bluuebunny/crossref_metadata_2025_split huggingface dataset:
A morphological subset of circulating tumor cells in advanced prostate cancer reveals a potential biomarker for clinical outcomes.
Authors: Wang Jasmine Jiemei , Cavassani Karen Angelica , Teng Pai-Chi , Chen Jie-Fu , Jan Yu Jen , Chu Gina Chia-Yi , Lee Yi-Te , Gao Allen , Di Vizio Dolores , Chung Leland WK , You Sungyong , Zhu Yazhen , Freeman Michael , Rogatko Andre , Yang Ju Dong , Tseng Hsian-Rong , Posadas Edwin Melencio 
Published: June 2021

e17008 Background: A morphological subset of prostate cancer (PCa) circulating tumor cells (CTCs) with particularly small nuclei (< 8.5 μm), named very-small-nuclear CTCs (vsnCTCs), were found to be correlated with the presence of visceral metastases. It is reported that the depletion of nuclear envelope protein emerin promotes PCa metastasis and is associated with nuclear shape instability. In this study, we hypothesize vsnCTCs as prognostic biomarkers in metastatic castration resistant PCa (mCRPC), and aim to investigate the correlation between emerin level and vsnCTCs. Methods: PCa CTCs were enriched using the NanoVelcro CTC Assay from 76 patients with mCRPC. The Kaplan-Meier analysis and log-rank test were used to estimate and compare the overall survival (OS) and progression free survival (PFS) of androgen receptor signaling inhibitor (ARSI), taxanes and other therapy in patients stratified by the presence of vsnCTCs. The correlation between the presence of vsnCTCs and OS and PFS were evaluated using the Cox proportional hazard regression. The expression level of emerin in patients with and without vsnCTC were compared using Mann-Whitney U test, and the correlation between emerin level and CTC nuclear size was tested by Pearson correlation coefficient. Results: Patients with vsnCTC (i.e, vsnCTC+) had significantly shortened OS and PFS compared with those without vsnCTC (i.e, vsnCTC-). The median OS was 34 (vsnCTC+, n= 49) vs. 149 (vsnCTC-, n= 27) weeks (hazard ratio [HR] = 2.6, 95% confidence interval [CI]: 1.5-4.5, P< 0.001). The median PFS was 12 (vsnCTC+, n= 32) vs. 26 (vsnCTC-, n= 18) weeks (HR = 2.2, 95% CI: 1.3 -4.0, P= 0.004). The emerin expression level was significantly higher in vsnCTC+ compared to vsnCTC- ( P= 0.009). In addition, we observed a significantly positive correlation between emerin expression and CTC nuclear size (r = 0.52, P< 0.001). Conclusions: This study casts light on the importance of the vsnCTCs in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for mortality. vsnCTC represents a new hallmark of an aggressive subtype of mCRPC and is related to emerin dysregulation, which promotes lethal progression and metastasis of PCa.
Nationwide trends in in-patient chemotherapy hospitalizations, cost, and mortality for patients with testicular carcinoma.
Authors: Abbasi Saqib , Wulff-Burchfield Elizabeth Marie , Parikh Rahul Atul 
Published: June 2021

e17012 Background: Salvage therapy for advanced Testicular Carcinoma involves patients receiving ifosfamide are treated in hospital for risk of neuro-toxicities. We evaluated annual trends to assess the health care burden of testicular patients admitted for chemotherapy, as well as co-morbidities and complications associated with mortality. Methods: The National Inpatient Sample is a nationwide sample of all US hospital discharges. We collected data from the years of 2002 to 2017 on patients with Testicular Carcinoma who were receiving chemotherapy, to capture patients recieving ifosfamide and cisplatin in an in-patient setting. Patients undergoing an autologous stem cell transplant were excluded. Annual trends for inpatient mortality, length of stay, and total costs of admission were assessed. A univariate logistic regression analysis was used to calculate odds ratios (OR) for the effect of comorbid conditions and acute inpatient complications on in-patient mortality. Results: Hospitalizations for ifosfamide and cisplatin based treatment among patients with Testicular Carcinoma remained stable from a weighted national estimate of 2,261 in 2002 to 2,160 in 2017. Length of stay increased from 4.6 days to 5.5 days (p=0.01). Cost of stay increased from $26,140 to $53,193 (p <0.001) when adjusted for inflation. The average age of patients was 32.6 years. In-patient mortality was low at 0.2% in 2002 to <0.1% in 2017. Among comorbid conditions, heart failure was associated with increased mortality (OR 21.9). Among acute complications – acute kidney injury (OR 32.6), infection (OR 15.3), neurotoxicity (OR 12.3) were associated with significantly higher mortality. Conclusions: The increase in cost of stay is out of proportion to increases in length of stay. Indicating a disproportionate increase in financial toxicity for these patients. Patients with underlying heart disease are at increased risk of complications. Care needs to be taken to specifically identify patients at risk for renal failure and infectious complications.[Table: see text]
Phase 2 analysis on Covid-19-adopted etoposide (E) and cisplatin (P) regimens for patients (pts) with an advanced germ cell tumor (GCT): The CovGCT study.
Authors: Naban Nabeel , Tiemeier Gesa , Kocache Arwa , Taylor Rory , Keogh Georgina , Hennah Lindsay , Sarwar Naveed , Seckl Michael , Gonzalez Michael 
Published: June 2021

