bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival (OS) in metastatic uveal melanoma: A summary of recent prospective trials.
Authors: Piulats Josep M. , Shoushtari Alexander Noor , Ochsenreither Sebastian , Abdullah Shaad Essa , Holland Chris , McCully Michelle L. , Baurain Jean-Francois 
Published: June 2022

e21598 Background: Metastatic uveal melanoma (mUM) historically has a poor prognosis where chemotherapy and checkpoint blockade, including combination, has had no impact on OS. Tebentafusp (tebe), a TCR bispecific (gp100 x CD3), is the first therapy to demonstrate an OS benefit in a mUM randomized trial (IMCgp100-202) against pembrolizumab (pembro), ipilimumab (ipi) or dacarbazine. Here we present a summary of OS from recent prospective trials in mUM in both previously untreated (1L) and previously treated (2L+) mUM including cross trial comparison with checkpoint blockade combination. Methods: A literature review of prospective Ph2/3 clinical trials of systemic therapies in mUM published recently (2019-2021) identified 8 trials: in 1L mUM (n = 2) a randomized Ph3 of tebe (N = 252) vs investigator’s choice (IC; N = 126) of pembro, ipi or dacarbazine (IMCgp100-202) and a single arm Ph2 of nivolumab (nivo) + ipi (N = 52; Piulats, 2021) (Table); in 2L+ mUM (n = 1) a single arm Ph2 of tebe (N = 127; IMCgp100-102); and in mixed line mUM (n = 5) a randomized Ph2 of cabozantinib (N = 31) vs chemotherapy (N = 15; Luke, 2019), a single arm Ph2 of nivo + ipi (N = 35; Pelster, 2021), a single arm Ph2 of pembro + entinostat (N = 29; Ny, 2021), a single arm Ph2 of glembatumumab (N = 37; Hasanov, 2020), and a single arm Ph2 of IMC-A12 (IGF-1 receptor inhibitor; N = 18; Mattei, 2020). The PUMMA (Khoja, 2019; N = 912) and Rantala, 2019 (N = 2494; n = 510 1L pts) meta-analyses were included to provide historical benchmarks for OS. Results: In previously untreated mUM, 1-yr and median OS were 73% and 21.7 months for tebe, 59% and 15.7 months for pembro, 52% and 12.7 months for nivo + ipi and 45% and 11.3 months for conventional chemotherapy. In previously treated mUM, 1-yr and median OS were 61% and 16.8 months for tebe, 34% and 7.0 months for checkpoint inhibitors, and 43% and 10.5 months for conventional chemotherapy. In mixed line (1L+) mUM, 1-yr and median OS were 56% and 19.1 months for nivo + ipi and 59% and 13.4 months for pembro + entinostat, 13.8 months for IMC-A12, 11.9 months for glembatumumab and 6.4 months for cabozantinib. Related AEs (any grade) leading to discontinuation and death for tebe were 2% and 0% vs 5% and 0% for IC control, and 23% and 3.8% for nivo + ipi in 1L pts. Conclusions: Tebe is the only therapy demonstrated to prolong OS in mUM. The 1-yr OS for tebe in 1L and 2L+ is superior to all recent published studies, including nivo + ipi. Both tebe and checkpoint combination therapy have high rate of any grade AEs, although checkpoint combination has a higher rate of treatment related discontinuations and deaths.[Table: see text]
Systemic bevacizumab for aggressive recurrent respiratory papillomatosis: A single center experience of five cases.
Authors: Liu Zengjun , Xiao Yang , Xu Jing , Zhu Dongyuan 
Published: June 2022

