bluuebunny/crossref_metadata_2025 huggingface dataset:
Naxitamab (NAX) treatment for refractory/relapsed (R/R) high-risk neuroblastoma (HR-NB): Response data and efficacy in patient (pt) subgroups.
Authors: Mora Jaume , Chan Godfrey Chi-Fung , Morgenstern Daniel A. , Nysom Karsten , Bear Melissa , Tornøe Karen , Sørensen Per Settergren , Kushner Brian H.
Published: June 2022

e22019

Background: Almost half of pts with NB present with high-risk disease, most of whom experience persistence of disease or disease progression. Further, residual disease in the bone/bone marrow (BM) can drive relapse. NAX is a humanized GD2-binding monoclonal antibody indicated under accelerated approval in the US with GM-CSF for the treatment of R/R HR-NB in the bone/BM in pts ≥1 year of age with a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we characterize the response data of NAX overall and efficacy in pt subgroups. Methods: Trial 201 is an ongoing registrational phase II trial evaluating NAX in pts with R/R HR-NB. Pts with progressive or residual soft tissue disease were excluded. NAX was administered over 30-60 min in the outpatient setting on Days 1/3/5 at 3 mg/kg/day with GM-CSF at 250 µg/m2/day on Days –4 to 0 and 500 µg/m2/day on Days 1 to 5; cycles were every 4 wks. Efficacy was evaluated by independent pathology and radiology review per revised International Neuroblastoma Response Criteria. Results: Results presented here are from an ad hoc interim analysis (Aug 5, 2020) of 48 pts (safety population) and 36 (efficacy population). Pts in the efficacy population received a median of 7 cycles (range 1–11). Overall response rate (ORR; complete response [CR] + PR) was 58% (44% CR; Table). Of the 9 responders who had PR initially, 4 improved to CR. Median number of cycles before onset of response (CR or PR) was 2 (range 2–8) and median time to onset of response (CR or PR) was 7.3 wks (95% CI 6–17). Median duration of response was 24.9 wks (95% CI 25–not estimable). The most common adverse events (CTCAE graded) were infusion-related reactions including hypotension and pain, which occurred in 98% and 96% of pts, respectively. Adverse events were managed with established guidelines. Conclusions: NAX provided a clinically meaningful response in pts with R/R HR-NB limited to bone/BM – frequent sites of residual disease. Response rates were generally consistent across subgroups. These efficacy results combined with a manageable safety profile and use in the outpatient setting demonstrate that NAX addresses a significant unmet medical need. Clinical trial information: NCT03363373. [Table: see text]
Mammography screening is associated with more favorable breast cancer tumor characteristics and better overall survival: Case-only analysis of 3,739 Asian breast cancer patients.
Authors: Hartman Mikael , Lim Zi Lin , Ho Peh Joo , Khng Alexis Jiaying , Yeoh Yen Shing , Ong Amanda Tse Woon , Tan Benita Kiat Tee , Tan Ern Yu , Tan Su-Ming , Lim Geok Hoon , Tan Kiak Mien Veronique , Li Jingmei
Published: June 2022

e22500

Background: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilisation in a multi-ethnic Asian population. Methods: This study included 3,739 BC patients from the Singapore Breast Cancer Cohort (2010–2018). Self-reported socio-demographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤two years before diagnosis), non-screeners (aware but did not attend or last screen > 2years) and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. Results: Patients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I(Ref) [95%CI]:4.94[3.45-7.07], p < 0.001), high grade (ORpoorly- vs well-differentiated(reference): 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR> 5cm vs ≤2cm(reference): 5.06 [3.10-8.25], p < 0.001), and HER2-positive tumors (ORHER2-negative VS -positive(reference): 0.72[0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups(non-screeners HR: 1.89 [1.22-2.94], p = 0.005; unaware HR: 2.90[1.69-4.98], p < 0.001). Non-screeners and those unaware were less health-conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. Conclusions: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.
The incidence and comparative prognosis of primary cancers with metastasis to non-common sites: A SEER database analysis of 2016-2018.
Authors: Abbas Kirellos Said , Abdelazeem Basel , Rao Deepti Nagaraja , Tariq Rabeet , Wahab Ahsan
Published: June 2022

e22506

Background: Primary tumors can present late with metastasis to uncommon sites (such as adrenals, bone marrow, pleura, malignant pleural effusion, peritoneum, and skin, among others) as well as common sites (such as liver, bone, lung, and distal lymph nodes). Our study aimed to investigate the characteristics and comparative survival for metastasis to uncommon sites at the time of diagnosis using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We extracted the data from the SEER database for the years 2016-2018 to include all patients presenting with metastasis to uncommon sites at diagnosis without restrictions on age, race, year of diagnosis, or histological type. Uncommon sites of metastasis were coded as other sites in the SEER database and did not involve liver, bone, brain, lung, and distal lymph nodes. We used R software to perform the descriptive analysis for uncommon sites according to the primary sites and co-metastasis along with their survival. Results: A total of 25,345 patients were included with metastasis to uncommon sites with a female predominance of 13,033 (51.4 %); the mean age at diagnosis was 68 ± 17 years. Lung and bronchus primaries represented the largest proportion with metastasized to uncommon sites 10,612 (41.9%), followed by non-Hodgkin's lymphoma-nodal 1,871 (7.4%), pancreas 1,690 (6.6%), stomach 940 (3.7%), and ovarian 885 (3.4%). The incidence was most common in respiratory cancers in ages 61-80 years (25%) and least in breast primaries in ages 18-40 years (0.1%). Whites compared to other races had a higher incidence. Liver cancer had the worst prognosis with a median survival of 1 month, whereas small intestine tumors were associated with a better prognosis with a median survival of 13 months. Further survival data is mentioned in the table. Conclusions: Our study concluded that the lung and bronchus cancers were the most common primaries metastasized to uncommon sites at diagnosis while the liver had the worst survival. These findings will help redirect the available screening tools to improve survival in patients with primary tumors with metastasis at diagnosis and may also play an essential role in future research and achieve a better prognosis for cancer patients.[Table: see text]
The BC Generations Project as a tumor tissue resource for cancer research.
Authors: Zanif Umaimah , Bhatti Parveen , Chu Jessica , Simkin Jonathan , Dummer Trevor , Belanger Eric
Published: June 2022

