bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of family studies of heritable breast cancer in Africa.
Authors: Dhahri Amina , Adebamowo Sally Nneoma , Adebamowo Clement Adebayo
Published: June 2021

e22508

Background: The incidence of breast cancer (BC) in Africa (40.4 per 100,000) is 49% that of Europe and North America (81.9 per 100,000) but the mortality rate is 42% higher (19.4 versus 13.7 per 100,000). The high mortality is due to lack of screening. However, more targeted screening based on genomic risks are also missed because of stigmatization, poor family history, and limited information on BC susceptibility gene mutations. Internationally based family members are influencing cultural attitudes to BC in Africa leading to reduced stigmatization, increased better family history and uptake of genomic screening. Family-based studies of BC in Africa would provide useful information on prevalence of mutations that can inform genomic screening panels. We conducted systemic review of all family-based studies of BC in Africa to document state of the art, identify barriers and facilitators of this research method and methods of advancing the science. Methods: Using a comprehensive research strategy, we reviewed articles indexed in PubMed and African Journals Online (AJOL) to identify studies of familial BC in Africa. Specifically, we searched for family-based, study design papers on BC in each country in Africa using the following keywords: breast cancer, family-studies, hereditary, genetic, gene, mutations, and Africa. We excluded case-control, and registry studies, and clinical trials. We extracted relevant information from each study using standardized criteria: number of first- and second-degree relatives affected by BC, mutations, genetic variations, and polymorphisms. Results: A total of 12 out of 727 studies met our inclusion criteria. 80% of these studies were published after the year 2010. There were 9 publications from North Africa evaluating 191 families in total. One study reported novel breast cancer candidate genes: MMS19, DNAH3, POLK and KATB6 and nine publications investigated the mutation spectrum of BRCA genes. One publication from West Africa and one publication from Southern Africa included 1 and 219 families, respectively. All the studies done in these two regions reported targeted genomic screening for only BRCA genes. No study was done in Central and East Africa. Conclusions: There is paucity of family-based studies of breast cancer in Africa. Given the high level of heterogeneity in African genomes, these types of studies may be needed to identify high penetrance, germline mutations to better understand hereditary BC risk and ultimately develop a multigene panel testing to for diagnosis of heritable BC in this population.
Factors associated with cancer screening adherence amongst Latinos in Indiana: Results of an electronic survey.
Authors: Espinoza Gutarra Manuel Ricardo , Rawl Susan M , Valenzuela Robin E. , Parker Erik , Golzarri-Arroyo Lilian , Caeli Malloy L. , Reid Tisha R. , Haunert Laura A. , O'Leary Heather A. , Maupome Gerardo , Haggstrom David A.
Published: June 2021

e22513

Background: Latinos are the fastest growing ethnic group in the US: cancer is the leading cause of death. Cancer screening is designed to decrease cancer-specific mortality among age- and gender-appropriate populations, but is implemented less frequently among Latino populations. Barriers to screening among Latinos are less well understood. Methods: A cross-sectional, online survey was used to assess perspective on cancer information-seeking behavior, demographic, economic, healthcare access and COVID-related factors among Latino adults (>18) living in Indiana able to read and write in Spanish or English. Respondents were recruited using Facebook targeted advertisement and data were collected through Qualtrics. USPSTF recommendations for breast (BC), cervical (CC) and colorectal cancer (CRC) screening were used to evaluate screening adherence. The influence of explanatory variables on cancer-related outcomes was analyzed using univariate chi-squared tests for categorical variables and t-test for scale variables. Following this, significantly influential factors (p < 0.05) were included in multivariate logistic regression models for each response variable. Model selection was performed using stepwise regression. Results: A total of 1624 respondents participated, with 832 (51.2%) completing the survey in Spanish. Median age was 52 years old (range 18-71) for English and 54 (18-77) for Spanish respondents. 80% of respondents were located in urban areas. Cancer screening adherence rates were 45.2% for BC, 61.8% for CC and 68.0% for CRC. The main factor associated with screening adherence across all malignancies (Table) was white self-identification, other factors included having children (OR: 1.79) and having received a COVID test (OR: 1.91) for CRC, having Spanish as chosen language for the survey for CC and BC respectively. Having higher income was associated with less adherence in CRC (OR: 0.50 when expressed as subjective income adequacy, compared with people finding difficult on present income) and CC (OR: 0.18 when expressed as > 75,000 USD annual income, compared with 0-35,000 USD annual income). Conclusions: In this interim analysis of the largest Latino survey in Indiana, our findings were counter-intuitive regarding the association of income and language with cancer screening adherence. For income, these findings may have been due to lower out-of-pocket costs among vulnerable populations covered by Medicaid or Medicare insurance. For Spanish differences may be explained by increased language specific outreach for certain screening tests but not for others. Overall, these results highlight the necessity for targeted awareness campaigns for the Latino population in Indiana.[Table: see text]
Chromosomal instability associated with pathogenesis in adenomyosis.
Authors: Chao Xiaopei , Wu Wendy , Li Lei , Li Hui , Li Zhenzhen
Published: June 2021

