bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful allografting for relapsing pediatric ALL: The results of two decades.
Authors: Zulfikar O. Bulent , Koc Basak
Published: June 2021

e22000

Background: The prognosis of children and adolescents with acute lymphoblastic leukemia (ALL) has dramatically improved. This success is associated with both by multiagent chemotherapy regimens and by definition of clinical, biological and treatment response that allow the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). In treatment of relapsed and resistance ALL, allogeneic HSCT continues to play a major curative role. In the present study, we desciribed the patients who underwent HSCT in our clinic in the last 21 years. Methods: From 1999 to 2020, 147 patients who diagnosed with ALL and treated with the COG protocols at the Istanbul University Oncology Institute were retrospectively reviewed and 17 of them relapsed. HSCT was applied 7 of the relapsed cases and also 3 resistant cases who had suitable matched donors. The demographic features, laboratory findings and treatment responses of 10 patients were recorded from the patients’ medical records. Results: All 10 patients were B-ALL with median diagnosis age of 79.5 months (range: 32-195) and 5 were male. Characteristics of patients given in Table 1. HSCT was performed due to late relaps in 7 patients. Three of the 7 relaps were only bone marrow and other 4 had combined. Patient #2 had both breast, conjunctiva and bone marrow for the 1st relaps and only conjunctiva for the 2nd one and this patient had also t(9;22) in the 1st relaps. Patient #3 had bone marrow+central nervous system relaps and patient #7 had bone marrow for the 1st relaps and testis and bone marrow for the 2nd one. Other 3 had poor response to treatment and Minimal Residual Disease (MRD) was high in End of Introduction (EoI) and End of Consolidation (EoC)). All patients had allogeneic HSCT and 8 are alive. Conclusions: HSCT remains the standard-of-care treatment for ALL patients who carry high-risk features predicting leukemia recurrence and for those experiencing high-risk first relapse or multiple relapses. Additionally, defining the indications of HSCT are dynamic and it could change according to treatment options as well as new molecular and biological findings. It is important to identify the patients who have high relapse risk and HSCT should have priority in patients whom MRD is high in EoI and EoC.[Table: see text]
Comprehensive genomic and transcriptomic profiling of pediatric malignancies using the Tempus xT Next-Generation Sequencing Assay to identify clinically meaningful alterations.
Authors: Toll Stephanie , Kwiatkowska-Piwowarczyk Aneta , Schaeffer Jeff , Schwarzbach Anna Ewa , Thomas Stefanie Marie , Kaneva Kristiyana
Published: June 2021

e22002

Background: Our understanding of the genomic makeup of childhood cancers has accelerated over the past decade largely due to next-generation sequencing (NGS) utilized to identify genetic drivers, aid diagnostics and risk stratification, and detect therapeutic targets. Here, we present the genomic and transcriptomic landscape of pediatric malignancies tested with a broad NGS panel at a large commercial CLIA/CAP laboratory, Tempus Labs. Methods: We used the Tempus LENS platform to analyze DNA- and RNA-seq data from a cohort of 150 de-identified records of patients with pediatric cancer aged 0 to 18 years who underwent NGS with the Tempus xT platform. Results: The cohort included 139 solid tumors, 46 of which were central nervous system (CNS) tumors, and 11 hematologic malignancies. A total of 115 samples (77%) had at least one clinically meaningful pathogenic somatic variant detected, with TP53 variants being the most common (n=26; 17.3%). Gene fusions, most commonly EWSR1-FLI1 and KIAA1549-BRAF, were observed in 31 cases (20.7%). Matched tumor/normal testing revealed at least one incidental pathogenic germline variant in six patient records, with two cases harboring two distinct variants. Four cases had tumor mutational burdens (TMBs) greater than 10 mutations/megabase, including two that also exhibited high microsatellite instability (MSI). Conclusions: The Tempus xT tumor/normal-matched platform detects clinically meaningful genomic alterations in pediatric cancers important for diagnosis, prognosis, therapeutic target identification, and incidental germline findings. We continue to accumulate and structure data to meet the need for a large, accessible pediatric cancer clinical and molecular dataset. [Table: see text]
Clinical value of Next Generation Sequencing in Chinese pediatric soft tissue sarcoma: A multicenter data.
Authors: Lu Suying , Sun Feifei , Yuan Xiuli , Huang Junting , Wang Juan , Guo Haixia , Zhen Zijun , Zhu Jia , Sun Xiaofei , Que Yi , Zhang Lian , Wang Chen , Wang Dan , Zhang Yizhuo
Published: June 2021