e22005 Background: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV) driven benign neoplasm, affecting larynx, trachea, and even lung, leading to voice disorders, airway obstruction, and post-obstructive pneumonia. Currently, there is no curative therapy for RRP.Patients require frequent debulking operations for symptomatic palliation. However, several case reports documented promising results on inhibition of vascular endothelial growth factor (VEGF) by systemic administration of bevacizumab. Methods: We retrospectively analyzed clinical, radiological, and bronchoscopy data of aggressive RRP patients treated with systemic bevacizumab since January 2021. Results: 5 consecutive patients were included. Median age (range) was 8 (4-30), 60% (3/5) were male. The locations of RRP were as follows: localized in the major airway (including vocal cords, larynx, trachea, and main bronchus), n = 1; extensive from major airway to lung parenchyma, n = 4. The median number (range) of local interventions was 8 (2-17) throughout the 12 months prior to bevacizumab treatment. The administration of systemic therapeutic agents, such as HPV vaccine and interferon had been tried in two patients. Bevacizumab was administered at a dose of 5 mg/kg (n = 4) or 7.5 mg/kg (n = 1) intravenously. Treatment intervals were initiated every 2-3 weeks and subsequently extended after achieving the maximum response. The patients received median 6 cycles of bevacizumab (range 4-7). The bevacizumab was given as adjuvant therapy in 2 patients on the 3rd and 5th day after laser operation, and as salvage therapy in the other 3 patients. All patients with major airway RRP displayed improvement in disease burden. No patients required surgery during a medain 7 (range 3-8) months follow up periods after initiating bevacizumab treatment. A rapid response was demonstrated in a patient with long-standing extensive pulmonary disease. Except from mild and transit abdominal pain and hemoptysis in 2 patients, systemic treatment with bevacizumab was well tolerated. Conclusions: Inhibition of VEGF by systemic bevacizumab seems to be a well tolerated and effective treatment option for localized and extensive forms of RRP.
Lerociclib diminishes stemness in pediatric sarcoma cell lines.
Authors: Hutchins Sara , Bownes Laura V. , Quinn Colin H. , Julson Janet R. , Stewart Jerry E. , Aye Jamie , Yoon Karina J , Beierle Elizabeth A. 
Published: June 2022

e22010 Background: The outcomes for children with osteosarcoma and synovial sarcoma remain poor and are even worse for metastatic or relapsed disease. Those who do survive frequently suffer from long-term toxicities from current standard-of-care therapies. It is evident novel therapeutics are warranted to improve the outcomes for patients with these difficult tumors. Stem cell-like cancer cells (SCLCCs) are a subpopulation of tumor cells thought to be responsible for treatment resistance, development of metastases and tumor recurrence, making the targeting of this cell population critical. We sought to evaluate the effect of lerociclib, a CDK4/6 inhibitor, on pediatric sarcoma cell stemness. Methods: We investigated two established human osteosarcoma cells lines (U2-OS and MG-63), two metastatic synovial sarcoma patient-derived xenografts (PDXs) (COA-30 and COA-79) and a metastatic epithelioid sarcoma PDX (COA-171). Cells were treated with the CDK4/6 inhibitor, lerociclib, at concentrations below the known LD50. Synovial sarcoma stemness markers Octamer-binding transcription factor 4 (Oct4), homeobox protein Nanog, SOX 2 and nestin were evaluated by qPCR. CD117, a marker of stemness in osteosarcoma cells, was examined by flow cytometry. Finally, long-term passaged U2-OS and MG-63 cells were placed in low attachment serum-free conditions, and tumorsphere formation was evaluated using extreme limiting dilution assay (ELDA) in all cell lines. Results: Lerociclib treatment significantly decreased abundance of Oct4 (by 54%), Nanog (by 29%), SOX 2 (by 60%) and nestin (by 63%) mRNA in COA-30 synovial sarcoma cells. Cell surface expression of CD117 decreased from 17% to 11% in MG-63 cells when treated with lerociclib 2μM. Treatment of all cell types with lerociclib led to significantly decreased tumorsphere formation (Table). Conclusions: Treatment with lerociclib led to a decrease in mRNA abundance in known synovial sarcoma stem cell markers, a decrease in CD117 cell surface expression in osteosarcoma cells and decreased the ability of cells to form tumorspheres. These findings indicate lerociclib leads to decreased sarcoma cell stemness, which plays a key role in tumor progression and recurrence and should be further investigated for potential translation to the clinical setting.[Table: see text]
Clinical significance of next generation sequencing (NGS) in Chinese patients with relapsed/refractory Wilm’s tumor.
Authors: Wang Juan , Chai Huizi , Zhao Lele , Yang Xueyu , Xiao Mingzhe , Qi Chuang 
Published: June 2022

