bluuebunny/crossref_metadata_2025 huggingface dataset:
Confirmatory germline testing for presumed germline pathogenic variants using tumor-only testing.
Authors: Kondo Tomohiro , Yamada Takahiro , Yoshioka Masahiro , Nishigaki Masakazu , Yamamoto Yoshihiro , Kou Tadayuki , Matsubara Junichi , Kanai Masashi , Matsumoto Shigemi , Muto Manabu , Kosugi Shinji
Published: June 2021

e22524

Background: Presumed germline pathogenic variants (PGPVs) can be detected in tumor tissues using comprehensive genomic profiling. Clinicians and patients can decide whether to conduct confirmatory germline testing or not. However, the promoting and obstructive factors for confirmatory germline testing are unclear. Methods: This single institutional retrospective study aimed to identify factors related to confirmatory germline testing in patients with PGPVs. Between April 2015 and April 2019, 270 consecutive patients with cancers of unknown primary site, rare tumors, or solid tumors refractory to standard chemotherapy, who underwent tumor-only comprehensive genomic profiling were reviewed. PGPVs were proposed to be disclosed as variants to the patients by our institutional molecular tumor board. Univariate logistic regression analysis was conducted to investigate the relationship between each patient’s characteristics and confirmatory germline testing. Factors showing a statistical relationship (p < 0.10 in univariate analyses) were included in multivariate logistic regression analysis with a backward selection of variables. Statistical significance was set at p < 0.05. Results: Of the 270 patients who underwent tumor-only comprehensive genomic profiling, 77 possessed PGPVs. The most common PGPVs were TP53 (n = 56), APC (n = 9), PTEN (n = 7), RB1 (n = 6), and BRCA2 (n = 6). Among the 77 patients, only 11 (14.3%) chose to undergo confirmatory germline testing. Multivariate logistic regression analysis revealed that the person disclosing the results (experienced oncologists with knowledge of cancer genome medicine vs. others, odds ratio [OR]: 27.7, 95% confidence interval [CI]: 4.60–167) and study period (OR: 0.110, 95% CI: 0.015–0.787) were independently and significantly associated with confirmatory germline testing. Conclusions: These findings indicate that fostering genomic competency in oncologists and collaborating with genetic experts would facilitate cancer patients and their families to receive genetic medical services in the process of cancer genomic profiling.
Real-world experience of pancreatic cancer molecular profiling in a tertiary center.
Authors: Sun Kai , Mylavarapu Charisma , Crenshaw Aubrey , Zhang Yuqi , Hsu Enshuo , Xu Jiaqiong , Niravath Marilyn , Nicolas Juan Carlos , Jones Stephen , Abdelrahim Maen
Published: June 2021

e22526

Background: NCCN has recommended universal genetic testing of pancreatic cancer. Liquid biopsies have been approved by the FDA to facilitate detection of targetable mutations in various solid tumors. Methods: To investigate how oncologists follow NCCN guidelines and utilize liquid biopsies in pancreatic cancer, we retrospectively queried patient records from 7/2016 to 6/2020 in our institutional system. Those retrieved but with pancreatic cancer care from other 2 local institutions are also included. Demographics, cancer stage on diagnosis, year of diagnosis, molecular profiling (MP) and treatment setting (community vs academic) are recorded and analyzed. Results: A total of 500 pancreatic cancer patient records were identified. Of these, 234 patients were excluded due to incomplete records. Among the remaining 266 patients, 113 (42.5%) had MP performed. Younger patients and those treated at an academic setting were more likely to have MP (P= 0.0051 and 0.0010 respectively). The trend of increased utilization of MP over the years is also statistically significant (p< 0.0001). Gender, ethnicity or stage on diagnosis are not statistically significant between groups. (Table). Conclusions: MP is being increasingly utilized. However, more awareness is needed among oncologists, especially those who practice in the community setting.[Table: see text]
Addressing gaps in care for patients with rare cancers and blood disorders: The impact of a collaborative digital education initiative.
Authors: Turell Wendy , Ackbarali Tariqa , del Nido Elizabeth L. , Pucci Kathryn , O'Hara Randi , Kowalski Katie , Hopper John , Palma Jim
Published: June 2021

