bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

75 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

76 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

79 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

84 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

85 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.
Outcome of preoperative concurrent radiation and infusional gemcitabine in locally advanced rectal cancer, a phase 2 trial.
Authors: Bazarbashi Shouki , Gad Ahmed Mostafa , Badran Ahmed Ali , Elshenawy Mahmoud , Aljubran Ali H , Al Zahrani Ahmad , Al Manae Hadeel , Alsuhaibani Abdullah , Elashwah Ahmed , Neimatallah Mohammed , Abdul Jabbar Alaa , Ashari Luai , Al Homoud Samar , Ghebeh Hazem , Alsanea Nasser , Mohiuddin Mohammed 
Published: January 2022

94 Background: The achievement of a pathological complete response with preoperative concurrent chemoradiotherapy in locally advanced rectal cancer has been found to correlate with a reduced incidence of local and distant recurrences. With the radiosensetizing properties of gemcitabine, we tested the efficacy and toxicity of preoperative concurrent infusional gemcitabine and radiotherapy in locally advanced rectal cancer. Methods: This was a phase II, single-arm, single-institution trial. Eligibility included a diagnosis of rectal adenocarcinoma with stage T2–4 and/or nodal involvement by MRI and endoscopic rectal ultrasound, age ≥ 18 years and no prior chemotherapy or radiotherapy. Patients received preoperative radiation at a dose of 50.4–54 Gy over 28 days with concurrent infusional gemcitabine administered at a dose of 100 mg/m2 over the course of 24 hours weekly for 6 weeks. The primary endpoint was a pathological complete response (pCR). The trial was registered at clinicaltrials.gov (NCT02919878). Results: Forty patients were enrolled in the study. All of the patients completed the planned therapy, except for one patient who died at the end of his concurrent chemoradiation. Eight patients did not undergo surgery, with 1 patient dying (mentioned above), 2 patients progressing to nonresectable disease and 5 patients withdrawing consent. Six patients progressed prior to or had metastases identified at surgery, with 2 patients having unresectable metastases, 3 patients having resectable liver metastases and 1 patient having a peritoneal metastasis (not resected). Serious adverse events were reported in 8 patients (20%). The most common grade 3–4 toxicities in the preoperative period included lymphopenia (50%), neutropenia (41%), anemia (15%), diarrhea (12%), abdominal pain (12%) and proctitis (8%). Out of the 32 patients who underwent surgery, 7 patients achieved pCR at a rate of 20%. With a median follow-up of 30 months, 4 additional patients relapsed (all of these patients had distant metastases, with one subsequently having a local recurrence). The 3-year event-free and overall survival rates were 70% and 85%, respectively. Conclusions: Concurrent preoperative chemoradiotherapy using infusional gemcitabine for locally advanced rectal cancer achieved an encouraging local control. Distant metastasis remains not decreased. Further investigations of a preoperative regimen containing gemcitabine is warranted. Clinical trial information: NCT02919878.
Phase II study of durvalumab following neoadjuvant chemoRT in operable rectal cancer: NSABP FR-2.
Authors: George Thomas J. , Yothers Greg , Jacobs Samuel A. , Finley Gene Grant , Wade James Lloyd , Rocha Lima Caio Max Sao Pedro , Rose Jeffrey Scott , Pahuja Shalu , Krishnamurthy Anuradha , Krauss John C. , Deutsch Melvin , Fabregas Jesus C. , Lee James J. , Allegra Carmen Joseph , Wolmark Norman 
Published: January 2022

99 Background: Although immunotherapy shows no benefit in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. Using a “window-of-opportunity” study design, this prospective phase II trial will determine the safety and activity of this approach with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: Stage II/III patients (pts) with MSS rectal cancer undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT) followed by definitive surgery were eligible. Treatment included durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion followed by surgery within 8-12 wks of the final CRT dose. Primary end point (EP): Improvement in modified neoadjuvant rectal cancer (mNAR) score (goal 10.6) compared to historical controls (15.6) targeting a 20% DFS RR reduction and 3-4% absolute OS improvement. Secondary EPs: toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, and exploratory assessments of tumor-infiltrating lymphocytes, tumor Immunoscore, circulating immunologic profiles, and molecular predictors of response. We test H0: mNAR ≥15.6 vs HA: mNAR <15.6 at alpha 0.10 one-sided with statistical significance defined as p<0.1. Results: From May 2018 to October 2020, 45 pts were enrolled with 40 pts evaluable for mNAR. Mean mNAR was 12.03 (80% CI: 9.29-14.97) (p=0.06 one-sided). pCR=22.2%; cCR=31.1%; R0 resection=81.0%, and sphincter preservation=71.4%. Side effects were consistent with both CRT and durvalumab safety profile. Most common grade 3 AEs included diarrhea, lymphopenia, and back pain. There was one grade 4 AE (elevated amylase/lipase) and no grade 5 AEs. Remaining secondary and correlative immunologic end points are still being assessed. Conclusions: Durvalumab immediately following CRT prior to surgery for definitive management of rectal cancer was safe and without unexpected short-term toxicities. The primary end point of mean mNAR score was significantly less than our historical control, warranting further investigation. Correlative analyses for immunologic markers of response including PD-(L)1 expression and Immunoscore are ongoing. NCT 03102047. Support: AstraZeneca-Medimmune, NSABP Foundation. Clinical trial information: NCT03102047.