bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between symptoms and health-related quality of life in patients with cancer with prior or ongoing immune checkpoint inhibitor therapy exposure.
Authors: Jones Salene M.W. , Chan Anissa , Enright Emily , Raczka Aleksandra , Nguyen Vivian , Bhatia Shailender , Tykodi Scott S. , Veatch Joshua , Thompson John A. , Lee Sylvia , Lashey Matt , Hall Evan Thomas 
Published: June 2023

e24085 Background: There is a growing appreciation that patients exposed to immune checkpoint inhibitors (ICI) may experience long-term symptoms that impact health-related quality of life (HRQoL). We conducted an app-based, electronic patient reported outcomes (ePRO) study to explore the relationship between the symptom experience and HRQoL in a population of patients with cancer exposed to ICI therapy. Methods: Eligible patients had a history of advanced skin cancer or kidney cancer treated with ICI (adjuvant or metastatic) with ongoing, clinician-assessed disease control. Patients may have completed a course of ICI or continued on therapy if ≥ 6 months had passed since initiation. We conducted a single-center, observational, prospective cohort study where participants completed ePRO assessments via smartphone (ImmunoWave) measuring eleven symptoms (PRO-CTCAE) and HRQoL (PROMIS-29) weekly for 12 weeks. We used generalized estimating equations to assess the changes in PROMIS scores over study and to test the association of PRO-CTCAE symptoms with PROMIS scores and subdomains. Results: Forty-seven patients (77% melanoma, 15% renal cell carcinoma, 8% non-melanoma skin cancer) consented to the study. 70% were on active therapy while 30% had completed therapy. Most (62%) were treated in the metastatic setting. 43 patients who completed questionnaires were included in the analysis. Among subdomains of HRQoL at the study population level, social function was observed to have a significant linear trend (p = 0.013) and potentially meaningful (3.9 points overall) increase over the 12 weeks. Other subdomains were felt to have no clinically meaningful change at the population level over the 12 wk study period. Several PRO-CTCAE symptoms were significantly associated with health-related quality of life (PROMIS) subdomains (Table). Joint pain was significantly associated with fatigue (B = 1.006, p = 0.045), pain interference (B = 2.579, p = 0.002) and physical function (B = -1.532, p = 0.042). Itch was associated with anxiety (B = 1.017, p = 0.007) and social function (B = -1.136, p = 0.030). Numbness and tingling was associated with fatigue (B = 0.891, p = 0.027) and sleep disturbance (B = 1.436, p < 0.001). Conclusions: We observed high concordance between patient symptom report by PRO-CTCAE and corresponding PROMIS HRQoL subdomains. Addressing specific symptoms such as itch, numbness/tingling and joint pain in patients with current or prior ICI exposure could improve HRQoL. [Table: see text]
Immune-related adverse events after ≥12 months of starting immune checkpoint inhibitors.
Authors: Jovaisaite Agne , Serrano Marina , Jackson-Spence Francesca , Young Matthew , Toms Charlotte , Wang Yishen , Nally Elizabeth , Szabados Bernadett , Powles Thomas 
Published: June 2023

e24086 Background: Immune checkpoint inhibitors (ICIs) are well established in the treatment of metastatic renal cell (mRCC) and urothelial carcinomas (mUC). The profile of ICI immune-related adverse events (irAEs) is well described, however, data on timings of toxicity and irAEs occurring at ≥12 months are lacking. Methods: A single-site retrospective audit of mRCC and mUC patients receiving ICI-based therapy for ≥12 months between January 2014 and December 2022. ICI-based therapies included monotherapy and combination therapy with other ICIs or anti-VEGF tyrosine kinase inhibitors (TKIs). Best response to ICI-based therapy and irAEs were described. Results: 199 patients received ICI-based therapy, of which 34% (68/199) received treatment for ≥12 months. Of those on therapy for ≥12 months, 44% (30/68), 25% (17/68), and 31% (21/68) were treated with ICI monotherapy, combination with other ICIs, and TKIs, respectively. At data cut-off, 69% (47/68) were alive. 