bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse events and estimated costs with the combination of ipilimumab and nivolumab in metastatic melanoma patients.
Authors: Moura Bianca Gautron , Gérard Camille Léa , Testart Nathalie , Caikovsky Marian , Wicky Alexandre M. , Aedo-Lopez Veronica , Berthod Grégoire , Homicsko Krisztian , Prior John , Dromain Clarisse , Kandalaft Lana E. , Cuendet Michel A. , Michielin Olivier
Published: June 2021

e21529

Background: The combination of ipilimumab and nivolumab in metastatic melanoma patients increases response rates (RR) and survival outcomes. As checkpoint inhibitors bear a significant financial impact on the healthcare system, we performed a study that addresses the global costs of the treatment, focusing on immune-related adverse event (irAE) management costs. Methods: We conducted a retrospective analysis of 62 metastatic melanoma patients treated with ipilimumab and nivolumab at the Oncology Department of Lausanne University Hospital (CHUV) between June 1, 2016 and August 31, 2019. The frequency of irAEs, the duration, management, and outcomes were evaluated. All melanoma-specific costs were analyzed by mining the electronic healthcare record and billing data of the hospital. Results: The median follow-up was 32 months (range 20-1066 days). In our cohort, 54/62 (87%) patients presented at least one irAE, and 22/62 (35%) presented a grade 3 irAE. One patient died from an irAE (pneumonitis). The most common irAEs were diarrhea 23/62 (37%) any grade, 8/62 (13%) grade 3-4; hepatitis 22/62 (36%) any grade, 9/62 (15%) grade 3-4; and skin rash 21/62 (34%) any grade, 6/32 (10%) grade 3-4. The overall response rate was 29/62 (47%), with 15/62 (24%) of complete response (CR) and 14/62 (23%) of partial response (PR). The majority of patients who had a CR 13/15 (87%) and 20/28 (71%) of overall responders presented a grade 3-4 toxicity, and there were no responses in patients without toxicity. However, toxicity does not imply response, as only 29/54 (54%) of patients with toxicity (any grade) and 20/31 (65%) (grade 3-4) responded. The toxicity costs represent only 3% on average of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%, mainly disease-related hospitalization costs). Patients with a CR had the lowest global cost per week (2,860 USD, converted from CHF) despite the associated toxicities and patients who had progressive disease, the highest one (9,999 USD). Except for the one patient who had a grade 5 toxicity (7,472 USD/week), we observe that less severe toxicity grades (11,603 USD/week for grade 1), or even the absence of toxicity (12,266 USD/week), are associated to higher median costs per week (against 4,039 USD/ week for grade 4 and 3,524 USD/week for grade 3). Conclusions: The cost of toxicities was unexpectedly small (only 3%) compared to the total costs, especially medication costs (44%). Also, patients with a higher degree of toxicity had lower costs and better outcomes.
Contextualizing a single-arm trial of ceralasertib (cer) plus paclitaxel with real-world data (RWD) in patients (pts) with advanced melanoma previously treated with anti-PD-(L)1(PDx) therapies.
Authors: Jiang Miao , Lee Jeeyun , Jackson Daniel , Smith Simon , Khosla Sajan , LoembE Bienvenu , Dean Emma , Smith Claire
Published: June 2021

e21542

Background: Metastatic melanoma, especially in pts who do not respond to PDx therapy, is an area of high unmet need. Chemotherapy may be used but clinical efficacy is limited. A recent Phase I study (NCT02630199) showed that cer + paclitaxel had promising anti-tumor activity with durable responses in 34 melanoma pts after failing PDx therapy. Given the lack of published prospective clinical trial data in the post-PDx setting, RWD was used to contextualize the results of the trial. Methods: Adult pts (≥18 years) diagnosed with advanced melanoma between Jan2011-Jun2020, who received PDx therapy alone or in combination with anti-CTLA4, and also received chemotherapy immediately after the PDx line (chemo cohort) were selected from the nationwide US-based Flatiron Health EHR-derived de-identified database. A subgroup of pts who received taxane was also selected. Overall survival (OS) was assessed using Kaplan-Meier methods. Key covariates such as age, gender, LDH level, number of prior lines of therapy, presence of brain and liver metastases, and prior BRAF/MEK treatment, were adjusted using propensity score-based weighting approach. Cox regression models were used to obtain the effect estimates for OS comparing the trial arm against the RWD cohorts. Results: A cohort of 114 pts met the inclusion criteria, of which 69 received taxane. Compared with the trial arm, the RWD cohorts were older, contained more males, with higher proportions receiving prior BRAF/MEK inhibitors, with brain metastasis, and LDH≤ULN. Median OS was 7.4 months (mo) in the trial arm, compared to 5.6 (unadjusted) and 3.5 mo (adjusted) in the chemo cohort. Hazard ratio of 0.49 (95% CI: 0.29-0.83, trial vs. chemo) indicated significant benefits of the trial arm over the chemo cohort. Analyses using taxane subgroup showed similar findings. Conclusions: The RWD cohorts demonstrated poor outcomes for the pts receiving chemotherapy, in particular taxanes, confirming this is a population of unmet need. The results show the potential for improved outcomes using cer + paclitaxel in pts previously treated with PDx.[Table: see text]
Talimogene laherparepvec with systemic immunotherapy in melanoma: A real-world experience.
Authors: Behera Tapas Ranjan , Chen Yanwen , Song Jung Min , Huang Steve Shih-lin , Funchain Pauline , Gastman Brian
Published: June 2021

