bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning what matters in allogeneic transplant: Insights into older patient preferences in an age-friendly multidisciplinary clinic.
Authors: Braun Adam , Dale William , Moreno Jeanine , Curtin Peter T. , Dadwal Sanjeet , Hung Terence , Huynh Nini , Al Malki Monzr M. , Nakamura Ryotaro , Forman Stephen J. , Artz Andrew S.
Published: June 2023

e24029

Background: HCT is increasingly being considered for older adults (60+) with blood cancers, with emerging data suggesting HCT imparts a survival benefit for eligible patients (pts). HCT-related morbidity and mortality remains significant in older adults, with no consensus on how to best prospectively evaluate HCT versus other approaches. Shared decision making (SDM) may help reconcile such treatment options for older adults. Understanding pts preferences (PP) and values is a cornerstone of SDM, yet no data exist in how to elicit and apply PP for older adults facing this treatment choice. Methods: We analyzed documented PP among the first 40 older adults from an ongoing IRB-approved prospective protocol enrolling HCT candidates ≥60 years to participate in a multi-disciplinary optimization clinic, the Aging & Blood Cancers (ABC) clinic. The ABC clinic is comprised of pre-HCT consultations with a geriatrician, HCT physician, physical therapist, dietician and social worker and an ID physician. We reviewed the primary treating team documentation relative to the ABC clinic documentation, notes reviewed from HLA typing orders or documented plan for HCT. Categorization of PP consisted of any of the following: (1) care goals after HCT (e.g. cure, disease control, functional recovery, spending time with family/friends, attending life events), (2) toxicity concerns, and (3) pt rationale for proceeding to HCT. We included PP when summarized in the advanced care planning (ACP) documents if signed by a team member or referenced in their note. Findings were extracted by one physician and then reviewed by a second physician to adjudicate assignment as a PP. P-values were derived from incidence rates and chi-squared testing. Results: Among 40 pts with a median age of 74 yrs (range 60-), 856 notes and 38 ACP documents were reviewed. We found PP in 26 notes (2.9%) in 19 pts (47.5%). Of pts with PP documented, the primary team accounted for 4, compared to 14 pts in the ABC clinic (p < 0.02). Notably, the primary team documented a risk:benefit discussion about HCT in 31 patients (p < 0.0001). Among total PP (n = 19) the most common included functional recovery (73.6%), spending time with family or specific people (73.6%) and minimizing toxicity (42.1%). Less common PP were disease control/cure (31.6%) or avoiding the need for future disease treatments (15.8%). Conclusions: To our knowledge, this is the first study to document older adult PPs before HCT, finding them to be rarely documented. The older adult specific HCT clinic enhanced preference documentation, yet still in less than half of pts. Future studies to develop tools to better elicit and incorporate pt preferences should be prioritized to facilitate shared decision making for HCT among older adults.
Dual language interview guide to improve understanding of risk perception among newly diagnosed breast cancer patients who are limited English proficient (LEP).
Authors: Schiaffino Melody Karen
Published: June 2023

e24031

Background: In the U.S. 60% of those diagnosed with cancer are over age 65. This group is also larger, living longer, and more diverse than previous generations. This diversity includes increased proportions of older adults who are limited English proficient (LEP) which is defined as speaking English less than “very well” as measure by the U.S. Census. Access to language services is a protected right both via Title VI of the Civil Rights Act of 1964, the 2000 Executive Order 19166 mandating language services and the 2010 Patient Protection and Affordable Care Act. However, research remains limited in addressing linguistic and cognitive barriers experienced by LEP patients. Methods: Using an adapted forward-translation method from the World Health Organization the goal is for conceptual equivalence not direct translation. This approach includes multiple independent forward translations, a bilingual adjudicator with content expertise and community and expert reviewers. This approach allows for codification of divergence of semantic, conceptual, and normative equivalence. Semantic relates to words and equivalence or eloquence, conceptual refers to the general idea and normative relates to the social-cultural relevance or appropriateness of the topic itself (Pan, de la Puente, 2005). Two trained interpreters conducted forward translations, a third adjudicated. The interview guide was reviewed by two radiation oncologists and tested with a bilingual breast cancer survivor. Results: Semantic and conceptual equivalence were confirmed with expert panel review and are the equivalent of previously used “back-translation” however, we were also able to ensure normative equivalence, or the socio-cultural relevance to our study participants which were LEP Latina breast cancer patients. A final semi-structured interview guide was finalized and approved by the UCSD IRB to be fielded in March 2023. Conclusions: Adapting existing validated instruments requires more than just consideration of terminology, an understanding of semantic, conceptual, and normative equivalence is critical for improving culturally and linguistically appropriate research among minoritized and LEP geriatric oncology populations.
Predictive factors of early death in older women with gynecological cancer: A prospective cohort study.
Authors: Telles O. Lima Jurema , Sales Letícia telles , Lima Emanuel P. B. , Gonçalves MAria Eduarda M. , Costa Jose Iran , Gonsioroski Lucas P. , Rebello Mirella , Cavalcanti Zilda , Mello Maria Julia Gonçalves ,   BLOGG
Published: June 2023