e22517

Background: Uterine adenomyosis is a benign condition in which endometrium-like epithelial and stromal tissue appear in the myometrium, but easily concurrent with uterine cancer and other diseases. To date, few investigations have explored the molecular mechanism of adenomyosis. This research is the first report that found the association between chromosomal instability and pathogenesis in adenomyosis. Methods: Whole exome (̃39Mb CDS of over 18,000 genes; WES) and RNA sequencing were conducted on a total of 57 adenomyosis patients enrolled in this study from 2018 to 2020, including 57 normal endometrium (EN), 57 adenomyosis (AM) and 11 endometrioses (EMT) samples. Genomic test results including somatic SNVs and CNVs as well as the whole genome duplication status were determined, which were all analyzed correlated with clinical factors. Results: We identified the presence of whole genome doubling event in 19 specimens from 16 adenomyosis patients (grouped as WGD, the other 41 patients grouped as noWGD), related to 7 normal endometrium (EN), 9 adenomyosis (AM) and 3 endometriosis (EMT) samples, which was significant with p value of 4.5e-12 by means of Wilcoxon rank sum test. Disease Free Survival (DFS) of WGD patients was significantly shorter than noWGD patients (Wilcoxon rank sum test: P = 2.42e-04), which indicated that WGD group has early on-set in adenomyosis. Estrogen therapy was applied to 31 patients before uterectomy (11 in WGD group and 20 in noWGD group), and the effectiveness of the treatment was significantly higher in WGD patients (Fisher’s exact test: P = 0.02). We found that one third adenomyosis performed whole genome doubling events, which leaded to the early on-set of this disease and significantly sensitive to estrogen therapy. Cellular stressors are extensive correlated with the generation of polyploid cells in a diploid organism form by cell proliferation progress. Compared with the normal and energy-intensive cell differentiation process, cell proliferation offers a “fast but cheap” solution under stress. Our results suggested that when cell differentiation in uterine could not be carried out properly, cell proliferation would have performed instead and produced more polyploid cells, shown as whole genome doubling events. While this circumstance would have been relieved when easing the metabolic stress with estrogen treatment. Conclusions: Our results explored the strong association between chromosomal instability and pathogenesis of adenomyosis and assumed that polyploidy caused by abnormal cell proliferation might be the molecular mechanism of uterine adenomyosis. More accurate verdict could be concluded through larger scale cohort study.
The feasibility and potential role of pharmacogenetics to improve drug safety in patients with advanced cancers.
Authors: Darabi Sourat , Weatherill Chelsey , Dalili-Shoaie Valentina , Eisenberg Burton Larry , Demeure Michael J.
Published: June 2021

e22522

Background: Pharmacogenetics is the study of genetic variants that define drug metabolism and dosing requirements, response or toxicity. Knowledge regarding drug-drug interactions and individual variations in genes involved in drug metabolism is increasing. Since patients with cancer often take several drugs (polypharmacy), they have a higher risk of severe drug interactions. The FDA lists several pharmacogenetic biomarkers in drug labeling, including genetic variants that impact how certain medications are prescribed. The drugs listed span multiple medical applications, including but not limited to oncology, primary care, psychiatry, neurology, cardiology, and many more. Adverse drug reactions are a significant cause of morbidity and mortality, yet the use of pharmacogenetic testing has not yet become established as a routine in clinical practice. Herein we sought to study the feasibility of applied pharmacogenetics in a pilot drug safety program in patients with advanced cancer. Methods: We enrolled patients in a prospective single-center IRB approved study. Patients with advanced cancer on three or more drugs about to begin chemotherapy at the Hoag Family Cancer Institute were eligible. Informed consent was obtained from the study participants, and their samples were sent to a CLIA laboratory to conduct a 25-gene pharmacogenetics testing panel, which includes “major drug-metabolizing enzymes” CYP2D6, CYP2C19, CYP2C9, CYP3A4, and CYP3A5 as well as other genes with known drug implications. We recorded patients’ demographics and clinical information. In addition, participant’s drug lists were assessed for potential polypharmacy interactions. Results: We analyzed the results from 36 patients, 20 females and 16 males, enrolled between December 2017 and June 2020. Pharmacogenetics results from these patients showed that 61% (22 patients) had a variant with gene drug interaction indication. The most common variants were identified in the CYP2D6 gene, followed by CYP2C19, CYP3A4, and CYP3A5. Of these 22 patients, seven patients had at least one major criterion (drug interactions may lead to severe clinical effects), and eight patients with reported moderate criteria (may lead to substantial clinical effects). Additionally, seven patients had variants with both major and moderate criteria. Patients were taking an average of 10 medications per person ranging from 3-19 drugs. No patient, however, experienced significant drug toxicity during the observation interval. Conclusions: Patients with advanced cancer are at particular risk for polypharmacy and adverse drug reactions. Our data report supports pharmacogenetics testing as being feasible for oncology patients. Therefore, programs to prevent or limit the frequency and severity of drug reactions warrant further exploration as they offer the potential to improve patient safety and decrease healthcare costs.
Challenges in lung cancer multidisciplinary collaboration experienced by specialists in four countries.
Authors: Murray Suzanne , Subbiah Vivek , Grohé Christian , Nakagawa Kazuhiko , Zahabi Sacha , Sireci Anthony , Sherman Steven I. , Kelly Elizabeth , Lazure Patrice
Published: June 2021