e21549

Background: Talimogene laherparepvec (TVEC) is an FDA approved oncolytic herpes virus for intralesional therapy in unresectable metastatic melanoma. Real world data is sparse regarding the efficacy of TVEC in combination with other systemic therapies used in melanoma. We present outcomes of the largest single institution observational study of the off-label use of TVEC in combination with systemic immunotherapy. Methods: Patients with metastatic melanoma receiving TVEC simultaneously with ipilimumab-nivolumab (Ipi/Nivo) or single agent immunotherapy (either nivolumab or pembrolizumab) were evaluated. The demographics, clinicopathological characteristics, responses to injected lesions and remote metastatic lesions were evaluated. Clinical documentation was used to assess improvement in injected lesion size; time points for initial response and best response were identified. Review of imaging by a radiologist was evaluated to assess responses in remote metastatic lesions. Results: A total of 67 patients receiving TVEC from 2016 to 2020 were evaluated, of which 50 remained evaluable after excluding Merkel cell carcinoma, patients on clinical trial, TVEC monotherapy or those on BRAF-MEK inhibitors, and patients lost to follow up. In total, 29 received systemic immunotherapy simultaneously with TVEC and had been followed for at least a year, with a median follow-up time of 34 months (range, 12-56). At the time of analysis, 14 of 29 patients were alive. 6 of the 29 patients had received prior lines of therapy. Four patients received Ipi/Nivo, while 25 patients received monotherapy including 9 on nivolumab and 16 on pembrolizumab. The median number of TVEC doses received was 6 (range, 2-55) with median average TVEC dose being 3.47 ml (0.5-4 ml). Median time to initial local response was 6 weeks, whereas time to best local response was 14 weeks. Overall response rate in the injected target lesions was in 19 (66%), with complete local response (CR) in 12 (41%), partial response (PR) in 7 (24%), and progressive disease (PD) in 8 (28%). The response rate in distant non-injected lesions was 4 out of 16 (25%), 2 of which had previously progressed on prior systemic therapy. Stable disease was observed in 8 (50%) patients, and progression of disease in 4 (25%). The 1-year overall survival rate in patients receiving TVEC with systemic monotherapy was 80%, 95% CI 0.651-0.9730. Progression free survival at 1-year in the monotherapy group was 71.6%, 95% CI 0.557-0.918. Conclusions: This is the largest single institution, real world experience to our knowledge, which assesses the efficacy of TVEC in combination with systemic immunotherapy. Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with combination TVEC and anti-PD1 than seen with historical data from clinical trials of anti-PD-1 monotherapy.
Study on the correlation between the expression of basic transcription factor 3 (BTF3) and the efficacy and prognosis of patients with malignant melanoma (MM).
Authors: Niu Ning Ning , Li Yong Qi , Guo Liang , Liu Qiong Yang , Zhang Yi Qun , Guo Zhen , Lan Shi Jie , Wu Di
Published: June 2021

e21554

Background: BTF3 is an RNA polymerase II transcription factor, studies have confirmed that BTF3 is abnormally expressed in several types of tumors and closely related to the proliferation and prognosis of gastrointestinal tumors. However, the function of BTF3 in MM remains unknown. The present study aim to detect the expression and proliferation of BTF3，to explore the correlation between the BTF3 expression and the efficacy and prognosis of MM patients. Methods: We explored the effect of BTF3 through silencing BTF3 expression by siRNA transfection with lentivirus in human melanoma cell lines. The cell proliferation, cell cycle and apoptosis were determined by methyl-thaizolyl-tetrazolium assay, flow cytometry and western blot, respectively. Then we investigated the effect of BTF3 in nude mice by tumor formation experiment. The expression of BTF3 was determined by immunohistochemistry (IHC) from 32 patients with different subtypes of MM during October 2014 to October 2020. Among them, 28 cases could be resected (stage I-III), 4 cases could not be resected (stage III-IV). Cutaneous MM 7 cases, Acral MM 14 cases, mucosal MM 9 cases, unknown primary MM 2 cases. The correlation of BTF3 expression and RFS (recurrence-free survival) /OS (overall survival) in 28 patients with resected MM was explored by Student’s t test. Results: The increased viability of negative control virus infection group was 4.706 times than that of BTF3-siRNA group. Compared with the former, BTF3-siRNA group had more cells in G1 and S phase (P< 0.05) and more apoptotic cells (P< 0.05). BTF3-siRNA reduced tumor formation in the nude mice (P<0.01). The relative IHC scores of BTF3 was 5.50±3.19 in tumor tissues (the higher the score, the higher the expression of BTF3), 6.52±4.13 in adjacent noncancerous tissues. The expression of BTF3 in different subtypes of MM tissues are shown in the table. In the median follow-up time of 27 months (6-68 months), 13 cases survived without recurrence or metastasis, 10 cases survived with recurrence or metastasis, 8 cases died. In 28 resectable MM patients, the median RFS/OS of high BTF3 expression (IHC score>5) and low expression (IHC score:0-4) were 18.57 / 24.62 months and 20.42 / 22.78 months. The corresponding RFS/OS P values of patients with high and low expression were 0.323 and 0.607. Conclusions: The study suggests that BTF3 play a role in the proliferation, cell cycle regulation, apoptosis and tumorigenicity of MM. Preliminary small-sample retrospective clinical study did not suggest that BTF3 was related to the efficacy and prognosis of patients, which needs to be further verified by large-sample prospective studies.[Table: see text]
Association of pre-existing autoimmune diseases in melanoma patients receiving immune checkpoint inhibition with improved survival and increased toxicity.
Authors: Gulati Nicholas , Celen Arda , Johannet Paul , Sawyers Amelia , Kim Min Jae , Mehnert Janice M. , Weber Jeffrey S. , Krogsgaard Michelle , Osman Iman , Zhong Judy
Published: June 2021

