bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness of systemic treatments in desmoid tumors.
Authors: Costa Philippos Apolinario , Arora Arshia , Tan Heng , Fernandez Yanelys , Campoverde Leticia , Barreto Coelho Priscila , Bialick Steven , Espejo-Freire Andrea P. , Jonczak Emily , D'Amato Gina Z. , Subhawong Ty , Trent Jonathan C. 
Published: June 2022

e23534 Background: Many systemic treatment options are described for desmoid tumors, including hormonal therapies, non-steroidal anti-inflammatory drugs, cytotoxic chemotherapeutic agents, and most recently, tyrosine kinase inhibitors. Although many options are described, randomized data is scarce. The lack of comparative studies precludes a definitive sequence of the existing systemic treatments in the management of desmoid tumors. Here we retrospectively compare sorafenib with cytotoxic chemotherapy to generate objective data to guide treatment choice. Methods: We analyzed all patients with desmoid tumors treated with doxorubicin, dacarbazine, vinblastine, vinorelbine, methotrexate, or sorafenib in the first-line setting at a single center from 2000-2021. The primary endpoint was investigator-assessed progression-free survival. The secondary endpoint was the rate of toxic effects recorded accordingly to the Common Terminology Criteria for Adverse Events. We calculated progression-free survival (PFS) using the Kaplan-Meier method with Log-Rank Test to estimate the 95% confidence interval. Results: 79 patients ultimately received systemic therapies. Median follow-up was 5.6 years (0 to 7.9), 69% were women, and median age at diagnosis was 37 (range 5-77). Regarding race and ethnicity, 74% were White, 26%, Black and 45%, Latino. The tumor was in the lower extremity in 21 (27%) cases, trunk in 18 (23%) cases, abdominal wall in 13 (16%), intra-abdomen in 9 (11%), upper extremity in 7 (9%), head-neck in 7 (9%) and breast in 4 (5%). Surgery before systemic treatment was used in 20 (25%) patients. The regiments used were sorafenib (n = 32), doxorubicin with dacarbazine (n = 13), liposomal doxorubicin (n = 11), methotrexate with vinblastine (n = 11), methotrexate with vinorelbine (n = 8) and methotrexate monotherapy (n = 1). The 2-year progression-free survival rate was 80% (95% confidence interval [CI], 0.64 to 0.96) in the cytotoxic chemotherapy group and 66% (95% CI, 0.46 to 0.86) in the sorafenib group (P = 0.06). The most frequently reported adverse events on the cytotoxic group were grade 1 or 2 events of nausea (25%) and rash (15%), and on sorafenib were grade 1 or 2 events of palmar-plantar erythrodysesthesia (40%) and fatigue (25%). There were no treatment-related deaths reported. Conclusions: There was no statistical difference between the analyzed treatments, although there was a trend toward lower progression rates with cytotoxic therapy.
Establishment of PD3D models of sarcomas: A promising preclinical tool for improvement of sarcoma treatment.
Authors: Regenbrecht Manuela , Sauer Rica , Niethard Maya , Regenbrecht Christian RA , Loskutov Jürgen 
Published: June 2022

