bluuebunny/crossref_metadata_2025 huggingface dataset:
Early integration of exercise into breast cancer care: The MSK healthy living program.
Authors: Rowed Kylie , Shen Sherry , Smith Andrea , Kelly Bridget , Magnoli Rocco , Corcoran Stacie , Emerzian Melissa , Ackerman Kerri , Cruz Cynthia , Salehi Erica , Anselmo Cara , Robson Mark E. , Iyengar Neil M.
Published: June 2023

e24047

Background: In patients diagnosed with breast cancer, quality of life (QoL) has been reported to decrease during and after treatment. Physical activity (PA) mitigates adverse effects from treatment and improves QoL, and insufficient PA is associated with cancer recurrence and mortality. However, PA interventions are not included in standard cancer care. Early intervention to increase PA levels may improve QoL during active cancer therapy. The Healthy Living Program (HLP) at Memorial Sloan Kettering Cancer Center (MSK) is a lifestyle and survivorship program that engages early-stage breast cancer patients at the time of diagnosis using lifestyle risk stratification and matched referrals. We investigated whether early exercise intervention through the MSK HLP impacts QoL within the first months after cancer diagnosis. Methods: At the time of diagnosis, patients complete a lifestyle questionnaire (LQ), which is a composite of validated instruments, including the Godin Leisure Time Exercise Questionnaire (GLTEQ). Patients not meeting PA guidelines per the GLTEQ are offered a referral to an exercise physiologist (EP). The EP creates an individualized, home-based exercise program using the FITT Principle (Frequency, Intensity, Time, and Type). Patients meet with the EP every 4 weeks for 16 weeks; if exercise recommendations continue to be unmet, the program is extended. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and 36-Item Short Form Survey Instrument (SF-36) were completed at baseline (BL) and follow-up (FU). Results: 206 patients enrolled between April 2020 – September 2022, of which 72 volunteered to complete the QoL assessments (median age 53 years [range 23-84]; 11.1% ductal carcinoma in situ, 69.4% Stage 1, 16.7% Stage 2, and 2.8% Stage 3). Among these patients, 30.6% received chemotherapy, 66.7% received radiation, 83.3% received hormone therapy, and 6% declined treatment. The mean baseline FACT scores were FACT-B: 116, FACT-G: 87, and FACT-B Trial Outcome Index (TOI): 72. At FU, scores were maintained with no significant changes (means FACT-B: 117, FACT-G: 88, and TOI: 74). Improvements were observed among the subscales of the SF-36 from BL to FU. The largest improvements were observed in physical and emotional role function scores, with 26% and 15% improvements from BL to FU, respectively. Conclusions: A clinically implemented exercise intervention embedded in standard of care prevented decreases in QoL and improved physical and emotional functioning during the initial course of adjuvant breast cancer therapy. These findings support early implementation of lifestyle modification after a breast cancer diagnosis.
Safety and serum estradiol levels in hormonal treatments for vulvovaginal atrophy in breast cancer survivors: A systematic review and meta-analysis.
Authors: Marin Comini Ana Carolina Carolina , Murad Carvalho Bruno , Barbosa Moreira Matheus José , Reis Pedro Cotta Abrahão , Colapietro Luisa , Northern Jane , Batalini Felipe
Published: June 2023

e24049

Background: Vulvo-Vaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Methods: Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. Results: We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67pg/ml (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < 0.001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but one study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. Conclusions: In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Statin use for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in breast cancer (BC) patients (pts).
Authors: Melson John W. , Koethe Benjamin , Mohanty Sharanya , Babroudi Seda , Bao Chen , Chunduru Amar , Dwaah Henry , Finn Matthew , Jain Annika , Lalla Mumtu , Patnaik Paras , Studley Rachael , Buchsbaum Rachel J. , Huber Kathryn , Parsons Susan K. , Upshaw Jenica N
Published: June 2023

