bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uveal melanoma: Real-world analysis of immune checkpoint inhibitors efficacy and lymphocyte-to-monocyte ratio as a biomarker of response.
Authors: Desilets Antoine , Beland Chloe , Hladky Valerie , Pang Steph A. , Elkrief Arielle , Stepanov Andreea , Routy Bertrand , Belanger Karl , Miller Wilson H. , Larochelle Olivier , Jamal Rahima 
Published: June 2022

e21590 Background: Uveal melanoma (UM) is a rare subtype of melanoma. Real-world data is needed to guide management since patients with advanced UM were excluded from immune checkpoint inhibition (ICI) phase III clinical trials. Lymphopenia and elevated monocyte count, which represents a surrogate marker of systemic inflammation and a source of pro-angiogenic tumor-associated macrophages (TAM), have been associated with poor treatment outcomes in various solid tumors. We sought to characterize ICI efficacy in patients with UM vs cutaneous melanoma (CM) and to investigate pre-treatment lymphocyte-to-monocyte ratio (LMR) as a biomarker of response. Methods: We conducted a multicentric cohort study across 3 academic centers in Canada. Best overall responses as per the investigators were recorded. Overall survival (OS) and progression-free survival (PFS) were compared using the log rank (Mantel-Cox) test, with univariate analyses performed using Cox proportional hazard regression model. Results: A total of 122 patients with metastatic melanoma were included, either UM (n = 60) or CM (n = 62). UM patients were treated either with anti-PD-1 monotherapy (69%) or combination with anti-CTLA-4 (31%). Median OS was 35.4 months for CM versus 8.0 months for UM (HR 0.38, 95%CI 0.24-0.60, p = 0.0001). Median PFS was 10.7 months for CM versus 3.5 months for UM (HR 0.38, 95%CI 0.22-0.65, p = 0.0001). Best overall response in the UM group was progressive disease (74%), stable disease (10%) or partial response (16%). In UM patients, higher baseline LMR (HR 0.48, 95%CI 0.24-0.97, p = 0.04) and presence of immune-related adverse events (HR 0.42, 95%CI 0.20-0.89, p = 0.02) were associated with improved OS in univariate analysis. In CM, such association with high LMR was not significant (HR 0.58, 95% 0.28-1.21, p = 0.10) unless excluding patients with corticosteroid-induced lymphopenia due to recently treated brain metastases (HR 0.42, 95%CI 0.19-0.92, p = 0.03). Conclusions: Advanced UM treated with ICI have inferior survival outcomes compared with cutaneous primaries. Higher pre-treatment LMR is associated with improved OS to ICI in UM patients and could represent a surrogate marker of immune activation. Our findings reinforce the need for new treatment strategies in UM.
Efficacy and safety of outpatient based therapy in childhood acute lymphoblastic leukemia.
Authors: Zulfikar Osman Bulent , Koc Basak 
Published: June 2022

e22001 Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. With the improvements in effective antileukemic drugs and the risk stratification treatment approach, the cure rate for pediatric ALL has increased to >90%. The effect of outpatient treatment and developing supportive care have a very important role in this success. We evaluated the disease outcomes and severe complications (complication causes hospitalization in ICU, encephalitis) of children who had been treated with the Children’s Oncology Group (COG) protocols, and follow-up protocol during a 20-year study period. Methods: From 1999 to 2020, 134 patients who had been diagnosed with ALL in the Department of Pediatric Hematology-Oncology at the Istanbul University Oncology Institute were included in the present study. Nine patients excluded from all analysis that 5 of them admitted with relapse, 2 had been diagnosed with mature aggressive B-cell acute leukemia, and 2 had been diagnosed with mixed phenotype and 7 who had been lost to follow-up were also excluded from survival analyses. Results: Mean age was 7.7±4.89 years old in 125 patients (Table). The 5- and 10-year and 20-year Event Free Survival (EFS) rates were 90.2% (standard error [SE], 4.2%) in standart risk B-ALL (n=54) and Overall Survival (OS) rates were 100%, 96% and 96% ([SE], 3.9%), respectively. In high risk group B-ALL (n=53) 5-year EFS was 80.7% (standard error [SE], 5.8%) and 78.2% ([SE], 6.1%) for both 10 and 20 year period and OS rates were 76.9% ([SE], 5.9%) for all periods. Although the number of patients is low in T-ALL (n=11), 5- and 10-year and 20-year EFS and OS rates were 63.6% (standard error [SE], 14.5%) for all periods. Fifteen severe complication recorded in 12 patients (10 B-ALL, 2 T-ALL). One patient hospitalized in ICU due to gram negative sepsis for 3-times and epidural hemorrhage. Conclusions: The survival rate for pediatric ALL has increased in recent years according to improvements of treatment.In our cohort, 20-year OS rate is 96% for standart risk B-ALL and 76.9% for high risk B-ALL. Additionally, regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated. In our study, the short hospitalization period, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children increased the success of the therapy and ensured low complication rates. [Table: see text]
Epidemiology, clinical features and outcomes of ganglioneuroblastoma: An analysis of the National Cancer Database.
Authors: Nelson Bridgett , Silberstein Peter T. , Cichon Gregory 
Published: June 2022

e22013 Background: Ganglioneuroblastoma (GNB) is a rare tumor of the sympathetic nervous system composed of both immature neuroblasts and mature ganglion cells. It has an intermediate malignant potential that lies between a low grade ganglioneuroma and a high-grade neuroblastoma and has the capability to transform into a neuroblastoma. While more information is known regarding pediatric neuroblastoma, little is known regarding the epidemiology and clinical features of GNB. To our knowledge, this is the first analysis of ganglioneuroblastoma using the National Cancer Database (NCDB) and potentially the largest and most comprehensive studies of this subtype of tumor to date. Methods: Using the National Cancer Database (NCDB), 273 patients diagnosed with ganglioneuroblastoma (ICD-0 9490/3) from 2004-2018 were identified. Kaplan-Meir analysis was used to estimate survival and log-rank tests were used to compare survival between stage groups. Results: The median age of diagnosis for patients with ganglioneuroblastoma was found to be 4 years. Girls were affected more commonly than boys, with a male to female ratio of 1.6/1. A majority of patients were white (77.7%) and African American (13.6%), followed by minor representations from multiple other races. The most common primary site of ganglioneuroblastoma was the thorax (40.5%), followed by the abdomen (35.7%). A minority of patients (14%) had distant metastases at diagnosis. At the time of disease presentation, 56% of patients were classified as stage I, 9.2% as stage II, 18.4% as stage III and 16.3% as stage IV. Stages I, II, and III conferred an excellent prognosis with a 99.2% survival rate as compared to patients with stage IV disease who had a survival rate of 65.2% (p < 0.001). Nearly all patients underwent surgery of the primary site, with the most common approach being local excision. Around one quarter of patients received chemotherapy while very few patients required radiation or immunotherapy. Conclusions: A number of unique findings help to distinguish ganglioneuroblastoma from the more common variant neuroblastoma. GNB seems to affect slightly older children (median age of 4 years) compared to a median age of 22 months in neuroblastoma. Interestingly, GNB was found to occur significantly more frequently in girls. On the contrary, neuroblastoma has been reported to be slightly more common in males than females. Additionally, the majority of ganglioneuroblastomas arise in the thorax. This is in comparison to neuroblastomas, of which the large majority arise in the abdomen, specifically in the adrenal glands. Stage IV GNB carries a significantly worse prognosis than stages I-III, with a survival rate of 62.5% which is similar to stage IV neuroblastoma.
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.