bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal distribution of liver cancer mortality rate in Peru between 2003-2017.
Authors: Flores Claudio J. , Lopez Pereyra Mariano Francisco , Chirinos Luis , Carrion Pamela , Enriquez Daniel
Published: June 2022

e22521

Background: Liver cancer represents the sixth most frequent neoplasm and the third leading cause of cancer death worldwide, although it possesses an heterogenous incidence and mortality. In Peru, its mortality rate distribution is unknown. We aimed to explore the spatio-temporal distribution of liver cancer mortality rate according to Peruvian geographical regions. Methods: We obtained data from liver cancer deaths between 2003-2017 from the Peruvian Ministry of Health Registry. Population data was obtained from The National Institute of Statistics and Informatics (INEI, Peru). Age-standardized mortality rate (ASMR) was calculated based on the 2011 world standard populations. Spatial autocorrelation was determined according to Moran’s Index and the Local G Cluster Map to explore the cluster patterns between regions. Results: During the study period, 18,427 deaths for liver cancer were reported on the national death system. The liver cancer mortality rate in Peru increased from an ASMR of 4.1 (95% CI: 3.4, 4.8) in 2003 to 4.4 (95% CI: 3.8, 5.0) in 2017, with an average mortality rate of 4.9 (95% CI: 4.6, 5.2) by 100 000 persons-year. According to the political regions of Peru, the mortality rate distribution showed a spatial variation (ASMR of 0.6 to 12.2 per 100 000 persons-year); the mortality rate was high in coast regions and low among highlands regions. The ASMR spatial distribution showed a significant spatial autocorrelation (Moran’s I: p < 0.05). During the study period, the ASMR showed a significant increasing and decreasing mortality in several geographic regions and remained constant in other regions. Conclusions: In Peru, the liver cancer mortality rate shows a spatial and temporal variation according to geographical regions. The increase in the mortality rate in some regions requires further identification of local risk factors to implement programs aimed at reducing incidence and mortality.
Unusual prevalence of cancer genetic mutations in a cohort of predominantly non-Caucasian cancer patients.
Authors: Kyaw Nay Yee Wint , Natarajan Vijaya , Durana Theresa , Bhasin Pooja Gogia , Best Jacob , Toom Sudhamshi , Xu Yiqing
Published: June 2022

e22524

Background: Genetic testing has been applied increasingly widely in oncology, as detection of hereditary cancer syndromes can guide prophylactic surgery, intensive surveillance and family member testing. We hypothesized that the profile of mutation prevalence may be different from the general knowledge in patients with immigrant background. Methods: Cancer patients who have been treated in Maimonides hospital and have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Patients were randomly approached for consenting for the study. The results from the first 122 patients enrolled in this study were analyzed. Results: Among 122 patients, there were 86 breast, 22 GYN, 8 GI, 5 GU and 1 lung cancer. The ethnicities were African American (n = 38), Asian (n = 36), Caucasian (n = 32), Hispanic (n = 10) and mixed races (n = 6). Six patients had 2 primary cancers and 2 patients had 3 primary cancers. 25 patients (20.49 %) had germline mutations. A complete list of cancer type, mutation type, age of onset and cancer characteristics is shown in the table below. All of the 13 mutation positive breast cancer patients met the NCCN criteria for genetic testing, including 7 for age < 50 and 6 with family history of breast cancer. Among the 2 patients with NF1 mutation, one had no skin change while the other had neurofibromatosis; both had family history, with pancreatic or breast cancer respectively. The patient with APC mutation had family history of numerous cancers including gastric, but no colon cancer. 48% patients had the onset of disease at older than 50 years old. Conclusions: In this multi-ethnicity cohort, 20.49% mutations were detected in patients who met the genetic testing criteria. A higher prevalence of BRCA 2 were found in both breast and ovarian cancer patients, and rare mutations of NF1, APC, FH and ATM were also detected. A large percentage had onset at an older age. More studies should be done in communities enriched with immigrants to gather further knowledge of unusual prevalence of genetic mutations, and an extensive panel for gene testing should be offered.[Table: see text]
Identified potential pathogenic variants of BARD1 in 1449 Chinese high-risk breast cancer patients.
Authors: Wang Rong , Ye Weiwu , Chen Zhanhong , Shao Xiying , Cao Wenming , Wang Xiaojia , Zheng Yabing
Published: June 2022