e24051

Background: CVD is the leading cause of non-cancer mortality for BC survivors. Clinical practice guidelines support the assessment and management of ASCVD risk factors among BC pts, including lipid-lowering therapy when indicated. We performed a single-institution, retrospective, longitudinal study of ASCVD risk factors and statin use for primary and secondary ASCVD prevention among BC pts. Methods: Pts diagnosed with BC from 2009-2015 were identified from the institutional cancer registry. Pts with non-metastatic BC or ductal carcinoma in situ and at least 2 years of follow up were included. Records were reviewed at 12-month intervals from BC diagnosis until last follow up or the study end date of 12/31/19. BC characteristics and treatment, prevalent and incident CV risk factors, CV diagnoses, CV medications, and CV events were manually abstracted and confirmed by a second reviewer. 10-year estimated ASCVD risk, based on non-laboratory predictors, was calculated for each pt. Chi-square tests were performed to assess the relationship between race/ethnicity, age category, and statin exposure. Results: 326 pts were included (median age at diagnosis 60.7 yrs; 67% White, 16% Asian (Chinese), 10% Black; 54% with stage I disease). At baseline, 53% had hypertension, 40% had hyperlipidemia, 37% were former or current smokers, 32% had a BMI ≥30, 7% had a history of ASCVD, and 5% had a family history of premature coronary artery disease. 52% received radiation therapy. 114 pts had radiation dosimetry available; 59 (18%) received a mean heart dose ≥1 Gy. Median follow up was 6.5 yrs. At the time of BC diagnosis, 64% of pts had an established indication for lipid-lowering therapy: history of ASCVD, diabetes, or estimated 10-year ASCVD risk ≥7.5% (Table). Of these pts with an indication for statin, 35% were prescribed a statin at baseline and 57% were prescribed a statin at any time during the study period. No association between baseline statin exposure and pt age category (X2 = 3.75, p = 0.290) or race/ethnicity (X2 = 2.64, p = 0.562) was observed. Among 11% of pts with ASCVD at any time, 83% were prescribed a statin but only 40% received a guideline-recommended high-intensity statin. Conclusions: A majority of pts in our study were candidates for statin therapy for primary or secondary ASCVD prevention at the time of BC diagnosis. 43% were never prescribed a statin, predominantly pts whose indication was primary prevention. There is opportunity for improvement in ASCVD prevention during BC treatment and follow up. [Table: see text]
The impact of 4R Care Delivery Model on timing and sequence of bone density screening among breast cancer patients.
Authors: Brookhart Carolyn , Weldon Christine B. , Trosman Julia R. , Zhu Zheng , Linehan Elizabeth Shurell , Lin Amy Ying Ju , Abbe Thea , Sakoda Lori C. , Gordon Nancy P. , Ravelo Arliene , Shiraz Aida , Kwan Marilyn L. , Liu Raymond
Published: June 2023

e24061

Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to start of endocrine therapy is highly important, especially because endocrine therapy is recommended as the first line of adjuvant treatment in patients with ER+ breast cancer. However, implementing bone density assessment in a timely manner is challenging, particularly early in the care trajectory, which involves many specialties and includes many other tests and procedures. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right, Right Patient, at the Right Time), a novel approach to optimizing patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this optimization. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between the cohorts. Patients in the 4R cohort were significantly more likely than those in the control cohort to have received a consultation for bone density screening prior to the start of endocrine therapy. They were also more likely to receive a bone density test result during their care. These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density test before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial. [Table: see text]
Understanding the late immune checkpoint inhibitor (ICI) symptom experience using an electronic patient reported outcomes (ePRO) app-based platform: The immunowave study.
Authors: Chan Anissa , Jones Salene M.W. , Enright Emily , Raczka Aleksandra , Nguyen Vivian , Bhatia Shailender , Thompson John A. , Lee Sylvia , Veatch Joshua , Tykodi Scott S. , Lashey Matt , Hall Evan Thomas
Published: June 2023