26% (18/68), 59% (40/68) and 15% (10/68) achieved complete response (CR), partial response (PR) and stable disease (SD), respectively. Overall, 83 irAEs were observed in 74% (50/68) of patients receiving therapy for ≥12 months. Of these, 71% (59/83) occurred at < 12 months and 28% (24/85) at ≥12 months. Corticosteroid therapy was required in 31% (18/59) of irAEs at < 12 months and 63% (15/24) at ≥12 months. Endocrine and cutaneous irAEs mostly occurred at < 12 months, while rheumatic irAEs were more frequently observed at ≥12 months. No ICI-related deaths occurred. At ≥12 months, 71% (17/24) of irAEs were grade 1/2 and 29% (7/24) were grade 3/4. Grade ≥3 irAEs at ≥12 months included colitis (n = 1), proctitis (n = 1), tubulointerstitial nephritis (n = 1), bullous pemphigoid (n = 1) and transaminitis (n = 3). Four patients discontinued treatment, the remainder restarted therapy after irAE resolution. All patients with late-onset grade ≥3 irAEs responded to therapy (CR in 2/7, PR in 5/7). A patient with grade 2 seronegative inflammatory arthritis with onset at ≥12 months also discontinued treatment. Conclusions: Although irAEs are less frequent after 12 months of ICI-based therapy, they remain clinically relevant requiring treatment interruption and discontinuation. Patients require ongoing safety monitoring irrespective of the duration of ICI-based therapy.
A systematic review with meta-analysis of radiotherapy adverse events in patients with cancer and lupus erythematosus.
Authors: Lopez-Olivo Maria A. , Qureshi Sehrish , Sharma Gaurav , Hicklen Rachel S. , Tayar Jean H. , Suarez-Almazor Maria E. 
Published: June 2023

e24092 Background: Multiple reports of serious adverse events (AEs) in people with lupus erythematosus who have received radiotherapy for their cancer exist. This systematic review determined the incidence of radiotherapy-related AEs in patients with cancer and lupus and evaluated if these patients have an increased risk of AEs compared to patients without lupus. Methods: We ran a comprehensive search in 4 electronic databases until October 2022. We included studies reporting data on AEs in patients with cancer and lupus receiving radiotherapy (palliative or definitive). Two investigators independently selected studies for inclusion, extracted data, and appraised the quality of the studies. A meta-analysis was performed for acute (≤ 90 days) and late ( > 90 days) AEs. Results: Ten cohort studies (6 with control groups) and 19 case reports (30 patients) met our eligibility criteria. Cohort studies reported on 126 patients with systemic, 26 with cutaneous lupus (mostly discoid), and 5 with unspecified lupus. The age of the patients ranged from 31-68. Median follow-up ranged from 1 to 12.5 years. Minimum and maximum radiation doses reported were 10 Grays and 87.6 Grays, respectively. The pooled incidence of acute AEs for patients with lupus when considering controlled and uncontrolled studies was 50% (95%CI 35%, 65%). When analyzing controlled studies only, no statistically significant differences were observed in the pooled rate of acute AEs in patients with lupus when compared to controls (Relative risk [RR] 1.2; 95%CI 0.84, 1.7). For late AEs, the pooled incidence for patients with lupus when considering controlled and uncontrolled studies was 21% (95%CI 9%, 34%). Although the pooled rate of late AEs in patients with lupus was higher compared to the control group, the difference did not reach statistical significance (RR 1.6; 95%CI 0.96, 2.8). Three cohort studies reported separate data for SLE patients regarding the type of AEs. The acute AEs reported were mucositis, pain, erythema, infection, pruritus, pulmonary embolus, and encephalopathy. The late AEs reported were hearing loss, telangectasia, alopecia, actinic keratosis, osteomyelitis, necrosis, bowel obstruction, and pneumonitis. Out of the 30 patients reported as case reports, 18 had systemic lupus, 10 cutaneous lupus (7 discoid), and 2 had lupus-like syndrome. Twenty-one cases reported acute AEs (mucositis, erythema, moist desquamation, and fibrosis) and the remaining cases did not report AEs. Conclusions: Almost half of the participants in the included studies reported acute AEs. Although, no statistically significant differences were observed between the lupus erythematosus and control groups, caution is advised given the possible severity of AEs in lupus patients. As most publications were old additional controlled studies are needed comparing the rates of severe AEs in this population with controls.