e22525

Background: BARD1 (BRCA1-associated ring domain 1), nuclear partner of BRCA1, has been recognized as a breast cancer predisposition gene. Recently, two large-scale population-based case–control studies confirmed that germline loss-of-function mutations in BARD1 were associated with a risk of breast cancer. Since the germline mutation frequency of BARD1 is much less than that of BRCA1/2, the distinct mutation spectrum of BARD1 is still obscure, especially in Chinese breast cancer patients. To verify the utility of BARD1 genetic testing in Chinese population, we assessed the mutational frequency and spectrum of BARD1 in a sequential series of Chinese high-risk breast cancer patients. Methods: A cohort of high-risk breast cancer patients (n = 1449) were collected in Zhejiang Cancer Hospital from 2008 through 2020, including 608 familial breast cancer (BC) cases, 173 bilateral BC cases, 222 triple negative BC cases, 436 early-onset BC cases (≤40 years) and 10 male BC cases. The complete coding sequence and intron–exon boundaries of BARD1 were screened by a 98-gene panel sequencing assay. The SIFT, Polyphen2 and MutationTaster prediction programs were used for analyzing the effect of the variants of unknown significance (VUS) on the BARD1 protein function. Results: A total of three BARD1 pathogenic mutations (c.1348_1349delinsCAT, c.70_71insGT and c.373G > T) were identified, which had been all reported, and accounting for 0.2% (3/1449) in Chinese high-risk breast cancer patients. The frequencies were 0.33% (2/608) and 0.12% (1/841) in familial and non-familial breast cancer patients, respectively. In total, 19 VUSs including 17 missenses, one inframe deletion and one inframe insertion of BARD1 were identified in this study. Based on in silico analysis, nine BARD1 missense variants (c.76A > G, c.1912G > A, c.1693C > T, c.2191C > T, c.127C > A, c.1601C > T, c.443G > A, c.233G > A and c.1972C > T) were classified as potentially damaging. However, the two newly variants c.420_422del and c.68_69insTCCGGGAACGAGCCTCGTTCC still remain VUS, and the other eight variants were classified as benign. Conclusions: Our data presented the germline mutations of BARD1 in a large-scale Chinese high-risk breast cancer population, which accounted for 0.2% in our cohort. Moreover nine potential pathogenic variants were found based on in silico analysis. Clinically, these data may be helpful in genetic counseling of breast cancer patients with BARD1 germline mutation. While the further research on the VUS are needed.
MUTYH-related polyposis syndrome associated with a variant of uncertain significance mutation: A new pathogenic mutation?
Authors: Picanço-Albuquerque Clarissa Gondim , Sant'Ana Rosane Oliveira , Luciano Maria Claudia dos Santos , Bezerra Maria Júlia Barbosa , Bitencourt Flávio da Silveira , Barbosa Oliveira Francisca Fernanda , Souza Thuany Pinto Rocha de , Silva Paulo Goberlânio de Barros , Lima Marcos Venício Alves , Silva-Fernandes Isabelle Joyce de Lima
Published: June 2022

e22528

Background: The familiar history is indispensable to clinical investigation during genetic counseling and the new molecular techniques allowed the identification of hereditary cancer predisposition syndromes (CPS). However, the classification systems of these syndromes are difficulty and very complex. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases to reduce the subjectivity bias of mutation variants classified as risk. Methods: To show the difficulty of classification of these variants we describe a case report of a family from countryside of Brazil in which there is a high rate of inbreeding. This family has three brothers with polyposis and colorectal cancer between 51 and 60 years-old. Results: The index-case had multiple polyps, developed colorectal cancer at 51 years-old and had a familiar history of two brother dead by colorectal cancer after polyposis and nine brother without familiar history of cancer, a father dead at 38 years-old by non-specific lung-disease and a mother alive at 83 years-old. There was no description of other cases of cancer among uncles and grandparents. The index-case performe a NSG genetic painel to CPS and showed a homozygosis variant in MUTYH gene: NM_001048174.1: c.253T > C:p.(Trp85Arg), that was classified as variant of uncertain significance (VUS). MUTYH is a base excision repair enzyme, it plays a crucial role in the correction of DNA errors and may be considered a cell protective factor and is associated with MUTYH-related polyposis (MAP). MAP is an autosomal recessive CPS and presents a phenotype that overlaps attenuated polyposis and familial adenomatous polyposis, increasing the risk of colorectal cancer in 43-63% up to 60 years or 80% if there is no surveillance/tracking. In view of the family history that suggests autosomal recessive inheritance, with a homozygous variant absent in the database of population controls (gnomAD) and in which in silico predictors indicate the effect of this variant as deleterious, the management of this family must be carried out considering it as a potential high-risk pathogenic variant. Conclusions: While the classification criteria for the variants are being refined, we reinforce the importance of a careful family history in the approach to CPS in order to offer an appropriate clinal conduct in the prevention of hereditary cancer.
Reduction in local tumor recurrence in a murine R2 resection model comparing locally administered docetaxel-releasing product, OncoPLEX, versus systemic docetaxel.
Authors: Emanuel Noam , Nedvetzki Shlomo , Rosenfeld Yosef , Kozloski Goldi A. , Reichart Malka , Senagore Anthony J.
Published: June 2022