e22005

Background: To uncover the genomic characteristics as well as to, within the scope of pediatric soft tissue sarcoma (psts), assess the clinical value of Next Generation Sequencing (NGS), we present the first report of genomic profiles in Chinese psts. Methods: Tumor tissue, as well as peripheral blood from 41 psts patients, were collected in Sun Yat-Sen University Cancer Center, Shenzhen Children's Hospital and Nanfang Hospital. Samples were sequenced in a CLIA/CAP-accredited laboratory with a targeted NGS panel (Onco PanScan plus; GenetronHealth.inc) consisted of all exons of 831 cancer-related genes and mRNA of 395 genes. Bioinformatics analysis was conducted using a build-in computational pipeline. Results: A total of 41 samples consisted of five major histology types including rhabdomyosarcoma (RMS) (n = 11), fibrosarcoma (n = 4), Ewing's sarcoma (n = 4), INI1-deficient mesenchymal tumor (n = 4), and other mesenchymal tumors (n = 18). All patients were with doubtful diagnosis,advanced, relapsed, or refractory sarcoma, of which 85% samples were from initial diagnoses. In totally, we identified 116 somatic aberrations and 4 pathogenic or likely pathogenic germline mutations, with a median tumor mutational burden of 0.47/Mb (0–6.57). Genomic analysis revealed frequent alterations in TP53 (10%), NTRK fusion (10%), PAX3/7 fusion (8%), and ARID1A (7%). ARID1A (18% vs. 0%) and TP53 (18% vs. 3%) mutations were found with higher frequency compared with pediatric RMS data in a previous study (Jack et al 2014). ARID1A mutation was only reported in a RMS case report (Cramer et al 2017). Furthermore, the mutation of ARID1A potentially match PARP inhibitors, which may provide more therapeutic options. In addition, NGS aided pathologic diagnosis in 63% (26/41) patients. The proportion of confirmed diagnosis, differential diagnosis, and the excluded diagnosis was 41.5%, 12.2%, and 9.7%, respectively. Druggable alterations were detected in 39% patients (Table). Four patients received the treatment recommended by genetic testing, three of them with NTRK fusion were recruited in a matched clinical trial could be evaluated and showed partial remission upon Larotrectinib. Conclusions: We discovered ARID1A mutations, which potentially sensitive to PARP-inhibition, were at a higher incidence in Chinese RMS. This study demonstrated the value of NGS test in guiding the clinical practice of psts in Chinese population. [Table: see text]
Localized osteosarcoma analysis of very poor responders subgroup (Huvos I).
Authors: Longhi Alessandra , Carella Antonio , Broll Valquiria , Palmerini Emanuela , Cesari Marilena , Paioli Anna , Hakim Rossella , Gambarotti Marco , Righi Alberto
Published: June 2021

e22010

Background: Osteosarcoma is a malignant primitive bone tumor whose prognosis is not changed since 4 decades, after the introduction of neoadjuvant chemotherapy with Methotrexate, Cisplatin, Doxorubicine and Ifosfamide. Histologic response to preoperative chemotherapy is a significant prognostic factor. Huvos I (necrosis ≤ 50%) has worst prognosis . Previous studies reported a 3 years EFS of this Huvos I patients around 25% (Tsuda Y,2020). In order to evaluate if survival has changed in recent years in this unfavourable prognostic group we evaluated the outcome of osteosarcoma patients with Huvos I. Methods: from our Pathology archieves we retrieved all cases of localized osteosarcoma treated at Rizzoli with neoadjuvant chemotherapy who reported an histologic necrosis below or equal to 50% (Huvos I grade) after preoperative chemotherapy MAP (Ethical C. Approval 917/2020/Oss/IOR). Results: from 2003 to 2019 we had 70 cases of localized osteosarcoma with Huvos I necrosis after neoadjuvant chemotherapy ( MAP in 66 and MAPI in 4) evaluable. Median age 21,5 (3-70); M:F = 44:26. 10/70 had axial localization vs extremity(60), subhistotype distribution:46 osteoblastic,11 chondroblastic, 7 fibroblastic, 5 teleangectatic, one not classified. In 24 cases PgP was available(14 PgP positive). With a median follow up of 86.7 ms (IQR 41-136) 43/70 had already relapsed. The median EFS was 25 ms (95% CI 15-42) and the 3 yrs EFS was 40.6% (95% CI 29-52). The 3 yrs overall survival was 80% (95%CI 68-88) and median OS was not reached. Axial tumor site was associated with significant inferior EFS (P = .004). Conclusions: these data confirm the poor prognosis of patients with necrosis ≤50% and the need of new drugs to improve their survival in this sub-group.
Germinal mutations landscape, which is responsible for cancer predisposition in multinational Republic of Bashkortostan.
Authors: Sultanbaev Alexnder Valerievich , Lipatov Oleg , Sultanbaeva Nadezda , Izmailov Adel , Nasretdinov Ainur , Musin Shamil , Menshikov Konstantin , Pushkarev Vasiliy , Pushkarev Alexey
Published: June 2021