e23538 Background: Compared to the progress in understanding and treating carcinomas in the past decade, the options and related clinical benefit in terms of response rates and overall survival for sarcoma patients lacks behind. Increasing incidence, low 5-year-survival rates and nearly endless heterogeneity of sarcomas are challenging oncologists every day. The necessity of so far missing representative preclinical models is obvious. PD3D cell culture models have already proven to be a useful tool to reverse clinical engineer patient outcome in carcinomas. Here we report the establishing and refining of PD3D models for the plethora of sarcoma entities. Methods: We obtained viable sarcoma tissue samples from incisional biopsies or tumor resections. We continuously optimized media conditions. For quality control and pathological evaluation, we embedded the cells in FFPE, stained patient-specific models according to original tumor samples and evaluated them pathologically. Upon histopathological evaluation, we performed semi-automated drug response assays on patient-specific models with up to 12 drugs and drug combinations, including standard of care drugs plus a selection of additional drugs. In the fashion of a prospective observatory study, we compared the results from the in vitro screen with the actual clinical outcome. Results: More than 25 patient derived 3D-cell culture models have been established from various subtypes of sarcomas. Optimized media conditions and sampling operation improved the take rates from ca. 10 to 80% irrespective of the tumor subtype. Pathological examination of the models confirmed original diagnoses and revealed that the patient-specific models recapitulate the key properties of the original tumor. Negative predictive value of drug sensitivity testing was close to 100 %, while the positive predictive value was > 80 %. These results in a limited number of cases puts the predictive value en par with recently published data about the predictive value of patient-derived organoids in carcinomas. Conclusions: Patient derived 3D-cell culture models of sarcomas can be routinely established, irrespective of subtype Models can be used for multi-omics analyses including drug sensitivity screenings Pretherapeutic drug sensitivity screenings could support clinical decision making Findings need to be confirmed in a prospective observatory trial.
The impact of classic Hodgkin lymphoma (cHL) on informal caregivers: Results from the cHL—Real-world observations from physicians, patients, and caregivers on the disease and its treatment (CONNECT) study.
Authors: Flora Darcy R. , Evens Andrew M. , Liu Nicholas , Yu Kristina S. , Byrd Rachel , Kumar Supriya , Fanale Michelle , Holmes Katie , Flores Avile Carlos , Surinach Andy , Parsons Susan K. 
Published: June 2022

e24004 Background: The health and work productivity burden informal cHL patient (pt) caregivers face is unknown. As part of the US-based CONNECT study, we evaluated caregivers’ burden and role in treatment (tx) decisions by relation to the pt: spouse/partner (SP) vs other (parent, child, friend, other relative). Methods: The CONNECT caregiver survey was an IRB-approved online survey administered from Dec 2020-Mar 2021 to self-identified current or former adult cHL pt caregivers. Health-related quality of life (HRQoL, PROMIS-Global), work impact (WPAI), decision-making, tx selection, and physician communication were assessed. Statistical significance was at the 95% confidence level. Results: 209 caregivers (58% women; median age 47 yrs; 54% employed; 53% SP) completed the survey. At completion, 69% cared for pts diagnosed in the past 1-2 yrs; 48% of pts cared for had stage III/IV cHL and 58% were in remission/not receiving active tx. While caregiver HRQoL was similar to that of the general population on the PROMIS-Global, employed caregivers had work impairment (29%) from caregiving activities (Table) which was higher when the pt was on vs off tx. Caregiving began at pt symptom onset for more SP vs other caregivers (61 vs 27%), and after the pt’s first tx for more other vs SP caregivers (34 vs 5%). 88% of caregivers discussed tx options with the pt. Cure, caregivers’ top tx goal (49%), was rated higher by SP vs other caregivers (56 vs 42%). Tx decisions with the pt (54 vs 23%) and tx option discussions with the doctor (52 vs 28%) were more common for SP vs other caregivers. More SP vs other caregivers had extensive tx option discussions with the pt (88 vs 68%), said it was important the doctor discussed managing side effects (94 vs 84%), felt the doctor provided adequate information about side effects (91 vs 71%), and felt aligned with the pt’s tx goals (93 vs 79%). Caregivers noted COVID-19 impacts like limiting daily activities to reduce COVID-19 risks (72%). Conclusions: Although cHL pt caregivers reported good HRQoL, caregiving impacted their work productivity regardless of relation to the pt. Cure was caregivers’ top tx goal. SP vs other caregivers were more involved and earlier, reporting alignment with pt tx goals and decision-making.[Table: see text]
The analgesic compound palmitoylethanolamide reduces inflammation in human cardiomyocytes and vascular endothelial cells exposed to doxorubicin and anti-HER2 monoclonal antibody through PPAR-α and NLRP3-related pathways.
Authors: Iovine Martina , Quagliariello Vincenzo , Buccolo Simona , Paccone Andrea , De Laurentiis Michelino , Maurea Nicola 
Published: June 2022