e22530

Background: Local recurrence (LR) negatively impacts long-term survival and patients’ quality of life in many solid tumor malignancies, despite advances in surgical techniques and neoadjuvant and adjuvant treatments. Systemic treatment-related morbidity and mortality remains an unmet need, especially if only an R2 resection is achievable. OncoPLEX is a biodegradable, extended-release formulation of docetaxel that is applied in the form of a paste to the resection bed at surgery. We evaluated OncoPLEX efficacy in preventing local recurrence in an R2 tumor resection model generated with cell lines that exhibit high or low docetaxel sensitivity. Methods: Cell lines sensitivity to free docetaxel and OncoPLEX-released docetaxel were determined in a cytotoxic assay. CT26 (murine colorectal carcinoma--resistant) and U-87 (human primary glioblastoma—sensitive) were tested. A murine subcutaneous (SC) tumor resection model using a predetermined tumor size (400-600 mm3) and a standardized R2 resection (̃90%) was developed. OncoPLEX was applied once on the tumor bed post-resection, docetaxel was IV injected every 4 days (6 times total), and animals were followed for tumor regrowth. The overall docetaxel dose in OncoPLEX (0.78 mg docetaxel) is lower than the maximal tolerated dose and non-lethal reported dose (TAXOTERE [10 mg/kg IV]; prescribing information). Results: The IC50 concentrations of free docetaxel in CT26 and U-87 cell lines indicated resistance and sensitivity to docetaxel respectively (112.6 nM vs 4.2 nM). The cytotoxic potency of OncoPLEX-released docetaxel exhibited a similar relationship with greater potency (IC50 values in CT26 56.7 vs. 1.2 nM in U-87). At the completion of the CT26 SC study (37 days), there were more tumor-free animals in the OncoPLEX group (6/8, 75%) compared with the control IV docetaxel treated (3/8, 38%) or the untreated control (0/8, 0%). A similar trend was observed in the U-87 study; OncoPLEX (4/10, 40%), Control intraperitoneal-injected taxel (2/10, 20%), and untreated control (0/10, 0%). In both studies, the average tumor volume was significantly smaller with either OncoPLEX or systemic treatment compared with untreated controls (CT26: 375 mm3, 485 mm3 and 1500 mm3 (p<0.05); U-87, 403 mm3, 780 mm3 and 2059 mm3; p<0.001). There was no effect on behavior or weight in the OncoPLEX treated animals. Conclusions: Locally administered OncoPLEX in this R2 resection model reduced local tumor recurrence and systemic adverse outcomes. OncoPLEX offers a potentially enhanced local adjuvant chemotherapy option with reduced side effects for solid tumors, independent of the tumor sensitivity or resistance to docetaxel.
Treatment advances in metastatic triple-negative breast cancer (TNBC): Addressing the knowledge gap.
Authors: Heller Elizabeth Jean , Smith Keira P , Williams Sarah L
Published: June 2022

e23006

Background: The dearth of effective treatment options for patients with metastatic TNBC has enabled the rapid development of more effective treatments for this condition, but research indicates that clinicians face challenges in maintaining a working knowledge of evolving data. This study was conducted to determine if an online, case-based continuing medical education (CME)/nursing continuing professional development (NCPD)–approved activity could identify and address gaps in clinicians’ knowledge regarding the personalized care of patients with metastatic TNBC. Methods: The activity, Metastatic Triple-Negative Breast Cancer: Applying Treatment Advances to Personalized Care, chaired by Sara A. Hurvitz, MD, FACP, was made accessible starting on July 23, 2021. Learners participated in a 1-hour activity that highlighted emerging therapeutic targets in TNBC, with an emphasis on current challenges and new opportunities in the management of metastatic disease. Learners completed a repeated-pairs pre- and post-activity assessment consisting of case-based questions that gauged their ability to apply emerging data to clinical decision making. Knowledge gaps and learning gains were calculated based on percentages of learners obtaining correct responses on the pre- and post-activity assessments. Significance was assessed using a chi-squared test. Results: As of February 2, 2022, 632 clinicians had completed the activity for credit. Baseline assessment data revealed gaps in knowledge regarding emerging actionable targets and management of treatment-related adverse events (Table). The activity resulted in significant gains in knowledge and competence related to these topics, with P < 0.0001 for all learning gains. Conclusions: These data indicate that a substantial knowledge gap exists regarding the latest developments in the treatment of metastatic TNBC. They also demonstrate that online, case-based CME/NCPD-approved activities can result in statistically significant improvements in clinicians’ knowledge of therapeutic advances and management of treatment-related adverse events for patients with metastatic TNBC. Acknowledgements: This activity was supported by an independent educational grant from Merck.[Table: see text]
Engaging continuing medical education in evaluating knowledge gaps and preferences in advanced BRAF+ melanoma.
Authors: Robinson Katie , Scavone Jillian L , Scully Emily , Lewis Emily , Esgro Robert A. , Kirkwood John M.
Published: June 2022

e23007

Background: Given the rapid evolution of treatments for advanced melanoma, oncology providers are challenged to stay current on evidence-based recommendations for optimal patient care. Integrating practice-based polling into continuing medical education (CME) activities is a proven way to increase engagement, address knowledge gaps, and assess attitudes on specific topics. Methods: We provided a CME activity designed to educate oncology and dermatology providers on the latest advances regarding the management of advanced BRAFmut+ melanoma. Interspersed engagement opportunities further assessed practice preferences and elucidated persisting educational needs. The CE activity was available for credit from December 31, 2020 to December 30, 2021. Results: 305 medical oncology or dermatology providers who each see an average of 25 patients with melanoma per month participated. These providers scored an average 38% on pretest topics related to the use of triple therapy and patient and/or tumor characteristics that guide clinical decision-making. Post-learning, providers scored 84%, highlighting the impact of the education on knowledge gaps. Notably, while 51% of these providers indicated that they were guessing on the pre-test, the percentage of those who were confident and correct on the post-test rose from 3% to 28%, demonstrating a rise in confidence among participants. While 50% of participants noted a positive perception of triple therapy (BRAF inhibitor + MEK inhibitor + anti-PD1) in the front-line setting, case-based polling questions showed that providers lack consensus regarding the use of combinations of treatments in other clinical scenarios. While 45% would recommend triple therapy in the first-line setting, dual checkpoint inhibitor (CPI)-based treatment is preferred after progression on a first-line CPI or dual-targeted therapy. Conclusions: CME is a useful method to address knowledge gaps regarding evolving treatment options. As data regarding the use of triple therapy for patients with BRAF+ melanoma emerges, oncology and dermatology providers will require further education on how to apply these options in practice.[Table: see text]
Educational impact of inpatient hematology-oncology service structure.
Authors: Cooperrider Jennifer H. , Patel Anand Ashwin , Brondfield Sam
Published: June 2022