e17013 Background: The Covid19 pandemic has imposed risks to healthcare delivery for all cancer pts including young adults diagnosed with a GCT. Here, we examine Emergency EP (EmEP, Cohort A) and a novel 1-day Escalated-dose EP (EscEP, Cohort B) administered every 2 weeks as upfront or first-relapse therapy to minimise hospital days. Methods: Single-centre analysis in GCT pts receiving emergency and routine chemotherapy following our first National lockdown on 23rd March 2020. In Cohort A, eligible pts receive EmEP E100mg/m2, P20mg/m2 prior to EscEP within the acute setting as previously defined. In Cohort B, EscEP E500mg/m2, P60mg/m2 is compared to standard care chemotherapy BEP or POMB-ACE. Data collection includes demographics, treatment details, clinical outcome and Covid19 complications. Results: To date, we have accrued 19 pts with a median age 32 (range 18 to 65). In Cohort A, 7 pts with symptomatic high-volume disease received a median 1 cycle EmEP, 6/7 for a new GCT diagnosis and 1/7 for a first relapse, including 2 males with IGCCCG intermediate-prognosis disease, 5 females with FIGO Stage III (n = 2) and IV (n = 3) disease. One pt required higher-level support for organ dysfunction at presentation. In Cohort B, 19 pts including 7 pts from Cohort A received a median 4 cycles EscEP: 8 males (2 seminomas, 6 non-seminomas; IGCCCG good-prognosis in 4, intermediate-prognosis in 2, poor-prognosis in 2), 11 females (1 dysgerminoma, 10 non-dysgerminomas; FIGO Stage Ic in 6, III in 2, IV in 3). A majority (14/19, 74%) received EscEP for a new cancer diagnosis, 5/19 (26%) for a first relapse. Total median hospital stay: EscEP 5 days, BEP 21 days, POMB-ACE 28 days. Grade 3/4 neutropenic events: EscEP 28%, BEP 50%, POMB-ACE 43%. From April 2020, 16/16 pts were SARS-CoV-2 screened prior to each cycle: 3/19 (16%) testing positive, one prior to intubation and ventilation, 2 with asymptomatic infection. For Cohort B, at median follow-up 121 days (range 9-323 days), we have observed a complete response in 10 pts (53%), partial response in 3 pts (16%) and disease progression in 1 pt (5%). Five pts are still on treatment (26%). All pts remain alive. Conclusions: EmEP and EscEP represent safe options during the pandemic that minimise myelosuppression and total length in hospital days whilst bypassing the potential pulmonary toxicity from Bleomycin. Further follow-up will inform on long-term efficacy including a multicentre evaluation.
Burden of chemotherapy-induced peripheral neuropathy and associations with long-term sexual impairment in testicular germ cell tumor survivors.
Authors: Chovanec Michal , Galikova Dominika , Vasilkova Lucia , De Angelis Valentina , Rejlekova Katarina , Obertova Jana , Sycova-Mila Zuzana , Palacka Patrik , Kalavska Katarina , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Mego Michal 
Published: June 2021