e23002

Background: The importance and challenges of Multidisciplinary Team (MDT) collaboration in managing lung cancer have been increasingly recognized in an ever more complex therapeutic environment. Data on physicians’ viewpoints regarding MDT collaboration in lung cancer care, collected in a broader study assessing challenges related to lung/thyroid cancer patient management, are presented. Methods: A mixed-methods approach was used to analyze this data, combining qualitative interviews and a quantitative survey. Pulmonologists (PLM), oncologists (ONC) and pathologists (PTH) from Germany (GE), Japan (JP), the United Kingdom (UK) and the United States (US) were recruited. Results: A total of 44 specialists participated in interviews and 377 in a survey. Quantitative data reveal that 53% of pulmonologists in JP and 39% in GE have suboptimal knowledge of the timing of patient referral to an oncologist. Fewer PLM/PTH from JP (43%/47%) report a fully integrated MDT team approach in their clinical setting, compared to those from GE (80%/95%), the UK (96%/82%) and the US (82%/97%). Qualitative data indicate that current MDT team practices are perceived as delaying patient care due to significant inefficiencies (sometimes due to lack of knowledge/skills) and unclear responsibilities within the team. Around half of ONC in each country and 78% of PLM from the UK report a gap in knowledge and relevance of each genetic biomarker test according to clinical presentation. PTH in the UK (70%), the US (50%), and JP (72%) report sub-optimal skills identifying biomarker tests to inform the progression of lung cancer (also a challenge for PLM/ONC). Conclusions: This study indicates a need for multi-level interventions addressing systemic and attitudinal barriers as well as knowledge gaps which affect physicians’ ability to collaborate in lung cancer care.
Fostering interspeciality learning in cancer survivorship care: Learning suite results.
Authors: Chaput Genevieve , Sussman Jonathan , Williams Tristan
Published: June 2021

e23003

Background: As survivorship provision declines within cancer centres, primary care providers are increasingly entrusted in the follow-up care of cancer survivors. Empowering specialists and primary care providers about survivorship through educational interventions is essential. Interspecialty education is poorly integrated into residency training, which may impede collaboration between different providers in practice. Interspecialty partnership can positively impact patient and resource-use outcomes. The aim of this study was to assess if a cancer survivorship learning suite (LS) impacts attitudes of family medicine, radiation oncology and medical oncology trainees towards interspecialty collaboration in Montreal, Canada. Methods: A survivorship (LS) developed by a Manitoba-based team under the sponsorship of a Canadian Partnership Against Cancer grant held by Cancer Care Ontario was delivered to 49 McGill University family medicine, radiation oncology, and medical oncology trainees. The LS comprised in-person delivery of a 3-hour case-based workshop, presented by a radiation oncologist and a family physician, both experienced in the field of survivorship. An adapted version of the Readiness for Interprofessional Learning Scale (RIPLS) was completed by participants before and after workshop delivery. Statistical analyses included non-parametric (Wilcoxon Signed rank tests) comparisons. Results: Response rate was 63.2%, and included family medicine (65%), radiation oncology (26%), and medical oncology (10%) trainees, respectively. Following the workshop, participants were significantly more likely to agree that interspecialty learning in residency “would help physicians become better team workers”, (Z = 2.7, p < 0.008, n = 31), and “improves relationships between physicians of different specialties in independent practice afterwards”, (Z = 2.6, p < 0.009, n = 31). Participants were also significantly more likely to agree that “shared interspecialty learning < would > increase < their > ability to understand clinical problems”, (Z = 2.8, p < 0.005, n = 31). Conclusions: While much literature has focused on interprofessional collaboration at different levels of education and practice, few studies have assessed interspecialty collaboration of physicians of different specialties. This survivorship LS demonstrated favorable changes in attitudes towards interspecialty learning.
Apatinib plus ifosfamide and etoposide (IE) versus IE chemotherapy alone for relapsed or refractory osteosarcoma.
Authors: Xie Lu , Guo Wei , Xu Jie , Gu Jin , Tang Xiaodong , Li Yuan , Sun Kunkun
Published: June 2021