e21586

Background: Immune checkpoint inhibition (ICI) improves progression-free (PFS) and overall survival (OS) for patients with metastatic melanoma (MM), but induces immune-related adverse events (irAEs). Pre-existing autoimmune disease (pre-AI) is considered a relative contraindication due to concerns of inciting autoimmune flare. We here tested the impact of pre-AI on both the survival and irAEs in MM patients treated with ICI. Methods: We examined MM patients treated with ICI who were enrolled in a clinicopathological database at NYULH with protocol-driven prospective follow up. We compiled a comprehensive list of 23 autoimmune diseases and examined the presence of these diseases prior to ICI treatment. We tested the associations between pre-AI and PFS, OS, and irAEs both in univariate and multivariate models. Results: 74/485 (15.3%) patients, who received 718 lines of ICI treatment as either standard of care or in clinical trials, had pre-AI, most commonly asthma (n=42), inflammatory bowel disease (n=9), psoriasis (n=9), rheumatoid arthritis (n=7), and eczema (n=6). In patients receiving ICI as standard of care (n=535), pre-AI was associated with irAEs (P=0.05) as well as with significantly improved PFS (P=0.024) and OS (P=0.007), controlling for patients’ sex, age, stage, ECOG status, and treatment line (1st line versus 2nd or 3rd line). However, no associations were observed between pre-AI and PFS (P=0.2) or irAEs (P=0.54) in the clinical trial group. Conclusions: Our data demonstrate the disparate impact of pre-AI on response and irAEs in standard of care versus the highly controlled clinical trial settings, and underscore the importance of examining the complex interaction between autoimmune disease before and after initiation of ICI. Our data also challenge the notion that clinicians should avoid use of ICI in pre-AI patients. More mechanistic research is needed to understand how to uncouple ICI response from toxicity.
The prognostic significance of lymphovascular tumor invasion in localized high-grade osteosarcoma: Outcomes of a single institution over ten years.
Authors: Gusho Charles , Miller Ira , Clayton Bishir , Colman Matthew W. , Gitelis Steven , Blank Alan T.
Published: June 2021

e22013

Background: Lymphovascular tumor invasion (LVI) has shown evidence of an association with worse survival in high-grade osteosarcoma. The purpose of this investigation was to prognosticate LVI as a predictor of survival in these patients. Methods: This study was a retrospective review of high-grade, localized osteosarcoma patients diagnosed over a consecutive ten-year period. Cox proportional hazards regression was used to assess the prognostic significance of LVI on overall survival (OS). Results: A total of 42 cases met inclusion criteria with a median follow-up of 64 months (range, 6-158 months). LVI was present in 21.4% (n = 9) cases. The five and ten-year probabilities of OS in LVI (+) were 40% and 20%, respectively, compared to LVI (-) with five and ten-year estimates of 93% and 81%, respectively (p < 0.001). After controlling for confounding variables, advanced age at diagnosis (HR, 1.134; 95% CI, 1-1.2; p = 0.01) and LVI (HR, 21.768; 95% CI, 3-135; p = 0.001) were found to be significantly negative predictors of OS. Using a competing risk analysis and Gray's test of equality, LVI (+) and LVI (-) were not statistically different with respect to cumulative incidence of recurrence (p = 0.8118), though were highly significant for cumulative incidence of mortality over time (p = 0.0029). Conclusions: The presence of LVI in the setting of high-grade, localized osteosarcoma is associated with greater rates of mortality and tumor recurrence and portends a dismal prognosis.
Cancer beliefs and screening across three NYC neighborhoods.
Authors: Layne Tracy M. , Agarwal Parul , Jandorf Lina , Rapkin Bruce , Bickell Nina A.
Published: June 2021