e22512

Background: Population-based cohort studies can be a resource for tumor specimens, annotated with demographic, lifestyle, and health history data, that support innovative studies of cancer. These data are increasingly important for clinical studies as they can be useful predictors of prognosis and treatment response (1,2) Our aim was to establish and test a process for accessing tumor samples, held at pathology laboratories around British Columbia (BC), for participants of the BC Generations Project (BCGP). Methods: Through the BC Cancer Registry, pathology reports linked with each BCGP solid cancer case were manually reviewed to extract information (e.g., location of pathology laboratory, sample type (i.e., biopsy or excision), and accession number) needed to request tumor samples. From among the successfully abstracted pathology reports, we randomly selected a total of 200 breast, lung, bladder, and pancreatic cancer cases for which to attempt retrieval of formalin-fixed, paraffin-embedded (FFPE) blocks from pathology laboratories across BC. We selected these cancer sites as they capture a representative range of cancer characteristics (e.g., tumor sizes) with which to evaluate the effectiveness of our access process. Results: We successfully identified pathology reports for 1,100 (93%) of the 1,180 incident solid cancer cases diagnosed in BCGP as of 2019 and we successfully retrieved 183 (92%) of the 200 FFPE that we requested from pathology laboratories. No important differences in retrieval rates by cancer site, sample location (Greater Vancouver vs. Outside Greater Vancouver), sample type (biopsy vs. excision) or year of diagnosis were identified. Conclusions: This linkage exercise demonstrates the tremendous potential for BCGP to serve as a population-based resource for highly annotated tumor tissue samples. A text mining solution recently implemented by the Registry will allow us to automate the process for data abstraction and should capture pathology reports for 100% of all newly diagnosed BCGP cancer cases moving forward. This will further enhance the utility of BCGP as a high-quality tumor tissue research resource. References: Lugo D, Pulido AL, Mihos CG, Issa O, Cusnir M, Horvath SA, Lin J, Santana O. The effects of physical activity on cancer prevention, treatment and prognosis: A review of the literature. Complement Ther Med 2019; 44:9–13. Peppone LJ, Mustian KM, Morrow GR, Dozier AM, Ossip DJ, Janelsins MC, Sprod LK, McIntosh S. The Effect of Cigarette Smoking on Cancer Treatment–Related Side Effects. The Oncologist 2011; 16:1784–92.
The correlation between tumor mutation burden and TP53 or CHEK2 germline mutations in malignant tumors.
Authors: Gao Xiaohui , Zhang Yali , Li Mengmeng , Wu Yaqing , Luo Ningning , Zhu Xiaofeng , Qi Yingxue , Sun Tingting , Qi Chuang
Published: June 2022

e22527

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome, mainly caused by the lack of tumor suppressor gene TP53. The LFS related tumors include breast cancer, brain tumors, malignant sarcoma, bone cancer and central nervous system tumors. In addition to TP53 germline mutations, studies have shown that CHEK2 is also a susceptibility gene for LFS, and CHEK2 germline mutations is related to a series of cancer types. However, the correlation between tumor mutation burden (TMB), age, gender, PD-L1 expression and TP53 or CHEK2 germline mutations in malignant tumors remains unknown. Methods: In this study, we retrospectively analyzed the mutation characteristics of TP53 or CHEK2 germline mutations in patients with solid tumors without selecting age or family history. We identified 631 patients harboring TP53 or CHEK2 mutations from 9337 patients with malignant solid tumors. According to the ACMG (American College of Medical Genetics and Genomics) guidelines in pathogenicity, the 631 patients in the retrospective cohort were divided into three groups, including P/LP group (with pathogenic or likely-pathogenic mutations), VUS group (with uncertain significance mutations) and B/LB group (with benign or likely-benign mutations). We also analyzed the differences in TMB, age, gender and PD-L1 expression among the three groups. Statistical significance was defined as P-value less than 0.05. Results: The 631 (631/9337) patients carried TP53 or CHEK2 germline mutations were identified, in which 33 patients with pathogenic mutations and 15 patients with likely-pathogenic mutations. These pathogenic or likely-pathogenic mutations mainly occurred in lung cancer, brain tumors, colorectal cancer and liver cancer, accounting for about 35.4%, 20.8%, 16.7% and 12.5%, respectively. Among the three groups, TMB was significantly different between P/LP group and B/LB group (P = 0.037), and the B/LB group was higher. In addition, we found that the three groups had no significant differences in age, gender and PD-L1 expression. Conclusions: Our data showed that 0.823% (48/8535) malignant solid tumor patients carried TP53 (28/48) or CHEK2 (20/48) germline pathogenic or likely_ pathogenic mutations. In addition, the TMB value in B/LB group was significantly higher than that in P/LP group. The other characteristics of LFS will be studied in the future.
Improving clinician knowledge of cancer-related anemia (CRA) and chemotherapy-induced anemia (CIA) through the execution of a hybrid educational initiative focused on the evolving role of intravenous iron.
Authors: Taylor Bryan Carson , Rodgers George M. , Gitzinger Susan H. , Trieu Tina , Carranza Vanessa , Hall Jessica , Weaver Rebecca
Published: June 2022