e23013

Background: Literature suggests that inpatient hematology-oncology (heme-onc) clinical experiences may have a deleterious impact on trainee interest in heme-onc. However, the impact of inpatient heme-onc service structure on trainee education is not known. To delineate the factors affecting trainee education, we aimed to characterize the structure of inpatient heme-onc services at comprehensive cancer centers (CCCs) and the associated impact on trainees. Methods: We designed a survey with Likert-type and open-ended questions using established procedures. We surveyed heme-onc fellowship program directors (PDs) at all 50 U.S. CCCs with fellowship programs. We performed point biserial and Pearson correlations on Likert-type responses and content analysis on open-ended responses. Results: Eighteen out of 50 (36%) PDs responded and described 117 services. Services were either primary (35%), consult (44%), or both (21%). Fellows were present on 93% and residents on 54% of services. PDs rated the educational value of most inpatient services as either “very high” or “somewhat high” for both fellows (73% very high, 13% somewhat high) and residents (49% very high, 33% somewhat high). PDs perceived that fellows derived greater educational value from consult-only vs primary/mixed services [R(105) = 0.25, p= 0.01] and provided greater reciprocal benefit to consult-only vs primary/mixed services [R(100) = 0.28, p= 0.004]. Hospital type (county, university, or veteran’s) and the presence or absence of a formal curriculum on the service did not correlate with perceived educational benefit. Multiple open-ended comments suggested that heme-onc attendings and fellows should be consultative rather than primary service providers, programs should separate teaching and non-teaching services, and service/education balance optimization should be prioritized. Inadequate service staffing and lack of institutional support were identified as barriers to inpatient education. Conclusions: PDs felt that inpatient heme-onc services had high educational value for trainees, particularly for fellows. Both fellows and services may derive mutual benefit from fellow participation on inpatient consult services structured separately from non-teaching primary services. Hospital type and the presence or absence of a structured curriculum may not be critical for education on inpatient heme-onc services. Appropriate service/education balance, staffing, and institutional support are crucial to optimize inpatient education. Future studies should explore the trainee perspective around the educational value of inpatient clinical experiences. PDs and institutions can use the study findings to craft beneficial inpatient educational experiences for heme-onc trainees.
Improving resident education on the inpatient solid tumor oncology rotation through development of an asynchronous video curriculum.
Authors: Walsh Laura , Agarwal Parul , Brondfield Sam , Chida Natasha , Donehower Ross C. , Marrone Kristen
Published: June 2022

e23014

Background: As the oncology patient population grows, continued recruitment of talented individuals is essential. Meaningful and highly educational clinical exposures play a crucial role in a resident’s decision to pursue fellowship in oncology. Currently, the majority of oncology exposure occurs in the inpatient setting, where trainees are confronted with many competing clinical demands, leaving minimal time for teaching. Prior work has demonstrated that dedicated time for teaching supplemented with high-yield educational material improves trainee satisfaction and interest in a particular field. We hypothesize that implementing an asynchronous inpatient video oncology curriculum will improve resident clinical competency and satisfaction. Methods: This is an ongoing, single institution educational intervention using the Kern method for curriculum development in the Johns Hopkins Osler Internal Medicine Residency (IRB00307077). A targeted needs assessment has been developed to identify gaps in medical knowledge, assess preparedness in managing common solid tumor inpatient diagnoses, and explore satisfaction with prior educational experiences on this service. Based on these results, ten educational videos will be created by content experts and aligned with the learning objectives of the Osler residency program and ABIM blueprint. Trainees will have dedicated time to watch the videos during their solid tumor rotation. We plan to evaluate effectiveness of our curriculum by measuring completion rates and pre- and post-video multiple choice responses. We will also assess knowledge retention and resident satisfaction at three and six months post-rotation with online questionnaires. Results: Annual Osler program ACGME survey data review revealed a high level of resident dissatisfaction with the oncology clinical experience compared with other rotations. While 83.3% of residents rated their general internal medicine experience as “excellent,” only 52.4% rated their oncology experience as “excellent.” Needs assessment data collection has been delayed by the COVID-19 pandemic but is ongoing. Following topic selection, videos will be created in April 2022 with plans for video curriculum implementation in July 2022. Conclusions: In order to attract and retain trainees in the field of oncology, it is imperative that educational curricula adapts to meet learners’ needs. Efficient, evidence-based instructional strategies designed to promote clinical competency for internal medicine residents on an inpatient solid tumor service may foster engagement and rotation satisfaction. We are currently evaluating how an asynchronous video inpatient oncology curriculum may significantly improve the inpatient internal medicine trainee experience. If successful, this curriculum can be adapted for other trainees and practitioners new to the field of oncology.
Heterogeneity in treatment regimens for AYA bone sarcomas: A comparison of outcomes at a single sarcoma center.
Authors: Espejo-Freire Andrea P. , Campoverde Leticia , Kropotova Yana , Statz-Geary Kurt , Costa Philippos Apolinario , Barreto Coelho Priscila , Bialick Steven , D'Amato Gina Z. , Jonczak Emily , Trent Jonathan C. , Dhir Aditi
Published: June 2022