e23005

Background: Clinicians are uniquely challenged to manage patients with rare cancers and blood disorders due to a lack of knowledge of diagnosis and management guidelines for these conditions. These conditions comprise a larger proportion of diagnosed cancers in minority populations, among whom a worse 5-year survival is realized in adults versus adolescents and children. Patients often experience delayed diagnoses, have limited treatment options, access to specialists, and limited clinical trials. Education surrounding rare cancers and blood disorders, diagnostic criteria, approved agents, and emerging novel agents is essential to improve treatment outcomes for patients with these rare malignancies. Methods: A 2-part CE and American Board of Internal Medicine (ABIM) Maintenance of Certification activity was launched live-online in October and November, 2020, and remains on-demand through November, 2021 at OMedLive.com, comprising 9 hours of virtual education. This first annual activity was launched in partnership with National Organization for Rare Disorders (NORD), and featured key opinion leaders with extensive expertise in rare cancers and blood disorders. Session components included case presentations, downloadable resources, live polling, and audience real-time Q&A. Knowledge and competence questions were administered pre- and immediate post-activity. Patient and clinical practice impact questions were also asked at 2-month follow-up. Data from these questions were analyzed to determine engagement, remaining gaps, and the unique challenges of managing rare cancers and blood disorders. Results: 996 clinicians have participated in the activity to date. All 28 CE test questions reflected improvements in knowledge and competence regarding symptom recognition, diagnosis, clinical trial data, guidelines, treatment options, and adverse event management. At 2-mos. follow up, 71% reported improvements in clinical practice and 67% reported improvements in patient impact (n = 66). Almost half (48%) indicated diagnosis as their most significant challenge, with other noted barriers including: limited access to molecular testing (29%) and limited knowledge of tests to order (17%). The top 3 reported treatment challenges were: a lack of clinical evidence (24%), limited treatment options (22%), and high treatment cost (16%). Updated and expanded data will be shared. Conclusions: Following the targeted collaborative educational initiative, clinicians demonstrated clear knowledge and competency improvements in critical areas such as recognition, diagnosis, and management, and reported significant improvements in patient outcomes and clinical practice. The results of the two-month impact survey demonstrated a need for further tailored education on diagnostic testing and clinical evidence on treatment options for rare malignancies.
Patient and provider education on HER2-positive metastatic breast cancer: Defining gaps in clinician practice, patient behaviors, patient-provider alignment, and clinical knowledge.
Authors: Turell Wendy , Ackbarali Tariqa
Published: June 2021

e23007

Background: Current breast cancer management is driven by inherent heterogeneity of disease. Therapeutic options for later lines of HER2 therapy have expanded, shifting practice patterns to incorporate the latest evidence and guidelines. Health care providers (HCPs) require education to synthesize new evidence in the context of clinical practice including three approved HER2-directed therapies between December 2019 and April 2020. Concurrent patient and caregiver education is imperative to improve collaborative treatment decisions for HER2+ metastatic breast cancer (MBC). Methods: Two, 1-hour online video-based programs were hosted in June, 2020 for HCPs and patients/caregivers, respectively. Practice and knowledge gaps among HCPs, and knowledge, communication and self-efficacy behaviors among patients were assessed. Each activity was interactive, consisting of slides, polling and live questions, and both remain on-demand (and on social media for patients/caregivers) for 12 months. Assessments were administered at 3 time points (pre-, immediate post-, and 2 mos. post-activity). Data from these questions, responses to live polling questions, and learner-submitted questions during live Q&A were analyzed to determine engagement, lessons learned, and continuing education gaps. Results: As of February 2021, 525 HCPs and 9,582 patients (9,449 Facebook Video; 133 CancerCoachLive.com) participated in the ongoing activities. Post education, HCP learners anticipated the education would positively impact practice behavior (77%) and patient clinical outcomes (73%). HCP improvements in pre/post knowledge and competence questions were realized in 3/4 of the questions. Of patients/caregivers, 34% more learners reported confidence in managing their condition post vs. pre-education. They listed “affording therapy” and “understanding treatment options” as their greatest challenges, and reported “self-care strategies” as their most sought information during the COVID-19 pandemic. At 2-mos. follow-up, 83% of patients reported improvements in communication with their HCPs, and 77% of HCPs reported improvements in their clinical practice. Updated data will be shared, including aligned HCP and patient questions pertaining to care challenges and communication goals. Conclusions: CME and patient education can yield gains in clinical practice behaviors, patient healthcare communication and confidence, and treatment knowledge of HER2-postive breast cancer. Together, aligned education directed to HCPs and patients can improve the ability to provide evidence-based treatment for patients.
CME curriculum improves clinician knowledge, competence, and confidence in managing patients with NF1-related tumors.
Authors: Worst Michelle Arielle , Caracio Rich , Lucero Katie , Cohen Jacob
Published: June 2021

e23009

Background: Neurofibromatosis type 1 (NF1) is an uncommon complex autosomal dominant disorder caused by germline mutations in the NF1 tumor suppressor gene. Therapeutic options have historically been limited with surgical debulking being the preferred treatment modality. However, recent clinical data have shown improved outcomes with the use of MEK inhibitors. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of physician learners with respect to the treatment of NF1-related tumors. Methods: The educational series consisted of four online, CME-certified activities. For each activity, educational effect was assessed with a repeated pairs pre-/post-assessment study including a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question, with each participant serving as his/her own control. To assess changes in knowledge, competence, and confidence data from all clinicians who completed both pre- and post-questions were aggregated across activities, stratified by learning theme, and evaluated by target specialty. A repeated pairs pre-/post-assessment study design was used and McNemar’s test or paired samples t-test (P < .05) assessed educational effect. The first activity in the series launched Dec. 2019 and the last launched June 2020; data were collected until Dec. 2020. Results: Overall significant improvements were seen after education for oncologists (N = 258, P < .001), neurologists (N = 474, P < .001), surgeons (N = 427, P < .001), neurosurgeons (N = 93, P < .05), and pediatricians (N = 56, P < .001), regardless of practice setting. A sub-analysis of community specialists also showed significant improvements after education: oncologists (N = 117, P < .01), neurologists (N = 188, P < .001), and surgeons (N = 206, P < .001). Outcomes assessed by learning themes and specialty showed relative percent increases, with the majority being statistically significant. Conclusions: This analysis demonstrates that oncologists’ and other specialists’ knowledge, competence, and confidence regarding the treatment of NF1-related tumors improved after education, as measured through a comprehensive analysis of CME outcomes data from a variety of activities designed to achieve these ends. These results have the ability to translate to improvements in clinical care. Despite the improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in this clinical setting.
Online CME closes gaps in CSCC management revealed in a virtual patient simulation.
Authors: Dermer Shari , Betz Briana , Chatterjee-Shin Piyali , Patel Vishal , Khushalani Nikhil I.
Published: June 2021