e24054 Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid mediator that is synthetized from membrane phospholipids by N-acyl phosphatidylethanolamine phospholipase D. It is a new analgesic drug with anti-inflammatory effects through the induction of PPAR-related pathways. We aimed to assess whether palmitoylethanolamide co-incubated during doxorubicin and trastuzumab, reduces anticancer drugs-related cardiotoxicity in cellular models. Methods: Human vascular endothelial cells and cardiomyocytes were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) combined to trastuzumab (at 100 and 200 nM) alone or in combination with a formulation composed by palmitoylethanolamide 500 nM for 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator-activated receptor-α; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Palmitoylethanolamide co-incubated with doxorubicin exerts vasculoprotective and cardioprotective effects, enhancing cell viability of 56.3-78.7 % compared to untreated cells (p < 0,001 for all). Notably, PEA reduced significantly the cardiotoxicity through peroxisome proliferator-activated receptor-α –related pathways and NLRP3 inflammasome but without the involvement of calcium homeostasis. Several cytokines and chemokines were also reduced confirming its anti-inflammatory effect. Conclusions: The present study demonstrates that palmitoylethanolamide protects against vasculotoxicity and cardiotoxicity of doxorubicin and trastuzumab by promoting an anti-inflammatory phenotype, representing a new therapeutic approach to resolve doxorubicin-induced vasculo-cardio toxicity and inflammation.
Breast cancer survivors: Main physical and psychosocial problems after completion of treatment at a Brazilian cancer center.
Authors: Vidal Brito Thiago , Reboucas Camilla Vieira de , Alves Rafaela de Brito , Magalhaes Trindade D. Yamada Alayne , do Nascimento Martins Adriana , Cruz Felipe Melo 
Published: June 2022

e24057 Background: The number of breast cancer survivors has grown worldwide in recent years due to advances in treatments, however, increased survival lead to the appearance of signs and symptoms after the end of treatment that affect the quality of life of these patients in the long term. Methods: Women aged 20-60 years with a diagnosis of breast cancer and primary treatment for at least 1 year were selected. The Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was used and sociodemographic data, life habits and clinical conditions of the participants were collected. The primary end point was to identify the main repercussions of breast cancer and its treatments. Results: A total of 87 women were enrolled for this study. The mean age was 48.5 years. The main symptoms identified were pain (15.48%), nausea (13.10%), fatigue (11.90%), hot flashes (9.52%) and insomnia (5.95%). The total FACT-B+4 score was 110.75 (SD 20.02). No statistically significant variables were identified as predictors of worsening quality of life. Conclusions: The main residual problems in breast cancer survivors 1 year after curative treatment at Hospital São Camilo Oncologia were identified, however, it was not possible to establish significant predictors of worsening quality of life. We will conduct a new interview in 1 year using others quality of life assessment instruments.
The burden of long-term complications among adolescent and young adult cancer survivors: An international comparison of two large cohorts.
Authors: Hayek Samah , Libresco Gilad , Barda Noam , Chao Chun , Lanfang Xu , Cannavale Kimberly L. , Izraeli Shai , Armenian Saro 
Published: June 2022