e23001

Background: Anemia is an extremely common and robustly deleterious complication experienced by patients with cancer, with impacts ranging from patient-reported quality-of-life metrics, to functional capacity, to morbidity and mortality implications. Cancer-related anemia (CRA) and chemotherapy-induced anemia (CIA) arise from a complex pathogenesis and are often associated with multifactorial etiology, but iron deficiency (ID) is an especially prominent genesis in these patients and is a preeminent clinical focus for hematology/oncology clinicians, not only because of its frequency, but also because it is directly treatable and reversible. Recent positive data readouts examining intravenous iron as a mechanism to improve anemia outcomes in comorbid oncologic states illustrates a compelling and exigent need to educate the hematology/oncology clinicians managing patients with cancer. These clinicians are optimally positioned to ensure improved CRA/CIA patient outcomes. That was the formative objective of this educational initiative. Methods: We conducted a 180-minute symposium at the 2021 American Society of Hematology (ASH) Annual Meeting, with a panel of 5 hematology/oncology experts. The activity was delivered live, in-person in Atlanta, and was also live streamed to a national and international audience on a virtual basis; the session was then provided as an online on-demand offering for those couldn’t attend the live meeting. Clinician knowledge metrics were evaluated from pre-activity to post-activity via audience response software (in-person) and Zoom polling (virtual); all test questions were directly correlated with activity learning objectives. Results: Across all 3 delivery modalities, the educational initiative reached a vast audience of nearly 8,000 learners. Meaningful knowledge advancements were achieved across each of the following clinical topics of emphasis (statistics reflect differential between pre-test and post-test performance): Diagnosis of CRA/CIA using clinical signs, symptoms, and laboratory diagnoses (+17%). Differentiation of functional vs. absolute iron deficiency (+33%). Identifying how elevated hepcidin levels impact iron supplementation strategies (+37%). Knowledge of improved safety profiles of next-generation IV iron products (+75%). Correctly evaluating the benefits of IV iron given a real-world CIA patient case (+33%). Conclusions: Our outcomes illustrate both the relatively low baseline knowledge of hematology/oncology clinicians related to CRA/CIA management and the transformative impact of timely educational programming. Ongoing educational efforts focused on this clinical topic and target audience are warranted.
Surgical subtypes and survival in stage II osteosarcoma: A National Cancer Database (NCDB) analysis.
Authors: Eaton Vincent , Tupper Connor , McMahon Kevin , Silberstein Peter T.
Published: June 2022

e23513

Background: Osteosarcoma (OSC) is the most common primary malignancy of bone and is most commonly diagnosed in its earlier stages (I and II). Standard of care involves a combination of chemotherapy and surgical resection and, to date, there are few reports examining different surgical subtypes in these patients. This study aims to analyze different surgical subtypes in OSC patients to assess survival, particularly in stage II. Methods: Using the NCDB, patients diagnosed with stage II OSC between 2004-2018 were identified using ICD-O-3 histology codes 9180-9193. The cohort was analyzed to determine if they received any of the following surgical subtypes: local tumor destruction/excision, partial excision, radical excision with limb salvage, limb amputation, and major amputation. Univariate analysis was performed assessing patient survival length for each surgical subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 3827 patients were analyzed. Patients who received surgery survived significantly longer than those who did not (p < .00001). Patients who underwent major amputations had shorter median survival times ranging from 24-74 months. Patients who received radical tumor excision with limb salvage had the longest survival of any surgical subtype with a mean of 130.1 months and survived significantly longer than patients receiving local tumor resection, partial resection, partial and total limb amputations, or any major amputation (p < .001). Patients with local tumor destruction survived similarly to those with local tumor excision (p > .05). Patients with partial or total limb amputation had significantly better survival than patients with major limb amputation (p < .01). Conclusions: We found numerous significant differences between the different surgical subtypes used to treat patients with OSC. Radical excision with limb salvage proved to yield the best survival outcomes, with significantly higher survival when compared to almost all other surgical subtypes (excluding local tumor destruction). Future studies should investigate additional parameters within each surgical subtype to assess the impact that variables like patient demographics and socioeconomic status, tumor characteristics, and surgical center may have on access to care and survival outcomes.[Table: see text]
The long-term analysis of prognostic role of mutational status in primary resectable gastrointestinal stromal tumors (GIST).
Authors: Sobczuk Pawel , Bylina Elzbieta , Klimczak Anna , Rutkowski Piotr
Published: June 2022