e23013

Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer type. Although highly curable in its early stages, advanced or metastatic CSCC has been associated with mortality rates as high as 70%. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists on the assessment and management of CSCC. Methods: The educational series consisted of 4 online, CME-certified activities in multiple delivery formats, including an initial virtual patient simulation, followed by a clinical practice assessment (CPA) and 2 video discussions with synchronized slides. For the video discussions, educational effect was assessed with a repeated pairs pre-/post-assessment study including a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question, with each participant serving as his/her own control. To assess changes in knowledge, competence, and confidence data from all clinicians who completed both pre- and post-questions were aggregated across activities and stratified by learning theme. McNemar’s test or paired samples t-test ( P <.05) assessed educational effect. The first activity launched June 2019 and the last launched August 2020; data were collected until December 2020. Results: Following education oncologists had significant improvements in knowledge and competence compared with responses from the CPA. Improvement in knowledge and competence measured as relative % change in correct responses pre/post education across the learning themes identified in the virtual patient simulation are reported: Identifying patients who are not candidates for surgical intervention: 9% increase (56% CPA/ 77% pre/ 84% post; n=123-314; P <.05). Tailoring treatment: 30% increase (41% CPA/ 56% pre/ 73% post; n=119-314; P <.05). Tailoring treatment–cemiplimab: 22% increase (32% CPA/ 55% pre/ 67% post; n=123-314; P <.05). Tailoring treatment–cetuximab: 16% increase (15% CPA/ 37% pre/ 43% post; n=123-314; P <.05). New and emerging immunotherapies for CSCC: 47% increase (28% CPA/ 30% pre/ 44% post; n=119-314; P <.05). Conclusions: These results demonstrate the effectiveness of curriculum-based education for oncologists to address specific gaps in care as identified in a virtual patient simulation. This series of CME-certified online educational activities resulted in significant improvements in knowledge and competence in the assessment and treatment of patients with CSCC.
Secret sauce in collaborative tumor boards: Team-based characteristics that optimize tumor board functionality.
Authors: Oureilidis-DeVivo Barbara
Published: June 2021

e23015

Background: Interdisciplinary teams are an indispensable characteristic of modern organizations, particularly in healthcare settings that require specialists to work together to solve multifaceted patient care problems. Multidisciplinary tumor boards (TBs) aim to coordinate multidisciplinary perspectives to help the oncology team devise the best treatment program for the patient. Yet, while this is their purpose, studies have found that TBs do not always achieve that goal effectively. Why are some tumor board (TB) teams more effective than others? This study shed light on key characteristics found among highly effective TBs. It provides a theoretical explanation of their organizational behaviors and structures and their effect on cancer treatment decision-making. The research is grounded in organizational behavior theories that have historical prominence in group decision-making, social hierarchy, and interdisciplinary collaboration, and are used to explain the phenomenon under investigation best. Methods: Qualitative research was used in the study. Data from 44 different TB observations and 18 interviews were gathered over four years at seven research hospitals in the United States and United Kingdom. The data were then coded, analyzed and synthesized with organizational behavior theory to explain the social phenomena under investigation. Results: The study revealed that certain TBs practice strong collaboration displaying high levels of partnership, cooperation, equality, and interdependency, which was incorporated explicitly into their meeting systems to achieve their common goal. Team-based characteristics such as members’ consistent shared preferences and identity, coordinated interactions, a collective learning process, and shared power and partnership are key markers found within these teams that positively influenced treatment decision-making processes and outcomes, earmarking best practices in TB groups. Conclusions: Organizational theory that suggests that for a collaborative process to be effective, team-based mechanisms need to be adopted in which each member respects, trusts, and acknowledges the skills and expertise of other disciplines in the organization, shares team values, decision-making processes, responsibilities, and planning, relies mutually upon other team members, and works outside normal professional boundaries openly and willingly. In an egalitarian structure like that of the TBs reviewed in this study, where preferences and identities are consistent and groups are collaborative, treatment decisions are less biased and incorporate multidisciplinary perspectives. Thus, this study suggests that by possessing both team- and task-based characteristics and practices, TBs engage in best practices, and thereby optimize their functionality.
Methylation of MMP2 and MMP9 in patients with localized and generalized forms of Ewing's sarcoma.
Authors: Petrusenko Natalia A. , Gvaldin Dmitry Yu. , Yurchenko Darya Yu. , Kuznetsov Sergey A. , Burtsev Dmitriy V. , Kit Oleg I.
Published: June 2021