e24034

Background: Comprehensive geriatric assessment (CGA) correlate with risk of early mortality in older adult patients. Methods: a prospective cohort study. older woman with a recent diagnosis of gynecological cancer were from eight community hospitals and cancer center in Northeast Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. A basal CGA was done before the treatment decision (ADL, Charlson Comorbidity Index- CCI, Karnofsky Performance status – KPS, GDS15, IPAQ, MMSE, MNA, MNA-SF, PS, PPS, Polipharmacy, QLQc30, TUG). During the follow up of six months, information about the treatments performed, the targeted interventions and early death was collected. Overall survival was estimated using the Kaplan–Meier method, and survival curves were compared using the Log rank test for categorical variables. A multivariate Cox proportional hazards model was used to select early death risk factors. Results: 274 patients with a median age of 72 years, 13.5% died within 180 days. 29,7% cervical cancer, 122 (44,5%),endometrial cancer, 53(19,3%) ovary cancer and 17( 6,2%) vulvar cancer. The mean global QL was higher among survivors and the probability of survival was higher in patients who had better QL (p < 0.001). After adjustments for risk factors (cervical cancer topography, metastatic disease and Karnofsky ≤ 50), Global QoL was a protective factor (HR = 0.99; 95%CI 0.98-1.00; p = 0.031). Cervical cancer topography 95%CI HR = 2.28 1.18-4.40 p = 0.014). MNA < 17 95 %CIHR = 9.72 (3.85-24.50 , p < 0.001) TUG ( HR = 3,87 ; 95 % CI 1,93 - 7,74 p = 0.004). Conclusions: A better score in the Global QoL assessment , a good nutritional status by MNA and low risk of falls by TUG were protective factor for early death in older women with gynecological cancer.Cervical cancer is the highest risk of early death topography. Risk factors for early death can be identified in the admission of older women with gynecological cancer, allowing better care planning.
Efficacy of BNT162b2 vaccine and its correlation with serum vitamin D in staff at the national comprehensive cancer center in slovakia.
Authors: Slopovsky Jan , Cingelova Silvia , Svobodova Alena , Skokanova-Krempaska Lucia , Rejlekova Katarina , Babela Robert , Drgona Lubos , Mego Michal , Vulganova Martina , Pechan Juraj , Palacka Patrik
Published: June 2023

e24037

Background: With established efficacy and safety, BNT162b2 was one of the first licensed mRNA vaccines against SARS-CoV-2. However, it is unclear whether vitamin D serum concentrations affect vaccine efficacy after three doses. Methods: This prospective, single-center study included 273 staff members (85.4% females) of the National Cancer Comprehensive Center in Slovakia. Median age of participants was 47 years (range: 22–80) and median body mass index (BMI) was 24.8 (16.3–44.6) kg/m2. The primary objective was to determine the efficacy of BNT162b2 defined as no Covid-19 disease ≥7 days after its administration. The secondary objective was to monitor IgG neutralizing antibodies and total vitamin D in serum after vaccination and test the hypothesis on correlation of total vitamin D concentrations with the vaccine efficacy. If appropriate, results were stratified by gender (males vs females) and BMI ( < 30 vs ≥30 kg/m2). Results: At median follow-up of 4.7 (2.9–5.0) months, vaccine efficacy was 86.1%. The most common adverse events (AEs) were injection site pain (73.3%), fatigue (44.0%), and limb pain (33.0%). No grade 3/4 AEs were observed. Median time from vaccine administration to measurement of IgG and vitamin D concentrations was 3.4 (2.1-4.8) months. IgG concentrations were significantly higher in males compared to females, as well as in subjects with high vs low BMI ( p< 0.0004 and p< 0.0001, respectively). Total vitamin D concentrations were significantly lower in individuals with high vs low BMI ( p< 0.0144). No differences in the rate of Covid-19 positivity were identified based on gender, BMI, and total vitamin D concentrations. Conclusions: This study confirmed high efficacy of third dose of the BNT162b2 vaccine with an acceptable safety profile. The vaccine efficacy was not affected by gender, BMI, and total vitamin D concentrations. These results suggest that serum vitamin D monitoring after third BNT162b2 dose is not beneficial for an estimation of its efficacy. This study was supported by the National Cancer Institute, Bratislava, Slovakia & OncoReSearch, Rovinka, Slovakia. Keywords: BNT162b2; total vitamin D; efficacy; safety profile; IgG.
Patient understanding of immunotherapy and its side effects for women with triple negative breast cancer.
Authors: Canning Madison , Liu Yi , Aldrich Jeffrey , Switchenko Jeffrey M. , Bhave Manali A.
Published: June 2023