e23508

Background: Bone sarcomas account for about 5% of cancers in adolescents and young adults (AYA). Outcomes in this population are consistently inferior than children. It is poorly understood whether this is related to the tumor biology or the therapeutic approach. In addition, regimens used in AYAs are heterogeneous due to poor tolerance of pediatric regimens and lack of clinical trials specific to this population. We sought to study the therapeutic regimes and outcomes of AYA bone sarcoma patients (pts) to understand the optimal therapeutic approach better. Methods: From our institutional database, we extracted data of pts with the diagnosis of “osteosarcoma” (OS) and “Ewing sarcoma” (ES) in the AYA (15-39 yo) population from 2011-21. We included only pts with efficacy documented to different regimens. Descriptive statistics were used for patient demographics, presentation, regimens, and outcomes (Table). Objective response rate (ORR) was defined as the number of patients achieving a partial or complete response. Relapse rate (RR) was calculated for the pts that progressed after undergoing definitive curative intent treatment. Survival comparison between groups was made using the Kaplan Meier method and Log Rank Test. We used Fisher's exact test to compare differences in ORR between treatment groups. Results: We identified 30 ES and 44 OS pts. For both ES and OS, Kaplan Meier survival analysis showed no difference in presentation adjusted overall survival between treatment groups; ( x2 .351, p .55) for ES and ( x2 1.94 p .378) for OS. Importantly, in OS, ORR difference between Adria/IVCis and Adria/IACis was statistically significant ( p .0188). Conclusions: Our study shows the heterogeneity in first-line treatment strategies for AYA pts with bone sarcomas. For ES, response rates for VAC/IE and VAI were similar. In the OS cohort, we found ORR for Adria/IACis was 81% which was statistically different to pts receiving Adria/IVCis (ORR 30%). However, we saw relapses in 43% of pts treated with Adria/IACis. This indicates that the intra-arterial approach could be helpful for limb preservation but suggests the need for intense adjuvant chemotherapy to prevent relapses. There were no statistically significant differences in the survival outcomes of AYA bone sarcoma pts treated with pediatric versus adult regimens.[Table: see text]
Primary site and survival in osteosarcoma: A National Cancer Database (NCDB) analysis.
Authors: Eaton Vincent , Tupper Connor , Silberstein Peter T.
Published: June 2022

e23512

Background: Osteosarcoma (OSC) is the most common primary bone tumor and typically affects the appendicular skeleton (specifically, the long bones of the upper and lower extremities). However, this cancer can affect other regions of the body as well, such as the skull, mandible, ribs, vertebral column, and other areas involving bone and/or any articular cartilage and, to the author’s knowledge, all possible primary sites have not been investigated. The aim of this study is to see whether or not the primary site of the tumor in OSC patients may have an effect on survival outcomes. Methods: Using the NCDB, patients diagnosed with OSC between 2004-2018 were identified using ICD-O-3 histology codes 9180 through 9193. The cohort was analyzed to investigate survival outcomes in different primary sites. Univariate analysis was then performed assessing patient length of survival for each primary site subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 9826 patients with known primary site that had survival data were included. The site with the best survival was the lower limb which had significantly better survival than all other primary sites. Tumors of the upper limb had highest median survival (153 months) of those with median survival reported (which was all except for lower limb). Patients with primary tumor of ribs, sternum, clavicle had a significantly better survival than both vertebral column and pelvis/sacrum/coccyx (all p < .01). Upper limb patients survived significantly longer than all groups other than the skull, face, and mandible (p < .05). The labeled primary site with the highest mean survival was the lower limb at 123.1 months and the lowest survival was the pelvis, sacrum, and coccyx, with a median survival of 54.6 months. Conclusions: This study found numerous survival differences between patients diagnosed with OSC of different primary sites. Labeled primary sites of the lower limb and upper limb were associated with best survival while the pelvis, sacrum, and coccyx were associated with worst survival. Future studies should be done to investigate variables that may impact the survival of different primary sites, including staging, treatments, time from diagnosis to treatment, socioeconomic factors, and insurance status.[Table: see text]
Genomic signatures in young and old Chinese patients with bone and soft tissue tumors.
Authors: Jin Gu , Yu Yangyang , Zhao Lele , Xiao Mingzhe , Qi Chuang
Published: June 2022

e23516

Background: The tumor onset of bone and soft tissue at young or old age was associated with different clinical features. However, the genomic differences between young and old patients with bone and soft tissue tumors were not well elucidated. Therefore, a comprehensive molecular profile in young and old patients should be defined, which will enhance our understanding of the unique biology of bone and soft tissue tumors and help to improve the treatment options for this population. Methods: Tumor tissue samples from 103 young (age < = 50 years) and 81 old (age > 50 years) patients with bone and soft tissue tumors were enrolled, between 2019 to 2021. Targeted sequencing of 539 cancer-related genes was conducted to characterize the genomic landscape. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations (CNV) and gene fusions were assessed and germline alterations were excluded. Tumor mutation burden (TMB) was calculated by counting all nonsynonymous mutations per megabase of coding sequences. Results: The most common mutant genes in the younger and elderly groups were TP53 (20%), MUC16 (13%), KRT2 (8%) and TP53 (37%), MUC16 (19%), LRP1B (10%), FAT3 (7%), respectively. KRT2 mutations were significantly higher in the younger group (7.8% vs. 1.2%, p = 0.041), while TP53 mutations were more common in the elderly group (20.4% vs. 37%, p = 0.012). MUC4 and FADS6 mutations were only observed in the younger group (5.8% and 4.9%). Mutation of some genes were observed simultaneously in certain patients, for instance, TRIOBP/ KRT2, GATSL3 / KRT2, GATSL3 / SSUH2 in the younger group and P53 / LRP1B, MUC16 / PTEN, MUC16 / FAT2, MUC16 / LRP1B, APC / CARD11 in the elderly group. The most frequently affected pathways in the younger and elderly groups were TP53(23.3% vs 37%), RTK-RAS (16.5% vs. 29.6%), NOTCH (16.5% vs.16%), PIK3 (7.8% vs18.5%), Hippo (8.7% vs. 17.2%), respectively. The tumor mutation burden (TMB) was positively correlated with age (Pearson's r = 0.33, p < 0.001), and the old patients had higher TMB. Up to 97.8% (180/184) evaluated samples were microsatellite stable. Conclusions: These findings revealed different molecular characterization between young and old Chinese patients with bone and soft tissue tumors, which may further provide novel insights for the personalized treatment.
Predictive value of cystatin c in methotrexate elimination in patients with osteosarcoma.
Authors: Liu Zengjun , Wang Yonggang , Xu Jing , Hu Wenyu , Yang Changsheng , Zhu Dongyuan , Zhou Lei , Liu Mengyao , Li Hongtao
Published: June 2022