e23503

Background: MMPs play a critical role in tumor growth and progression, metastatic development, angiogenesis, and tumor invasion. Epigenetic regulation of MMP2 and MMP9 levels is often disrupted in cancer and is considered as potential biomarkers. In this study, we tried to assess the methylation of the MMP2 and MMP9 genes in patients with localized and generalized forms of Ewing's sarcoma (ES). Methods: As a material used DNA from FFPE of primary tumor of 20 patients with localized forms ES and 20 patients with generalized forms ES. After bisulfite conversion of total DNA and PCR, the level of CpG methylation was assessed by sequencing on a Genetic Analyzer Applied Biosystems 3500. Results: The analysis showed the presence of hypomethylation of the MMP2 in the group with generalized forms (100%) 1.25 times more often than in the group with localized forms (80%), and hypermethylation was observed only in the group with localized forms–20% of cases (χ2 = 4.234, p = 0.040). On the other hand, hypermethylation was 1.9 times more common in the group with localized forms of ES (90%) (χ2 = 8.313, p = 0.004). Differences in the methylation status of the MMP2 and MMP9 indicate that the presence of hypomethylation at two loci increases the risk of developing generalized ES by 22 times (OR = 22.2, p < 0.05; CI95% 2.460-20.769). Conclusions: Specific methylation of the matrix metalloproteinases genes MMP2 and MMP9 identified in the groups of localized and generalized Ewing's sarcoma. At the same time, the group with generalized forms of ES was characterized by gene hypomethylation.
Overall survival after perioperative chemotherapy in the management of pulmonary metastasis in osteosarcoma.
Authors: Siddiqui Zeba , Delisle Megan E , Srikanthan Amirrtha , Wang Ying
Published: June 2021

e23508

Background: Pulmonary metastasectomy is performed on a select cohort of patients with advanced osteosarcoma with the potential for long term survival. However, evidence on peri-operative chemotherapy at time of metastasectomy is not completely understood and difficult to summarize without a systematic examination of existing literature. The purpose of this project is to perform a meta-analysis of existing studies to determine overall survival (OS) and prognostic factors in adults and children with advanced and recurrent osteosarcoma receiving chemotherapy around time of metastasectomy. Methods: We reviewed survival studies conducted in children and adults with advanced and recurrent osteosarcoma who undergo pulmonary metastasectomy published in English with more than 5 patients. The primary outcome was overall survival. Literature searches were performed in multiple electronic databases including Ovid MEDLINE (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Two investigators independently screened all citations, abstracts, and full-text articles. Results: 24 out of 80 observational studies between 1977 to 2018 were included. 2146 patients were studied of which 987 underwent pulmonary metastasectomy for osteosarcoma. 822 patients received perioperative chemotherapy in this setting. No randomized controlled trials were identified. Studies included patients from Asia, Africa, Europe, and North America. The median OS ranged between 20 to 90 months. 5-year OS ranged between 15 to 63%. Factors associated with survival included: age, number of lesions, disease free interval, time of development of metastases, number of lesions and laterality of pulmonary disease. Conclusions: Overall survival in study has a significant range. Factors influencing survival included intrinsic factors such as patient age and disease characteristics, as well as extrinsic factors such as evolution of chemotherapy regimen over the past four decades. The main limitations are related to the inherently low-quality evidence as a result of lack of randomized controlled trials. More comprehensive data is needed to guide shared decision making in this area.
Various treatment options for the management of Campanacci III giant cell bone tumor.
Authors: Gillani Syed Faraz-ul-Hassan Shah , Taqi Muhammad , Haq Muhammad Ayyaz Ul , Aslam Anam , Masood Faisal , Haider Mobeen Zaka , Mushtaq Muhammad Umair
Published: June 2021

e23509

Background: To assess the treatment effectiveness of Campanacci III giant cell bone tumours. Methods: This prospective cohort study was done using a non-probability purposive sampling technique in the orthopaedic surgery and traumatology unit-I department from February 2013 to October 2017. The sample size of 21 patients aged 33 to 60year Campanacci III giant cell bone tumour diagnosed on biopsy were included, and all patients with uncontrolled diabetes mellitus, decompensated liver disease, chronic renal failure, previously treated for giant cell tumours and malignant transformation were excluded. Treatment options included wide margin excision with fibular vascular graft with plating, mega prosthesis, and chirolin prosthesis. Treatment effectiveness was observed in terms of superficial & deep infection, limb length discrepancy, implant failure and function using musculoskeletal tumour society rating scale (MSTS). Follow-p of the patients was five years. All patients were followed up for six months in the first year and yearly till five years. Results: Out of the total 21 patients, male were 11 (52.4%) and female were 10 (47.6%). The mean age of the patients was 34.8±14.6 years, with a median age was 30year. Four (19.1%) had proximal humerus, o5 (23.8% had distal radius, 09 (42.8% had distal femur, and 03 (14.3%) had proximal thigh involvement. The MSTS was 21.8±6.8 with a median score of 22 till the last follow-up. Kaplan Meier curve was plotted, and median survival rate was 50% at 54 months for the patients treated with fibular vascular graft, 57 months for mega prosthesis and 58 months for the patients treated with chirolin prosthesis. Conclusions: Treatment of Campanacci III with mega prosthesis, fibular vascular graft and chirolin prosthesis is a good outcome except with implant failure in mega prosthesis and limb length inequality with fibular vascular grafts. [Table: see text]
Role of biogenetic markers in differentiation and prognosis of giant cell tumor: A systemic review.
Authors: Taqi Muhammad , Haider Mobeen Zaka , Tariq Mishaal , Gillani Syed Faraz-ul-Hassan Shah , Ali Munawar , Zamani Zarlakhta , Rasool Muhammad Haseeb ul , Shahzad Moazzam , Mushtaq Muhammad Umair
Published: June 2021