e24046

Background: Immunotherapy (IO) is now an integral part of treatment for most patients with triple negative breast cancer (TNBC). The mechanism of action and associated side effects of IO differ significantly from conventional chemotherapy and patient comprehension of these novel treatments can be difficult to assess. Previous research has demonstrated that patient understanding of anti-cancer treatments is hindered by multiple barriers including education level and healthcare literacy. Standardized educational tools to improve patient comprehension of immunotherapy are integral to improving patient engagement with their treatment plan and providing informed consent. Methods: This is a prospective pilot study investigating the efficacy of standardized educational materials (2 animated videos and 1 pamphlet) to improve patient comprehension of IO. Patients with TNBC were recruited from Emory University between 2021-2022 and were asked three questions related to their understanding of the immune system, immunotherapy, and IO-related side effects before and after viewing the educational tools. Audio-recordings of the patients’ answers were coded as correct or incorrect by two independent reviewers using the video’s definitions as the standard. Clopper-Pearson method and exact McNemar’s test were used to calculate pre- and post-education correct definition rates and paired rates, respectively. Multivariate analyses were conducted investigating the impact of age, highest level of education, and race on patient comprehension. Results: 46 patients with TNBC were enrolled with mean age of 57 years (range 27-84 years). The majority of patients were Black (65%), while the remaining patients were Non-Hispanic White (30%) or unknown (5%). Highest level of education was reported as high school (13%), undergraduate (61%), and graduate school (26%). Comprehension of the terms "immune system" and "immunotherapy" significantly improved after viewing the patient educational material with an increase in correctly defining these terms from 50% to 89.1% (p-value < 0.01) and 41.3% to 82.6% (p-value < 0.01), respectively. Patients' ability to describe two or more side effects of IO also increased from 11% to 87% post-education (p-value < 0.01). Patients with graduate degrees had a 4.24 times greater odds of correctly answering the questions compared to those with undergraduate or high school degrees (p-value 0.057). There were no differences in patient comprehension by race or age. Conclusions: Patient education on novel therapeutics in cancer care including immunotherapy presents a challenge to providers given time constraints in clinic and lack of standardized educational resources. Through easily implemented patient education, we were able to significantly improve patient comprehension of immunotherapy and IO-related side effects in a diverse population of patients with TNBC.
The sit to stand test in cancer patients and survivors.
Authors: Cristian Adrian
Published: June 2023

e24058

Background: The sit to stand test in 30 seconds has been used to measure power, strength, endurance, and balance. It has also been described as a useful tool in identifying presence of sarcopenia. Methods: Retrospective chart review of cancer patients and survivors referred to cancer rehabilitation clinic over a 5-year period from 1/1/2018-12/31/2022 at a large cancer institute in the southeastern part of the United States. Patients were assessed at their initial evaluation using the sit to stand test in 30 seconds (STS-30). Scoring for the sit to stand score was divided into 2 groups (impaired and good scores) based on age and gender specific normative data. Data was also collected for patients/survivors with different body mass index (BMI) ranges: underweight: (BMI < 18.5); normal weight (BMI 18.5-24.99); overweight (BMI: 25.-29.99), obese ( > 30) as well as stages of cancer (stage 0-4). Results: 1406 cancer patients and survivors underwent STS-30 at their initial evaluation in cancer rehabilitation clinic. This included cancers of breast, GI, GU, lung, gynecologic, brain/spine, hematologic, head and neck, musculoskeletal, endocrine and skin. 749/1406 (53.27%) had impaired STS-30 with an average score of 6.45 repetitions in 30 seconds and 657/1406 (46.73%) had good scores with an average of 14.75 repetitions in 30 seconds. BMI and STS-30: 1,298 patients had BMI data available. 912/1298 (70.3%) were overweight or obese. 501/912 (54.93%) had an impaired STS-30 with an average of 6.76 repetitions in 30 seconds. 411/912 (45.07%) had a good STS-30 with an average of 14.66 repetitions in 30 seconds. 386/1298 (29.7%) had a normal BMI or were underweight. 173/386 (44.82%) had an impaired STS-30 with an average of 6.57 repetitions in 30 seconds. 213/386 (55.18%) had a good STS-30 with an average of 15.06 repetitions in 30 seconds. Stage of cancer and STS-30: The stage of cancer was known for 647 patients/survivors. 462/647 (71.4%) had stage 0-3 cancer. 218/462 (47.2%) had an impaired STS-30 with an average of 6.91 repetitions in 30 seconds.244/462(52.8%) of them had a good STS-30 with an average of 14.54 repetitions in 30 seconds. 185/647 (28.6%) had stage 4 cancer. 114/185 (61.62%) had an impaired STS-30 with an average of 6.04 repetitions in 30 seconds. 71/185 (38.38%) had a good STS-30 score with an average of 14.27 repetitions in 30 seconds. Conclusions: The STS-30 was impaired in a significant percentage of cancer patients and survivors across all stages, implying the possible presence of sarcopenia in this population. Stage 4 cancer patients and overweight/obese patients were at especially high risk of having an impaired STS-30. Clinicians should utilize the STS-30 to screen cancer patients and survivors and if scores are impaired, further assess for presence of sarcopenia and introduce interventions to address it.
Subjective and objective hearing loss among US adult cancer survivors: A national cross-sectional study.
Authors: Wang Qian , Jiang Changchuan , Wen Chi , Xie Hui , Li Yannan , Zhang Yaning , Mady Leila Jean , Bruno Debora S. , Dutcher Giselle , Chiec Lauren , Dowlati Afshin , Hsu Melinda Laine
Published: June 2023