e24067

Background: Chronic toxicities of ICI cancer therapy remain largely uncharacterized. With increasing use of ICIs in early cancer stages, the number of cancer patients exposed to ICI therapy will continue to increase. We undertook a smartphone app-based ePRO pilot study to examine symptom experience of patients with prior or ongoing (≥ 6 months) treatment with ICIs. Methods: Eligible patients had a history of advanced skin cancer or kidney cancer treated with ICI therapy (adjuvant or metastatic setting) with ongoing, clinician-assessed cancer control. Patients may have completed a course of ICI therapy or continued on therapy if ≥ 6 months had passed since initiation. We conducted a single-center, observational, prospective cohort study where participants completed weekly ePRO assessments measuring 11 PRO-CTCAE symptoms over 12 weeks. We assessed the feasibility of this app-based ePRO monitoring strategy (defined as the fraction of weekly assessments completed) and described the prevalence and severity of symptoms in this population. Results: Forty-seven patients (77% melanoma, 15% renal cell carcinoma, 8% non-melanoma skin cancer) consented to the study. At enrollment, 70% were on active therapy while 30% had completed therapy. 38% received adjuvant therapy and 62% were treated in a metastatic setting. The majority (N = 43, 91%) completed ≥ 1 weekly ePRO assessment (median 8, IQR 5.5-10). These 43 patients were included in the analysis. 61% (317/516) of the scheduled ePRO symptom assessments were completed. The prevalence, severity, and persistence of symptoms are noted in the Table. Fatigue and joint pain were most commonly reported (85% and 66% of assessments, respectively) and most commonly Grade ≥ 3 symptoms (23%, 20%). More than half of the patients reported persistent (present ≥ 50% of a patient’s assessments completed) symptoms of fatigue, joint pain, muscle pain, itchiness, rash, depression, anxiety, and numbness. Conclusions: Weekly app-based ePRO monitoring allowed for longitudinal assessment of symptoms with reasonable completion rates. Patients reported frequent, persistent, and sometimes severe symptoms, most notably fatigue, mental health symptoms, and musculoskeletal symptoms. This study suggests that patients during and after ICI therapy may experience high symptom burden, warranting further study in a larger population with longer study duration to identify candidate symptoms for interventions. [Table: see text]
Fear of cancer recurrence inventory scores and their correlation with quality of life and stress levels in breast cancer survivors.
Authors: Morrissey Christy , Szuhany Kristin , Malgaroli Matteo , Jennings Emma , Meyers Marleen Iva , Ross Stephen , Adams Sylvia , Simon Naomi
Published: June 2023

e24073

Background: For survivors of early stage breast cancer, the fear of cancer recurrence (FCR) can be distressing. A clinical challenge is recognizing which patients reporting FCR may need psychological intervention. Prior studies have suggested clinically significant FCR if the validated FCR Inventory (FCRI) scale score is > = 22 while others suggest as low as > = 13 may be an optimal threshold. Our goal was to understand the optimal thresholds for detection of clinically significant impairments in quality of life and high levels of stress. We thus examined FCRI thresholds that optimized detection with two standardized screening modalities of quality of life and perceived stress respectively: the Functional Assessment of Cancer Therapy-General (FACT-G) and the Perceived Stress Scale (PSS). Methods: A previously published cohort of breast cancer survivors at our institution consented to complete self-reported psychological measures and gave access to their medical records. The 2 measures being compared to the FCRI were PSS and FACT-G. FCRI, is a 9-item self-report measure, that evaluates worry about health status and illness returning, triggers that influence worry, uncertainty, and the concerns of significant others. FACT-G, a 28-item self-report measure, assesses quality of life in cancer patients, including physical well-being, social/family well-being, emotional well-being, and functional well-being; we examined the binary threshold score for reduced health related quality of life ( < = 62) vs not reduced health related quality of life (> 62). PSS, assesses the degree to which situations in one’s life are appraised as stressful; we examined the threshold score for low stress (0-13) vs moderate or high stress ( > 13). Sensitivity (Sen) and specificity (Spe) were calculated for each cutoff value for the FCRI score between 16 and 22 (two proposed cutoffs) when compared to the FACT-G and the PSS binary cut points. Results: A total of 177 breast cancer survivors participated in the study. The mean age of participants was 57.6 (SD 13.1) years. Mean scores were 18.6 (SD 7.5) for the FCRI (n = 170), 13.92 (SD 7.0) for the PSS (n = 176) and 80.6 (SD 14.9) for the FACT-G (n = 155). FCRI > = 20 appeared to optimize sensitivity and specificity both on the FACT-G (Sen: 82.4, Spe: 56.1) and PSS (Sen: 63.2 Spe: 69.1) in our patient population. Conclusions: Our results suggest that a FCRI cutoff of 20 may optimize inclusion of patients likely to have poorer quality of life and higher levels of stress. This may allow for more patients in this vulnerable population to be identified for possible intervention, without losing specificity to those with significant distress.[Table: see text]
The mortality burden of cachexia in patients with non-small cell lung cancer: A meta-analysis.
Authors: Bonomi Philip D. , Crawford Jeffrey , Dunne Richard Francis , Roeland Eric J. , Smoyer Karen E. , Siddiqui Mohd K. , McRae Thomas D. , Rossulek Michelle I. , Revkin James H. , Tarasenko Lisa C.
Published: June 2023