e23514

Background: Giant cell tumor (GCT) is a locally aggressive bone tumor. Early diagnosis and potential for recurrence are often difficult to assess due to a lack of bio-genetic markers and radiographic findings overlap with other osteolytic lesions. The purpose of this study is to explore biological and genetic markers that can be used for detection, differentiation, recurrence, and prognosis of GCT. Methods: We conducted a literature review including 24 articles out of 1568 articles, summarizing the role of biogenetic markers in the prognosis of GCT. Results: P63 is 98.6% sensitive and relatively specific for GCT as compared to other multinucleated giant cells containing neoplasms. MDM2(Mouse double minute 2 homolog), IGF1(Insulin-like growth factor 1), STAT1(Signal transducer and activator of transcription 1), and RAC1(Ras-related C3 botulinum toxin substrate 1) are associated with GCT recurrence. Increased expression of proteins like STAT5B, GRB2, and OXSR1 are related to a higher probability of metastasis. Neutrophil to lymphocyte ratio > 2.70, platelets to lymphocyte > 215.80, lymphocyte to monocyte ≤ 2.80, and AGR albumin to globulin < 1.50 ratio were significantly associated with decreased disease-free survival (DFS) (p < 0.05). Large amounts of osteoclast-related mRNA in GCTs (P < 0.05) are associated with the grade of bone resorption. We propose that subarticular primary malignant bone sarcoma with H3.3 mutations represent true malignant GCTB. IMP3 and IGF2 might be potential biomarkers in regulating the angiogenesis of GCT spine and predicting the patients’ prognosis. Conclusions: This review study has shown serological markers are significant in determining the diagnosis, differentiation, prognosis, and recurrence of GCT, which can be added to tumor work-up for definitive diagnosis and prognosis. [Table: see text]
Comorbidity: Chronic neurogenic pain affects malignant growth and changes balance of neurosteroids in brain of rats.
Authors: Pogorelova Yulia A. , Surikova Ekaterina I. , Frantsiyants Elena M. , Bandovkina Valeria A. , Kaplieva Irina V. , Neskubina Irina V. , Cheryarina Natalia D. , Kotieva Inga Movlievna , Shalashnaya Elena V. , Trepitaki Lidia K. , Pozdnyakova Viktoria V.
Published: June 2021

e23516

Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.
Simultaneous stimulation of growth of malignant tumors with epithelioid and sarcomatous nature in experiment.
Authors: Kaplieva Irina V. , Frantsiyants Elena M. , Trepitaki Lidia K. , Surikova Ekaterina I. , Bandovkina Valeria A. , Neskubina Irina V. , Kotieva Inga Movlievna , Shumarin Konstantin A. , Zhukova Galina V.
Published: June 2021

e23517

Background: The relevance of studying multiple primary malignant tumors (MPMTs) is determined by poor understanding of their pathogenesis. Our purpose was to create an experimental model of synchronous MPMTs with the stimulation of malignant growth of tumors with different histostructure. Methods: The study included 20 male BALB/c Nude mice. The main group included mice with simultaneous subcutaneous inoculation of tumors: murine B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline solution) below the left scapula and rat sarcoma 45 (0.5 million tumor cells in 0.5 ml of saline solution) below the right scapula. Control groups included males with melanoma or sarcoma inoculated at the same dosage and volume as in the main group. Results: In the model of synchronous MPMTs, tumors appeared faster than in controls: melanoma–by 3 times, sarcoma–by 2 times; their volume was larger: melanoma–by 2.2 times, sarcoma–by 3.2 times. Melanoma metastasized, in addition to typical sites (the lungs, spleen, liver), into sarcoma 45 to the side adjacent to the chest, under the tumor node. The survival of mice with MPMTs was lower. The morphological structure of melanoma metastasis into sarcoma 45 was represented by large lamellar-rounded epithelium-like cells of melanosarcoma type with transparent cytoplasm and nuclei with a high frequency of pathological mitosis figures. Bundles of elongated spindle-shaped melanocytes with processes of the cytoplasm were determined in some melanoma areas, as well as alveolar and concentric structures. Conclusions: Synchronous subcutaneous inoculation of murine B16/F10 melanoma and rat sarcoma 45 to male BALB/c Nude mice increases their malignant potential due to an exchange of “structural information"; as a result, sarcoma acquires impulses of proliferative activity of melanoma, which, in turn, adapts and “mimics” a tumor into which it is going to metastasize.
Comparison of clinicopathological features and outcomes in patients with primary leiomyosarcoma of bone and soft tissue.
Authors: Blank Alan T. , Gusho Charles , Gitelis Steven
Published: June 2021