e22512

Background: Differences in breast cancer screening exist between the NYC neighborhoods of East Harlem (EH) and Central Harlem (CH), and the Upper East Side (UES). Here we assess the relationship between six cancer beliefs and breast cancer screening among women in these neighborhoods. Methods: We include women aged ≥40 who responded to the Community Cancer Needs Survey between 2018-2019 and were eligible to undergo screening mammography within 2 years (“recommended screening”). All estimates use weighted data generated using raking techniques. We compared categorical variables using Chi-square tests & estimated odds ratios (OR) and 95% confidence intervals (CI) from logistic regression model associating beliefs and reported mammography receipt (results and covariates listed in Table). For each belief, we compared women who reported “agree” (combined strongly or somewhat agree) to those who “disagree” (combined strongly or somewhat disagree). Results: Of the weighted sample of 76,610 (41.3% CH, 34.4% EH, and 24.3% UES) women eligible to undergo screening mammography, 75.1%, 81.2%, and 90.3% of women in CH, EH, and UES, respectively reported recommended screening. There was no difference by neighborhood in prolonged (>2 years ago) screening intervals: 10.6% in CH, 7.9% in EH, and 9.8% in the UES, while never use was reported by 11.3% in CH, 7.6% in EH, and none in the UES (p=<0.0001). The table summarizes agreement between cancer beliefs and timely receipt of mammography. Conclusions: In this study, cancer beliefs are inconsistently associated with use of breast cancer screening across three NYC neighborhoods. Assessment of beliefs reveal important opportunities for breast cancer (and other cancer) prevention by promoting awareness of risk factors and screening in these communities.[Table: see text]
An unmatched case-control study evaluating the relationship between cancer diagnosis and drinking water source on the lower Eastern Shore of Maryland.
Authors: DeRidder Angela Marie , Masood Adeel
Published: June 2021

e22514

Background: The lower Eastern Shore of Maryland is an agricultural and rural region with high cancer rates. Prior research has suggested that cancer patients on the lower Eastern Shore of Maryland rely on residential private well water more than municipal water, and that cancer patients rely on residential private well water more than individuals in the general county population. The purpose of this unmatched case-control study was to further clarify the relationship between cancer diagnosis and residential private well water use. Methods: A water consumption survey was provided to new hematology/oncology clinic patients seen at a regional hospital on the lower Eastern Shore from October 2020 through February 2021. Participants were asked their age, county of residence, residential water source, daily tap water consumption, presence of a water filtration system, and current or prior cancer history. A case was defined as an individual using residential private well water, and a control was defined as an individual using municipal water. Fisher’s exact test and binominal logistic regression were used to evaluate the relationship between residential water source and cancer history. Results: 334 patients were surveyed and 270 were included in analysis, with 133 cases and 137 controls. Median age of cases was 64 years (SD ± 16.6) and median age of controls was 62 years (SD ± 16.87). Our study found that compared to individuals utilizing municipal water, individuals utilizing residential private well water were more likely to live in their homes for > 5 years (61% vs. 46%, p = 0.015), drink tap water (61% vs. 41%, p = 0.015), and utilize a water filtration system (31% vs. 16%, p = 0.006). Controlling for age, subjects who reported drinking at least two glasses of unfiltered private well water per day were more likely to have a current or prior cancer diagnosis compared to individuals relying on municipal water (OR = 2.57; 95% CI: 1.07-6.12, p = 0.03). Among subjects who drank less than 2 glasses of tap water per day or utilized a water filtration system, there was no difference in cancer history between individuals utilizing private well water versus municipal water. There were no relationships between county of residency, length of home residency, and cancer diagnosis. Conclusions: Individuals on the lower Eastern Shore of Maryland who consume at least 2 glasses of private well water without a water filtration system were more likely to indicate a current or prior cancer history compared to individuals consuming at least 2 glasses of municipal water. Interpretation is limited by small sample size and lack of causality, however, the results signal a need for additional studies evaluating well water use and cancer risk in this region.
Psychosocial impacts of COVID-19 upon a diverse Australian oncology workforce: From doctors to ancillary staff.
Authors: Ahern Elizabeth Stephanie , Roberts Natasha Anne , Chan Bryan Anthony , Gasper Harry Michael , Pelecanos Anita , Kennedy Glen , Wyld David , Lwin Zarnie
Published: June 2021

e23016

Background: Potential moral hazards from COVID-19 for patient-facing oncology staff include rationalizing treatment, but prior research into staff distress has not included ancillary/administrative staff or compared geographic settings. We sought to document measures of distress and perceived preparedness from diverse oncology staff during the COVID-19 pandemic response, and correlate these with unfolding events. Methods: We utilised a mixed-methods approach comprising weekly diarising of executive communications and events-by investigators, and prospective self-administered online surveys-by staff. Survey domains included perceived institutional preparedness, personal wellbeing, and perceived stress using a distress thermometer (0-10, no-extreme distress). Responses were Likert-scaled or free-text. Quantitative responses were aggregated by role/site and analysed using R. These were correlated with emergent qualitative themes using the Framework Method. The study was conducted at a metropolitan and a regional hospital in Queensland, Australia. Results: 12 surveys across 18 weeks commencing April 3, 2020 (encompassing 1st lockdown, lockdown easing, and 2nd lockdown) had 993 individual responses. 40% respondents were located regionally. Role categories included: nursing (50%), allied health (18%), medical (16%), administrative (15%), ancillary (e.g. cleaner, food service) (1%). Emergent themes were: S trategies for protection- at work and home. Up to 27% respondents reported being able to attend to critical personal needs only sometimes or less, although patients were perceived to be well supported most/all of the time (>90% responses). Navigating rules and keeping up-high levels of perceived institutional preparedness in >75% responders coexisted alongside fluctuating levels of self-reported distress, from median 5 (IQR 3-7) at 1st lockdown outset to 1 (IQR 1-4) after lockdown restriction easing. Tempered optimism-pride in one’s place was reported both as reflecting healthcare worker identity and as Australians in the context of low local infection rates. No significant differences in distress or preparedness perceptions were evident comparing geographic sites. Framing the new normal-although respondents longitudinally reported increasing familiarity with pandemic directives, distress levels increased concurrently with the announcement of 2nd lockdown. Conclusions: In the context of low local COVID-19 infection rates, oncology staff regardless of role and geographic setting reported high perceptions of institutional preparedness. Distress levels increased concurrently with lockdown phases and reports of distress and psychosocial workload fatigue were made by various workers including administrative and ancillary. These should be considered frontline staff for the purpose of workplace psychosocial support in pandemic responses.
Dedifferentiated chondrosarcoma: A report of the clinicopathologic features and outcomes of 16 cases treated at a single institution.
Authors: Gusho Charles , Gitelis Steven , Blank Alan T.
Published: June 2021