e23502

Background: Results of previous study showed promising objective response but short-lived activity of apatinib in the treatment of osteosarcoma refractory to first-line chemotherapy, from which we observed the disease control of musculoskeletal lesions were worse than pulmonary lesions. This treatment failure has partly been overcome by the addition of Ifosfamide and etoposide in OLIE study. We aimed to retrospectively compare the activity of apatinib in combination with IE in relapsed or refractory osteosarcoma with synchronous patients receiving IE chemotherapy alone in two sarcoma centers in China. Methods: We retrospectively analyzed medical files and radiographic materials of patients with osteosarcoma relapsed or refractory to first-line chemotherapy, who had received combination of apatinib and IE regimen or IE chemotherapy alone between June 3rd, 2017 and July 17th, 2020. Seventy-nine patients were included, of whom 33 patients received apatinib in combination with IE and 46 patients received single IE chemotherapy. Results: Patients’ tumor burden and general status were obviously different between these two groups with 16/33 (48.5%) patients receiving apatinib+IE having both Lung and musculoskeletal lesions at baseline and 39/46 (84.8%) patients receiving single IE having just pulmonary lesions at baseline. However at last follow up 16/33 (48.5%) of patients receiving apatinib+IE had all lesions resected while 23/46 (50.0%) of patients receiving IE alone had their lesions resected, which might partly due to down-staging of the diseases. With median follow-up time of 28.4 (IQR, 16.1-38.3) months, 21/33 (63.6%) patients receiving apatinib+IE had objective responses while 13/46 (28.3%) patients receiving single IE chemotherapy had responses. The median event-free survivals (EFS) were respectively 11.4 (IQR, 6.7-18.4) months for apatinib+IE and 11.2 (IQR, 4.4-21.8) months for IE alone without significant statistical differences (P = 0.47). The overall survival (OS) was obviously different because of disease stage and tumor burden according to Kaplan-Meier analysis with median OS time of 30.4 (IQR, 21.8-not reached) months for IE alone and 19.8 (IQR, 13.1-30.6) months (P = 0.019). Conclusions: For osteosarcoma with multiple sites’ metastasis, apatinib plus IE demonstrated clinically meaningful antitumor activity in patients with recurrent or refractory osteosarcoma after failure of MAP/I chemotherapy or even single apatinib or IE treatment alone, with a positive effect on delaying disease progression. This combination deserves further investigation in prospective trials with manageable toxicity.
Efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic Ewing sarcoma.
Authors: Dogan Izzet , Iribas Ayca , Ekenel Meltem , Basaran Mert
Published: June 2021

e23510

Background: The purpose of the study was to evaluate the efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in heavily pretreated adult patients with metastatic Ewing sarcoma. Methods: We evaluated data of the patients with metastatic Ewing sarcoma retrospectively. We recorded clinical, pathological, radiological, and treatment features of the patients and used SPSS 25. version for statistical analysis. Kaplan-Meier and Cox regression analysis were used for survival analysis. Results: Sixteen patients were included in the study. The median age was 25 (range, 20-42) years. Eleven (68.8%) of the patients were male. The origin of the tumor was bone (75%) and soft tissue (25%). The most common primary tumor localization was pelvic (41.7%), extremity (33.3%), and other sites (25%), respectively. Six (37.5%) patients were de-novo metastatic at diagnosis. The most common metastatic site was the lung (75%). Before the vincristine, irinotecan, and temozolomide (VIT) combination, patients had received at least two different chemotherapy regimens (87.5%) and palliative radiotherapy (37.5%). Median progression-free survival was 3.4 (95% CI, 1.8-4.9) months. The partial response was observed in five (31.3%) patients, and all other patients (68.7%) had progressive disease. Grade 1-2 adverse events were observed in thirteen (81.3%) patients and grade 3-4 in five (31.3%) patients. The most common adverse events were hematological (87.5%). Median overall survival was 5.6 (95% CI, 3.6-7.5) months. Conclusions: In this study, we showed real-life efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic osteosarcoma. Toxicities were concern about in these heavily pretreated patients. Treatment options of metastatic Ewing sarcoma are limited. VIT regimen may be considered in patients who have a good performance.
Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.
Authors: Tararykova Anastasia Alekseevna , Bokhyan Beniamin , Konev Andrey A. , Falkina Polina A. , Kumekhov Zaur Yu. , Valiev Aslan K.
Published: June 2021

e23528

Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.
Health-related quality of life after isolated limb perfusion compared to extended resection, or amputation for locally advanced extremity sarcoma: Is a limb salvage strategy worth the effort?
Authors: Reijers Sophie J.M. , Husson Olga , Soomers Vicky L.M.N. , Been Lukas B. , Bonenkamp Han J. , van de Sande Michiel A.J. , Verhoef Cornelis , Van Der Graaf Winette T.A. , van Houdt Winan J.
Published: June 2021