e24075

Background: Cachexia and weight loss have been linked to poor outcomes in patients with cancer. This study’s aim was to conduct a meta-analysis to estimate the risk of mortality associated with cachexia in patients with non-small cell lung cancer (NSCLC) in studies identified through a systematic literature review (SLR). Methods: A feasibility assessment was undertaken to determine the suitability of conducting a meta-analysis evaluating the impact of cachexia, defined per International Consensus criteria (ICC) or previous weight loss (WL) ≥5% (without specifying a 6-month duration), on overall survival (OS) in patients with NSCLC. The meta-analysis was conducted using a random-effects model, considering variability across studies, and using the identified studies as base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. Standard measures of statistical heterogeneity were calculated for each meta-analysis. Results: Of the 40 NSCLC publications identified in the SLR, 20 (50%) used the ICC definition or reported WL ≥5%. Sixteen studies (80%, n = 6,225 patients, published in 2016 to 2021) met the criteria for inclusion in the meta-analysis: 11 (69%) studies per ICC and 5 (31%) studies per WL ≥5%. Combined criteria (ICC or WL ≥5%) were associated with 82% higher mortality risk versus no cachexia or WL < 5% (pooled hazard ratio [95% CI]: 1.82 [1.47, 2.25]). A subgroup analysis of studies using the ICC definition (hazard ratio [95% CI]: 2.26 [1.80, 2.83]) or WL ≥5% (hazard ratio [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Although high statistical heterogeneity (I-square = 88%) was observed across studies, this variability could be disregarded because effect estimates (hazard ratios) from included studies were directionally aligned with considerable overlap in CIs of individual studies. A meta-influence analysis did not identify any potential outliers. Results of the sensitivity and subgroup analyses were consistent with the base case analysis. Cumulative meta-analyses by publication year or data collection midpoint identified no time-varying effect, indicating results were robust to the differing timeframes of publication or data collection. No substantial publication bias, measured via funnel plot analysis, was identified in the meta-analysis. Conclusions: Based on thorough methodologic, clinical, and statistical heterogeneity assessments, the meta-analysis results are robust. ICC-defined cachexia or WL ≥5% were associated with inferior OS in patients with NSCLC. Identifying cachexia or WL ≥5% has important implications for prognosis and treatment of NSCLC.
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]
Dermocosmetics in management of cancer-related skin toxicities: International expert consensus.
Authors: Dreno Brigitte , Khosrotehrani Kiarash , De Barros Silva Giselle , Ryan-Wolf Julie , Kerob Delphine , Trombetta Mark G. , Atenguena Okobalemba Etienne , Dielenseger Pascale , Pan Meng , Lacouture Mario E.
Published: June 2023