e22504

Background: In oncology hereditary forms of malignant neoplasms occupy a special position due to the frequent cases at a young age and poor prognostic factors. The aim of this work is to determine in cancer patients germinal mutations which are responsible for cancer predisposition. Methods: The study included patients with burdened family history or those with a manifestation of malignant neoplasm at a young age residing on the territory of multinational Republic of Bashkortostan. The patients were diagnosed with one of these diseases: breast cancer, prostate cancer, pancreatic cancer, gastric cancer, colon cancer. The study is based on analyses of the molecular genetic blood testing n cancer patients using real-time polymerase chain reaction (PCR) for detection of 8 widely spread mutations among Russian population: in BRCA 1 gene were detected such mutations as 185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, 2080delA; in gene BRCA 2 - 6174delT. Blood samples of the rest amount of patients which proved no mutations by PCR method was tested by the “next-generation” sequencing method (NGS). Results: The results of the study showed territorial features of presence of germinal mutations of Russian multinational region. The results of the study aimed to reveal the spectrum and frequency of gene mutations characteristic for the particular region: BRCA 1 - c.5266dupC, c.3143delG, c.5161C>T, c.5382 insC, c.3819delGTAAA, c.300T>G, c.5136G>A, 185delAG, 4153delA, 2080delA; BRCA 2 - c.6621_6622del, с.39-1_39delGA, c.961_962insAA; CHEK2 - c.470T>C, c.444+1G>A; PALB2 - c.1592delT; RAD50 - c.2157delA; MLH1 - c.1637A>G; MSH6 - c.2554_2556del; STK11 - c.368A>G; MSH2 - c.815C>T. According to the mutation detection the patient consulted a geneticist for making a genealogic tree for future molecular genetics exam. Hereinafter the control group included relatives of patients who remain potential carriers of pathogenic mutations of the proband using Sanger sequencing method. When penetrate mutations are identified in healthy population, a set of measures is taken to prevent and early diagnose malignant tumors. Conclusions: The results of the study showed features of presence of each detected mutation which is characteristic for south-eastern part of the Russian multinational region. This study plays an important role in the process of optimization of screening of germinal mutation carriers among healthy population and as a result it helps to conduct prophylactic measures to early diagnose malignant neoplasms.
Clinical and genetic characterization of cancer patients with multiple germline variants.
Authors: Zheng Hong , Gao Min , Gao Weijiao , Zhang Nan , Wang Hongguo , Song Nan , Zhang Naiyi , Wang Wei , Li Qian , Yuan Mingming , Chen Rongrong , Xia Xuefeng , Gao Yunong
Published: June 2021

e22523

Background: Hereditary tumors are generally monogenic diseases with autosomal dominant inheritance. However, we noticed that some individuals may harbor ≥2 germline mutations in one or multiple genes, which remains to be explored. Methods: Genetic mutations were reviewed in more than 50,000 cancer patients who underwent hybridization capture based next-generation sequencing (NGS). Germline variants were interpreted following ACMG guideline, and only pathogenic and likely pathogenic variants were included in this study. Results: Multiple germline variants were identified in 42 individuals with the detection rate of 0.075%. The median age at diagnosis was 48 years (range 31-73). Two thirds of patients were female and 26.2% of patients has cancer family history. Prostate cancer is the most common cancer type (0.6%, 2/332), followed by carcinomas of ovarian or fallopian tube (0.48%, 7/1461), breast (0.24%, 8/3302), pancreas (0.2%, 2/982) and so on. Surprisingly, 7 patients with lung cancer also harbored ≥2 germline mutations (0.02%). Most of these germline variants affected DNA damage repair pathways [75.6% homologous recombination repair (HR), 8.1% mismatch repair (MMR), 1.2% base excision repair (BER)]. Four patients had two germline variants identified on a single gene (2 ATM, 1 BRCA1, 1 BRCA2). Three variants were identified in 2 patients, and 2 variants were identified in the remaining 36 patients. Two or more germline variants in HRR pathway were identified in 64.3% of patients, among which 18.5% patients had BRCA1+ BRCA2 double variants. The efficacy of poly ADP-ribose polymerase inhibitors (PARPi) in this specific population should raise concern. Besides, double variants in HRR and MMR pathway were found in 5 patients, which suggested the potential benefit of immunotherapy and PARPi combination therapy. Conclusions: In addition to identify variants contributing to the personal and family cancer history, NGS can accidentally identify germline variants that may suggest the susceptibility of other hereditary tumors. Multiple variants on HRR or MMR genes may have important implications for the treatment strategy for these patients.
Multiple primary malignancies among patients with advanced melanoma.
Authors: Ebia Matthew Isaiah , In Gino Kim
Published: June 2021

e22531

Background: Multiple primary malignancies (MPMs) describe two or more primary tumors arising in a synchronous or metachronous manner in the same individual. Patients with a primary cutaneous melanoma are at high risk of developing MPMs. While melanoma and other tumors are highly immunogenic and may cause immune suppression at the individual level, the molecular underpinnings of immune suppression among patients with MPMs remains to be elucidated. Here, we attempt to describe this rare, but unique group of patients who have both advanced melanoma and at least one other primary malignancy. Methods: Patients with advanced melanoma (stage III-IV disease) and at least one other non-melanoma cancer were identified. Synchronous tumors were defined as those occurring within 6 months of the first primary cancer. Metachronous tumors were defined as those occurring at least 6 months after the first primary cancer. Patients who had melanoma first, before a second cancer, and those who had a prior other cancer first, followed by melanoma were included. Overall survival (OS) describes the time from diagnosis of the first primary cancer to death due to any cause. Two-sample t-tests were used to compare OS among these groups with statistical significance if p < 0.05. Results: Eleven patients with MPMs including advanced melanoma were identified. Advanced melanoma was the first primary tumor in 5 patients and the second primary in 6 patients. A synchronous second primary was observed in 4 patients, whereas a metachronous second primary was observed in 7 patients. The median time between the diagnosis of the first primary cancer to the second primary was 21 months and the median time between the diagnosis of a second primary to a third primary was also 21 months. The median OS for all patients was 73 months. The median OS for synchronous MPMs and metachronous MPMs were 64.5 months and 82 months, respectively (p = 0.013). For patients with melanoma as the first primary cancer, the median OS was 73 months, compared to 87 months when melanoma was the second primary cancer (p = 0.785). Among all 11 patients, two are deceased, while the remaining patients are under surveillance. Among the remaining 9 patients, 100% have no evidence of disease with respect to melanoma. Conclusions: Despite the favorable outcomes from early detection and the advanced treatments available such as immunotherapy, a robust treatment plan should be in place when advanced melanoma is diagnosed as a synchronous tumor or second primary cancer. Further research is warranted since there are no guidelines available for the treatment of MPMs.
Internal medicine residents’ awareness on cancer survivorship care plan: A cross sectional study.
Authors: Riano Ivy , Pomares-Millan Hugo , Prasongdee Klaorat , Park Robin , Duma Narjust
Published: June 2021