e23539

Background: Induction isolated limb perfusion (ILP) followed by limb-sparing resection or extended resection are frequently used limb salvation strategies (LSS) in locally advanced extremity soft tissue sarcoma (eSTS) to prevent amputation. However little is known about the long term health-related quality of life (HRQoL) in these patients. The aim of this study was to compare long-term patient reported outcomes (PROs) such as HRQoL after ILP compared to extended resection or amputation. Methods: Patients treated with an ILP, extended resection, or amputation were selected from the respondents of a multi-institutional cross-sectional cohort survivorship study (SURVSARC) conducted 2-10 years after diagnosis among sarcoma survivors registered in the Netherlands Cancer Registry (NCR). Extended resection was defined as resection for stage III eSTS, details regarding amputation levels other than upper or lower extremity are unknown. Used PROs were the EORTC QLQ-C30, Cancer worry scale (CWS), the Hospital Anxiety and Depression Scale (HADS), and the Toronto Extremity Salvage Score (TESS). Results: We identified 96 eSTS survivors and assigned them into four groups: ILP (N = 20), extended resection (N = 48), primary amputation (N = 20), and amputation after ILP (N = 8). While there were no differences in PROs between ILP and extended resections, results showed better functioning and functionality after these two LSS groups versus the amputation groups. The amputation groups scored significantly lower on the EORTC QLQ-C30 physical functioning scale (p < 0.001, 62.7 and 65.7 versus 78.0 and 84.1) and role functioning scale (p = 0.038, 67.5 and 52.8 versus 79.2 and 80.9), which both account for a difference with ‘medium’ clinical relevance. Also for the TESS, the scores were significantly lower for the amputation groups compared to the LSS groups (upper extremity p = 0.007 with 68.9 and 71.6 versus 93.3 and 91.1; lower extremity p < 0.001 with 72.2 and 50.9 versus 84.5 and 85.5). There were no significant differences on cancer worry, anxiety and depression were found between all groups. Conclusions: Based on this survivorship study, HRQoL in eSTS survivors treated with ILP followed by limb-sparing resection is not inferior to extended resections, however it is superior in maintenance of physical functioning and functionality compared to an amputation.[Table: see text]
A retrospective study to evaluate the safety and efficacy of anlotinib plus camrelizumab in management of advanced retroperitoneal sarcoma.
Authors: WU Jianhui , Qiu Hui , Lv Ang , Liu Bonan , Liu Qiao , Li Chengpeng , LIU Daoning , Wang Zhen , Tian Xiuyun , Hao Chunyi
Published: June 2021

e23545

Background: Several studies have demonstrated the antitumor activity of single-agent anlotinib in the treatment of soft tissue sarcoma (STS). However, the most effective results were from cases of alveolar soft part sarcoma (ASPS), which was a rare subtype in retroperitoneal sarcoma (RPS). The therapy of RPS is still dismal. Thus, we evaluated the effectiveness and safety of anlotinib plus camrelizumab for the treatment of RPS. Methods: We retrospectively reviewed the data of 36 patients with advanced/metastatic RPS in Sarcoma Centre of Peking University Cancer Hospital from July 2019 to February 2021. Anlotinib was given 12mg Qd 2 weeks on and 1 week off, and camrelizumab was transfused 200mg at Q3w. Patients that underwent at least 4 cycles of therapy were enrolled in this study. The primary endpoint is objective response rate (ORR) and evaluated according to the irRECIST 1.1 criteria. Results: The pathologic subtypes of enrolled cases include liposarcoma (LP) (n = 16), leiomyosarcoma (LMP) (n = 5), uncertain differentiation sarcoma (n = 7), fibroblastic and myofibroblastic tumours (n = 4), rhabdomyosarcoma (n = 2) and malignant peripheral nerve sheath tumour (MPNST) (n = 2). Two patients (5.6%) achieved CR and 9 patients (25.0%) achieved PR, with an ORR of 30.6%. Eighteen patients (50.0%) achieved SD and 7 patients (19.4%) were evaluated as PD, with the disease control rate (DCR) of 80.6%. The progression-free rate (PFR) at six months was 60.0%. Five patients underwent further radical surgical resection. The two CR cases were diagnosed as dedifferentiated liposarcoma (DDLP) and MDM2 amplified MPNST respectively, and both patients have been under CR status for over 12 months until now. The only grade 3 or higher treatment related adverse event was hypertension (22.2%). Camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) was not observed in this group of patients. Conclusions: The combination of anlotinib and camrelizumab demonstrated encouraging efficacy and safety in the treatment of RPS. A further clinical study with biomarker exploration should be performed in the future.
Activity of single-agent gemcitabine in patients (pts) with advanced angiosarcoma: A retrospective study.
Authors: Watson Sarah , Verret Benjamin , Ropert Stanislas , Adam Julien , Bahleda Rastilav , Briand Sylvain , Cavalcanti Andrea , Chamseddine Ali N. , Court Charles , Fadel Elie , Faron Matthieu , Haddag Leila , Henon Clemence , Le Pechoux Cecile , Levy Antonin , Mercier Olaf , Ngo Carine , Honoré Charles , Le Cesne Axel , Mir Olivier
Published: June 2021