e23526

Background: Leiomyosarcoma is a rare malignancy that may occur in bone. This investigation described the characteristics and outcomes of primary leiomyosarcoma of bone (PLB) compared to soft tissue leiomyosarcoma (SLMS). Methods: This study was a retrospective review using the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Continuous and categorial variables were described, and Cox regression were used to identify factors of prognostic significance. Results: Seven thousand five-hundred two patients met inclusion criteria. Seventy-four (1%) were PLB and 7428 (99%) were SLMS. On multivariable analysis for high-grade SLMS radiation (neoadjuvant: HR, 0.56; 95% CI, 0.4-0.8; p = 0.003, and adjuvant: HR, 0.75; 95% CI, 0.6-0.9; p = 0.008) and surgery (procedure specific) improved DSS, while age (HR, 1.013; 95% CI, 1.0-1.1; p < 0.001), tumor size greater than or equal to 5 cm (HR, 3.16; 95% CI, 2.3-4.2; p < 0.001), abdomen/pelvis/trunk/thorax tumors (HR, 1.31; 95% CI, 1.1-1.6; p = 0.006), and distant metastases at presentation (HR, 2.6; 95% CI, 2.1-3.3; p < 0.001) negatively influenced DSS. Conclusions: Radiation and surgery positively influence survival in high-grade SLMS while chemotherapy appears to have no benefit. Surgery alone appears to lower the mortality risk in PLB.
The role of ifosfamide-doxorubicin chemotherapy in the treatment histology-specific, high grade, locally advanced soft tissue sarcoma: A 14-year experience.
Authors: Goy Barry W
Published: June 2021

e23529

Background: To compare long-term outcomes of high grade, locally advanced, primary soft tissue sarcoma (STS), using Ifosfamide-Doxorubicin vs local therapy alone, in histology-specific sarcomas. Methods: Retrospective analysis was performed on 127 patients from 2005 to 2018, who had STS of extremity or trunk, > 5cm, that were either Synovial Cell, Dedifferentiated Liposarcoma (DDL), Myxofibrosarcoma, Round Cell Liposarcoma (RCLS), Undifferentiated Pleomorphic Sarcoma (UPS), or Undifferentiated Sarcoma not otherwise specified (NOS), with central pathology review. Ifosfamide-doxorubicin was generally given neoadjuvant, followed by radiation and wide excision, with chemotherapy given in 38 patients, while 89 received local therapy alone. Multi-variable analysis of prognostic factors was performed, and local-recurrence-free-survival (LRFS), distant-metastases-free-survival (DMFS), disease-specific-survival (DSS), and overall-survival(OS) were estimated using Kaplan-Meier. Results: Median follow-up was 4.5 years. Younger age (p < 0.0001) and Synovial histology (p = 0.0002) had significantly higher rates of receiving chemotherapy. Size > 10cm and trunk location were poor prognostic features on multivariable analysis (MVA) affecting DMFS, DSS, and OS, while DDL histology had a more favorable effect; although size, trunk location, and DDL histology were not significantly different between treatment groups. Ifosfamide-Doxorubicin vs local therapy alone improved 5-year DMFS at 70.2% vs 49.5% ,p = 0.02, DSS 83.5% vs 57.9%, p = 0.009, and OS 80.6% vs 53.8%, p = 0.002. Sub-analysis of non-synovial histologies still showed a significant improvements in favor of chemotherapy in DMFS,(p = 0.04), DSS (p = 0.02), and OS (p = 0.003). Conclusions: Ifosfamide-Doxorubicin chemotherapy benefits younger patients with > 5cm, high grade, STS of the trunk or extremity, with histologies of Synovial Cell, DDL, Myxofibrosarcoma, RCLS, UPS, or Undifferentiated Sarcoma NOS.
Efficacy and safety of anlotinib combined with liposomal doxorubicin in first-line treatment of advanced soft-tissue sarcoma.
Authors: Sun Xin , Guo Wei , Zhang Ranxin , Xie Lu , Xu Jie
Published: June 2021

e23530

Background: Anthracycline-based chemotherapy is the main first-line treatment option for advanced soft-tissue sarcoma (STS). Anlotinib has been approved for the treatment of STS by the Chinese agency. This study was performed to evaluate the efficacy and safety of Anlotinib combined with liposomal doxorubicin in first-line treatment of patients with advanced STS. Methods: This is a single-center, retrospective study. Eligible patients were those ≥14 years old, ECOG performance state of 0-1, with histologically confirmed locally advanced, unresectable or metastatic STS, previously untreated, with measurable disease by RECIST v1.1. All patients received Anlotinib (12mg once daily, 2 weeks on and 1 week off) and liposomal doxorubicin (40-50 mg/m2, IV, D1, every 3 weeks) until disease progression or unacceptable adverse events. The primary endpoint was progression-free survival (PFS). Disease control rate (DCR), objective response rate (ORR), and side effects were also calculated. Results: Between April 2019 and December 2020, 8 patients were evaluated, including 2 undifferentiated pleomorphic sarcoma, 1 liposarcoma, 4 fibrosarcomas, and 1 synovial sarcoma. The median age was 42 years. 2 patients (25%) achieved a confirmed partial response (PR) and 3(37.5%) had stable disease (SD). The ORR and DCR were 25% and 62.5% respectively. The median PFS was 11.3 months, and the PFS rate at 4 months was 50%. Treatment-related adverse events included hand-foot syndrome (3/8, 37.5%), pneumothorax (1/8, 12.5%), oral mucositis (2/8, 25%), epistaxis (2/8, 25%), hypertension (2/8, 25%), arrhythmias (1/8, 12.5%), and pharyngeal pain (1/8, 12.5%). Three patients experienced grade 3 or 4 adverse events, 2 hand-foot syndrome (2/8, 25%) and 1 pneumothorax (1/8, 12.5%). Conclusions: This study suggested that the combination of Anlotinib and liposomal doxorubicin might have anti-tumor activity and acceptable toxicity in first-line treatment of patients with advanced STS.
A retrospective study of anlotinib combined with adriamycin and ifosfamide in unresectable soft tissue sarcoma.
Authors: Long Zuoyao , Lu Yajie , Li Minghui , Chen Guojing , Li Jing , Fu Zhanli , Akbar Yunus , Zhang Hong-Mei , Wang Zhen
Published: June 2021