e24059

Background: Approximately 13% of adults had some degree of hearing loss (HL), and the prevalence is higher among adults aged 65 and over (30.9%). Approximately 50-80% of the childhood, adolescent and young adult cancer survivor population report HL following treatment with high-dose platinum-based chemotherapy, head or brain radiotherapy. We aimed to 1) estimate the prevalence of subjective and objective hearing loss (HL) among cancer survivors and compare to the general population; 2) assess the performance of subjective HL questions in detecting HL by audiometry among cancer survivors. Methods: Adults aged 20-80 years old were selected from the National Health and Nutrition Examination Survey. The weighted prevalence of subjective HL (having troublesome hearing and tinnitus) and objective HL (speech-frequency HL and high-frequency HL) by audiometry test was calculated. Chi-square test and multi-adjusted logistic regression models were used to compare HL between cancer survivors and the general population. To evaluate the performance of subjective HL questions as a tool to screen for objective HL by audiometry, area under the curve (AUC) were estimated using age-and gender- adjusted logistic regression. Results: Compared to the general population, cancer survivors had a statistically significantly higher prevalence of troublesome hearing (aOR = 1.43; 95%CI:1.22-1.68), tinnitus (aOR = 1.28; 95%CI:1.08-1.53), speech-frequency HL (SFHL) (aOR = 1.44; 95%CI:1.20-1.73) and high-frequency HL (HFHL) (aOR = 1.74; 95%CI:1.45-2.09). The sensitivity and specificity of the combined subjective questions “whether having troublesome hearing and/or tinnitus” in detecting HL was shown in Table. The age- and gender- adjusted AUC for detecting SFHL and HFHL using combined questions was 0.88 and 0.90. Conclusions: Cancer survivors have a significantly higher prevalence of both subjective and objective HL, but a lack of hearing examination. Two subjective HL questions could accurately identify those have true HL and provide a simple and efficient screening tool for providers. Cancer survivors and their families should be educated and encouraged to discuss hearing concerns, and providers should facilitate raising awareness and provide early screening and timely referral when HL is identified.[Table: see text]
Survivorship in patients with cardiac metastases defined by cardiac magnetic resonance imaging in relation to lesion hypoperfusion.
Authors: Jain Raina , Liberman Nicole , Agoglia Hannah , Park Michael , Park Robert , Jessurun Jose , Tap William D. , Kim Jiwon , Steingart Richard , Liu Jennifer , Weinsaft Jonathan W. , Chan Angel
Published: June 2023

e24070

Background: Cardiac metastases (CMET) can occur in late-stage cancer, but limited data exists on prognostic implications in context of current day cancer care. Cardiac magnetic resonance imaging (CMR) provides a new, well validated, means to identify CMET in vivo, and assess magnitude of lesion vascularity – which can vary in relation to tumor etiology and be compromised with tumor necrosis. Survivorship in pts with CMET and modifying impact of lesion vascularity are unknown. Methods: The population comprised adult (≥18yo) pts with metastatic cancer derived from a dual site CMR registry, including pts with and without CMET on CMR. CMR was performed via a uniform protocol for which CMET was defined using established criteria as a cardiac mass with late gadolinium enhancement; lesion vascularity was measured on perfusion-CMR. Cancer type was categorized by pathological review and follow-up was performed for all-cause mortality. Results: 330 pts (59±15 yo; 55% M) were studied, inclusive of CMET and controls matched for cancer etiology/stage. Among pts with CMET, cancer etiology varied (sarcoma 24% | GI 18% | GU 13% | lymphoma 13% | lung 10% | skin/melanoma 7% |); cases and controls were similar with respect to age, sex, anti-cancer regimen, and cardiac function on CMR (all p = NS). Median duration of post-CMR follow-up was 19 months [IQR 11.9 – 43.6]; 92% had clinical follow-up ≥ 1 year or mortality within this interval, including an aggregate 1-year mortality in pts with CMET of 53% (43% in CMET - controls; p = 0.09). Among cancer categories, pts with lymphoma were at decreased risk for death (HR 0.44 [0.26 – 0.75], p = 0.002); risk was increased in pts with GI malignancies (1.63 [1.12 – 2.37], p = 0.01) or those treated with antimetabolites or kinase inhibitors (both p < 0.05): Neither age, sex, cardiac risk factors nor function granted increased risk for death (all p = NS). Regarding Cmet tissue characteristics, decreased lesion perfusion conferred increased mortality risk irrespective of whether assessed as a continuous variable (HR 1.29 [1.08 – 1.56]) or via graded tertiles (HR 1.32 [1.05 – 1.66]) of hypoperfusion (both p < 0.05). Decreased CMET perfusion conferred increased mortality risk (1.30 [1.03 – 1.64], p = 0.03) independent of cancer type or anticancer regimen. Conclusions: Among systemic cancer pts with CMET, survivorship varies and nearly half are alive ≥1 year post cardiac MRI diagnosis. Prognosis in pts with CMET varies inversely to lesion perfusion, with low vascularity lesions conferring increased mortality risk.[Table: see text]
Comparison among three predictive models for cancer-associated thromboembolism in a Hispanic population.
Authors: Ramos-Esquivel Allan , Hernández-Romero Gabriel , Marenco-Flores Ana , Umaña Carlos , Céspedes-Calvo Ana , Mora-Hidalgo Raquel
Published: June 2023