e23547

Background: Gemcitabine has shown clinical activity against angiosarcoma in single cases or small series, as a single agent or in combination with taxanes. We aimed to evaluate its activity in a larger, homogeneous series of pts with advanced angiosarcoma. Methods: We retrospectively reviewed the electronic medical records of consecutive adult pts with advanced angiosarcoma treated with gemcitabine(1000 mg/m2 IV days 1, 8 and 15 of a 28-days cycle) at our institutions from January 2010 to January 2021. All cases were confirmed by an expert pathologist from the French network of Sarcoma pathologists (RRePS). Response was evaluated according to RECIST 1.1, and survival was estimated using the Kaplan-Meier method. Results: Fourty-two pts [median age : 52 years (range : 25-90), median PS : 1 (range : 0-2), 36 women)] were identified. Ten (24%) had locally advanced disease; the median number of metastatic sites was 2 (range : 1-4) in the remaining 32 pts. Primary tumor site was breast/chest wall (12), face/scalp (9), heart (8), other viscera (7) or limbs (7). Eleven (26%) occurred in previously irradiated field. All pts but 4 had received prior anthracyclines (peri-operatively or in the metastatic setting) and weekly paclitaxel, and 9 (21%) had received pazopanib. Gemcitabine was given as second, third and fourth line in 7 (17%), 20 (47%) and 15 (36%) pts, respectively. Best tumor response by RECIST 1.1 was PR (16 pts, 38%), SD (10 pts, 24%) or PD (16 pts, 38%). All pts with cardiac angiosarcoma experienced a PR, as well as 4 of 10 pts with angiosarcoma arising in irradiated field and 3 of the 4 pts with CNS metastases. Median PFS was 5.4 months (95%CI : 3.1-6.5), and median OS was 9.9 months (95%CI : 6.6-13.4). Two febrile neutropenia occurred. No new safety signal was observed. Ongoing studies are exploring whether candidate biomarkers such as hENT1 expression could help predicting the benefit of gemcitabine in pts with angiosarcoma of the heart and large vessels. Conclusions: Single agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma (including cardiac angiosarcoma). This series may serve as a benchmark for future clinical trials in angiosarcoma.
Outcomes of VAC temporization following the excision of microinvasive sarcomas pending negative formal pathologic margins.
Authors: Fourman Mitchell Stephen , Ramsey Duncan C. , Newman Erik T. , Schwab Joseph H. , Chen Yen-Lin , DeLaney Thomas F. , Mullen John Thomas , Raskin Kevin , Lozano-Calderon Santiago
Published: June 2021

e23559

Background: Microinvasive sarcomas can yield a high number of false negative intraoperative pathology margin analyses. Additional oncologic resection after soft tissue coverage is technically challenging and oncologically inaccurate. As a result the rate of local recurrence for these histologies can be 25% or higher. In select patients we have temporized the sarcoma tumor bed with a wound VAC pending final pathologic margins. If positive, the patient can return to the OR for a tumor bed excision. If negative, soft tissue coverage can proceed. Here we evaluate our outcomes using this approach. Methods: We retrospectively studied patients with primary sarcomas managed with a VAC temporizing approach from from 1/1/2003 to 12/1/2019 with a minimum of 2 years of oncologic follow-up. Patients with unplanned ("oopsie") excisions were also included. Our primary outcome was local recurrence. Data is presented as percentages or mean ± standard deviation where appropriate. Results: Sixty-three patients were included (Table). Mean age was 62.3 ± 22.3 (median 67.3) years, 23 (36.5%) were female, and mean age-adjusted charlson comorbidity index was 5.3 ± 1.9. Twenty-four (38.1%) had undergone “oopsie” excisions. R0 margins were achieved in 59 (93.7%) patients, while the other 4 were known R1 resections due to patient tolerance or anatomy. Five local recurrences (7.9%) were diagnosed 3.2 ± 1.5 years after surgery, of which 3 had known positive margins. Free flaps were needed in 17 (27.0%) patients. Metastatic disease was diagnosed in 8 (12.7%) patients, who all died of disease. Mean follow-up was 4.4 ± 2.9 years. Conclusions: VAC temporization results few local recurrences in patients with formally confirmed negative margins. This technique is particularly useful in the treatment of microinvasive disease or in the management of vulnerable hosts who may not be able to tolerate additional surgery in the future.[Table: see text]
Impact of the geriatric assessment on clinical treatment decision in older Indian persons with cancer.
Authors: Noronha Vanita , Ramaswamy Anant , Patil Vijay Maruti , Gattani Shreya , Menon Nandini , Mahajan Sarika , Castelino Renita , Dhekle Ratan , Daptardar Anuradha , Gota Vikram , Banavali Shripad Dinanath , Prabhash Kumar , Badwe Rajendra A.
Published: June 2021