e24115

Background: Skin toxicities – one of the most frequent adverse events associated with cancer therapies – can occur with all types of cancer therapeutic interventions. New side effects emerge as new oncology drugs are approved (eg, targeted therapies, immunotherapies), which are associated with a negative impact on quality of life, oncologic treatment dose reductions and/or treatment discontinuation. From a pathophysiologic point of view, skin toxicities during cancer treatment result mostly from alterations in skin barrier function, inflammation, altered immune responses, and phototoxicity. Minimizing alterations in skin barrier function and photoprotection facilitate prevention and management of adverse events to optimize treatment outcomes. Methods: In partnership with the Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC), a group of international experts (dermatologists, oncologist, radiation oncologist, oncology nurse) involved in management of cancer patients performed a literature review and a consensus meeting to discuss the role of dermocosmetics to prevent or manage skin adverse events induced by oncology treatments. Dermocosmetics, or cosmeceuticals, include a range of products that can have both therapeutic and cosmetic value. These products help support and maintain the epidermal skin barrier and cutaneous microbiome. Some have been formulated for skin that is fragile, pathological, and sensitive. Results: General recommendations: 1) skin care should be implemented at initiation of therapy for drugs associated with skin toxicities, since prevention is a crucial aspect of management. 2) Skin hydration relieves symptoms and reduces exacerbations of xerosis. 3) Cleansers should have a pH close to 5, while basic and neutral pH cleansers should be avoided. 4) Urea, particularly in the case of some oncology treatments leading to hand foot syndrome, is important due to its exfoliating and hydrating actions. Urea should be avoided with irritated skin. The group also developed recommendations for the management of specific skin toxicities. Conclusions: Emerging evidence is providing support for the beneficial impact of dermocosmetics in management of treatment-related skin toxicities.
Symptom burden and end of life care in patients with acute myeloid leukemia undergoing intensive induction chemotherapy in a rural setting.
Authors: O'Neil Sean , Frankki Susan M , Rosenstein Lori J.
Published: June 2023

e24117

Background: Patients with acute myeloid leukemia (AML) who receive intensive induction chemotherapy (IC) face a prolonged hospitalization and a life-threatening illness. As a result, patients experience a high physical, psychological, and emotional symptom burden which can significantly affect their quality of life (QOL).1 There is also a high mortality rate associated with IC, with one study showing 12.3% chance of in-hospital death and 3.7% discharge to hospice.2 Early integration of palliative care (IPC) has shown improvements in QOL, decrease in psychological stress and improved end-of-life care.3 The aim of this study was to examine the historic use of IPC during IC and assess the symptom burden in a rural healthcare setting and to provide a rationale for early incorporation of palliative care into IC. Methods: We performed an IRB approved retrospective study of all patients with AML who were admitted to Gundersen Health System for IC from January 2013 to September 2021. Data collection included basic demographics, disease and treatment specific variables, and admission variables. Symptom burden was also assessed by reviewing daily progress notes. Statistical analysis included descriptive statistics, Wilcoxon signed-rank test, and Fisher’s exact test and was performed in SAS version 9.4 at a significance level of 0.05. Results: Our study included 33 patients with an average age of 62 years. Our sample was 100% white, 58% male, 82% married and 58% former smokers. Average length of stay was 29 days and 5 (15%) patients died during this time. Individuals experienced an average of 9.8 (range 4-17) of the 20 recorded symptoms, most commonly pain (97%), fevers (88%), edema (73%), anorexia (67%), rash (61%), and diarrhea (61%). Only 6 patients (18%) received a palliative care consultation during IC. For patients without a palliative care consultation during IC, advanced care planning (ACP) documents were found in only 37% during or before IC. However, when palliative care was consulted, ACP documentation increased to 83% demonstrating a trend towards significance (p = 0.07). There was a significant difference between the number of symptoms observed in those who received a palliative care consultation (median = 13 symptoms) and those who did not (median = 9 symptoms, p = 0.007). Conclusions: Despite our patients experiencing a high symptom burden and a significant chance of death, there was a low rate of early integration of palliative care. This retrospective study was unable to determine if IPC improved symptom burden, but we did find that IPC increased the rate of ACP documentation from 37% to 83%. The presence of ACP documentation has been shown to significantly reduce ICU utilization and improve the quality of care at the end of life.4 Given these findings; we plan to move forward with routine integration of palliative care into the management of patients undergoing IC for AML.