e23542

Background: Soft tissue sarcoma (STS) is a group of malignant tumors with high heterogeneity that originates from mesenchymal tissue. Considering that the reliable anti-tumor efficiency of tyrosine kinase inhibitor (TKI), we attempted to combine the TKI and chemotherapy to observe the synergistic effect in STS. This study documented the result on the efficiency and safety of anlotinib+AI in 28 patients with unresectable STS. Methods: The key inclusion criteria of this retrospective study included: (a) age was 10-70 years; (b) histologically documented high-grade STS; (c) unresectable and sensitive to chemotherapy; (c) having measurable lesions according to RECIST 1.1; (d) haven’t received tyrosine kinase inhibitors; (e) adequate organ function and blood pressure. Patients were excluded when they had distal metastasis. Patients took 12mg of anlotinib once daily on a schedule of 2 weeks on and 1 week off, and received 20mg/m2/d of Adriamycin(A) and 3g/m2/d of ifosfamide(I) in the first three days. Four cycles after treatment, patients were evaluated to receive surgery or other therapies. The primary end points were objective response rate (ORR) and limb salvage rate, and other endpoints include PFS, disease control rate (DCR), rate of R0 resection and recurrence. Results: Finally, a total of 28 patients were eligible to analysis including 17 males. Mean age was 39.11±13.46. The pathological subtypes in the study were consist of fibrosarcoma (FS, n = 6), synovial sarcoma (SS, n = 6), myxoid liposarcoma (MLPS, n = 6), undifferentiated pleomorphic sarcoma (n = 4) and others (n = 6). Until the last follow-up, no CR or PD occurred. The best response of 8 patients (28.57%) were PR and others were SD (20/28, 71.43%). The ORR and DCR was 28.57% and 100.0% respectively. Additionally, the tumor regression of SS and MLPS were significantly than FS (p = 0.012，p = 0.042). Eventually, 24 patients received surgery including 19 of R0 resection, 3 of R2 resection and 2 of amputation. The rate of limb salvage and R0 resection was 91.67% (22/24) and 79.17% (19/24). The median PFS was 21 months (95%CI: 8.53-33.69 months). Only one patient had dead due to tumor progression with a OS of 10 months. All patients had experienced adverse events (AE, 100.0%). The most common grade 3-4 AE were leukopenia (57.14%), hypertension (14.29%) and hand-foot syndrome (7.14%). All AEs could be tolerated or relieved by expectant treatment. Conclusions: The results in our study revealed that anlotinib+AI could be an alternative strategy of unresectable soft tissue sarcoma.
Preoperative stereotactic ablative body radiotherapy with postoperative conventional irradiation of soft tissue sarcomas: Protocol overview with a preliminary safety report.
Authors: Ebert Mariia , Novikov Sergey , Zinovev Grigory , Gafton Georgy , Protsenko Svetlana , Gafton Ivan , Sinyachkin Mikhail
Published: June 2021

e23546

Background: Preoperative radiotherapy in patients with soft tissue sarcomas is characterized by important advantages: high precision of dose delivery, reduction of tumour volume and implantation potential, induction of immunologic response. Postoperative irradiation is associated with a reduced risk of complication, and a comprehensive radiotherapy planning in accordance with the pathologic report. Combination of pre- and postoperative irradiation gives the opportunity to use the best of both methods. Methods: from 06.2018 to 01.2021 24 patients with soft tissue sarcomas of extremities were included in the protocol (NCT04330456) and 14 cases with at least 12 months follow-up were eligible for analysis. Preoperative stereotactic ablative body radiotherapy (SBRT) was performed as 5 fraction of 7 Gy with dose reduction (5 fractions of 5 Gy) on the margins of the tumor. Postoperative radiotherapy started 5-8 weeks after the surgery and was performed as standard compartmental irradiation in 25 fractions of 2Gy. Complications were determined according to CTCAE and wound complication scales. Results: Preoperative SBRT and subsequent radical resection with tumor free surgical margins were performed in all 14 cases. Primary wound closure was mentioned in all patients. Postoperative radiotherapy started 51.8 days (range 33-99 days) days after the surgery. With a relatively short follow-up of 21.5 (13-30) months, we recorded 2 cases (14%) of severe complications (Canadian sarcoma group criteria), and there were no local recurrences. Conclusions: Our preliminary results demonstrate that the combination of preoperative SBRT and postoperative conventional radiotherapy is feasible and does not increase the risk of postoperative complications. Clinical trial information: NCT04330456.
Trabectedin (T) in desmoplastic small round cell tumor (DSRCT): Report of its effect in 3 relapsed patients (pts) and the comparison of different regimens in a patient-derived xenograft (PDX) model.
Authors: Stacchiotti Silvia , Frezza Anna Maria , Gronchi Alessandro , Pasquali Sandro , Radaelli Stefano , Fiore Marco , Morosi Carlo , Collini Paola , Dagrada Gianpaolo , Casali Paolo Giovanni , Tortoreto Monica , Zuco Valentina , Zaffaroni Nadia
Published: June 2021