e24015

Background: The geriatric assessment (GA) is a multidimensional evaluation of an older person. Identification of the non-oncologic vulnerabilities, estimation of life expectancy and chemotherapy risk prediction aid the clinicians in the therapeutic risk-benefit ratio analysis. Globally, GA leads to changes in oncologic decisions in 28% of patients. Methods: An observational study with a retrospective and prospective cohort of patients who underwent a GA in the geriatric oncology clinic at the Tata Memorial Hospital in Mumbai, India. The study was approved by the institutional ethics committee (IEC) and registered with Clinical Trials Registry of India-CTRI/2020/04/024675. Written informed consent was obtained from the patients enrolled in the prospective part of the study; the IEC granted a consent waiver for the retrospective portion of the study. Patients aged 60 years and older with a diagnosis of malignancy were evaluated in the geriatric oncology clinic. The results of the GA were entered in the electronic medical records (EMR). The systemic therapy plan prior to the GA and the actual therapy plan made were retrospectively captured from the EMR. The primary objective was to determine the proportion of patients in whom the systemic therapy plan was changed following the GA. Results: Between June 2018 and Feb 2021, 340 patients were evaluated in the geriatric oncology clinic for whom the pre-GA and post-GA systemic therapy plans were available. The median age was 70 years (range, 60-100); 264 (78%) were men. The common malignancies were lung cancer in 134 (39.4%) and gastrointestinal in 119 (35%). The intent of therapy was palliative in 190 (56%) patients. Following the GA, the systemic therapy plan was changed in 125 (36.8%) patients. The most common change was deintensification of therapy in 106 patients (31.2%), including dose reduction in 41 (12%), decrease in the number of chemotherapy medicines in 8 (2.4%), substitution of chemotherapy by targeted therapy (4, 1.2%)/oral hormonal therapy (4, 1.2%)/oral TKI (11, 3.2%)/immunotherapy (2, 0.6%) and withholding systemic therapy in 36 (10.6%) patients. Withholding systemic therapy consisted of a change from chemoradiotherapy to radical radiation alone in 17 (5%), withholding neoadjuvant or adjuvant chemotherapy in 5 (1.5%) and a change to best supportive care in 14 (4.1%). Conclusions: The results of the GA led to a change in the management plan in over one-third of older Indian patients with cancer. GA is an important tool in the oncologic decision-making process for older persons with cancer. Clinical trial information: CTRI/2020/04/024675.
Psychometric properties of patient reported outcome (PRO) instruments in patients with small cell lung cancer (SCLC) in RESILIENT part 1.
Authors: Kokhreidze Jaba , Allen Veleka , Ivanescu Cristina , Yao Xiaopan Valerie , Zhang Bin , Harrow Brooke
Published: June 2021

e24027

Background: The ongoing two-part phase 2/3 RESILIENT study (NCT03088813) is investigating the efficacy and safety of liposomal irinotecan monotherapy in patients with SCLC who have progressed on or after first line platinum-based chemotherapy. This exploratory analysis from RESILIENT part 1 was conducted to confirm the psychometric properties of established PRO instruments that had not previously been validated in patients with SCLC. Methods: Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (C30) and the EORTC QLQ Lung Cancer 13 (LC13) before treatment assignment (baseline), every 6 weeks thereafter, at treatment discontinuation and at the 30-day follow-up visit. Psychometric methods included descriptive statistics (items and scales), correlations (item-to-item and item-to-total), internal consistency (Cronbach’s α), test-retest reliability (intraclass correlation coefficient [ICC], two-way random effects model), construct validity and sensitivity to change. The analysis included patients who received at least one dose of study drug and completed at least one PRO assessment. Results: Thirty patients were enrolled in RESILIENT part 1 and included in the analysis. At baseline, 68% of patients reported ‘not severe’ or ‘mild’ symptoms. Floor effects (i.e. more than 25% of responses of ‘not at all’) were observed for several of the functioning/impact and symptom scales of the EORTC QLQ C30 and LC13. Moderate to strong correlations were found among most questionnaire items within their respective scales. Acceptable evidence for internal consistency and good test-retest reliability were observed. Selected results for the EORTC QLQ LC13, including dyspnea scales, are shown in the Table. The magnitude of correlations among PRO instruments supported evidence for convergent validity in this sample. Conclusions: In RESILIENT part 1, patients experienced low and tolerable symptoms at enrollment, limiting the potential for further improvement. Overall, these PRO instruments had acceptable psychometric properties (e.g. construct validity, reliability and ability to detect change) in this sample. However, these analyses should be repeated in a larger sample using data from RESILIENT part 2. Clinical trial information: NCT03088813. [Table: see text]
COVID-19 and cancer: Strategic health promotion for indigenous Australians during a pandemic.
Authors: Der Vartanian Carolyn , Milch Vivienne , Garvey Gail , Anderiesz Cleola , Salisbury Jane , Woods Candice-Brooke , Austen Melissa , Wang Rhona , Keefe Dorothy Mary Kate
Published: June 2021