e22014 Background: Medical advances have been greatly improved in the five-year survival rate for Wilms’ tumor, but the survival is still dismal for relapsed/refractory (R/R) patients. In the present study, we aimed to investigate the genomic profiling and the incidence of germline cancer susceptibility mutationsof Chinese patients with R/R WT. Methods: Next-generation sequencing (NGS) of tumor specimens with matched blood samples obtained from R/R pediatric WT in Sun Yat-Sen University Cancer Center were used in a CAP-certified laboratory (Simcere Diagnostic Co, Ltd). Clinical information including age, gender and tumor histology were collected. Somatic and germline mutations including single nucleotide variants (SNV), insertion-deletion variants (Indels), copy number variations (CNVs) and fusion, as well as tumor mutational burden (TMB) were analyzed. Results: Nineteen patients with R/R WT were enrolled in this study, including 10 males and 9 females, with a median age of 4 years old (range, 0-14). All of the pathology was identified as favorable histology WT (FHWT). Somatic mutations were detected in 84.21% (16/19) of patients, and CNVs accounted for the majority of the total somatic aberrations, followed by SNVs. The most common somatic mutations were identified in the following genes, CTNNB1 , ERBB2, MCL1 , CDK2 and MDM4. Of the top 3 frequently mutated genes, the mutation frequency and their most common mutation type were CTNNB1, 26%, in-frame deletion, missense mutation; ERBB2 21%, missense mutation, amplification; MCL1 21%, amplification. It is worth noting that MCL1 mutation has never been reported in Chinese R/R WT patients before, which may be a potential valuable mechanism. Germline mutations were detected in 89.47% (17/19) of patients, and CNVs accounted for the majority of the total germline aberrations, followed by SNVs. The most common germline mutations were identified in the following genes, MCL1, RET, ALK, EPCAM, and FANCA. Of the top frequently mutated genes frequency and most common mutation type were MCL1 21%, amplification; RET 21% missense mutation, multiple mutations. There are also some suspected clinically pathogenic germline mutation of genes CDK4 , ERBB2, and MDM4 . All the mutation type were amplification. Notable cancer driver mutations were also characterized, such as the amplifications of ERBB2 / MET/EGFR / FGFR1, and the point mutations of CHEK2/FBXW7/NF1. The median TMB was 1.47 (range, 0-7.8). Conclusions: Overall, clinical and new results were detected in 14 (73.68%) in Chinese R/R WT patients. We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients. Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.
Bone mineral density (BMD) deficits in adult survivors of childhood cancer: Attributable risks and long-term consequences.
Authors: Goodenough Chelsea Goodliffe , Baedke Jessica L , Li Nan , Brinkman Tara M. , Wilson Carmen Louise , Delaney Angela M. , Inaba Hiroto , Clark Karen L , Armstrong Gregory T. , Talleur Aimee C. , Pui Ching-Hon , Green Daniel M. , Merchant Thomas E. , Srivastava Deo Kumar , Yasui Yutaka , Hudson Melissa M. , Robison Leslie L. , Kaste Sue C. , Ness Kirsten K. , Chemaitilly Wassim 
Published: June 2022

e22021 Background: Survivors of childhood cancer are at risk for BMD deficits. Contributions of treatment, physical and lifestyle factors to overall risk are unknown as are long-term consequences of moderate and severe deficits. Methods: BMD deficits were evaluated in 3919 five-year childhood cancer survivors in the St. Jude Lifetime Cohort (median age 31.7 [range 18.0-69.9] years, 52.6% male, 80.4% non-Hispanic White) using lumbar quantitative computed tomography and classified by age- and sex-specific Z-scores as moderate (<-1SD) or severe deficit (<-2SD). Multivariable logistic regression estimated odds ratios (OR), risk factor attributable fractions (AF), and associations between BMD deficits and long-term outcomes (social/functional outcomes, fracture, mortality). Results: BMD deficits were moderate in 21.7% (95% CI 20.4%-23.0%) and severe in 6.9% (95% CI 6.1%-7.7%) of survivors. Risk factors for moderate deficit included age 5-9 years at diagnosis (OR 1.63, 95% CI 1.31-2.03), >20Gy cranial radiotherapy (OR 1.75, 95% CI 1.41-2.18), >3240 mg/m2 glucocorticoids (OR 1.34, 95% CI 1.09-1.66), and smoking (OR 1.55, 95% CI 1.27-1.90). AF were 7.2%, 0.7%, 5.9%, and 6.1% respectively; 80.1% of risk was unexplained. Risk factors for severe deficits included age 5-9 years at diagnosis (OR 1.95, 95% CI 1.36-2.80), BMI<18.5 kg/m2 (OR 3.95, 95% CI 2.28-6.85), >20Gy cranial radiotherapy (OR 5.22, 95% CI 3.74-7.30), testicular/pelvic radiation (OR 1.70, 95% CI 1.19-2.44), smoking (OR 1.71, 95% CI 1.21-2.43), and physical inactivity (OR 1.91, 95% CI 1.10-3.33). AFs were 10.9%, 7.0%, 2.9%, 11.5%, 6.7%, and 3.2% respectively; 57.8% of risk was unexplained. Those with deficits were less likely to live independently, to be employed, and more likely to require assistance with personal care needs (Table). Fracture risk was greatest among those with any BMD deficit, and mortality risk was greatest among those with severe deficits. Conclusions: Deficits in BMD among childhood cancer survivors are related not only to treatment, but also to modifiable health behaviors. In this population, children exposed to radiation or glucocorticoids are at greatest risk for poor bone quality and should be counselled to optimize health behaviors.[Table: see text]
Prevalence of HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Authors: Bolatbekova Raikhan , Kaidarova Dilyara , Dushimova Zaure , Shatkovskaya Oxana , Zhylkaydarova Alma , Kukubassov Yerlan , Sadykova Tolkyn , Satanova Alima , Bertleuov Orynbassar , Kaldybekov Dauren 
Published: June 2022