e23011

Background: Survivorship care plans (SCPs) is recommended as a tool for communication between oncologists and primary care physicians. According to the Institute of Medicine, it is necessary to lead a cultural shift to provide SCPs to all cancer survivors to improve the transition from the oncology clinic to primary care practices. Studies suggest residency training curriculums for internal medicine (IM) are lacking education about cancer survivorship and SCPs. We aimed to assess the awareness of trainees toward SCPs. Methods: A survey was distributed to IM trainees in an outpatient setting. We stratified the descriptive analyses by program type (transitional [TY] and categorical [CT] trainees) and year of training. Differences in the proportions were tested appropriately. Analyses were conducted in R v3.6.2. Results: 37 trainees were interviewed; 32.4% were TY and 67.6% CT trainees. A 54% were PGY-1, 21.6% PGY-2, and 24.3% PGY-3. None of the trainees reported following a SCP for cancer-free patients nor to use SCP as a source to obtain cancer-related information. 78.3% and 92.6% reported that they were not taught during residency or medical school about SCPs, respectively. 84.8% informed that cancer-related information was inaccessible during the encounter with patients; sources cancer diagnosis and treatment information included: patients/family members (97.3%), outside records (83.8%), and oncology notes (86.5%). By program type, there was a statistically significant difference between TY v. CT groups (p = 0.017) regarding how often cancer-related issues were discussed with patients; the TY group mainly reported ‘Not at all’ whether CT were more likely to engage in discussion about cancer. Differences in the trainees’ comfort level answering patients concerns about cancer recurrence were observed between TY v. CT trainees but was not statistically significant (p = 0.864). Most common barriers to discuss cancer history and/or SCP were insufficient information from patients (83.8%), perceived inaccuracy from patients’ information (81.1%), unclear if patient has a SCP (81.1%), lack of SCP in medical record (75.7%), and trainees’ low medical knowledge about side effects of cancer therapies (70.3%). Conclusions: The awareness of cancer SCP among the IM trainees is limited, and many have not accessed or received training in SCPs. Efforts intended to facilitate SCP use and educate residents about cancer survivorship may be effective to increase the comfort level of trainees managing the growing number of survivors and improve transition from oncology to primary care clinics.[Table: see text]
Phase II study of SM-88 in Ewing's and other sarcomas.
Authors: Chua Victoria S. , Chawla Sant P. , Zheng Kitty , Kim Ted , Del Priore Giuseppe , Kim Semmie
Published: June 2021

e23505

Background: Sarcomas are rare heterogeneous malignancies. Once recurrent, cure is uncommon. SM-88 (racemetyrosine) is an amino acid analogue with no known cross resistance to typical sarcoma regimens. Based on previous anecdotal experience in Ewing’s (EWS) we initiated a Phase 2 trial (HopES) in EWS and other sarcomas (Ss) after >1 prior systemic therapy. We now report preliminary data after having met prespecified continuation criteria. Methods: Open label prospective trial in 2 separate cohorts (EWS and Ss) of oral SM-88 used with MPS conditioning agents (SM-88 920 mg, methoxsalen 10 mg, phenytoin 50 mg, sirolimus 0.5 mg) all daily until progression. Results: As of Feb 5 2021, 10 pts with incurable sarcomas were enrolled; 4 had high risk but stable EWS. Average age 43.9 yrs (13–77); 70% white; 20% female. Median number of prior regimens 4 (1–9); 70% received prior RT; 50% prior surgery. Median time from initial diagnosis 39.5 months with 50% T2 (40% unknown), 30% M1 (30% unknown). Prespecified futility stopping was exceeded (i.e., >1 of first 5 subjects/cohort) upon achieving clinical benefit in each. Stable disease was achieved in 75.0% (6/8 with available data). Time on treatment (TTx) exceeded last known TTx in 80% (95% CI 44.4–97.5). Median SM-88 TTx was 4.9 vs 2.9 mo for prior TTx (logrank HR 0.53; p=0.12). One EWS subject had unresectable disease that became resectable, was completely resected, and remained disease-free for ≥ 6 months. Prior to SM-88, longest TTx was 12 mo (on IT*) and shortest TTx 1 mo (on IEV*) vs SM-88 TTx of 11.9 mo. An angiosarcoma subject had a 21% reduction in the sum of all target lesions and exceeded all prior TTx (including 8 mo on Ap/N* with 12+ mo duration of treatment of SM-88). There were no serious drug-related AEs. ECOG performance remained stable for all. Conclusions: SM-88 has exceeded pre-specified futility in both cohorts (EWS maintenance and Ss salvage). HopES continues to enroll toward the planned total of 12 subjects to more precisely define its benefit in this ultra-orphan, extremely recalcitrant disease. This trial now confirms the previously reported clinical utility of oral SM-88 in EWS and other high-risk sarcomas. Based on durable response (>6mo), SD and prolonged TTx, SM-88 warrants additional investigation in this setting. Clinical trial information: NCT03778996. [Table: see text]
Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors (GIST): A retrospective, multicenter, real-world study.
Authors: Nannini Margherita , Rizzo Alessandro , Nigro Maria Concetta , Vincenzi Bruno , Mazzocca Alessandro , Grignani Giovanni , Tolomeo Francesco , D'Ambrosio Lorenzo , Badalamenti Giuseppe , Bonasera Annalisa , Fumagalli Elena , Miliziano Daniela , Brunello Antonella , Chiusole Benedetta , Gasperoni Silvia , Novelli Marco , Pantaleo Maria A.
Published: June 2021

