bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.