e23500

Background: Dedifferentiated chondrosarcoma (DCS) is a rare and aggressive malignancy with a poor prognosis. The purpose of this investigation was to assess the clinicopathological features and outcomes of DCS patients treated at a single institution. Methods: This study was a retrospective review over a consecutive twenty-year period. Data including treatment details and outcomes were recorded. Results: A total of 16 cases from 2000 to 2018 were reviewed. The median age was 62 years (IQR, 52-69 years) and the majority of DCS arose in the femur (50%, n = 8) and pelvis (25%, n = 4). Fourteen (88%) cases received limb salvage/wide margin resection (n = 13) or intralesional surgery (n = 1). For all DCS, the median estimated overall survival (OS) was 46 months (95% CI, 1-90 months) with both a five and ten-year survival probability of 32%. On Kaplan-Meier analysis there was no difference between operative versus nonoperative management (p = 0.747), surgery alone versus surgery/chemotherapy (p = 0.265), nor surgery alone versus surgery/chemotherapy/radiation (p = 0.698). Conclusions: Our findings confirm the poor prognosis of DCS patients, though with a five-year estimate of 32%, higher than previous literature. Together with existing literature, our data may enable future strategic recommendation of DCS patients.
Clinical behavior of advanced giant cell tumor: 15 years observation study in N.N. Blokhin National Medical Research Center of Oncology.
Authors: Tararykova Anastasia Alekseevna , Fedenko Alexander A. , Musaev Elmar R.
Published: June 2021

e23501

Background: Giant cell tumor of bone (GCT) is a relatively rare, benign but locally aggressive osteolytic skeletal neoplasm of young adults, most frequently occurs at the epiphysis of long bones. Distant metastases occur approximately 2-6% of cases most often to the lungs. However, pulmonary metastases do not carry the same connotation as metastases associated with malignant tumors, such as lung cancer or sarcoma. Rarely, GCT undergoes true malignant transformation. The aim of this study is to analyze the clinical behavior of advanced GCT during long-term observer in N.N. Blokhin National Medical Research Center of Oncology. Methods: We observed 51 advanced cases among 298 GCT from 2005 till 2020 in N.N. Blokhin National Medical Research Center of Oncology. Disease was histologically confirmed by a sarcoma pathologist. Patients underwent CT/MRI every 2 or 3 months of treatment and every 3, 6 or 12 months of follow up period. Treatment options were included atypical pulmonary resection, palliative surgery, chemotherapy with CAP or AI combination, interferon alfa or observation until progression. After 2013 prefer treatment option for advanced GCT was denosumab with once in 3 month’s regimen after 2 years monthly therapy. All patients received daily calcium and vitamin D supplement. Logistic regression was using for statistic analyzes. Results: Median follow-up was 45 months. The average age of patients was 34,8 years, and the women and men ratio was about 1,8:1. The most commonly affected sites were tibia (23,5%, 12/21), sacrum (17,6%), radius (13,7%) and femur (9,8%). According Campanacci classification G3 was the most commonly grade (90%). 46 (56%) cases were anatomically compounded due to tumor localization and 19 (37%) cases were primary disease. 18/298 (6%) cases were with pulmonary metastases. Surgery in history (p < 0,001) and tumor localization in extremity (p < 0,001) were significant for metastasis development. The primary malignant GCT observed in 1% (3/298) cases and 1 % cases of malignant transformation GCT into sarcoma. Only 1/51 (1,9%) death was observed in advanced GCT group. Complications ≥3 grade were observed only in pre-denosumab era. Conclusions: In this study we showed long-term observation of advanced GCT and evaluated significant factors for metastasis development. Surgeries in history and tumor localization were associated with higher risk of metastasis. Denosumab for advanced GCT is a choice of treatment, we wasn’t observed any cases of GCT malignant transformation during denosumab treatment. Quality of live was better in compare with pre-denosumab era. Further investigation of long term denosumab complications is awaited.
Efficacy of sorafenib in heavily pretreated adult patients with metastatic osteosarcoma.
Authors: Paksoy Nail , Dogan Izzet , Ekenel Meltem , Basaran Mert
Published: June 2021