e23517

Background: Radical surgery is the primary treatment for GIST, but up to 50% of patients relapse, mainly in form of hepatic and peritoneal metastases. GISTs are a group of tumors with various pathological and molecular features as well as different clinical courses. The aim of the study was the long-term analysis of prognostic role of mutational status in primary GIST after radical resection. Methods: The material consisted of a group of 304 patients with primary GIST diagnosed till 04/2012, with known mutational status and treated surgically with curative intend without adjuvant imatinib. Data were collected prospectively as part of the GIST clinical register. Relapse-free survival (RFS) was calculated from the date of GIST resection to the date of local recurrence, distant metastatic disease or last follow-up. Overall survival (OS) was calculated from the date of resection to the date of last follow-up or death. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression was performed to asses impact of mutational status on RFS and OS. Results: The primary tumor (PT) locations were: gastric (57.6%) vs non-gastric (42.4%). The median of tumor size was 7cm (0.5-33 cm). Mitotic index was ≤5 in 54.3%, > 5 in 45.7%. Mutations in KIT gene exon 11 were as follow: del 557-558 in 22.7% or other (point mutations, other deletions or insertions) in 40.1% with similar rates in gastric and non-gastric GIST. KIT gene exon 9 dup 502-503 (7.2%) were more common in non-gastric vs gastric GIST (16.3% vs 0.6%). PDGFR D842V was observed in 26 patients (8.6%) while other mutations in PDGFRA gene in 17 (5.6%). The median follow-up was 25.1 months. Disease recurrence was observed in 124 cases (40.8%) resulting in median RFS of 84.4 (95%CI 48.3-120.5) months. The negative independent risk factors for RFS in univariate analysis were: primary tumor location, tumor size, mitotic index and KIT exon 9 dup 502-503 mutation (P < 0.05). In the multivariate analysis independent predictive factors for RFS were mitotic index > 5 (HR 4.38, 95%CI 2.82-6.78), PT location (HR 1.56, 95%CI 1.01-2.39). In multivariate analysis in patients with gastric GIST PDGFR D842V mutations were significantly correlated with better RFS (HR 0.16, 95%CI 0.04-0.61), what was not observed in non-gastric GIST. The median OS was 198.1 months. The negative independent risk factors for OS in univariate analysis were: primary tumor location, primary tumor size and KIT gene exon 9 dup 502-503 mutation. Mitotic index was also negative independent risk factors in a multivariate analysis (HR 1.70, 95%CI 1.15 -2.52). Conclusions: In the long-term analysis mutational status of primary resectable GIST is related to risk of relapse especially in gastric location, however it has no independent impact on overall survival. Genotype should be included in modern risk classification of GIST.
Multi-modal single-cell profiling of sarcomas from archival tissue reveals mechanisms of resistance to immune checkpoint inhibitors.
Authors: Caldwell Blake , Bose Sminu , Amin Amit Dipak , Tagore Somnath , Melms Johannes C , Berhe Simon , Ingham Matthew , Schwartz Gary K. , Izar Benjamin
Published: June 2022

e23518

Background: Single-cell RNA-seq is an enabling technology that may inform the molecular underpinnings of drug response and resistance in patient biopsies. This method is difficult to implement in the study of rare diseases such as sarcomas due to specimen requirements and technical limitations. Methods: Here, we evolved novel methods that we recently reported in melanoma ( Wang, Fan, et al., bioRxiv, 2022), which enable single-nucleus RNA, T cell receptor (snRNA/TCR)-seq, and pool-matched whole-genome sequencing (WGS) from archival, frozen sarcoma tissue. Results: This enabled profiling of 75,716 cells and 788 matched TCR clonotypes from six patients with intimal sarcoma (INS) and undifferentiated pleomorphic sarcomas (UPS), including two matched pair samples from pre/post-immune checkpoint inhibitor (ICI). Our analysis revealed substantial transcriptional cancer cell heterogeneity driven by varying copy number alterations (CNAs). In one patient with INS with a complete response to ICI followed by an isolated recurrence, we identified a rare cancer cell clone defined by CNA (confirmed with WGS) and resulting transcriptional outputs that pre-existed and emerged during resistance. Furthermore, in a patient with UPS with intrinsic resistance to ICI, we find adequate T cell clonal expansion and activation, suggesting appropriate T cell response to ICI dampened by intrinsic mechanisms of ICI resistance within the cancer cells. Non-negative matrix factorization (NMF) analysis identified cell states associated with either intrinsic or adaptive resistance to ICI that was distinct from resistance to doxorubicin. These observations are consistent with those previously reported from sequential biopsies obtained from KEYNOTE-001 in metastatic melanoma ( Wang, Fan, et al., bioRxiv, 2022), which also revealed emergence of pre-existing populations of resistant clones defined by their underlying aneuploidy patterns. Conclusions: Together, these results demonstrate feasibility of implementing single-cell genomics from archival tissue to study sarcoma and propel our understanding of drug resistance. Conceptually, this work suggests that large-scale CNAs may drive cell sub-populations associated with ICI resistance in sarcoma and in other diseases.
Increased phosphorylation of RB and protein expression of Cyclin E confers resistance to CDK4/6 inhibitors in dedifferentiated liposarcoma.
Authors: Hsu Jocelyn , Seligson Nathan David , Hays John L. , Chen James Lin
Published: June 2022