e22503 Background: Cervical cancer (CC) is the second most common type of cancer for women worldwide. 99% of cases of CC are associated with high-risk human papillomaviruses (HPV HR). Unfortunately, data on the epidemiology of HPV in Kazakhstan are limited, especially in young kazakhstani women. This study was provided to determine the prevalence of HPV HR and the cytological abnormalities in young Kazakhstani women, which will allow strengthening control in the existing CC screening in this age. Methods: 101 women aged 18-30 years were invited to this cross-sectional study. Women were mentally healthy and did not have a positive human papillomaviruses (HPV) history. Cervical samples for HPV were analyzed with using of Cobas 4800 HPV test. Cytological examination of smears with using the Bethesda terminology system and HPV test were conducted at Kazakh Institute of Oncology and Radiology. Results: The mean age of the study group was 21.0±2.8 years (range 18-30 years). Prevalence of HPV was 11,8% (12 cases). HPV 16 and 18 were the most common type in analyzed cases (5,9%). Cytological abnormalities occurred in 19,8% (20 cases). The Mann-Whitney test of the frequency of cytological abnormalities showed that the ASCUS and LSIL was significantly more found in the group up to 25 years. The HSIL was more common in a group of women 25 years and older and accounted for 1.9 % out of 2 cases (p < 0.05). Conclusions: The results of this study confirm the need for HPV vaccination of adolescent girls and improvement of the existing screening through the inclusion of women to screening from 25 years of age. Changing of CC screening through implementation of HPV screening with cytological triage of HPV - positive of women can reduce the burden of CC in young age in KazakhstanPrevalence of high risk HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Lethality of lung cancer in southeast of Brazil: Real-world data.
Authors: Aleixo Sabina B. , Parmanhane Narelle , Pulido Jose Zago 
Published: June 2022

e22515 Background: Lung Cancer (LC) is one of the most common neoplasm of all malignant tumors, with an increasing lethality and incidence, corresponding to 13.5% of all types of cancer. The world estimate for 2020 was 19 million cases of cancer worldwide, with 10 million deaths of which lung cancer represented 18% of the deaths. It is estimated that in Brazil, according to INCA (National Cancer Center of Brazil) that in the year 2022 there will be 30,200 new cases, the second most common among men and the fourth among women. Unfortunately most cases are diagnosed in late stages and have low survival. Methods: Retrospective study of data from SisRHC (brazilian cancer registry system) of patients diagnosed with LC, treated at the reference cancer center Hospital Evangélico de Cachoeiro de Itapemirim/ES, from January 1, 2010 to December 31, 2019. Results: A total of 440 patients were included and their main characteristics at diagnoses was advanced stages (73.2% III/IV) and only 58 % where able to receive first line treatment: chemotherapy concomitantly with radiotherapy (22,3%), isolated chemotherapy (21.4%) and isolated radiotherapy (14.6%). After first line treatment outcome status was death (49.4%) and disease progression (12.3%). Median survival was 10.3 months. Conclusions: Despite the limitations of the retrospective study these data are important for understanding the pattern of disease in a developing country where acess to health is limited. Unfortunately the barrier of 12 months survival common in developed nations is still not a brazilian reality. Public policies are necessary for improvement
The future landscape of cancer incidence and mortality until 2036 in the Russian Federation.
Authors: Tsimafeyeu Ilya , Rahib Lola 
Published: June 2022