e23511

Background: Osteosarcoma is a rare tumor and is commonly seen in young people. It arises from bone and rarely from soft tissue. Surgery is the primary treatment option for osteosarcoma. Osteosarcoma is radioresistant, except for rare variants. The choices of chemotherapy are limited in the treatment of metastatic osteosarcoma. The efficiency data of targetted therapies in metastatic osteosarcoma is limited. This study aimed to evaluate sorafenib's efficacy in adult patients with heavily pretreated metastatic osteosarcoma. Methods: We evaluated the patients aged over 18 years with metastatic osteosarcoma retrospectively. The clinical, pathological, and treatment data of the patients were recorded. We used SPSS 25. version for statistical analysis. Kaplan-Meier and Cox-regression analysis were used for survival analysis. Results: Fifteen patients were included in the study. Ten (66.7%) of the patients were male, and the median age was 25 (range,19-64). The primary localization of the tumor was the lower extremity (53.4%), head and neck (20%), upper extremity (13.3%), and other sites (13.3%), respectively. The most common metastatic sites were lung (93.3%), bone (46.7%,) and other (33.3%), respectively. Before sorafenib, fourteen (93.3%) patients had received at least two different cytotoxic chemotherapy regimens, six (40%) patients palliative radiotherapy. In addition, metastasectomy had performed on eight (53.3%) patients. The median progression-free survival was 5.5 (95% CI, 1.3-9.7) months with sorafenib. The stable response was observed in 8 (50%) patients and progressive disease 8 (50%) patients. Grade 1-2 toxicities were observed in 50% of the patients, and grade 3-4 toxicities in 14.3% of the patients. Conclusions: In the study, we showed real-life outcomes of sorafenib for disease control in heavily pretreated adult patients with metastatic osteosarcoma. Sorafenib was effective and well-tolerated in the patients. Sorafenib may be considered as a treatment option after chemotherapy in patients with metastatic osteosarcoma.
Comprehensive understanding of genomic profile of bone cancer by the combination of DNA and RNA detection.
Authors: Xie Xianbiao , Yin Junqiang , Bian Yiying , Zeng Ziliang , Qu Yueting , Shi Xiaoliang , Zhang Lin , Wang Liwei , Dong XiaoWei , Shen Jingnan
Published: June 2021

e23513

Background: The diagnosis of bone tumors is mainly based on clinical manifestations, imaging examination, tissue biopsy and laboratory examination. However, most of the bone tumors have no specific clinical manifestations, which makes the diagnosis and differential diagnosis difficult. The genomic profile of bone tumor is helpful to provide molecular basis for its molecular diagnosis. Methods: A total of 357 Chinese bone cancer patients were enrolled in this study. The NGS-based YuanSu S panel which includes both DNA and RNA detection was performed by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: The 357 Chinese bone cancer patients were enrolled, including 206 adult patients and 151 juvenile patients, with a median age of 20 years old (ranged from 1 to 88 years). Among them, there were 214 males and 143 females. The most commonly mutated genes with a mutation frequency more than 10% were TP53 (31.65%), NCOR1 (15.69%), VEGFA (13.73%), RB1 (12.61%), CCND3 (11.76%), CDKN2A, GID4, and CCNE1 (11.48%, for each), TERT (10.64%), and MAP2K4 (10.08%). Germline mutations were detected in 28 patients, including 13 patients with HRD related mutations, such as ATM, FANCA, BRCA2, RAD50, RAD51D and FANCD2. A total of 179 gene fusions were detected in 130 bone cancer patients. Notably, 19 gene fusions such as SH2D2A-NTRK1, EMILIN1-ALK, and SZRD1-SPEN, were detected in 16 patients with the assistance of RNA detection. Statistical analysis showed that the mutations of NCOR1 (P = 1.1X10-4), VEGFA (P = 3.4X10-6), CCND3 (P = 1.0X10-5), GID4 (P = 1.1X10-6), CCNE1 (P = 3.0X10-7), RB1 (P = 0.03), and MAP2K4 (P = 1.5X10-4)were significantly associated with juvenile patient group, as well as the mutation of H3F3A (P = 7.5X10-5) was significantly associated with adult patient group. Conclusions: Here we identified the mutational characteristics of Chinese bone tumor patients. In addition, the inclusion of RNA detection effectively increased the detection of gene fusions. Our results provided the evidence for the precise treatment of bone tumors in the future.
Different genomic profiling of sarcoma between Western and Chinese population.
Authors: Teng Sheng , Yang Yun , Zhang Jin , You Xia , Guo Taiyan , Zhang Qin , Duan Qianqian , Qi Chuang
Published: June 2021