e24074

Background: Several predictive scores have been developed to assess the risk of venous thromboembolism (VTE) among cancer patients. Although their use is currently recommended by several guidelines, it is unknown if these scores can accurately predict the risk of VTE in Hispanic patients that are at different risk for thrombosis. Methods: We retrospectively evaluated all outpatients with newly diagnosed solid tumors receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. For each patient, the Khorana, PROTECHT, and CONKO scores were calculated at the beginning of treatment. The sixth-month cumulative incidence of VTE was estimated using the Fine & Gray competing risk model for the overall population and stratified according to each risk category. A Kaplan-Meier analysis was used to compare the cumulative VTE incidences between high- and low-risk categories of the three predictive scores. The Cox regression analysis was used to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI). The receiver operating characteristic (ROC) curve was used to assess the performance of each predictive tool through the analysis of the c-statistic, sensitivity, and specificity. Results: 708 patients were included in the analysis. After a median follow-up of 8.13 months, the cumulative VTE incidence at six months was 4.45% (95%CI: 3.25-6.91%). At the conventional positivity threshold of 3 points, these scores classified from 17.7 to 27.5% of all patients as high-risk for VTE. The 6-month incidence of VTE among high-risk patients ranged from 7.6% for the Khorana score to 9.3% for the CONKO score. Patients belonging to the high-risk category of the Khorana, PROTECHT, and CONKO scores had significantly higher risk of VTE in comparison to low-risk patients (Khorana score: HR: 2.66; 95%CI:1.20-5.89; p = 0.042; PROTECHT score: HR: 3.44; 95%CI:1.63-7.21; p = 0.001; CONKO score HR: 3.68; 95%CI:1.72-7.85; p = 0.001). Table 1 resumes the performance of the studied scores. Table 1. Performance of the Khorana, PROTECHT, and CONKO scores for the prediction of venous thromboembolism. Conclusions: The Khorana, PROTECHT, and CONKO scores accurately predict the risk of VTE in Hispanic patients with solid tumors with similar performance among them. However, their sensitivity and specificity remain poor for identifying all patients at risk for thromboembolic events.[Table: see text]
Incidence of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving anti-CD38 monoclonal antibodies (mAbs): A systematic review and meta-analysis.
Authors: Mian Agrima , Naqvi Syed Arsalan Ahmed , Ayaz Ahsan , Husnain Muhammad , Aljama Mohammed A. , Mohyuddin Ghulam Reham , Koehn Kelly , Mohan Meera , Riaz Irbaz Bin , Chakraborty Rajshekhar
Published: June 2023

e24078

Background: The addition of anti-CD38 mAbs, daratumumab and isatuximab, to standard anti-myeloma regimens have drawn scrutiny towards long-term safety concerns, including the risk of SPMs. ICARIA-MM study reported SPMs in 3.9% patients (pts.) in the Isatuximab, pomalidomide and dexamethasone (Isa-Pd) arm compared to 0.7% in the Pd arm. We hypothesized that exposure to anti-CD38 mAbs could potentially increase risk of SPMs due to prolonged immunosuppression. An assessment of this association is warranted, given the improved life expectancy and growing prevalence of pts. with MM. Methods: We performed a meta-analysis on data obtained from RCTs published between January 2005 and April 2022 that compared anti-CD38 mAb-based regimens to other standard anti-myeloma regimens (control) in pts. with newly diagnosed or relapsed/refractory (r/r) MM. Total number of SPMs (including categories) were extracted for pts. in both groups. Malignant melanomas were included under solid SPM category. Binary outcome data were analyzed using fixed-effect Peto method. Treatment effect estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). I2 > 50% indicated substantial heterogeneity. Results: 10 RCTs involving 4980 pts. were included, with 2824 (57%) and 2156 (43%) pts. randomized to the anti-CD38 mAb and control arms, respectively (Table). Overall, 191 and 112 SPMs were reported in the anti-CD38 mAb and control arms, respectively. At a median follow-up of 35.3 months, anti-CD38 mAb exposure was associated with an increased risk of developing SPMs compared to control (6.8% vs. 5.2%; OR: 1.53 [95% CI: 1.20-1.95]; I2= 0%). Non-melanoma cutaneous cancers were the most common, and higher in the anti-CD38 mAb vs. control arms (92 versus 47; OR: 1.77 [95% CI: 1.25-2.51]; I2= 0%). The increase in solid cancers (including melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) and hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27] was not significant. On sensitivity analysis, the total number of SPMs were higher in the anti-CD38 mAb arm vs. control arm, regardless of the presence of immunomodulatory drugs in combination regimen. Conclusions: This meta-analysis shows an increased risk of SPMs in pts. with MM exposed to daratumumab or isatuximab, particularly that of non-invasive cutaneous tumors. This association should be further investigated in real-world settings using large databases. [Table: see text]
Risk factors and early biomarkers of nephrotoxicity associated with the use of anti-VEGF drugs.
Authors: Grechukhina Katerina , Chebotareva Natalia , Krasnova Tatyana , Zhukova Lyudmila
Published: June 2023