e24059 Background: There is a paucity of information on health outcomes of adolescent and young adult (AYA) cancer survivors outside of Northern Europe or North America. We compared long-term health outcomes of Israeli AYA cancer survivors to non-cancer individuals with similar demographics and access to healthcare, estimated the risk of developing chronic health conditions by cancer type, and compared the comorbidity burden in Israeli AYA survivors to AYA cancer survivors from the U.S. Methods: This was a retrospective cohort of 2-year cancer survivors diagnosed with invasive cancer between 15 to 39 years of age from 2000 to 2018 in Clalit Health Services (CHS), the largest payer-provider healthcare organization in Israel. Non-cancer CHS participants were matched 4:1 to cancer survivors on age, sex, ethnicity, and membership duration. Health conditions were limited to those requiring medical intervention. Incidence rates for health conditions were determined for the two cohorts, and Poisson regression was used to determine the incidence rate ratio (IRR) with associated 95% confidence intervals (CI). A sub-population of CHS AYA survivors was used to compare the incidence of chronic health conditions from the Israeli cohort to AYA cancer survivors from Kaiser Permanente Southern California (KPSC), using Standardized Incidence Rate (SIR). Results: There were 12,674 CHS AYA cancer survivors and 50,696 non-cancer participants. Among survivors, the mean age at diagnosis was 31.02 years (SD: 6.2), 61.7% were female, and 78.4% were Jewish. The most common cancer diagnoses were lymphoma (16.5%), breast (16.4%), and thyroid (14.0%). Cancer survivors were significantly more likely to have any (IRR 1.60 95%CI: 1.54-1.67) or multiple (IRR 1.82 95%CI: 1.72-1.94) chronic health conditions compared to non-cancer participants. Survivors had an increased risk across nearly all examined outcomes, with an especially higher risk for premature ovarian failure (IRR 6.02 95%CI: 2.14-16.91), osteoporosis (IRR 4.74 95%CI: 4.06-5.53), and cardiomyopathy (IRR 4.20 95%CI: 3.35-5.27). We also found clear differences in the risk of specific health conditions by cancer type. Compared to the KPSC cohort, CHS cancer survivors had an overall lower (SIR 0.82 95%CI: 0.79-0.84) incidence of developing any health condition, with noticeably lower incidences of hypertension, hyperlipidemia, chronic liver disease, but higher incidences of cardiopulmonary diseases and osteoporosis. Conclusions: AYA cancer survivors in Israel are at increased risk for developing chronic conditions, compared matched non-cancer individuals, but the overall incidence of was lower when compared to survivors living in the U.S. These findings may allow for refinement of surveillance recommendations for AYA survivors, taking into consideration regional differences in socio-demographics and cancer care.
Efficacy, safety and cost effectiveness of reduced-dose olanzapine versus aprepitant as a part of triple-antiemetic therapy in the prevention of chemotherapy induced nausea and vomiting.
Authors: Mohammed Owais , Thota Narender kumar 
Published: June 2022

e24078 Background: In Developing world, Olanzapine at a dose of 10mg is associated with excessive somnolence. Recently, reduced dose Olanzapine 5mg has been found to be equally effective with less sedation. Hence, we intended to conduct a study comparing the efficacy, safety, and cost effectiveness of reduced dose Olanzapine 5mg vs Aprepitant. Objectives: To compare Complete response (no emesis and no rescue therapy) rates between the two groups during three periods: 0 to 24 hours (acute), 25 to 120 hours (delayed), and 0 to 120 hours (overall) after chemotherapy. To compare nausea control rates in the acute, delayed, and overall periods. To evaluate potential adverse effects and compare cost effectiveness of Olanzapine, Aprepitant. Methods: All newly diagnosed cancer patients who were scheduled to receive highly emetogenic chemotherapy (either cisplatin at a dose ≥70 mg/ m2 body surface area, with or without other chemotherapeutic agents, or doxorubicin at a dose of 60 mg/m2 plus cyclophosphamide at a dose of 600 mg /m2) and had a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 were randomized 1:1 to receive triple anti emetic regimen comprising of 5HT3 antagonist (Palonosetron)+Steroid (Dexamethasone) + either NK1 antagonist (either Aprepitant 125mg on day 1, 80 mg on days 2, 3 or Fosapprepitant 150mg IV on day 1) or Olanzapine 5mg once daily on days 1-4). Number of Vomiting episodes, use of rescue therapy, nausea, other adverse effects were recorded. Results: A total of 154 patients were eligible for the study, 77 in each arm. The Complete response rates for Aprepitant and Olanzapine during the acute period were 79.22% and 81.81% respectively (p > 0.05), during the delayed period were 74.02% and 70.12% respectively (p > 0.05), during the overall period were 74.02% and 70.12% respectively (p > 0.05). Nausea control rates for Aprepitant and Olanzapine during the acute period were 74.42% and 84.82% respectively (p > 0.05), during the delayed period were 45.45% and 68.83% respectively (p < 0.05), during the overall period were 45.45% and 68.83% respectively (p < 0.05). Most common side effect in patients receiving Olanzapine was Somnolence which was observed in 12.98% patients (CTCAE Grade 2). Most common side effect in patients receiving Aprepitant was fatigue which was seen in 6.5% patients. A 4-day course of Olanzapine costs INR-20/- while a 3-day course of Aprepitant costs INR-1000/- and a single 150mg IV Fosapprepitant costs INR 2500/-. Conclusions: In the developing world, Olanzapine 5mg can be considered as an effective, safe, and a cheaper alternate to Aprepitant as a component of triple antiemetic regimen in the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.
Evaluation of cross-disciplinary educational material to improve patients’ knowledge and utilization of palliative radiation therapy.
Authors: Rizvi Faryal , Young Meredith , Habib Muhammad Hamza Hamza , Kra Joshua , Shah Ankit , Mayer Tina M. , Saraiya Biren , Mattes Malcolm David 
Published: June 2022