e23532

Background: Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. The clinical presentation and gene mutations in different subtypes are often atypical, and the profile of gene mutations vary widely. Meanwhile there are many genetic mutations difference between West countries patients and Chinese patients in many cancer types, however little is known about soft tissue tumors' difference. Methods: Next-generation sequencing data and clinical data were collected from 255 Western soft-tissue sarcoma patients (TCGA cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 271 Chinese soft-tissue sarcoma patients (Chinese cohort). Both somatic mutations and germline mutations were detected on the Chinese cohort, then we compared the somatic mutations between TCGA and Chinese cohort. Results: In Chinese cohort, top 5 mutant genes were TP53(35.69%), ATRX(14.12%), MUC16(12.94%), RB1(10.98%), CSMD1(8.24%); while in TCGA cohort were TP53(22.88%), MUC16(8.12%), RB1(6.27%), TERT(5.17%), NF1(4.80%). The mutation frequency of 7 genes were higher in TCGA cohort than in Chinese cohort: TP53(35.69% vs 22.88%, p = 0.0015), ATRX(14.12% vs 4.06%, p < 0.001), CSMD1(8.24% vs 1.85%, p < 0.001), LRP1B(6.27% vs 2.21%, p < 0.05), CSMD3(3.92% vs 1.11%, p < 0.05), EPHA7(3.92% vs 0.74%, p < 0.05) and PIK3C2G(3.53% vs 0.37%, p = 0.009). However, TERT showed the opposite, which in TCGA cohort(1.57%) was lower than Chinese cohort(5.17%)(p < 0.05). Meanwhile, we detected the germline mutations in Chinese cohort. There are three patients had BRCA1 mutations, the SLX4, TP53, MUTYH, ATM, ERCC3 and NBN were all only happened once. There were 21 patients from Chinese cohort had EWSR1-X fusions, including EWSR1-ERG(6/21, 28%), EWSR1-FLI1(6/21,28%), EWSR1-ATF1(4/21,19%), EWSR1-CREB1(1/21,5%), EWSR1-DCTN2 (1/21, 5%), EWSR1-POU5F1(1/21, 5%), EWSR1-WT1(1/21, 5%).Besides, we discovered a novel fusion gene EWSR1-DDIT3(1/21, 5%) in Chinese cohort. Conclusions: We described the general landscape and differences of genetic variation in Chinese and Western populations, we also discovered some new mutations such as novel fusion.In conclusion, comprehensive genomic profiling in a large cohort highlights the promise of targeted therapies.
Efficacy of targeted therapy in alveolar soft part sarcoma: A systematic review and meta-analysis.
Authors: Kim Na Hyun , Sun Chenyu , Prasad Apurwa , Mohammed Abdul Humaed , Batool Saba , Verghese Dhiran , Kozma Kelley Elizabeth
Published: June 2021

e23543

Background: Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma, characterized by a specific unbalanced translocation leading to the fusion of the TFE3 gene on chromosome-X to the ASPSCR1 gene on chromosome-17. Despite its indolent course, ASPS presents a challenge in treatment due to its resistance to conventional anthracycline-based chemotherapy and lack of large scale trial data for this rare sarcoma. This review aimed to assess the efficacy of tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) in metastatic alveolar soft part sarcoma. Methods: A systematic search was performed on Embase and Medline databases for studies that assessed best response of patients with unresectable or metastatic ASPS to TKI and ICI therapy, according to the Response Evaluation Criteria in Solid Tumors (RECIST) edition 1.0 or 1.1. This study followed the Preferred Reporting Items for Systematic Reviews (PRISMA) protocol. Four independent reviewers screened abstracts and extracted the data; any discrepancy was resolved by discussion among reviewers. Pooled objective response rate (ORR) and disease control rate (DCR) were obtained using the Freeman-Tukey double-arcsine transformation using random effects model on STATA software (version. 16.1, StataCorp). Results: 27 articles and abstracts published between 2011 and 2020 were included in the review, resulting in 2 randomized clinical trials (104 participants), 14 single arm prospective trials (214 participants), and 11 retrospective studies (120 patients). Among clinical trials, the pooled ORR and DCR were 18% (95% confidence interval [CI] 8 - 30%; I2 = 72.25%; p < 0.01) and 87% (95% CI 97 - 93%; I2 = 43.2%; p = 0.03) respectively. Conclusions: The response rate to targeted therapy in metastatic ASPS is not only clinically meaningful, but also comparable to that of first-line chemotherapy. The majority of patients receiving targeted therapy achieved disease control. Patients who had refractory or progressive disease to one targeted agent demonstrated response to other agents. More randomized trials are warranted to expand treatment options and compare to standard of care regimens.
Palliative care as a predictor of healthcare resource use at end-of-life in adult Albertan lung cancer decedents between 2008-2015: A secondary data analysis.
Authors: Sumar Nureen , Earp Madalene , Hao Desiree , Sinnarajah Aynharan
Published: June 2021

e24009

Background: Early utilization of specialist palliative care (SPC) in cancer patients may reduce healthcare resource use, aggressive interventions, and costs at end-of-life. We evaluated the impact of SPC on healthcare resource utilization and aggressive interventions at end-of-life in patients who have died from lung cancer. Methods: Descriptive and multivariable logistic regression analyses were conducted on lung cancer decedents in the Calgary Zone, Alberta Health Services from 2008 to 2015. The primary exposure was timing of SPC (Early: receipt of SPC > = 90 days before death; Late: < 90 days before death; No SPC). The primary outcome was end-of-life healthcare resource use (defined as any of: hospital death, > 1 emergency department visit, > 1 hospital admission, > 14 days of hospitalization, ≥1 intensive care unit admission, ≥1 new chemotherapy program (or any chemotherapy in the last 14 days of life) in the 30 days prior to death. Results: There were 3300 patients of which the majority (51.6%) of decedents were male. More female versus male lung cancer decedents (36.4% vs 28.7%) received early SPC. After adjusting for confounders, a strong association was found between early, late or no SPC and end-of-life healthcare resource use (ORno exposure 3.25 (95% CI 2.41-4.40) vs ORlate exposure 2.44 (95% CI 2.03-2.92) compared to those with early SPC; p < 0.001). Males had 1.53 the odds of aggressive care at end-of-life compared to females (p < 0.001). Stratified analysis by sex revealed a strong association between the absence of SPC utilization and end-of-life healthcare resource use. Young age ( < 50 at death) was a strong driver of aggressive care at end-of-life in females versus males [OR 5.44 vs 2.53]. Conclusions: Early specialist palliative care was significantly associated with less end-of-life healthcare resource use in both male and female lung cancer decedents, with less early specialist palliative care use in males. Keywords: palliative care, early palliative care, cancer, end-of-life, healthcare resource use, lung cancer.
Tobacco use, knowledge of harms, and cessation support among patients with non-tobacco related cancers.
Authors: Vater Laura , Trikannad Ashwini Kumar Anup , Sehgal Neha , Khan Maria , Bullens Kelsey , Hudmon Karen S , Buckles Deborah , Liu Hao , Hanna Nasser H. , Kunapareddy Girish
Published: June 2021