e24079

Background: Anti-angiogenic anticancer drugs that block VEGF can cause kidney damage (Fujii et al., 2019). Among the mechanisms of nephrotoxicity thrombotic microangiopathy (TMA) of renal vessels can be distinguished (Estrada et al., 2019). TMA can be accompanied the development of anemia, excessive schistocytes, as well as increased LDH levels and a low platelet count, which indicated the occurrence of endothelial dysfunction and microangiopathic processes (Hauser et al, 2009). The goal of this study was to assess the risk factors of early nephrotoxicity and the utility of NGAL, KIM-1, HIF-1α and nephrin levels in urine as early biomarkers of nephrotoxicity. Methods: The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab). Nephrotoxicity was determined as a decrease in glomerular filtration rate (GFR) to < 60 ml/min/1.73m2 at 8 weeks from the initiation of therapy. The laboratory parameters and the levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity we analyzed primary clinical and laboratory parameters. Results: Nephrotoxicity at 8 weeks was achieved in 21 (42%) of patients. A statistically significant decrease in hemoglobin and platelet count by 20 and 26%, respectively, from the initial level was observed. An increase in the number of schistocytes and a slight increase in LDH levels were also observed. The increase in NGAL, KIM-1 and nephrin levels was statistically significant in 1 weeks and the increase of HIF-1α in 2 weeks after the start of therapy (p = 0.001). The unfavorable predictors of nephrotoxicity as well as the favorable predictors in terms of decreasing renal function are presented in Table. ROC analysis demonstrated high sensitivity and specificity: NGAL – AUC 0.7; KIM-1 – AUC 0.69; HIF-1α – 0.7; nephrin – AUC 0.7. Conclusions: We report a significant increase in the parameters of microangiopathic hemolysis and in urine biomarkers of tubular and podocytic damage as well as hypoxia by the 8th week of treatment. We suggest that the TMA process can take part in renal damage. Increased levels of NGAL, KIM-1, HIF-1α and nephrin in the urine reflect the renal damage processes and have higher sensitivity and specificity then serum creatitine. The independent risk factors for nephrotoxicity are determined. [Table: see text]
A novel risk assessment metric for antimyeloma therapies and drug interactions.
Authors: Xu Xuan , Jaberi-Douraki Majid , Anwer Faiz , Faiman Beth , Williams Louis , Mazzoni Sandra Ann , Khouri Jack , Valent Jason Neil , Ramachandran Remya Ampadi , Riviere Jim , Gadara Nuwan Millagaha , Golmohammadi Mobina , Wyckoff Gerald , Samaras Christy Joy , Samala Renato Verayo , Raza Shahzad
Published: June 2023

e24082

Background: New treatments for multiple myeloma (MM) improved both the clinical course and survival. These differ in their mode of action, safety profile, and adverse events (AEs). The goal of this study is to establish the benchmark for an integrated systematic investigation to assess the toxicity of different anti-MM drug regimens (AMDR). Methods: We curated 342,213 MM patient information from 2016–2022 from the FDA Adverse Event Reporting System. A total of 71 AMDR were evaluated in 7 different system organ classes when mapped to MedDRA. Drug-associated genes and AEs were also quantified as genetic evidence of a drug-AE combination. Gene-gene associations were then explored using the STRING database. We then developed a novel risk assessment metric that combined historical data from MM patients with drug-AE scores regarding the AE occurrence, the number of reported AE, and the genetic evidence of drug-gene and gene-AE associations (GAA). This likelihood-based rating metric includes (vH): (very) high MDR risk–(very) frequent AEs and mortality with (very) significant GAA evidence; and similarly computed for M: medium risk; and L: low risk. Results: Our risk assessment findings revealed single agents (carfilzomib (K), bortezomib (V), daratumumab (D), lenalidomide (R), melphalan (Mel), thalidomide (T), ixazomib (Ix), elotuzumab (El), isatuximab (Is) or dexamethasone (d)) illustrated very low profile of toxicity compared to combination regimens. Overall, we found that AMDR profiles showed higher toxicities in 4 different SyOCs (hepatobiliary, cardiac, nervous, renal) with nominal issues in 3 SyOCs (vascular, neoplasm, GI). AMDR toxicity significantly increased when d was added to the treatment compared to AMDR without d. Cardiac and vascular AEs were higher with K-based combinations. Hepatobiliary toxicities were higher with V, K, or T-based combinations. Secondary neoplasms were seen more frequently in patients who received high dose Mel followed by R. Conclusions: Our analysis of large data shows the association of SyOCs and graded toxicity profiles with unique AMDR. The single drug or doublets without dexamethasone seemed to show an improved AE profile compared to those with dexamethasone used as doublets, triplets, or quadruplets. Secondary cancer risk was much higher with high dose Mel followed by R compared with other AMDR. Our assessment system provides a framework for AMDR comparison toward future precision MM therapeutics based on unique drug doses, combination regimens, patient phenotypic risk profiles, secondary cancer surveillance and interplay of genetics and comorbidities. [Table: see text]
Adverse events with the use of radiotherapy in patients with inflammatory arthritides and cancer: A systematic review and meta-analysis.
Authors: Lopez-Olivo Maria A. , Sharma Gaurav , Qureshi Sehrish , Hicklen Rachel S. , Tayar Jean H. , Suarez-Almazor Maria E.
Published: June 2023