e24082 Background: Palliative radiation therapy (PRT) is underutilized in the United States, in part due to misconceptions among patients and other providers about its risks, benefits, and indications. Empowered patients, who are more knowledgeable about how radiation can alleviate cancer-induced symptoms, may facilitate more appropriate and timely use of PRT. In this pilot study patient-directed educational material describing PRT was developed and used among patients being treated in medical oncology and palliative care clinics. The hypothesis is that most patients will gain new knowledge from educational content about PRT, and perceive it as useful in their care. Materials/Methods: A 1-page educational handout was developed to convey general information about the purpose, logistics, benefits, risks, and common indications for PRT. Patients undergoing treatment for a metastatic solid tumor were invited to participate during their regular clinic visit. Patients who chose to participate read the handout, and then completed a multiple choice questionnaire assessing how much they learned from the handout (nothing vs. little vs. lots), whether the information in the handout was useful (no vs. somewhat vs. very), as well as other questions. Responses were anonymous. There was no follow-up with participants. Descriptive statistics are reported, with Fisher’s Exact Test used to compare subgroups of patients. Results: A total of 70 patients from 1 palliative care physician and 4 medical oncologists participated between June – December 2021. Sixty-five patients (89%) felt they learned from the handout (38% learned “lots”) and 69 (94.5%) felt the information was useful (53% “very useful”). Twenty-one patients (28.8%) learned that PRT can help with symptom relief, 55 (75%) learned that PRT can be delivered in a course of 5 treatments or less, and 43 patients (59%) learned that PRT usually has few side effects. Furthermore, 16 (22%) felt they currently had symptoms not being treated well enough, and 34 (47%) felt they currently had symptoms that radiation might help with. Most patients felt more comfortable bringing symptoms to a medical oncologist’s (n = 57, 78%) or radiation oncologist’s (n = 51, 70%) attention after reading the handout. Forty-one patients (56.2%) reported a prior visit with a radiation oncologist, but this did not impact their responses related to learning from the handout ( p< 0.001) or finding the handout useful ( p< 0.001). Conclusions: Patient-directed educational material about PRT provided outside of a radiation oncology department was perceived by patients as improving their knowledge, and adding value in their care, independent of their prior exposure to a radiation oncologist. Further research will evaluate the impact of the educational material on referral patterns.
Shortening the baseline period in hot flash symptom control trials: Comparison of a one-day versus seven-day baseline hot flash diary.
Authors: Childs Daniel S , Novotny Paul J. , Marrell Paulina S , Ruddy Kathryn Jean , Loprinzi Charles L. 
Published: June 2022

e24094 Background: Hundreds, if not thousands, of participants are enrolled hot flash trials each year given the magnitude of the problem for breast and prostate cancer survivors. Classically, these studies have included a baseline period of 1-week, or longer, to understand the frequency and severity of hot flashes before starting a new treatment. The objective of the current study was to compare the accuracy of a 1-day baseline hot flash diary to a more traditional 1-week dairy. A shorter baseline period would be more convenient for patients and provide a more efficient study design. Methods: Raw data from 5 pilot studies and 15 phase III randomized, controlled trials (RCTs), all of which used a one-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p-values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. Results: A total of 2,573 participants were included. On average, participants had 8.5 hot flashes per day on Day 1. Mean hot flash frequencies and scores on subsequent days (Days 2-7) were within 6% of Day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Re-analysis for each pilot study revealed that no individual study conclusions would have been meaningfully altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. Conclusions: A 1-day hot flash diary appears to accurately reflect true frequency and severity of baseline hot flash symptoms in appropriately sized cohorts. Results support a shorter baseline period for pilot studies and RCTs.