Nora K. , Fintelmann Florian J. , Roeland Eric
Published: January 2022

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Background: We evaluated the impact of baseline sarcopenia on hematologic toxicity, treatment intensity, and healthcare utilization in patients with mCRC receiving FOLFOX or FOLFIRI. Methods: We retrospectively analyzed patients with mCRC who received care at our institution from 1/2011-11/2018 and were part of a biobanking protocol. Included adults received either first-line palliative FOLFOX- or FOLFIRI-based regimens and were followed for 6 months. We categorized sarcopenia based on skeletal muscle index measured at diagnosis of metastatic disease and pre-defined sex-specific cutoff values (F < 39 cm2/m2, M < 55cm2/m2). Our primary aim was to evaluate the association of sarcopenia and hematologic toxicity, defined as the incidence of grade ≥3 (G≥3) neutropenia, thrombocytopenia, or anemia (NCI CTCAE v5.0). Secondary endpoints included treatment intensity (dose reductions, treatment delays, relative-dose intensity [RDI]), and healthcare utilization (ED visits and/or hospitalizations). Bivariate analyses were used to evaluate associations between baseline sarcopenia and outcomes. Results: 126 of 177 screened patients met inclusion criteria (70 (56%) males, median age 61 yrs (range, 29-85)). 59 (46.8%) patients were sarcopenic. More patients received FOLFOX than FOLFIRI (92 [73.0%] vs. 34 [27.0%]). At baseline, patients had a median weight 76.9kg (IQR, 70.0-90.4 kg), BMI 26.6 kg/m2 (IQR, 24.1-30.5 kg/m2), and BSA 1.90 m2 (IQR, 1.72-2.01 m2). The incidence of G≥3 hematologic toxicity was 39.0% vs. 23.9% in sarcopenic and non-sarcopenic patients, respectively (p = 0.06). Patients with sarcopenia experienced higher incidence of G≥3 neutropenia (30.5% vs. 14.9%, p = 0.03), while G≥3 thrombocytopenia was similar (3.4% vs. 1.5%). The incidence of dose reductions and treatment delays did not differ significantly (86.4% vs. 89.5%, 72.9% vs. 71.6%, respectively). RDI was decreased for the 5FU bolus (52.5% vs. 65.0%, p = 0.02). Rates of ED visits (32.2% vs. 19.4%, p = 0.10) and hospitalizations (32.2% vs. 26.9%, p = 0.51) did not differ compared between patients with and without sarcopenia. Conclusions: Patients with mCRC and baseline sarcopenia receiving FOLFOX- or FOLFIRI experienced a higher incidence of G≥3 neutropenia and lower 5FU bolus treatment intensity. Studies are needed to understand how best to adjust treatment according to patients’ muscle mass.
Predictive factors for renal function deterioration during palliative first-line chemotherapy for metastatic colorectal cancer.
Authors: Lim AhReum , Kim Jwa Hoon , Hyun Myung Han , Kim Yeul Hong , Lee Soohyeon
Published: January 2022

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Background: Effective first-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers in metastatic colorectal cancer (mCRC). Considering the increased number of cancer patients with old age and their chronic diseases, it is essential to select a therapeutic agent by evaluating the toxicity that may occur due to long-term chemotherapy. This study assessed changes in renal function for 1 year in patients diagnosed with mCRC during chemotherapy and analyzed the factors and effect of each chemotherapy regimen on renal function. Methods: We retrospectively investigated patients with mCRC treated with palliative 1st line chemotherapy at our institution from 2015 to 2020. According to the common 1st line treatment regimen, we divided into 4 groups; FOLFOX/FOLFIRI with bevacizumab/cetuximab. We checked the baseline renal function and 3, 6, 9 and 12 months after the start of chemotherapy. The change in estimated glomerular filtration rate (△eGFR) was calculated as [(eGFR at each time point) - (eGFR at baseline)/(eGFR at baseline) X 100]. The clinical factors such as age, gender, chronic disease, BMI (body mass index), disease status, baseline proteinuria, and 1st line chemotherapy regimen were evaluated. Proteinuria was detected on urine dipstick protein ≥ 1+. Additionally, predictors for ΔeGFR ≤ −30% at each time points after therapy initiation were evaluated using multivariate logistic regression analysis. Results: Among 466 mCRC patients, the median eGFR values at baseline was 95.4 ml/min/1.73m2. The median eGFR at 6 months after chemotherapy initiation were significantly lower than baseline (88.3 ml/min/1.73m2, p < 0.001). As 1 year, patients with more than 30% worsening of renal function was observed in 27.6 % in FOLFIRI + bevacizumab, 26.3 % in FOLFOX + bevacizumab, 6.6 % in FOLFIRI + cetuximab, and 4.7 % in FOLFOX + cetuximab group. The FOLFIRI + bevacizumab was an independent predictor for ΔeGFR ≤ −30% at 6 months (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.05-3.47, p = 0.034) along with old age (≥ 65 years, OR 2.18, 95% CI 1.29-3.68, p = 0.004) and BMI (p = 0.012). Additionally, FOLFIRI + bevacizumab regimen causes more proteinuria (46.4%) than other chemotherapy regimens. Conclusions: Deterioration of renal function was more common with FOLFIRI + bevacizumab than other combination regimen. Old age, BMI were also associated decreasing eGFR. These results will be helpful to be suggested as important consideration when selecting the 1st line chemotherapy regimen for mCRC.