e24028

Background: Given the impact of COVID-19 on Indigenous and ethnic minority populations observed globally, keeping COVID-19 out of vulnerable Aboriginal and Torres Strait Islander (Indigenous Australian) communities remains a priority. Compared to non-Indigenous Australians, Indigenous Australians experience disparities in cancer incidence and outcomes due to social disadvantage, increased cancer-related modifiable risk factors, poorer access to health services and lower participation in screening. During the pandemic, cancer-related investigations and treatment reduced significantly in Australia, leading to potential decreases in cancer diagnoses and consequences for future survival outcomes. Concerned about the risk of morbidity and mortality due to COVID-19 for Indigenous Australians, as well as worsening cancer outcomes, Cancer Australia undertook strategic health promotion initiatives, to inform and support optimal cancer care. Methods: In consultation with respected Indigenous colleagues to ensure cultural appropriateness of language and information, we published a dedicated webpage titled ‘ Cancer and COVID-19 – what it means for our Mob*’ with tailored information, advice, and links to key resources and support services for Indigenous Australians. We also released a video titled ‘ Act early for our Mob’s Health’, providing targeted, culturally appropriate, consumer-friendly information to encourage Indigenous Australians to see their doctor or Aboriginal Health Worker with symptoms that may be due to cancer. Results: The information hub has been well-received among the Indigenous Australian community, receiving over 3,200 visits, and the social media campaigns have received over 1.4 million impressions and 46,000 video views between mid-March 2020 to mid-February 2021. This campaign has supported proactivity among the Indigenous population in keeping their communities safe during the pandemic, maintaining a population rate of COVID-19 of less than one percent of all confirmed cases in Australia. Conclusions: Culturally appropriate information and resources developed through the process of co-design can help to influence positive health behaviour change in Indigenous populations. We predict that our strategic, multi-channel health promotion campaign is contributing to keeping the Indigenous Australian community safe and informed during the pandemic, with additional work needed to monitor cancer rates and outcomes and address the ongoing information needs of the community. *Mob is a colloquial term to identify a group of Indigenous Australians associated with a family or community from a certain place.
An analysis of content of lay-press articles focused on cancer from leading U.S. newspapers from 2010 to 2019.
Authors: Adwetewa-Badu Abena A. , O'Keefe Ryan M , Callahan Joseph X. , Taylor Catherine A. , Gjino Chris P. , Hill-Kayser Christine E.
Published: June 2021

e24032

Background: Newspaper coverage of cancer-related topics has historically focused on research, treatment, survival, and impact of tobacco and diet on risk, with less coverage of prevention, death, and palliation/hospice. Coverage tends to be driven by celebrity and other seminal events, and highest during awareness-months, with over and under representation of breast and lung cancers, respectively, based on incidence. We sought to understand evolving trends in coverage over the last decade at 3 major U.S newspapers to identify areas for improvement for education, inclusion, and public health messaging. Methods: On 10/13/20, Factiva was queried with the keyword “cancer” for articles > 150 words published by NYTimes, Washington Post, and Wall Street Journal between 2010-2019. The top 100 articles by “relevance” were selected for each, representing 14.9% of all the 2016 hits. A coding scheme was created using articles from the same query for 2020; inter-rater reliability analysis between coders was conducted with a sample of 30 articles (10% of final set), and kappa-fleiss scores were calculated. Articles were excluded if they did not focus on cancer, or were an obituary, financial report, or editorial. Results: 230 articles were included. Kappa-fleiss scores were 0.74 - 1, suggesting excellent agreement between coders. 102 (44.3%) focused on research, 50 (21.7%) individual disease narratives, 22 (9.6%) drug development, 15 (6.5%) policy or regulation. 136 articles focused on one sub-type; breast (53, 39.0%) was most common, followed by colorectal (13, 9.6%), leukemia/ lymphoma (12, 8.8%), prostate (11, 8.1%), pancreatic (9, 6.6%), and lung (8, 5.9%). 154 articles discussed research; 22 (14.3%) non-human research. Commonly covered topics included pharmaceuticals (128, 55.7%), risk factors (71, 30.9%), cost of care (66, 28.7%) and adverse effects (58, 25.2%). Risk factors discussed included smoking (22, 31.0%), diet (21, 29.5%), and alcohol (7, 9.9%). Less common topics were radiation (18.7%), insurance coverage (13.9%), celebrities (12.6%), death (8.7%), race (4.3%), and disparities (3.9%). 156 (67.8%) provided quotes from HCPs/researchers, 59 (25.7%) patients, 17 (7.4%) families or other supports. 22 (9.6%) titles had “war” terminology; 13 (5.7%) had the word “may”. Conclusions: Most articles focused on research or personal narratives, most commonly in context of breast, colorectal, and leukemia/lymphoma. Pharmaceutical treatments were the most discussed content topic. Compared with previous analyses, risk factors, adverse effects, and cost of care were discussed more often. However, race, disparities, death, and end-of-life topics remain uncommon. There was good representation from the healthcare and scientific community; opportunities exist to include more educational information on risk and adverse events, as well as patient and family perspectives.