e23521

Background: Regorafenib (REG) is a multikinase inhibitor approved as third-line treatment in gastrointestinal stromal tumors (GIST). Although its proven activity, REG can present a relevant adverse profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract REG-related adverse events (AEs) and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of REG in metastatic GIST patients, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off schedule). Methods: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify GIST patients who had received REG from February 2013 to January 2021. The primary endpoint was Progression-Free Survival (PFS), with Overall Survival (OS) also assessed as secondary endpoint. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. The impact of variables on survival was assessed through univariate and multivariate analysis. Results: A total of 152 GIST patients (82 male and 70 female) were included and split in two groups on the basis of the REG treatment plan received (standard vs personalized). Among the 103 patients for whom the treatment was personalized (38 since the beginning and 65 during the treatment course), the main strategies adopted were the following: 120 mg/day d1-21 e28 (n = 56; 54.4%); 80 mg/day d1-21 e28 (n = 22; 21.4%); 160 mg/day d1-5 e7 (n = 13; 12.6%). At a median follow-up of 36.5 months, median Overall Survival (OS) was 16.6 months (95% CI 14.1-21.8) and 20.5 months (95% CI 15.0-25.4) in the standard-dose and the personalized schedule groups, respectively (HR 0.75; 95% CI 0.49-1.22; p = 0.16). Median Progression-Free Survival (PFS) was 5.6 months (95% CI 3.3-not reached) and 9.7 months (95% CI 7.9-14.5) in the same groups (HR 0.51; 95% CI 0.34-0.75; p = 0.00052). Conclusions: Despite the expected limits of a retrospective analysis, we confirm that REG personalized schedules are commonly adopted in everyday clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Based on these results, REG treatment optimization in GIST patients may represent the best strategy to maximize long-term therapy, preserving tolerability and quality of life.
A retrospective collection of diagnostic data from the desmoid tumor research foundation natural history study.
Authors: Lucas Amanda , Braggio Danielle , Hernandez Lynne , Mercier Kelly
Published: June 2021

e23549

Background: Desmoid tumors are a benign sarcoma diagnosed in 4-5 patients per million each year. The Desmoid Tumor Research Foundation (DTRF) launched the patient registry and natural history study (NHS) in 2017. This is a retrospective analysis of diagnostic data collected, tumor location, rates of misdiagnosis, how genetics testing is being incorporated into clinical practice, and additional clinical trial participation. Methods: The NHS launched September 2017 and contains 15 surveys covering diagnostics, disease, treatment, care management, and quality of life. Current reporting as of December 31, 2020, contains 619 participants or legally authorized representatives for which a subset have completed the surveys on desmoid tumor diagnoses. Results: Survey analysis documents that the most prevalent tumor locations were intra-abdominal 35.5% (220), joint / extremities 21.2% (131), and chest wall 14.7% (91). The majority of participants, 68.2%, reported that they had unifocal tumors (199/292), 19.5% reported that they had multifocal desmoid tumors (57). Biopsy procedures were the primary method of diagnosis according to 57.2% (167/292) of the participants, with needle biopsy comprising 19.8% (33/167). Biopsy as the primary method of diagnosis was most prevalent in tumors of the head and neck (18/26, 69.2%), chest wall (32/47, 68.1%) joint /extremities (50/90, 55.6%), and abdominal tumors (27/51, 52.9%). Additionally, imaging methods (CT, MRI) were the primary method of diagnosis in 22.6% (66/292) and surgical resection 14.4% (42/292). Misdiagnosis is common for this tumor type, as 41.0% (119/290) participants reported an incorrect initial diagnosis. The reported incorrect diagnoses are described in the table. Genetic testing is not standard of care for desmoid tumors but is increasing in practice. A total of 78 participants (28%) of 282 participants report they had genetic testing (germline or somatic) of their tumor tissue. The majority of those participants, 65.4% (51/78), reported having Familial Adenomatous Polyposis (FAP). Of the participants that had genetic testing, 89.0% live in the United States. 10.5% of participants (37/353) have reported having participated in clinical trials. The majority of participants (317/368, 86.1%) are willing to participate in other studies in the future, with 77.4% (285/368) willing to donate specimens for biomarker studies. Conclusions: Participants with desmoid tumors report many methods of diagnosis for their diverse tumor locations, high rates of misdiagnosis, and increased rates of genetic mutation testing. Data collection through the DTRF NHS is ongoing.[Table: see text]
A survey study of knowledge, attitude, and practice regarding oncofertility among health professionals in Uruguay.
Authors: Kimelman Dana , Palleiro Maria Clara Rodriguez , Boada Matilde
Published: June 2021