e24090

Background: Radiotherapy is a cornerstone for multi-modality cancer treatment. However, there have been concerns that in patients with inflammatory arthritides (i.e., rheumatoid arthritis, juvenile idiopathic arthritis ankylosing spondylitis, Still’s disease) radiotherapy could result in deleterious outcomes, and radiation oncologists may be hesitant to administer radiation therapy to these patients. Methods: We conducted a systematic review to determine the risk of developing adverse events (AEs) from radiotherapy in patients with cancer and inflammatory arthritides. We searched in 4 electronic databases from inception through October 2022. Study selection, data collection and risk of bias assessment were independently performed by two investigators. We performed random-effects meta-analysis to determine the incidence of acute (≤ 90 days) and late ( > 90 days) AEs and evaluated the risk of developing AEs in these patients compared with cancer patients without inflammatory arthritides. Results: Out of 9,723 records retrieved from our searches, we included 7 cohort studies (5 included a control group) and 14 case reports (describing 22 patients). The age of the included patients ranged from 16-72 years. The median follow-up ranged from 1.5 to 12.5 years. Median radiation doses ranged from less than 40 Grays (exact doses not provided) to more than 60 Grays. The pooled incidence of acute AEs for patients with inflammatory arthritides when considering controlled and uncontrolled studies was 32% (95%CI 14%, 53%). When compared with controls (cancer patients receiving radiotherapy without inflammatory arthritides) no statistical difference was observed (Relative risk [RR] using only controlled studies 1.3; 95%CI 0.67, 2.5). For late AEs, the pooled incidence for patients with inflammatory arthritides when considering controlled and uncontrolled studies was 20% (95%CI 8%, 34%). However, the AEs in patients with inflammatory arthritides was significantly higher than that of controls (RR using only controlled studies 2.3; 95%CI 1.3, 4.3). The most common acute AEs reported were radiation dermatitis, gastrointestinal or genitourinary toxicity, and flares of the autoimmune disease. The most common late AEs reported were fibrosis, lymphedema, and pneumonitis. Out of the case reports, 5 patients reported late AEs and the remaining patients did not report AEs. Conclusions: While there were no differences in the frequency of acute AEs, patients with inflammatory arthritides had a statistically significant increased rate of late AEs compared with people without arthritides. Our results can assist in providing evidence-based information to patients with inflammatory arthritides considering radiotherapy.
Building epigenetic clocks for estimating accelerating aging in patients with testicular cancer treated with cisplatin-based chemotherapy.
Authors: Wojewodzic Marcin W , Sydhagen K. Aurora , Rounge Trine B.
Published: June 2023

e24099

Background: DNA methylation is highly correlated with chronological age. This is essential for constructing epigenetic clocks. Epigenetic clocks can shade light not only about the biological age, but also describe the functional state of the body after chemotherapy (CT). Patients with testicular cancer (TC) treated with CT are prone to develop metabolic syndrome (MetS) later in life, that may be also mediated through epigenetic changes (Bucher, Clin Epigenetics. 2019; 11:179). If age acceleration is also a mediator in the CT~MetS relationship remains unknown. We developed an epigenetic clock, and then analyzed differences in biological age acceleration between groups of TC patients 16 years after CT. TC patients had undergone one of two treatments: either surgery or a combination of CT or surgery only. Half of the patients in both treatment-groups had developed MetS. Methods: First, we used an elastic net to develop epigenetic clocks based on DNA methylation from publicly available data sets (EPIC array). We tested the differences in age accelerations (residual and intrinsic age acceleration) between groups of TC patients that received CT and orchiectomy with those TC patients with orchiectomy only. Also, the linear regression used treatment type and MetS diagnosis as independent variables. Results: Five epigenetic clocks were developed, of which one, performing best, was chosen to be used in further analyses. This clock, the Aurora’s clock, had a root mean square error of 3.1/3.8 and R2 of 0.95/0.9 shown in two different test sets. In addition to Aurora’s clock, eABEC and Levine DNAm PhenoAge were used (Lee, BMC Genomics. 2020, 21, 747; Levine, Aging. 2018, 2018,10:573-591). The linear regressions indicated a lower age acceleration for the group treated with both CT and surgery, compared to the group treated with surgery only. The significance level varied between the clocks, with a p-value ranging from 0.03 to 0.17. All three clocks estimated a higher age acceleration for patients diagnosed with MetS, but this was only significant when applying Levine DNAm PhenoAge (p = 0.03 for residual age acceleration, and p = 0.045 for intrinsic age acceleration). Conclusions: These findings indicate that CT does not lead to increased age acceleration 16 years after treatment. However, individuals diagnosed with MetS can have an elevated age acceleration. These findings can have clinical implications for managing patients' after TC diagnosis (i.e. MetS can be predicted from age acceleration). Testing the clocks in an independent cohort of TC is needed for validation of our results.
Change in quality of life of metastatic breast cancer patients seeking treatment at Komfo Anokye Teaching Hospital, Ghana.
Authors: Agbeko Anita Eseenam , Bekae Adelaide , Boakye-Yiadom Jonathan , Arthur Joshua
Published: June 2023