Trastuzumab-induced cardiotoxicity in breast cancer patients: A meta-analysis and review of the literature (2012-2022).
Authors: Anamika Fnu , Chitkara Akshit , Saharan Komal , Choudhary Tushar , Soni Ujjwal , Harmon Gabriella Angelina , Saeed Anwaar 
Published: June 2023

e24101 Background: Breast cancer (BC) is the most common type of cancer diagnosed, and 10-15% of BC patients develop a HER2-positive disease with a poor prognosis. In a previous meta-analysis of NCCTG N9831 and NSABP B-31 trials, treatment of early-stage HER2-positive BC patients with Trastuzumab and chemotherapeutic drugs improved overall survival by 37%. Trastuzumab-induced cardiotoxicity (TIC) is characterized by cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and heart failure. Per package inserts, the incidence of TIC is 4-6 times higher than the control. An important risk factor for TIC is the administration of concomitant anthracycline chemotherapy. Several studies have reported that this treatment combination can significantly reduce LVEF compared to Trastuzumab alone. In this study, we compiled recent randomized controlled trials (RCTs) and clinical trial data to evaluate the incidence of cardiotoxicity in Trastuzumab-treated BC and study management guidelines specifically directed for TIC. This will help reduce the morbidity and mortality in these patients. Methods: Our search included PubMed, EMBASE, Web of Science, and Cochrane Library articles from July 2012 through July 2022. RCTs and clinical trials that used Trastuzumab as a therapy and reported its cardiotoxic effects were included. A random-effects model was utilized with Review Manager, and a P value < 0.05 was considered significant. The entire analysis of treatment and control groups had various guideline-directed chemotherapies, including anthracycline-based regimens. Results: Our initial search yielded 26 results. After a full literature review by two independent reviewers, we selected four studies that included 1481 patients with cardiotoxicity data in the treatment and control groups. The analysis pooled from clinical trials showed that the odds of cardiotoxicity (specifically LVEF reduction) in patients treated with Trastuzumab were about seven times higher than the control group (OR 6.78, 95% CI 2.85-16.09, p-value < 0.0001). The guidelines recommend withholding Trastuzumab for ≥ 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below normal institutional limits and ≥ 10% absolute decrease in LVEF from pretreatment values. The safety of continuation or resumption of Trastuzumab in patients with TIC has not been studied, and there are no standardized management guidelines. Conclusions: We conclude in our study that the odds of TIC are increased by almost seven times compared to chemotherapy alone. In addition to just regular monitoring of these patients with history, physical examination, and determination of LVEF by echocardiogram or MUGA scan per protocol, there is a need to formulate guidelines for continuation or resumption of Trastuzumab in patients with TIC.
Demographic and clinical factors associated with cardiovascular events in elderly long-term survivors of breast cancer.