e22518 Background: Understanding the future of the burden of cancer is important to plan for future research funding, allocations of resources and other efforts. In 2019, the most incident solid tumors in Russia were colorectal, breast, lung, prostate, and gastric cancers; most deaths were lung, colorectal, gastric, breast, and pancreas cancers. We project cancer incidences and death to the year 2036 utilizing population growth estimates and observed current rates and trends in Russia. Methods: Average annual percent change (AAPC) adjusted estimations of cancer incidences and death to 2036 were calculated for the 10 most incident and deadly cancers for male and female individuals. We combined the most recent sex and cancer-specific delay-adjusted incidence rates from the Herzen Russian Cancer Statistics (official Russian cancer statistics) and GLOBOCAN database with existing Federal State Statistics Service (Rosstat) demographic population growth projections by sex to calculate estimated incidences and death to 2036. Calculations assume that the annual percent change in the incidence and death rates observed will remain constant through 2036. Results: We project that by 2036 the incidence will increase by 19.5% and the most incident cancers in Russia will be different than the current rankings. Excluding non-melanoma skin cancer, breast is projected to be the most incident cancer with 99,700 diagnoses (currently second most incident; 73,918 diagnoses in 2019), colorectal is projected to be second with 95,200 diagnoses (currently first, 77,062 diagnoses in 2019). Lung (60,113 diagnoses in 2019) and prostate (45,763 diagnosis in 2019) will drop from fourth and third place to third and fourth place with 85,400 and 53,100 diagnoses in 2036 respectively. Despite the increase in incidence, cancer deaths will decline by 18% by 2036. Lung and colorectal cancer are projected to continue to be the top 2 leading causes of cancer related death with 35,800 deaths in 2036 due to lung cancer and 32,100 deaths due to colorectal cancer. Pancreas cancer is projected to surpass breast and gastric cancer to become the 3rd leading cause of cancer related deaths in 2036 (21,800 deaths in 2036). Breast cancer is projected to move from the fourth leading cause of cancer related deaths to fifth and gastric cancer will no longer be one of the top 5 causes of cancer deaths. Conclusions: We present projections on cancer incidence and deaths to 2036 in Russia. We show a shift in the rankings of the top 5 most common cancers and most markedly we show that pancreas cancer will be the third leading (currently fifth) cause of cancer related deaths by 2036. These projections can guide future research focus and planning.
Effects of anxiety and depression on the quality of life of male cancer patients undergoing genetic investigation for hereditary cancer predisposition syndromes.
Authors: Barbosa Oliveira Francisca Fernanda , Silva Paulo Goberlânio de Barros , Bitencourt Flávio da Silveira , Sant'Ana Rosane Oliveira , Silva-Fernandes Isabelle Joyce de Lima , Bezerra Maria Júlia Barbosa , Luciano Maria Claudia dos Santos , Picanço-Albuquerque Clarissa Gondim , Souza Thuany Pinto Rocha de , Lima Marcos Venício Alves 
Published: June 2022

e22529 Background: Genetic tests have been increasingly requested to identify families at risk of hereditary cancer. In a family with a known mutation, the offspring of a carrier, whether male or female, have a 50% risk of inheriting the mutation. Most studies on the psychological implications associated with genetic testing have focused on women and few studies have focused on the male population. Methods: A total of 56 men with a personal history of cancer underwent screening for mutations in a panel of 31 genes associated with hereditary cancer. Assessment of quality of life (QoL) and levels of anxiety and depression was performed after patients received the genetic test result. For this, the HADS and WHOQOL-BREF scales were used. Wilcoxon, X², and Spearman correlation tests were used (SPSS v20.0 for Windows). Results: Of the 56 participants, 28.6% had a pathogenic mutation, 32.1% had a Variant of Undetermined Significance (VUS), and 39.3% had no mutation. The presence of the mutation was not associated with QoL (p = 0.967) or anxiety (p = 0.436) or depression (p = 0.945). Mean QoL was 77.95±7.38 (range = 50.00-95.20), mean anxiety was 5.14±2.62 (range = 1-14) and mean depression scores were 4.14±2.55 (range = 0-14). QoL was inversely correlated with levels of anxiety (p < 0.001, r = -0.496) and depression (p < 0.001, r = -0.494), parameters that were directly correlated (p = 0.037, r = 0.279). Most patients had QoL > 80 (n = 38, 67.9%), and only 16 (28.6%) and 13 (23.2%) men had HAD scores > 5. Conclusions: The result of carrying a mutation did not influence the quality of life and anxiety or depression levels in the male population evaluated. However, it was observed that levels of anxiety and depression can compromise the quality of life. The data from the present study reinforce the importance of considering the psychological aspects in the process of genetic investigation for hereditary cancer. In addition, it suggests that educational levels must be investigated to assess whether the low levels of anxiety and depression observed are associated with a low level of understanding of the clinical significance of carrying a pathogenic mutation.