e24041

Background: Oncofertility is a field dedicated to preserve fertility of children, adolescents, and young cancer patients'. For young cancer patients, fertility preservation (FP) has become an important concern that needs to be addressed before cancer treatment. This study aimed to evaluate the general knowledge, attitudes, and practice towards FP and pregnancy-related issues of health care professionals in Uruguay. Methods: We conducted an online survey distributed to physicians from multidisciplinary areas (Oncology, Radiotherapy, Hematology, Pediatric hematology-oncology, Gynecology, Urology) involved in daily medical care to young cancer patients. Results: 208 physicians from 16 geographical regions completed the survey. 53 % of the subjects were less than 40 years old, and 77.7% identified themselves as women. Most of the responders (99 %) agreed that FP counseling should be part of cancer treatment; however, only 49 % discusses FP and refers their patients in their daily clinical practice. Regarding referral of patients to an Oncofertility specialist, 36% do it occasionally, and 15% have never referred. Half of the responders (50%) stated that they know the available FP options for young cancer patients, 49% have an idea, and 1% are not aware. 37 % of participants consider that FP treatments would delay cancer treatment initiation, impacting their attitude towards FP recommendation and referral. Regarding FP coverage, 51.7 % were not aware of financial coverage for fertility preservation treatments availableness. 57% of physicians directly involved in breast cancer (BC) care agreed with the statement that oocyte cryopreservation is safe in BC patients with positive hormonal receptors, 35% are not sure, and 8% believe it is not safe, 46% believe pregnancy is safe after BC, 34% is not sure, while 20% consider it is unsafe. Conclusions: This study demonstrates the need to increase FP awareness in Uruguayan health care professionals. Moreover, several misconceptions on FP and pregnancy-related issues in BC patients have been identified. Focused research and education to improve physicians' knowledge and adherence to available international guidelines are urgently required to improve the care of young cancer patients who desire future fertility. Key Words: Oncofertility, fertility preservation, oocyte cryopreservation, breast cancer, pregnancy.
Cardiac risk factors and adverse events among patients receiving first-line CLL treatment in a real-world community practice setting.
Authors: Mato Anthony R. , Tang Boxiong , Azmi Soraya , Yang Keri , Wallis Nicola , Stern Jennifer C , Hedrick Eric , Huang Jane , Sharman Jeff Porter
Published: June 2021

e24044

Background: First-line (1L) ibrutinib monotherapy (IM) is commonly prescribed for CLL but is associated with cardiovascular adverse events (CVAEs) that may lead to discontinuation. Existing data are largely from clinical trials (both 1L and relapsed/refractory), and real-world evidence is limited. The aim of this study was to compare baseline cardiac risk factors and CVAEs in patients (pts) receiving 1L IM vs intensive therapy (IT; aggressive, less tolerable, majority were bendamustine plus anti-CD20 antibody) or non-intensive therapy (NIT; less aggressive, more tolerable, majority were anti-CD20 antibody alone). Methods: We compared 3 treatment groups (IM, IT, and NIT) in terms of clinical characteristics, baseline CV risk factors, and subsequent CVAEs. Pts were selected from the Flatiron Health database based on the following criteria: aged ≥18 years, CLL/SLL diagnosis, had ≥2 clinic encounters, and initiated 1L treatment between 1/1/2016 and 12/31/2019. Baseline characteristics and subsequent CVAEs were descriptively compared between IM and IT/NIT groups; significance was assumed if p < 0.05. Results: Data on 515 pts were included (IM, 191; IT, 195; NIT, 129). Age at baseline differed significantly between the IM group (mean 71.2 years) and the other 2 groups (IT, 66.2 years; NIT, 74.5 years). The proportion of del(17p) was significantly higher in the IM group vs IT/NIT groups (IM, 26.7%; IT, 3.6%; NIT, 3.1%). Significant differences between IM and IT groups were seen in baseline ECOG (ECOG 0: IM, 28.8%; IT, 43.1%), diabetes mellitus (IM, 56.0%; IT, 44.1%), and hypercholesterolemia (IM, 68.6%; IT, 58.0%). Significant differences between IM and NIT groups were seen in baseline angina/coronary revascularization (2.6% vs 8.5%), atrial fibrillation/atrial flutter (AF; 14.1% vs 26.4%), and cerebrovascular disease (8.9% vs 20.2%). The rate of any CVAE was significantly higher in IM (35.6%) vs IT and NIT groups (IT, 20.0%; NIT, 24.8%) (Table). For IM vs IT treated pts, significant differences were observed in new or worsening (N/W) AF (11.5% vs 5.1%), other arrhythmias (9.4% vs 3.1), and hypertension (HTN; 20.4% vs 8.2%). Conclusions: This is one of the first real-world studies focused specifically on 1L CLL to describe baseline CV risk factors and compare CVAE events in CLL pts treated with IM as compared to IT or NIT. Results show higher CVAE rates of AF, other arrhythmias, and HTN for IM vs IT. [Table: see text]
Visual dysfunction in a mouse model of chemotherapy-related neurotoxicity.
Authors: Anderson David , Kedar Sachin , Van Hook Matthew J , Ghate Deepta A , Fan Shan , Smith Jennie C , Goeser Toni L , Reid Lisa M , Rishi Ekta , Haney Staci L , Holstein Sarah A.
Published: June 2021