Authors: Westvold Sarah , KC Madhav , Fan Jane , Hyslop Terry , Spees Lisa , Wang Shi-Yi , Silber Andrea , Oeffinger Kevin C. , Dinan Michaela Ann 
Published: June 2023

e24105 Background: Improvements in cancer-specific survival have led to a growing appreciation for non-cancer drivers of mortality, particularly cardiovascular disease (CVD), in long-term cancer survivors. However, studies of population-level, non-oncologic outcomes in long-term survivors as a function of treatment exposures remain limited. Our aim is to evaluate the risk of developing cardiovascular disease (CVD) based on demographic and clinical characteristics in long-term breast cancer survivors, defined as those alive five years after diagnosis. Methods: We conducted a SEER-Medicare retrospective study of patients over age 65 with non-metastatic breast cancer, treated with curative intent surgery, diagnosed between 2003-2011, and enrolled in fee-for-service Medicare. CVD events were defined by the presence of any claims corresponding to stroke, heart failure, myocardial infarction, or cardiomyopathy beginning at 5 years after initial diagnosis and extending through year 10. Chi-squared tests were used to examine associations between demographic and clinical characteristics and CVD status. LASSO regularization was used for variable selection in a cox-proportional hazards model using 10-fold cross validation showing CVD hazard ratios stratified by diagnosis year. Results: 43,347 patients met inclusion criteria, of which 5,444 had a diagnosis of CVD between five years after diagnosis and last follow-up. Compared to patients without evidence of CVD, patients experiencing CVD were more likely to be older, Black, live in impoverished neighborhoods, have stage III (vs. I or II) disease, and have been diagnosed during the latter part of the study period (2009-2011 vs. 2003-2008). Variables included in the model following the LASSO regularization process were age at diagnosis, race/ethnicity, % with poverty, metropolitan residence, cancer stage at diagnosis, receipt of radiation therapy, and diagnosis year. Age, race/ethnicity, and cancer stage at diagnosis were significant predictors of developing CVD during years 5-10 after an initial cancer diagnosis (P < 0.001). Risk of developing CVD increased with age and was associated with a threefold higher risk in women over age 85. Non-Hispanic Black patients were at the highest risk across race/ethnicity groups (HR: 1.48, 95% CI: 1.34 – 1.65), and patients with a stage III diagnosis were at the highest risk by stage (ref Stage I; HR: 1.56, 95% CI: 1.41 - 1.72). Those diagnosed in 2009-2011 were at higher risk of developing CVD than in earlier years (ref 2003-2005; HR: 1.67, 95% CI: 1.56 – 1.79). Conclusions: Age, race, poverty, and cancer stage at diagnosis were associated with increased risk of developing CVD in long-term breast cancer survivors. Patients with elevated non-oncologic risks may benefit from increased participation by primary care as a component of effective cancer survivorship.
Development of a palliative care lecture series for hematology-oncology fellows.
Authors: Rodenbach Rachel , Lubner Sam Joseph , Johnson Sara 
Published: June 2023

e24112 Background: Many major organizations endorse provision of palliative care (PC) services for patients with advanced cancers from both oncologists and PC specialists. While ACGME has outlined core PC competencies, PC education during hematology-oncology (HO) fellowship is highly variable, and many fellows feel inadequately trained. We assessed whether incorporation of a PC lecture series could improve fellows’ self-perceived preparedness in basic PC skills. Methods: In this educational quality improvement initiative, current HO fellows at an NCI-designated cancer center received lectures on PC topics. Members of both the HO and hospice and palliative medicine fellowship programs met to discuss key components of a PC curriculum and identify available experts. Seven multidisciplinary faculty members delivered eight one-hour video-recorded virtual lectures to HO fellows over a three-month period. Lecture videos remained available online for later viewing in the event of fellow absences. Within a few weeks both pre- and post-lecture series, HO fellows completed surveys addressing their level of preparedness on a 5-point scale (from 1-not at all prepared to 5-extremely prepared) in performing several key skills. Two-tailed paired t-tests were performed to analyze pre/post changes in fellows’ level of preparedness. Results: Eleven fellows participated in the PC lecture series. Fellows’ level of preparedness increased across several PC topics (Table). The greatest increases were in creating a survivorship plan, converting from one opioid to another, and managing pain in a patient at risk for a substance use disorder. Fellows ranked individual lectures as very helpful to their learning, especially lectures on management of GI symptoms (4.9 +/- 0.3), pain management with opioids (4.8 +/- 0.4), and communication (4.5 +/- 0.5). Conclusions: Incorporation of a structured PC didactics series into HO fellowship is feasible, perceived as very useful, and associated with increased self-perceived preparedness. While more longitudinal and hands-on PC experience would likely promote HO fellows’ PC skills more deeply and durably, dedicated PC lectures are an important adjunctive component that can be easily incorporated into HO fellowship education. [Table: see text]
Transitions of care with a community-based palliative care program: Results from a pilot project for advanced solid tumor oncology patients.