e23525

Background: Dedifferentiated liposarcomas (DDLPS) are malignant adipocytic cancers characterized by an amplification of the cell cycle regulatory gene, CDK4. Palbociclib, a CDK4/6-inhibitor, is a standard of care treatment; however, innate and acquired resistance to the drug limits efficacy in patients with DDLPS. Molecular mechanisms and biomarkers of palbociclib resistance have been posited in non-mesenchymal tumors but are poorly understood in DDLPS. To this end, we developed palbociclib-resistant DDLPS cell lines derived from several DDLPS patient samples to better characterize these phenotypic and genomic differences. Methods: Three human CDK4 amplified DDLPS cell lines (224A, 246, 863) and one control liposarcoma control cell line without CDK4 amplification and RB loss (LiSa2) were brought into culture. Each cell line was intermittently treated with palbociclib at their respective IC25 for 6 months to develop resistance in long-term treated cell lines. Surviving cells were allowed to recover for at least 2 weeks before retreatment. Parental lines were grown as controls in tandem with the developing resistant lines to compare molecular changes in response to palbociclib. Cell viability was measured by XTT, cell cycle analysis was measured with Flow cytometry using a PI stain, and protein expression was measured using whole cell lysates for Western blotting. Results: The four cell lines had IC50s to palbociclib ranging from 15.0, 14.8, 12.0, and 11.4 µM for LiSa-2, 224A, 246, and 863 cell lines respectively. Long-term treated strains demonstrated consistent reductions in the measured IC50s (8.99, 7.32, 8.27, and 7.08 µM respectively). After treatment with 10 µM of palbociclib for 48 hours, two parental cell lines showed a greater increase in cells in the G1 fraction than long-term treated cells: LiSa-2 (-2.4% increase in parental vs -16.5% increase in long-term treated) and 863 (16.2% vs 11.7%). 224A and 246 demonstrated the opposite where parental cell lines had fewer cells in G1 after treatment compared to long-term treated cell: 224A (12.6% vs. 20.5%) and 246 (12.6% vs. 21.6%). Western blots indicated that the initial response to palbociclib in parental cell lines decreased pRb protein levels and increased Cyclin E and CDK6. After 6 months of treatment for all cell lines, a significant increase in pRb and Cyclin E were observed in the long-term treated cell lines and no changes were seen in CDK4, Cyclin D, nor p16. Conclusions: Here we present the development of two novel, palbociclib resistant, DDLPS cell lines and two long-term treated cell lines. Our resistant cell lines indicated that the ability to bypass the G1/S-checkpoint in the presence of CDK4/6-inhibitors may result from increased phosphorylation of Rb and increased total of Cyclin E. Next generation sequencing of RNA expression in parental and resistant lines are underway.
Variation in survival rates among patients with angiosarcoma based on demographic and socioeconomic factors in academic versus non-academic settings: An NCDB analysis.
Authors: Creech Zachary , Truong Gia Thinh , Denny Regan , Hu Robert W. , Verplancke Kiana , Aurit Sarah J , Silberstein Peter T.
Published: June 2022

e23537

Background: Angiosarcomas are malignancies of endothelial-cell origin representing 2% of soft-tissue sarcomas. Although the number of cases of angiosarcoma continues to rise, the prognosis is generally poor and treatment options remain limited. Due to the rarity of angiosarcoma and limited available literature, this study is intended to analyze the impact of demographic and socioeconomic factors on patients’ survival rates in academic versus non-academic settings. Methods: We performed a retrospective analysis of 5,544 patients diagnosed with angiosarcoma from the National Cancer Database (NCDB) between 2004-2017. Patients were stratified by facility type and compared via Kaplan-Meier analysis, log-rank test, chi-square analyses, and ANOVA. Additionally, a cox proportional hazards multivariate regression model was used. The following demographic factors were examined: age, sex, reported race and ethnicity, mean survival rates utilizing the Charlson Comorbidity Index, facility type where patients received treatments, and treatment modalities. Furthermore, the assumption of proportionality was tested for each variable. Data was analyzed using Statistical Analysis Software (SAS). Results: Higher rates of death were seen in those of male sex, African American race, increased age (> 72), and increasing Charlson-Deyo scores. There was an increased risk of death for older African American males with non-zero Charlson-Deyo scores. Additionally, patients from areas of increased income had decreased rates of death. After adjusting for most variables, patients who were treated at academic facilities had an 8.5% decreased risk of death compared with patients treated at non-academic facilities (95% CI: 1.5% to 15.0%; P = 0.019). Conclusions: Our study results indicate that certain demographic and socioeconomic factors may be linked to poorer survival outcomes in patients with angiosarcoma. Further investigation of socioeconomic barriers and prognostic factors for angiosarcoma may help to identify populations at risk for poor treatment outcomes and guide disease management.
Anlotinib rechallenge combined with immune checkpoint inhibitor for advanced soft tissue sarcoma after the failure of anlotinib.
Authors: Fu Yang , Jiang Yu
Published: June 2022