e23522

Background: High-dose methotrexate (HDMTX) is a renally eliminated and nephrotoxic therapy for osteosarcoma (OS). Serum cystatin C (Cys C) has emerged as an alternative to serum creatinine (Scr) for estimation of glomerular filtration rate (GFR). We aim to analyze the value of the baseline Cys C in predicting MTX elimination in patients with OS. Methods: All consecutive patients who were treated with HDMTX in Shanghai Jiao Tong University Affiliated Sixth People¡¯s Hospital, between November 2011 and April 2018, were retrospectively reviewed. The baseline GFR was calculated by three different equations based on the Scr, Cys C and their combination. MTX concentrations at 24, 48 and 72 hours after the termination of infusion were routinely monitored using high performance liquid chromatography. Results: A total of 158 courses of MTX infusion were administered. The incidences of delayed excretion of MTX at 24, 48, and 72 hours (serum concentrations at 24 h > 10 μmol/L, 48h > 1 μmol/L, 72h >0.1 μmol/L) were 62.3%, 44.9% and 29.7%, respectively. The baseline Scr in the delayed excretion (DE) group were significantly lower than that in the normal excretion (NE) group at all three time points (24h: 58.8 µmol/L vs 47.86 µmol/L, P£¼0.05; 48h: 59.02 µmol/L vs 47.48 µmol/L, P£¼0.05; 72h: 62.29 µmol/L vs 51.51 µmol/L, P£¼0.05). However, the baseline Cys C in the DE group were similar to that in the NE group at all three time points (24h: 0.96 mg/L vs 0.90 mg/L, P = 0.11; 48h: 0.96 mg/L vs 0.92 mg/L, P = 0.17; 72h: 0.96 mg/L vs 0.93 mg/L, P£¾0.05). The Scr-based estimated GFR in the DE group were significantly lower than that in the NE group at all three time points (24h: 148.42 mL/min vs 186.79 mL/min, P£¼0.05; 48h: 147.24 mL/min vs 188.82 mL/min, P£¼0.05; 72h: 142.95 mL/min vs 171.04 mL/min, P£¼0.05). The Scr- and Cys C-based estimated GFR in the DE group were also significantly lower than that in the NE group at all three time points (24h: 140.33 mL/min vs 161.39 mL/min, P£¼0.05; 48h: 141.69 mL/min vs 159.04 mL/min, P£¼0.05; 72h: 138.33 mL/min vs 152.31 mL/min, P£¼0.05). However, the Cys C based estimated GFR in the DE group were similar to that in the NE group at all three time points (24h: 95.95 mL/min vs 101.31 mL/min, P = 0.183; 48h: 97.49 mL/min vs 98.64 mL/min, P = 0.763; 72h: 95.30 mL/min vs 99.06 mL/min, P = 0.375). Conclusions: Baseline Cys C alone is unable to predict MTX elimination in patients with OS.[Table: see text]
Prognostic value of vessels encapsulating tumor clusters (VETC) in sarcoma.
Authors: Renne Salvatore Lorenzo , Tassan-Mangina Marta , Santori Ilaria , Ruspi Laura , Sicoli Federico , Colombo Piergiuseppe , Cammelli Manuela , Quagliuolo Vittorio , Terracciano Luigi , Di Tommaso Luca , Cananzi Ferdinando
Published: June 2022