Authors: Garcia Christine Ann , Adelman Ronald D. , Silva Milagros D. , Waxse Sarah , Morellino Linda , Comfort Christopher , Cummings Kelly 
Published: June 2023

e24113 Background: Hospice underutilization among patients with advanced cancer at the end of life can result in patients not receiving the full benefit of hospice and lead to significant distress to patients, families, staff and caregivers. Through multidisciplinary root cause analyses, we identified a gap in services where hospice care, if pursued at all, did not occur until late in the course. A pilot program for community-based palliative services partnering with Calvary Hospital Advanced Healthcare Coordination was introduced for patients with advanced solid tumor cancer in February 2022. Methods: Solid tumor oncologists, social workers and palliative care physicians identified eligible patients with advanced stage cancer who may or may not be undergoing cancer-directed treatment with palliative intent. Patients received home-based support by palliative trained nurse practitioners, licensed social workers and spiritual counsel including symptom management, advanced care planning, care coordination and hospice transition if indicated. The pilot was launched initially in thoracic oncology in February 2022, with expansion to all solid tumor oncology patients in April 2022. Results: From February 1, 2022 to December 31, 2022, a total of 34 patients were referred for community-based palliative care services. Only 15/34 (44%) referrals were taken under care. Of the patients taken under care 7/15 (46.7%) were eventually transitioned to hospice services, and 4/15 (26.7%) patients expired while receiving community-based palliative care services. Of the remaining patients that were not taken under care (n = 19), 6/19 (31.5%) required a higher level of care and were hospitalized, 4/19 (21.1%) went directly to hospice care. Process measures including pain scores, completion of advanced care planning documents, depression scores, treatments given while in pilot, number of hospitalizations, as well as patient-reported outcomes are ongoing. Conclusions: Our pilot demonstrates that while community-based palliative care services can potentially bridge patients from palliative care services to hospice at the end of life, several patients may still have been referred “too late” in their course. Future plan-do-study-act cycles aim to continue to improve the number and timing of referrals to this pilot program and evaluate its impact in hospice utilization for patients with advanced cancer at end of life.
Nationwide utilization of palliative care in patients admitted for GI malignancies.
Authors: Litvin Rafaella , Turk Ekrem , Deenadayalan Vaishali , Ishaya Michelle , Dasgupta Mona , Olafimihan Ayobami Gbenga , Vakil Jay , Ibrahim Muhammad Bilal , Shah Mihir , Obeidat Khaldun , Chhabra Navika , Shaka Hafeez , Mullane Michael Russell 
Published: June 2023

e24114 Background: Gastrointestinal (GI) cancers account for a large proportion of cancer-related deaths and are often associated with significant impairment in quality of life, even at earlier stages. Although guidelines recommend early palliative care (PC) involvement in all patients with advanced cancer, and select patients at earlier stages, implementation of these practices has been highly variable. Methods: Using the National Inpatient Sample (NIS) database, we selected all adult patients admitted with a primary diagnosis of any GI malignancy from 2016 to 2020. We compared demographic characteristics as well as differences in in-hospital mortality, total hospital charges, and length of stay for patients who received a palliative care consultation during the admission and those who did not, with a goal of elucidating biases and informing future quality improvement efforts. Multivariate logistic regression analysis was conducted to adjust for confounders. Results: There were 1,123,075 admissions with a primary diagnosis of a GI malignancy from 2016 to 2020, which represented 0.8% of total adult admissions.10.5% of admissions included a PC consultation. Rate of PC consultation varied based on the site of primary malignancy (see table). Patients for whom PC was consulted were older (69.3 vs. 66.2 years, p < 0.01), less likely to be white (62.7% vs. 67.1%, p < 0.01), and more likely to have Medicare (60.4 vs. 55.5, p < 0.01). These patients were 12.8 times more likely to die during admission (mortality 24.2% vs. 1.9%, p < 0.01), had longer lengths of stay (8.5 vs. 6.9 days, p < 0.01) and lower total charges (84,400.2 vs. 96,637.6 USD, p < 0.01). Conclusions: Early PC involvement in cancer care has been associated with improvement in quality of life and decreases in costs and readmissions. Rates of PC involvement in our cohort were overall low. Different rates of consultations for different races signal possible provider bias. The significantly higher mortality in patients who received a PC consult reflects the still current practice of involving PC only at the end of life. Quality improvement efforts should focus on eliminating biases and implementing strategies to maximize early palliative care utilization among patients with locally advanced or metastatic GI malignancies. [Table: see text]