e24111

Background: Despite developments in breast cancer screening for early diagnosis and treatment, 20-85% of women go on to develop distant metastasis, based on tumor biology, stage at presentation and treatment modalities received. The primary goal of treating metastatic breast cancer (MBC) is to improve quality of life (QoL). This study assessed the change in QoL for patients with MBC seeking treatment at Komfo Anokye Teaching Hospital (KATH). Methods: Women with MBC seen at KATH had QoL assessed using the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire before, and 3 months after they were supposed to have received systemic treatment - chemotherapy, hormonal, target therapy. Data was analyzed using STATA v17 software. The higher the FACT scores, the better the QoL. Results: Fifty-six women with MBC were interviewed. Their mean age was 51.7 years. Only 27 (48%) of them received some systemic treatment – chemotherapy, hormonal, target therapy – over the study period. Baseline median QoL scores in the wellbeing domains were physical (PWB) = 17.5, social/family (SWB) = 16.0, emotional (EWB) = 12.0, functional (FWB) = 8.0, breast cancer subscale (BCS) = 22.0. Their median total QoL scores were FACT-B = 77.5; FACT-B TOI = 48.5 and FACT-G = 54.5. At follow up, 28 (50%) of participants were alive. About a third (9/28) of them received no systemic treatment. Of the remaining 19; 4, 1 and 14 received one, two and three cycles of systemic treatment respectively. Their median QoL scores were PWB = 20.5, SWB = 16.0, EWB = 16.0, FWB = 15.0, BCS = 22.5, FACT-G = 72.0, FACT-B = 94.5, and FACT-B TOI = 61.0. Fourteen had improved, and 14 had deteriorated QoL. The median minimally important difference (MID) for the improved QoL group was MID FACT-B = -22, MID FACT-B TOI = -10 and MID BCS = -4, and for the deteriorated QoL group was MID FACT-B = 26.9, MID FACT-B TOI = 18 and MID BCS = 5. Being dead at follow up was related to receiving no treatment (AOR = 6.97, CI: 1.91 – 25.47, p-value = 0.003) and having one metastatic site at baseline (AOR = 5.23, CI:1.43 – 19.12, p-value = 0.01). Conclusions: Mortality among women with MBC was high (50%), especially among those who did not receive any systemic treatment or had one metastatic site. Of the survivors, equal proportions had significantly improved and significantly deteriorated QoL scores albeit varying treatment courses received. Further studies are needed to explore how systemic treatment or not impact QoL changes and survival outcomes of MBC patients in KATH.
Nutrition assessment reports in oncology clinical trials.
Authors: Aung Ye Myint , Aktas Aynur , Shroff Vishal , Kadakia Kunal C. , Waldman Jake , Walsh Declan
Published: June 2023

e24142

Background: Malnutrition is common in cancer and associated with greater treatment toxicity and poor clinical outcomes. Validated screening tools can identify individuals at risk; however, they are underutilized in clinical practice. It is also unclear how nutrition status is assessed and reported in oncology clinical trials. We analyzed nutrition assessment protocols in clinical trials published in major US oncology journals. Methods: Three researchers (YA, AA, VS) identified studies published in the Journal of Clinical Oncology, JAMA Oncology, and the New England Journal of Medicine under the “original reports”, “original articles”, or “’ research” categories, respectively (1/1/2022-12/31/2022). We selected studies that reported outcomes of systemic therapeutic interventions in any Phase clinical trial. This included chemotherapy, hormone therapy, and immunotherapy alone or combined with radiation therapy or surgical procedures. Systematic reviews, meta-analyses, commentaries, retrospective studies, and secondary analyses of pooled data from completed trials were excluded. Descriptive statistics summarized how malnutrition risk was assessed and nutrition data reported. Results: 521 articles were reviewed; 153 (29%) studies met eligibility criteria. Most were randomized trials (103/153, 67%) and Phase II or III (126/153, 82%). Malnutrition risk assessment was absent from all studies. Overall, 15/153 (10%) reported either baseline Body Mass Index or pre-treatment weight changes. These variables were included in the survival analysis of 5/15 studies. The primary cancer sites studied were breast (5/15), gynecologic (3/15), hematologic (3/15), multiple sites (2/15), prostate (1/15), and pancreatic (1/15). Conclusions: Most oncology clinical trials ignore and/or underreport nutrition status. Only 10% of the studies reported nutrition status data, and not all cancer sites were represented. There is a need to routinely assess nutrition status and (given the major prognostic value) investigate its potential uses for patient selection and stratification in clinical trials.
Therapeutic evaluation on Chinese calycosin decoction for chemoradiotherapy induced thrombocytopenia.
Authors: Lv Guangmei , Hu Meng , Wan Haijun Wan , Liang Wei , Ha Wentao , Zhao Sunyan , Gong Yongling
Published: June 2023

e24153

Background: Chemotherapeutic thrombocytopenia is often accompanied with hospitalized cancer patients associated with anti-tumor therapy, so called CRIT (Chemoradiotherapy induced thrombocytopenia). In addition to the risk of thrombocytopenic hemorrhage, we also observed the implementation of the originally scheduled chemoradiotherapy with limits of dose and frequency. However, CRIT therapy administered with Chinese calycosin decoction may benefit those affected patients. Methods: Forty CRIT patients diagnosed in the Nanjing 1st Hospital,China, from 2019 to 2021, were enrolled and divided randomly into herbal group (n = 19) and control group (n = 21). Herbal group was treated with additional calycosin decoction, while control group received conventional treatment related to CRIT in the mean time. The primary endpoint of efficacy assessment was time to recovery (TTR) for CRIT. Secondary endpoints were delayed termination rate (DTR) of chemoradiotherapy, incidence of hospitalization (IH) and incidence of platelet transfusion (IPT). Results: The effective rate of herbal group (13/19, 68.4%) and control group (12/21, 57.1%), and no grade 3 or 4 adverse gastrointestinal reactions were observed during treatment. Compared with the control group, TTR of grade Ⅰ-Ⅲ CRIT patients in herbal treatment group was relatively shorter (11.1±1.8d vs 13.8±2.1d), DTR (3/15,20% vs 7/16, 44%), and IH (7/15,47% vs 11/16,69%) was significantly lower, difference was statistically significant (P < 0.01). TTR, DTR, IH and IPT of grade Ⅳ CRIT patients were not significantly different between the two groups (P > 0.05). Conclusions: Chinese herbal managing of CRIT with calycosin decoction might be an additional choose option, help to benefit stand dosage implementation of chemoradiotherapy and socioeconomic cost.