e23541

Background: The anti-angiogenic tyrosine kinase inhibitor (TKI) anlotinib has been approved for the treatment of advanced clear cell sarcoma, alveolar soft-part sarcoma, and other anthracycline-failed advanced soft tissue sarcoma (STS) in China. However, the management of refractory STS is still an unmet medical need. The formation of immunosuppressive microenvironment is one of the resistance mechanisms of anti-angiogenic therapy. This retrospectively observational study investigated the efficacy and safety of anlotinib rechallenge combined with immune checkpoint inhibitor (ICI) for advanced STS after progression on anlotinib treatment. Methods: A cohort of STS patients who had progressed after the anlotinib treatment were prescribed with anlotinib plus ICI were enrolled. Other concurrent systemic treatments were not allowed. Demographic features and clinical outcomes were reviewed and analyzed. Results: A total of 10 STS patients were included. The median of previous systemic treatment regimens was 3 (range, 1-5). Two cases (20%) were observed a partial response, including anlotinib plus nivolumab for a leiomyosarcoma and anlotinib plus toripalimab for an angiosarcoma. Another 4 patients achieved stable disease lasting more than 6 weeks. The median progression-free survival (PFS) were 4.8 months (95% CI: NA-12.5 months). Three (30%) patients developed grade 3 or higher adverse events including toxicity of skin/mucosal(n = 2) and neutrophile granulocyte decreased(n = 1). Conclusions: ICIs plus anlotinib rechallenges maybe a potential treatment for advanced STS patients after progression on anlotinib with acceptable adverse events.
Insulin-like growth factor 1 and its binding protein-2 in tumor and peritumoral tissues as important factors involved in recurrence of soft tissue sarcomas in older men.
Authors: Sagatelyan Susan A. , Kaplieva Irina V. , Frantsiyants Elena M. , Goroshinskaya Irina A. , Vashchenko Larisa N. , Chernogorov Pavel V. , Ausheva Tatiana V. , Pogorelova Yulia A. , Kachesova Polina S. , Gusareva Marina A. , Atmachidi Dmitriy P. , Kit Oleg I.
Published: June 2022

e23556

Background: The system of insulin-like growth factors (IGF) is involved in the pathogenesis of many malignant tumors. At the same time, the specificity of this system in recurrent soft tissue sarcomas is unknown. The purpose of this study was to analyze the IGF system in tumors and their peritumoral areas in men with recurrent soft tissue sarcomas. Methods: The study included 26 men aged 57.8±6.2 years with primary (n = 12, group 1, controls) and recurrent (n = 14, group 2, main group) soft tissue sarcoma of the extremities, T2bN0M0. Grade 1 tumors were diagnosed in 6 patients of group 1 and in 7 patients of group 2, while the other patients had G3 or G4 tumors. 95% of tumors were liposarcomas. All patients of group 2 had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Levels of the IGF system components were determined in tumor (T) and peritumoral (PT) tissues by ELISA, and ratios of IGF(T)/IGF(PT) were calculated. Results: Levels of the IGF system components in patients of group 1 were similar in T and PT. In group 2, levels of IGF1 and IGFВР2 in T were respectively 2.2 and 1.6 times (p < 0.05) lower than in PT, but did not differ significantly from the levels in group 1. The IGF1(T)/IGF1(PT) ratio in patients of group 2 was 1.8 times (p < 0.05) lower than in group 1. PT levels of IGF2 in group 2 depended on the tumor grade: they were 1.5 times (p < 0.05) higher in G1 than in G3-G4, while no such dependence was observed in T. Conclusions: The levels of the IGF system components in recurrent soft tissue sarcomas in older men had some peculiarities. Unlike primary sarcomas with similar levels of the studied components of the IGF system in tumors and in peritumoral tissues, recurrent tumors contained less IGF1 and IGFBP2 than the corresponding peritumoral areas. The levels of IGF2 in the peritumoral tissues of recurrent tumors depended on the tumor grade.
Sex dependence of hypothyroidism on malignant tumor growth.
Authors: Bandovkina Valeria A. , Frantsiyants Elena M. , Kaplieva Irina V. , Cheryarina Natalia D. , Surikova Ekaterina I. , Pogorelova Yulia A. , Arakelova Alina Yu , Salatova Ayna M. , Engibaryan Marina A. , Ulianova Yulia V. , Volkova Viktoriya L. , Rozenko Dmitry A. , Kit Oleg I.
Published: June 2022

e23558

Background: Experimental data showed proliferative and anti-apoptotic effects of thyroxine (T4) and triiodothyronine (T3) on cancer cells which regulate gene expression and stimulate estrogen-like effects. The purpose of the study was to analyze effects of hypothyroidism on the development of malignant tumors in male and female rats. Methods: Female (n = 15) and male (n = 15) white outbred rats weighing 150 g and more received mercazolil (2.5 mg/100 g of weight) daily for 30 days (total dose of 75 mg/100 g of weight). Blood levels of T3, T4 and TSH were measured in all animals. When persistent hypothyroidism was observed, Guerin's carcinoma (GC, group 1) and sarcoma 45 (S45, group 2) were inoculated at a dose of 2 million cells in 0.5 ml of saline under the skin of the back to animals of both genders. The control group included rats of both genders with subcutaneous inoculation of Guerin's carcinoma and sarcoma-45 in the same dosage and volume but without preliminary reproduction of the hypothyroidism model. Results: Average tumor volumes in females with GC and hypothyroidism were less than in animals of the control group: after 4 days by 1.3 times (p < 0.05), after 7 and 10 days by 1.4 times (p < 0.05), after 14 days by 1.5 times (p < 0.05), after 18 days by 1.3 times (p < 0.05), and after 21 days by 1.4 times (p < 0.05). The survival of female rats in the main group was 1.6 times higher (p < 0.05) than in rats of the control group. Average tumor volumes in females with S45 and hypothyroidism were less than in animals of the control group: after 4 days by 1.4 times (p < 0.05), after 7 and 10 days by 1.6 and 3.2 times (p < 0.05), after 14 days by 3.9 times, and after 18 days by 4.8 times. The survival of female rats in the main group was 1.8 times higher (p < 0.05) than in rats of the control group. Average tumor volumes in males of the main group with GC and hypothyroidism after 18 and 21 days were similar to the values in animals of the control group. Their survival did not differ from the survival of control males. Average tumor volumes in males of the main group with S45 and hypothyroidism after 10 and 21 days were similar to the values in animals of the control group. Their survival did not differ from the survival of control males. Conclusions: Hypothyroidism in female rats with GC and S45 inhibited the growth of malignant tumors and improved the survival of animals, while in males no such inhibiting effect was observed.
Illness perception and concordance between prostate cancer survivors and caregivers and adherence to self-management behaviors.
Authors: Pantaleon Karisma , Chan Courtney , Yuan Ying , Lin Jenny J.
Published: June 2022