e23523

Background: How sarcoma metastasize is unknown. VETC has been described as an epithelial-to-mesenchymal-transition independent process of metastasis: endothelium covers neoplastic clusters allowing tumor dissemination. It has also been shown to be a predictive of tyrosine kinase inhibitors (TKI) response. The objectives of the present study are: 1) to assess the presence of VETC in sarcoma; 2) to model its prognostic role. Methods: The study was retrospective. We selected 54 cases of sarcomas (6 DDLPS, 10 GIST, 6 retroperitoneal LMS, 9 MLPS, 8 MPNST, 10 SFT, 5 UPS); of them 31 were metastatic (M1 group), 23 were not (M0 group, defined as least 5 years of negative follow-up). High risk GIST and SFT, and grade 3 FNCLCC were considered high grade. VETC was assessed with CD31 immunohistochemistry and defined as a continuous endothelial lining around tumor clusters. We used Bayesian probabilistic modeling to detect small effects and multilevel hierarchical modeling to reduce overfitting. Models were fit using Stan and R. CI were computed with the HPDI method for 89%. The whole posterior probability (PP) was used for calculations. Results: The two groups (M0 & M1) were substantially homogeneous: the CI of the contrast PP (CPP) included 0 in each histology for sex, age, size, and grade; VETC was more expressed in M1 SFT cases with almost all the CPP mass above the 0. Also, UPS and GIST showed VETC to be more present in metastatic diseases with 79% and 78% respectively of the CPP mass above 0 (see table). Metastasis free survival (MFS) analysis showed that VETC in SFT and UPS with a coefficient of 2.42 (CI 0.73 – 4.65) and 1.94 (CI 0.16 – 3.67); for the latter the median was reached with a PP density of median MFS of 65 months (mo) (standard deviation, SD: 74 mo) for VETC- Vs 11 mo (SD: 14 mo) for VETC+. Similarly, disease specific survival analysis showed – in SFT and UPS – that VETC was negatively associated with prognosis with coefficients of 1.24 and 2.34; however the CI covered slightly the 0 (-0.54 – 3.96 and -0.09 – 5.73, respectively). Conclusions: We found VETC in sarcoma and highlighted its prognostic role in SFT and UPS. [Table: see text]
Quality of life in caregivers of cancer patients in Colombia.
Authors: Castro-Martinez Daniela A. , Ruiz-Cabrera Laura X. , Mariño-Ramírez Leonardo , Idrobo Henry
Published: June 2022

e24000

Background: It is well known that improvements in caregiver quality of life (QOL) could significantly impact the clinical outcome of cancer patients, which is why it is essential to study this population. Caregivers have extensive responsibilities, making them vulnerable to emotional, physical, social, and financial distress. Evaluation of cancer patient caregiver QOL in Latin America and validation of QOL metrics, such as the Caregiver Quality of Life Index-Cancer (CQOLC), has not yet been done in large populations. We sought to evaluate these characteristics in 5 regions in Colombia. Methods: Cancer patients (n = 165) receiving active treatment and their respective adult caregivers were evaluated. Both caregivers and patients completed a sociodemographic survey, along with the CQOLC, which was translated to Colombian Spanish and validated in a pilot cohort. CQOLC is composed of five subcategories with a total max score of 140. Higher scores are associated with better QOL. Internal consistency was determined by Cronbach’s alpha. Results: The patient’s median age was 63 years (58.8% females). The primary cancer diagnoses were breast, cervical, and lung cancer, with a median ECOG-PS of 1. 6.3% of patients did not have a caregiver, and their responses were also evaluated. The median caregiver age was 53 years (range 19-75 years, 60% females). 4.7% of caregivers were unemployed, and 59% reported financial or psychological distress. 93.8% of caregivers were family members, most frequently spouses or children. The median CQOLC score was 90 ± 15.2. The median score for each of the five subcategories “burden,” “disruptiveness,” “positive adaption,” “financial concern,” and “other” were as follows: 2, 3, 3, 3, and 3 (max score of 4). Conclusions: Most patients and caregivers were interested in participating in the study and reported no issues comprehending or answering the questions. This suggests no potential problems adapting the Spanish-translated CQOLC to future studies. Despite most caregivers reporting financial distress and low family income status, their overall CQOLC scores were relatively high compared to developing countries like the USA, potentially due to cross-cultural differences. The higher median score in the “disruptiveness” category suggests that Colombian caregivers feel strongly committed to caregiving and do not feel this activity interferes significantly with their daily life, possibly related to a sense of family responsibility and moral duty. However, the lower median score in the “burden” category indicates that caregivers feel a heavy emotional toll as a result of their caregiving role. Our results can help identify caregiver QOL areas of improvement, where government policies can be implemented to benefit both the caregiver and the patient.Keywords: caregiver burden, quality of life, Colombia, validation, CQOLC, cancer patients
Need of pretreatment support of breast cancer patient caregivers compared to patients.
Authors: Kim Terri , Lee Dasom , Lee Hajin , Ock Chan-Young , Yang Hyungkook , Kim Ki Hwan , Shin Jane , Paek Anthony S , Park Jamie Eunsu , Lee Yerin , Son Hyejin , Choi Hongseok , Shim Hyemin
Published: June 2022

e24001

Background: Through this research, Lunit is seeking to understand how the needs of breast cancer patient caregivers differ from those of patients. Moreover, we seek to gain insights into the potential impact of fulfilling such needs for caregivers through remote nurse support that can provide evidence-based information. Methods: We asked 330 breast cancer patients and 53 caregivers to participate in an online survey in Korea from 10/2021- 11/2021 to understand various needs throughout their cancer journey. Eight breast cancer patients and caregivers asked 25 questions through a remote nurse support model. Interactions took place either via phone or text, starting 12/20/2021 and is ongoing. The answers to asked questions were drafted by nurses and reviewed by a team of medical doctors to ensure delivery of clinically sound information. Results: While the top areas needing support during the entire cancer journey (prior, during, post treatment) were generally consistent for both caregivers and patients, caregivers showed a pronounced need for support that would help make treatment decisions specifically during the pre-treatment phase. (See table below) This difference was also reflected in the distribution of questions asked during the remote nurse support service. Caregivers asked questions about treatment options that required significant clinical knowledge to answer. In contrast, questions from patients were concentrated in understanding their cancer and in seeking dietary recommendations to keep their cancer at bay. Conclusions: We observed early evidence that improving access to evidence-based information for caregivers will not only contribute to improved outcomes for the patient but also have a positive impact on the well-being of caregivers, which again in turn is expected to have a positive impact on the patient.[Table: see text]
Unmet psycho-social needs of parents of children who die from cancer.
Authors: Josephs Isabel , Welch Jennifer JG , Mannix Margaret
Published: June 2022