e24059

Background: Chemotherapy-related neurotoxicity (CRNT) poses challenges to long-term outcomes of cancer survivors. Visual function remains relatively unexplored in CRNT. Preliminary clinical work from our group suggests contrast sensitivity may be impaired in patients receiving chemotherapy. Here, we sought to isolate effects of chemotherapy on visual dysfunction in a mouse model. Methods: 10-week old C57BL/6J mice received either 4, 7, or 10 weekly intraperitoneal injections of chemotherapy (CTX group; n=15) or physiologic saline (SAL group; n=12). CTX mice received cyclophosphamide (50 mg/kg) and doxorubicin (2 mg/kg). Contrast sensitivity was assessed using an optomotor response (OMR) chamber. Psychometric functions were fitted to OMR contrast response functions to derive measures of contrast sensitivity (K), stimulus responsivity (Rmax), and stimulus selectivity (n). Electroretinography (ERG) waveforms, which measure light-evoked retinal neural activity, were recorded under scotopic (rod-driven) conditions and decomposed to isolate photoreceptor (a-wave), bipolar cell (b-wave), and interneuron amacrine cell (oscillatory potentials [OP]) activity. OMR and ERG were measured prior to and following treatment. Dependent- and independent-sample t-tests assessed within- and between-group changes, respectively, in outcome measures. Results: Outcome measures are reported in Table 1. SAL relative to CTX mice showed greater weight gain (p=0.004). OMR revealed increases in Rmax (pCTX=0.002; pSAL=0.11) and K (pCTX=0.80; pSAL=0.06) parameters in SAL but not CTX mice. ERG results revealed significant declines in OP peak frequency in CTX relative to SAL mice (p=0.006). Other OMR and ERG measures showed no within- or between-group differences (p>0.10). Decreases in weight were associated with decreases in Rmax (R2=0.25, p=.008) and OP peak frequency (R2=0.20, p=.02). Conclusions: Our animal model showed chemotherapy-related visual dysfunction. Mice receiving chemotherapy showed relative declines in contrast sensitivity, stimulus responsivity, and oscillatory neural activity, suggestive of disrupted neuronal circuits within the visual pathway. Future studies will focus on understanding neuronal mechanisms of visual pathway dysfunction and translating findings to clinical studies. [Table: see text]
GLIM versus ESPEN criteria for the diagnosis of early malnutrition in oncological outpatients.
Authors: Gascon Ruiz Marta , Casas-Deza Diego , Torres Irene , Zapata-Garcia Maria , Alonso Marin Natalia , Sesma Goñi Andrea , Lambea- Sorrosal Julio Jose , Alvarez Maria , Quilez Elisa , Zurera Berjaga Maria , Ocáriz Maitane , Moratiel Pellitero Alba , Ruiz Moreno Ines , Goas Gomez Ana , Marti Pi Maria , Arbonés-Mainar José Miguel , Isla Dolores
Published: June 2021

e24065

Background: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. Methods: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. Results: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m² and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). Conclusions: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients. [Table: see text]
Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies in a real-world setting.
Authors: Ma Jun , Huang Huiqiang , Fu Peifen , Xu Nong , Mao Chenyu , Cheng Gang , Yan Haijiao , Li Yongqing , Shi Yanxia , Wang Yongsheng , Yao Yumin , Chen Liang , Chen Yong , Zhang Ningling , Zhang Guifang , Ren Zhangxia , Li Zengjun , Song Lihua , Qin Shukui
Published: June 2021