e24002

Background: Illness beliefs are important determinants of self-management behaviors (SMBs). Spousal or informal caregiver involvement improves clinical outcomes in non-cancer survivors with chronic diseases. However, very little is known about the influence that caregivers have on comorbid disease SMBs in cancer survivors. In this study, we aim to understand and identify concordance in illness beliefs and perceptions between caregivers and prostate cancer survivors and to determine their impact on hypertension (HTN) SMBs. Methods: Survivors and their caregivers completed surveys assessing their beliefs and perceptions and SMBs regarding survivors’ HTN. Both survivors and caregivers answered the Brief Illness Perception Questionnaire (BIPQ) to assess beliefs and perceptions of survivors’ HTN. The BIPQ score is a sum of eight questions with a higher sum score indicating a more threatening view of the illness. Survivors reported adherence to SMBs using the Medication Adherence Report Scale (MARS) and Hypertension Self-Care Activity Level Effects (HSCALE). MARS scores >4.5 were considered adherent. The HSCALE isdivided into five sub-scores – diet, physical activity, smoking behavior, weight management and alcohol intake and each was score was dichotomized. Cohen’s Kappa statistic assessed concordance between survivor and caregiver dyad responses to the BIPQ. Logistic regression assessed associations between survivor and caregiver BIPQ scores and odds of SMB adherence. Results: This analysis included 55 dyads. Mean age of survivors was 70.4 years ± 9.6; 12 (22%) were Black, 36 (65%) were White, 2 (4%) were Asian and 3 (5%) were other race. Mean age of caregivers was 64.4 years ± 10.5, 9 (16%) self-identified as Black, 35 (64%) White, 2 (4%) Asian and 3 (5%) other race. Survivors and caregivers had fair agreements about how much HTN affected survivors’ lives (k = 0.147, p = 0.008), how concerned survivors are about their HTN k = 0.130, p = 0.014), and HTN’s emotional impact on survivors (k = 0.185, p = 0.002). However, survivor-caregiver concordance about HTN had no significant impact on survivors’ SMBs. In contrast, caregivers’ beliefs about HTN was associated with survivors’ SMB such that a 1-point increase in caregiver’s BIPQ score was associated with 8% increase in the odds of survivors’ self-reported weight adherence (p = 0.0314). Survivors’ HTN beliefs were not associated with adherence to SMBs. Conclusions: Caregivers have a significant influence on prostate cancer survivors’ adherence to weight-related SMB, demonstrating that it is important to also educate caregivers who support cancer survivors with chronic comorbidities. Future analysis will include a larger cohort to better understand the interrelationship between caregivers’ illness beliefs and survivors’ SMBs and may help clinicians better direct interventions to improve survivorship outcomes.
Geriatric assessment as a predictor of survival among older Indian patients with cancer.
Authors: Rao Abhijith Rajaram , Ramaswamy Anant , Kumar Sharath , Gattani Shreya , Dhekale Ratan , Krishnamurthy Jyoti , Mahajan Sarika , Daptardar Anuradha , Deodhar Jayita , Nookala Manjunath , Goud Supriya , More Sucheta , Nakti Dipti , Mudliya Chetan , Menon Nandini Sharrel , Patil Vijay Maruti , Gota Vikram , Banavali Shripad Dinanath , Prabhash Kumar , Noronha Vanita
Published: June 2022

e24012

Background: ASCO guidelines recommend that geriatric assessment (GA) should be performed in all older adults with cancer. However, GA is labor- and time-intensive, hence the uptake is poor, especially in crowded resource poor-settings. There are no data correlating GA with overall survival (OS) outcomes from the Indian subcontinent. Methods: A prospective observational study in the geriatric oncology clinic of the Tata Memorial Hospital in Mumbai, India. Patients aged 60 years and above, with cancer who underwent a GA were enrolled. The domains assessed included: function (basic and instrumental activities of daily living, timed-up-and-go), nutrition (body mass index, unintentional weight loss, mini-nutritional assessment), comorbidities, cognition, psychological (depression, anxiety), social support, and medication (polypharmacy and potentially inappropriate medications). Patients with > 2 deranged GA domains were considered frail. Results: Between June 2018 and January 2022, 909 patients were enrolled. The median age was 69 (IQR, 60-88) years. Common malignancies included lung (40%), esophagus (21%) and head and neck (11%); 53% had metastatic disease. 80% had > 2 impaired domains in GA patients had vulnerabilities in a median of 3 (IQR, 0-5) domains. Median OS in fit patients based on the GA was 17.5 (95% CI, 13.9-21.0) months vs 12.1 (95% CI, 10.1-14.0) months in frail patients, (HR 0.66; 95% CI, 0.49-0.88, p = 0.005), which remained significant after adjusting for age, sex, and stage (HR, 0.71; 95% CI: 0.53-0.94, p = 0.021). In the multivariate analysis (Table), the domains that were predictive of survival were nutrition (HR: 0.65, 95% CI: 0.47-0.92, p = 0.014), cognition (HR: 0.65; 95% CI: 0.46-0.91, p = 0.012) and fatigue (HR: 0.74, 95% CI: 0.56-0.98, p = 0.038). Conclusions: In older Indian patients with cancer, GA is a powerful prognosticator of survival. In settings where a complete GA is not possible, nutrition, cognition, and fatigue should be the minimum domains assessed. Clinical trial information: CTRI/2020/04/024675. [Table: see text]
Outcome and surveillance pattern in older GIST population.
Authors: Ho Thanh P. , Siontis Brittany L , Thiels Cornelius A , Grotz Travis Edward , Okuno Scott H. , Robinson Steven Ian
Published: June 2022