e24005

Background: Cancer is the leading disease-related cause of death for children in the United States, but there is limited data on the needs of caregivers who have lost a child to cancer, and few evidence-based bereavement interventions exist. Parents whose children die from cancer have increased rates of depression, anxiety, and health problems. Prior studies have shown that bereaved parents desire continued contact with their child’s medical team and to connect with parents who have had similar losses. Methods: This is a cross sectional survey of primary caregivers of pediatric patients who died from cancer and were cared for at a moderate size pediatric oncology program (50 new diagnoses per year) from 2010 to 2020. Participation was solicited by mail in English and Spanish. Research packets contained five surveys: Demographic Survey, The Needs Assessment for Family Caregivers Bereaved to Cancer, Quality of Life Survey (SF-36), Brief Grief Assessment, and Social Support Questionnaire (SSQ-6). Interested subjects also participated in a semi-structured, in-depth qualitative interview. Results: One hundred six potentially eligible families were identified. 27 families consented, 10 were without a known address, and 2 opted out. Twenty research packets and 9 interviews were completed, representing 19% of the population of interest and 23% of the invited population. The sample was diverse in gender, age, income, and education level, but not race. The greatest unmet needs were finding meaning in the death, personal wellness, and social activities. Caregivers reported good physical functioning but poor emotional well-being and fatigue. Complicated grief was most profound in the interference (grief interfering with life) and intrusion (images and thoughts of the child) domains. Quantity of social support correlated with satisfaction with social support (P = 0.02). Bereaved parents with greater unmet needs were found to have poorer quality of life in the following domains: energy/fatigue (P = 0.005), role limitations due to emotional problems (P = 0.01), pain (P = 0.01), and emotional well-being (P = 0.02). Greater unmet needs did not correlate to more complicated grief (P = 0.30) or satisfaction with social support (P = 0.08). Interview themes elicited were inadequate current bereavement services, necessary support for siblings, desired contact with the medical team, and connections to other bereaved caregivers. Conclusions: Findings support the need for implementation of more intensive evidence-based bereavement programs for families of children who died from cancer. The data suggests that interventions targeting emotional well-being and increased social supports, in the form of connections to the medical team and other bereaved families, will be the most efficacious in mitigating poor bereavement-related outcomes.
Pilot study of the implementation of G8 screening tool, cognitive screening assessment and chemotherapy toxicity assessment in older adults with cancer in a tertiary University Hospital in Ireland.
Authors: AlSendi Maha , Flynn Calvin , Khan Muhammad Raheel , Selvadurai Paul , Crown John , McDermott Raymond S. , Walshe Janice Maria , Fennelly David William , Hanrahan Emer O. , Doherty Mark , Higgins Michaela Jane
Published: June 2022

e24019

Background: 11% of Ireland’s population is above the age of 65. This is projected to double to 1.4 million by 2040 corresponding to doubling of cancer cases. Clinical trials often exclude patients (pts) ≥70; therefore, it can be challenging to apply evidence based treatment (tx) to this population. Data from the National Cancer Registry of Ireland suggests under tx of older patients (pts). Comprehensive Geriatric assessment (CGA) is recommended by the National Comprehensive Cancer Network (NCCN) and the International Society of Geriatric Oncology (SIOG). In practice, CGA is limited by time constraints, lack of resources and expert interpretation. Geriatric screening tools can help identify frail pts who are most likely to benefit from CGA. The primary objective of this pilot study was to establish the prevalence of frailty (assessed by G8), presence of cognitive impairment (assessed by Mini-Cog), and risk of chemo-toxicity (assessed by Chemo-Toxicity Calculator) among pts ≥ 65 years (yrs) starting systemic anti-cancer tx. Methods: Pts ≥65yrs starting new systemic anticancer tx were identified between 1st of December 2020 to 31ST of September 2021 in St. Vincent’s University Hospital. Verbal consent was obtained. Printed versions of the G8 screening tool and Mini-Cog were used. CARG chemo-toxicity score was conducted online ( www.mycarg.org/tools ). .The assessment was conducted by consultants, specialist registrars and registrars. Data including pts’ age, type of malignancy, stage of cancer, and planned treatment were recorded. Analysis was conducted by SPSS statistical software, V.25(SPSS Institute, IBM Corp., 2017). Results: We identified 56 pts ≥65 years.27 (48.1%) were females and 29 (50.8%) were males. The majority of treated pts, N = 33 (58.1%) had metastatic cancer. The median G8 score was 12 (IQR 9.6-14). 83.9% of pts had a G8 score ≤14. Mini-Cog was found to be positive in 11 pts (19.6%). The median CARG score was 7 (IQR 6-11) and the median risk of toxicity 51% (IQR 44-78%). Of these, 44 (78.2%) received chemotherapy and 12 pts (21.4%) received non-chemotherapy systemic tx. In multi-variate analyses, age, type of cancer, planned treatment, and stage of disease did not impact G8, Min-cog, and CARG scores. Conclusions: In this single center study of elderly pts, more than 80% of pts had a positive G8 score representing a need for formal CGA assessment. The risk of toxicity was substantial with almost 50% risk of grade ≥ 3 toxicity in this cohort. Chronological age was not found to negatively impact patient’s frailty, cognition, or risk of toxicity. Interpretation of this pilot study is limited by small sample size, possible inter-operator variability, and lack of self-reported assessment.