e23553

Background: DSRCT is an ultra-rare soft tissue sarcoma marked by the presence of the EWS-WT1 translocation and a dismal prognosis. Anecdotal activity of T in DSRCT pts was reported. We describe herein three advanced DSRCT pts treated with T and a comparative assessment of doxorubicin (D), pazopanib (P) and T in a patient-derived xenograft (PDX) model of DSRCT. Methods: Three pts (#1, #2 and #3) suffering from progressive, metastatic, unresectable relapsing disease from a primary peritoneal DSRCT previously treated with 8 cycles of anthracycline-based neoadjuvant chemo and complete surgical resection, were started on T (1.3 mcg/sqm every 3-4 weeks). A PDX model was generated by subcutaneously implanting small tumor fragments obtained at surgery from a treatment-naïve DSRCT patient into the right flank of SCID mice. Consistency of PDX and the originating tumor was confirmed in terms of histomorphology and presence of the EWS-WT1 gene fusion. Mice were randomized to receive D, P and T, administered as single agents at optimal doses and schedules. Drug activity was assessed in terms of tumor volume inhibition (TVI) percentage in treated versus control mice. An orthotopic xenograft model was also generated by injecting DSRCT cells into the peritoneal cavity of SCID mice. Results: At the time of this report, pt #1 and #2 are on therapy with T, with a partial response by RECIST maintained after 48 and 36 months from treatment start, respectively, while #3 progressed after 4 months. In the DSRCT PDX model, T was the most effective drug, with a maximum TVI of 82%, while D and P showed lower, comparable activity (maximum TVI: 59% and 66%, respectively). In the orthotopic DSRCT PDX, DSRCT cells spreading in the abdominal cavity generated different tumor masses, properly recapitulating the dissemination pattern in patients, confirming the reliability of this preclinical model. Conclusions: Both our preliminary model and our further clinical observations support the potential of T in DSRCT. A confirmatory prospective clinical study is now warranted.
Desmoplastic small round cell tumor: A series of patients surgically treated at a single institution.
Authors: Radaelli Stefano , Altomare Michele , Frezza Anna Maria , Stacchiotti Silvia , Pasquali Sandro , Fiore Marco , Callegaro Dario , Ferrari Andrea , Casali Paolo Giovanni , Gronchi Alessandro
Published: June 2021

e23555

Background: Desmoplastic small round cell tumor (DSRCT) is an ultra rare sarcoma predominantly involving the abdomino-pelvic peritoneum and mostly occurring in male children and young adults. It is marked by the EWSR1-WT1 fusion gene. Prognosis is poor with reported 5-year overall of < 20%. Methods: Data of patients with primary intra-abdominal DSRCT, who had surgery at our institution between 2000 and 2020, were analyzed. Information regarding disease presentation, cytoreductive surgery (CRS) with or without hypertermic intraperitoneal chemotherapy (HIPEC) and perioperative treatments were reported. Kaplan-Meier survival analysis was performed for both the whole cohort (A) and separately for peritoneal (B) vs peritoneal + lymphnode involvement (C) at disease presentation. Also, patients who underwent CRS alone vs CRS + HIPEC were compared. Results: 43 patients (pts) were identified, only 18 (42%) underwent surgical resection with curative intent in addition to perioperative chemotherapy (CT) ± radiotherapy (RT). 6 pts had also synchronous abdominal nodal metastases and one resectable liver metastases. Median tumor size was 19cm (12-20). 9 pts received pre and postoperative chemotherapy (CT), 7 pts preoperative CT, 2 pts postoperative CT. Postoperative abdominal RT was administered in 3 pts. Partial response (PR) to preoperative CT was observed in more than 50% of pts. Complete cytoreduction was achieved in 14 pts (78%). HIPEC was performed in 5 patients (28%). Overall, 8 pts died (44%), 1 patient after developing liver and lung metastases while 7 had peritoneal and intra-abdominal lymphnode recurrence. Of 10 patients alive, 7 had a recurrence. Of them, 5 are alive with disease (1 presenting extra-abdominal recurrence, 3 lymph node involvement and 1 liver metastases) at 75, 38, 33, 15 and 31 months, respectively, from diagnosis. 2 are alive without disease (after having a further surgery for local recurrence) at 35 and 36 months, respectively, from diagnosis. 3 patients are alive without disease at 12, 64, and 213 months from diagnosis. As a result, 5-year OS was 39.6%, 35.6% and 40% for group A, B and C, respectively. Median survival time was 39.2, 39.2 and 57.7 months for group A, B and C, respectively. 5-year OS was 35.2% and 50% for CRS and CRS + HIPEC group respectively. Conclusions: Despite an intense multimodal approach, DSRCT prognosis remains poor. CRS may improve oncologic outcomes. Our data confirmed significant tumor shrinkage after administration of preoperative CT which may be helpful to achieve macroscopically complete resections. The value of HIPEC and radiation therapy is more controversial and needs to be further investigated in a larger series. Interestingly, the presence of synchronous nodal metastases was not a negative survival prognosticator showing comparable outcome to peritoneal disease.