e24016

Background: Recent studies of patients (pts) with gastrointestinal stromal tumor (GIST) have included an older patient population. The majority of these have focused on treatment, but little is known regarding the optimal duration of surveillance following surgery for localized disease. Methods: We conducted a retrospective study of pts age 70 years (yrs) and above (≥) at diagnosis (dx), who underwent surgery for their localized GIST. Charts were reviewed of GIST diagnosed between 1992 to 2016, to allow at least 5 yrs for surveillance, if performed. Demographics were analyzed and pts were risk stratified using modified NIH criteria. Results: We identified 42 pts with a median age of 74 yrs (70 to 89 yrs) at dx. The majority of pts were male (31, 74%) and non-Hispanic White (37, 88%). Most pts had gastric GIST (25, 60%). The median resected tumor was 47 mm (range 6 to 190). Thirty-nine of 42 pts had margin status documented R0 resection. The median overall survival for all pts was 7.9 yrs (1.1 to 17.7), with median recurrence free survival 5.6 yrs (1.1 to 13.7). Only 4 of 16 (25%) pts died from GIST recurrence, and all were detected under 5 yrs from surgery. Fourteen of 34 pts (41%) who survived over 5 yrs from resection had extended surveillance imaging. Demographics and risk stratification are shown in Table. None of the 16 low risk pts developed recurrence, including 6 (38%) whose surveillance imaging continued beyond 5 yrs. Among 7 intermediate risk pts, only 1 pt (14%) extended surveillance imaging beyond 5 yrs. Two intermediate risk pts (29%) developed recurrence and were symptomatic at dx. One intermediate risk pt died from GIST metastasis within 1 yr from surgery. Seven of 19 (37%) high risk pts had surveillance imaging beyond 5 yrs following surgical resection. Seven high risk pts (37%) developed recurrence within median 5.6 yrs (1.6 to 13.7) from surgery; five of these were detected on imaging. In the high risk pts with recurrence, 5 had received adjuvant imatinib and 2 declined any systemic therapy. Three pts (16%) in the high risk cohort died from GIST. Conclusions: In this cohort of pts age ≥ 70 yrs with resected GIST, the majority of pts were symptomatic at relapse. Older pts who undergo surgery for low risk GIST may not require extended surveillance. Fit, older pts with high risk GIST may benefit from extended surveillance imaging, even if they received adjuvant imatinib.[Table: see text]
Understanding women’s perspectives on breast cancer is essential for early breast cancer diagnosis and to avoid diagnosis delay: A mixed method study.
Authors: Sankar Uma V , Warrier Narayanankutty Edavalath , T S Rakhi , Wilson Roshna
Published: June 2022

e24036

Background: Breast Cancer is the most common cancer in women worldwide. Since 2017, MVR Cancer Centre is a tertiary care hospital, New national guidelines focused on clinical breast exam and mammogram require that women be aware of and seek care for breast concerns. Therefore, this study aims to understand women’s perspective on breast cancer diagnosis. Methods: Sequential explanatory method was used to satisfy the objectives of the study. A crossectional survey was conducted to conveniently sampled women aged 30 and older to assess women’s perspectives on breast cancer and care-seeking behavior. We did a qualitative interview among selected breast cancer women to know about the reasons of delayed diagnosis and treatment delay. Results: Among 378 women with a median age of 49 (IQR: 34–62) years, 73% have heard of cancer and 30% have received self-breast examination. Women self-evaluated their knowledge of breast cancer (from 1-none to 10-extremely knowledgeable) with a median response of 3 (IQR: 1–4). Only 24% felt they knew any signs or symptoms of breast cancer. Encouragingly, 42% of women were fairly-to-very confident they would notice changes in their breasts, with 22% of women practicing self-breast examination and 8% reporting they had received a past breast exam. Overall, 64% said they would be somewhat-to-very likely to seek care if they noticed breast changes, with 98% noting severity of symptoms as a motivator. However, altered sexuality (43%), fear of losing a breast - Womanhood(70%) and fear of a poor diagnosis (48%) were most frequent barriers to care seeking. In assessing knowledge of risk factors, about 70% of women did not know any risk factors for breast cancer whereas 12% of women believed long term contraceptive use a risk factor. However, 37% and 35% of women did not think that family history or being older were risk factors, respectively. Social recognition as woman, existence of womanhood, cost of treatment and related financial burden and fear of complications and death are the themes emerged from the qualitative study. Conclusions: The success of efforts to improve early diagnosis in a setting without population-based screening depends on women being aware of breast cancer signs and symptoms, risks, and ultimately seeking care for breast concerns. Unfortunately, most women said they would seek care if they noticed a severity in the signs and symptoms of cancer, but the low levels of cancer knowledge, symptoms, and common risk factors highlight the need for targeted community education and awareness campaigns.