e24072

Background: The prophylaxis of neutropenia has been evolving from short acting granulocyte colony-stimulating factors (G-CSFs) to long acting G-CSFs. The safety and effectiveness of long acting G-CSF in a real-world setting were still lacking. Methods: We performed a multi-center, non-interventional, real-world study to explore the tolerability and effectiveness of mecapegfilgrastim. Different prophylactic strategy (primary or secondary prophylaxis) were compared. The effect of mecapegfilgrastim by means of continuous administration was also explored. Results: This study included 638 patients who had complete the study from May 2019 to November 15, 2020. About half of the participants were breast cancer patients. The mean age of the patients were 56 years. The most frequently reported adverse event possibly related to study drug was white blood cell increase (6.2 %). No unexpected adverse events were reported. Overall, thirty-six (5.6 %) patients experienced grade ≥ 3 neutropenia in chemotherapy cycle one. The patients in the primary and secondary prophylaxis subgroups had incidence of grade ≥ 3 neutropenia of 4.3 % and 9.2 % in chemotherapy cycle one respectively. There was a decreasing trend of neutropenia from cycle one to cycle four when mecapegfilgrastim were administrated continuously. Conclusions: The mecapegfilgrastim was well tolerable and no unexpected adverse events were observed in real-world setting. Primary prophylaxis using mecapegfilgrastim had lower incidence of neutropenia than secondary usage.
Palliative care for cancer in Turkey: A comprehensive review of the literature.
Authors: Kutluk M. Tezer , Ahmed Fahad , Cemaloğlu Mustafa , Aydin Burca , Sengelen Meltem , Kirazlı Meral , Yurduşen Sema , Sullivan Richard , Harding Richard
Published: June 2021

e24088

Background: Palliative care is patient and family-centered care provided to optimize the quality of life in serious illness, and is an essential health service under Universal Health Coverage. Given the burden of cancer and other chronic disease diseases along with demographic changes, the need for palliative care is growing in Turkey. This study aimed to review of the available scientific literature on palliative cancer care needs, models and outcomes Turkey. Methods: A comprehensive literature review was conducted with English and Turkish keywords in PubMed, Scopus, Embase, ScienceDirect, Web of Science, Google Scholar, The Turkish Academic Network and Information Centre databases, Turkish Ministry of Health documents, Turkish Council of Higher Education’s doctoral thesis, and renowned national and international palliative care as well as cancer conferences 01/ 2000 to 07/ 2020. Results: Out of 27489 papers identified, 320 met the criteria for inclusion. The main focus of these studies was; historical development in palliative care, legislative regulation, professional training, use of opioids, symptom management, care for patients, palliative care centers, public awareness, psychosocial support, and end of life ethics. The majority of this literature used descriptive design, although a few case-control, cohort, and randomized control trials were also found. Our analysis showed that the development of PC in Turkey can be divided into three period. The first (early initiatives, before 2000), the second (dissemination phase, 2000-2010), and the third stage (government & societial engagement, after 2010). Several studies also analyzed the barriers such as low public & professional awareness, disconnection from cancer care, the opioidfobia and the lack of trained palliative care providers. The lack of integration of palliative care to cancer care is a major challenge for palliative care implementation. Conclusions: This review presents the evidence of the significant progress in PC during the last 20 years and the opportunities for further progress. Bringing research into practice is needed for shaping the integration of palliative care to cancer care in Turkey. The stakeholders and policy makers should not neglect the need for PC under the current pressure of COVID-19 pandemic on health and economy.
A network analysis approach to the needs of oncological patients.
Authors: Rossi Alessandro , Marconi Maria , Mannarini Stefania , Minelli India , Verusio Claudio
Published: June 2021

e24128

Background: In recent years, an ever greater importance is given to the needs of cancer patients which could impact medical treatments, adherence and compliance, and patients’ quality of life (Teo et al. 2019; NCCN, 2015). However, recognizing and addressing the needs of patients may not be enough. Indeed, on one hand, needs that clinicians might consider as 'important' could play a marginal role, and – on the other hand – needs that clinicians may perceive as 'unimportant' may be central for patients. An innovative approach – psychometric network analysis (PNA; Epskamp, 2017) – was used to assess the network among needs ( nodes). Notably, the more a central node (need) is modified (addressed), the more a cascade change will occur in all the other nodes (needs). This study aimed to evaluate: (A) the structure of relationships among needs ( edges) of cancer patients, (B) which needs ( nodes) are the most relevant ( central), and (C) play a key role in the network. Methods: Patients ( n = 511; mean age = 65.95, SD = 12.72; 280 males) were enrolled at the Oncology Day Hospital at the “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy. Patients were tested with the Need Evaluation Questionnaire (NEQ) which is composed of 23 items that investigate as many needs – divided into 4 areas: (1) information about diagnosis/prognosis, (2) information about exams and treatment, (3) communicative, and (4) relational needs. Results: Preliminary analysis revealed that all of the items were informative (SDitem < 2.5SDall_itemsSD) and there was no redundancy between items (redundancy index < 0.25). An Ising model (5,000 nonparametric bootstraps) with LASSO regularized nodewise logistic regression was performed. PNA showed a high accuracy: CS-coefficient = 0.56. On one hand, PNA showed that item#2 ( “I need more information about my future condition”; z = 2.039), item#17 ( “I need to speak with a psychologist”; z = 1.209), and item#13 ( “I need to be reassured more by the doctors”; z = 1.201) were the strongest (central) nodes. On the other hand, item#14 ( “ I need the hospital to provide better services”; z = -2.261) was the weakest node in the network. Conclusions: These findings show useful implications for clinical practice. Clinical interventions should address the needs showing the strongest connections in the network. These central nodes can influence all the other connected needs, thus representing important needs to be targeted by clinicians – allowing to tailoring more targeted and efficient therapeutic approaches to meet patients’ needs, with beneficial effects for medical treatments and quality of life.