e24029

Background: Continued cigarette smoking among patients with cancer leads to numerous adverse health outcomes, even among patients with non-tobacco-related cancers such as breast, colon, and prostate cancer. Continued smoking is associated with poorer response to cancer treatment, increased risk for treatment-related toxicities, and shorter overall survival. While some patients with a smoking-related cancer make efforts to quit smoking at the time of diagnosis, patients with other forms of cancer might not understand the negative effects of continued smoking. In this study, we assessed patient knowledge of the harms of continued smoking, previous cessation attempts, and cessation support. Methods: We surveyed 102 adults with breast, colon, and prostate cancer at three locations: an NCI-designated cancer center, an urban safety-net medical center, and a rural cancer center. Patients were asked about current smoking behaviors, beliefs about the harms of continued smoking, quit attempts and resources used, and cessation support. We also surveyed seven oncologists to assess beliefs about harms of continued smoking, cessation support provided to patients, training and confidence in cessation counseling, and barriers to providing cessation support. Results: Most patients (82%) agreed or strongly agreed that continued smoking may shorten life expectancy, and 70% agreed or strongly agreed that continued smoking increased the risk of getting a different type of cancer. Only 41% of patients agreed or strongly agreed that continued smoking may cause more side effects from cancer treatment, and only 40% agreed or strongly agreed that ongoing smoking may affect treatment response. The majority of patients (86%) had tried to quit smoking for good, with an average 4.1 quit attempts per patient. Patients reported that physicians advised them to quit the majority of the time (92%), prescribed medication 33% of the time, and followed up on cessation attempts 43% of the time. Overall, oncologists had higher knowledge of the harms of continued smoking on treatment outcomes and survival. Those in practice for 20 years or more had higher confidence in cessation counseling than those in practice less than 4 years. Oncologists described lack of time and lack of confidence in cessation counseling as barriers to providing more cessation support. Conclusions: Among 102 patients with breast, colon, and prostate cancer who currently smoke, there was incomplete knowledge of the harms of continued smoking. Oncologists believe that tobacco cessation is important and frequently advise patients to quit, however they less frequently prescribe medication or follow up on cessation efforts. Interventions are needed to educate patients with cancer about the harms of continued smoking and to provide further cessation support.
A pilot study of individualized exercise prescription to improve physical activity in cancer survivors.
Authors: Pophali Priyanka Avinash , Durani Urshila , Shin John , Larson Melissa C. , Shultz Adam , Becker Julie , Bowman Melissa , Thompson Carrie A. , Cathcart-Rake Elizabeth Jane
Published: June 2021

e24030

Background: Physical activity (PA) in cancer survivors improves quality of life (QOL), functioning, fatigue, and reduces the risk of treatment complications, cancer recurrence and death. However, the optimal intervention for increasing PA is not established. Most prospective studies have shown a 6-12-week program to be an effective intervention but this is often not feasible. Therefore, we piloted a one-time individualized exercise prescription in our cardiac rehabilitation center to improve PA in cancer survivors. Methods: We prospectively enrolled cancer survivors who had completed curative intent treatment, with no evidence of active disease in this pilot study. Survivors who consented underwent a consultation with an exercise physiologist for needs assessment followed by a supervised exercise session with a tailored exercise prescription. Survivors also filled out surveys assessing their PA and QOL at baseline (bl), 3, 6 and 12 months after intervention. Clinical information was collected via chart review. We estimated longitudinal PA score and change in PA using mixed models incorporating scores from all available time points using SAS (v 9.4). Results: Between May 2018 and January 2020, 50 participants (26 lymphoma and 24 solid tumor survivors) completed the intervention. 20% participants were on maintenance therapy during the study. Clinical characteristics of 42 evaluable participants are summarized in Table. The survey response rate was 82%, 58%, 58%, 46% at bl, 3, 6 and 12 months respectively. The level of PA improved with time [mean (SE) PA score: 58.5 (4.3) bl, 63.9 (4.8) at 3, 57.6 (4.8) at 6, 62.6 (5.3) at 12 months]. The change in PA from baseline to follow-up time-points [bl vs 3m p=0.41; bl vs 6m p=0.88; bl vs 12m p=0.55] or between the lymphoma and solid tumor survivors was not statistically significant and limited by sample size. No significant trend in QOL was seen. Conclusions: Individualized exercise prescription using the cardiac rehabilitation program may be a feasible, widely applicable tool to implement a PA intervention among cancer survivors. The trend towards improvement in PA in this novel one-time intervention provides intriguing evidence and deserves future study in larger sample sizes to understand if it can improve and create sustainable PA change comparable to longer term exercise interventions.[Table: see text]