e17014 Background: Chemotherapy-induced peripheral neuropathy (CIPN20) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. The association of CIPN with long-term sexual function in GCT survivors remains unclear. Methods: European Organization for Research and Treatment of Cancer (EORTC) CIPN20 and PROMIS modified sexual function (SexF) questionnaires were prospectively completed by GCT survivors (N = 128) at National Cancer Institute in Slovakia during their annual follow-up visit. The median follow-up after completion of treatment was 10 years (range 4-25). Upon obtaining the scores from each questionnaire per recommended guidelines, each score from SexF was correlated with CIPN defined as high or low (above and below median) as obtained from CIPN20. Survivors were treated with cisplatin-based chemotherapy, radiotherapy to the retroperitoneum or both. Results: GCT survivors with CIPN reported a self-perceived sexual impairment. The overall perceived sexual impairment was higher in survivors with high vs low CIPN (mean score ± SEM: 7.44 ± 0.24 vs. 6.76 ± 0.21, P = 0.05). However, the overall perceived sexual abilities were not significantly different in CIPN high vs low (16.9 ± 0.68 vs. 16.8 ± 0.59, P = 0.97). The trend towards higher difficulty in maintaining erection was seen in CIPN high vs low survivors (3.94 ± 0.21 vs. 4.12 ± 0.18, P = 0.07). Furthermore, survivors with CIPN high were more disappointed with the quality of their sex life compared to those with CIPN low (1.96 ± 0.12 vs. 1.47 ± 0.11, P = 0.01). Patients with CIPN high had trend towards more anxiety from sexual relationships compared to CIPN low survivors (1.66 ± 0.11 vs. 1.33 ± 0.10, P = 0.06). The level of sexual desire, number of attempts to initiate sexual intercourse, ability to achieve erection, achieve orgasm were not different ( P all > 0.05). Conclusions: GCT survivors with higher burden of CIPN have certain impairment in sexual functioning. We hypothesize there may be a common pathogenetic mechanism of induction in these long-term toxicities of curative treatments.
The association of ATM alterations with clinical and molecular features in metastatic castration-resistant prostate cancer.
Authors: Xi Guo , WANG Qing , Zhang Qin , Duan Qianqian , Liu Yaqin 
Published: June 2021

e17019 Background: Ataxia telangiectasia-mutated（ATM）is a serine/threonine kinase involved in DNA-damage repair (DDR) system and regulating cell cycle checkpoints, senescence, and apoptosis. Several clinical studies provide evidence about the DDR-mutated metastatic castration-resistant prostate cancer (mCRPC) benefit from PARP inhibitors (PARPi). However. the efficacy of PARPi was limited for mCRPC patients harboring ATM aberrations. We aimed to determine the association of ATM mutations with clinical and molecular features in patients with mCRPC. Methods: A total of three independent prostate cancer cohorts (MCTP, N = 61; SU2C-PCF, N = 429; MSKCC, N = 451) were used for analysis. We selected patients with characteristics “mCRPC” and “histology type: prostate adenocarcinoma”. Both the somatic and germline pathogenic alterations were analyzed, including single nucleotide variations (SNVs), in-frame insertions or deletions (Indels), frameshifts, homozygous deletions and fusions. The statistical analysis was conducted by R software (v.3.6.2). Results: We merged the three mCRPC cohorts, generating a new cohort consisting of 507 mCRPC patients. The median age was 62 (range, 38.6-89). The number of biopsies was 1-3 per patient. Of the 527 sequenced specimens, 39% were lymph node, 27% were bone, and 14% were liver. Forty percent of the patients had exposed to or on-treatment with next-generation androgen receptor signaling inhibitor (ARSI). A total of 44 patients (8.7%) harbored deleterious variations in ATM, including 10 homozygous deletions. The coexistence mutations were most commonly located in androgen receptor ( AR), followed by TTN/KMT2C/MUC16/TP53. Furthermore, we explored the association of pathogenic ATM alterations with clinical features. Compared with noncarriers of ATM mutations , carriers were diagnosed at a younger age (median: 59 vs 62.4, P = 0.022). In the subgroup from SU2C-PCF cohort, prostate specific antigen (PSA) at diagnosis and the proportion of Gleason score between 8-10 were analyzed, both showed no significant differences between the two groups. Notably, we observed a statistically significant higher TMB in ATM-altered group than ATM wildtype group (median, 2.04 vs 1.61, P = 0.013). Overall survival (OS) was not compared because of the limited clinical outcomes in ATM-mutated population. Conclusions: This study involving 3 cohorts identified the prevalence of pathogenic somatic or germline ATM mutations and explored the association of ATM alterations with both clinical and molecular features. Patients with ATM mutations tended to diagnose prostate cancer at an earlier age. Meanwhile, significantly higher TMB might imply potential immunotherapy opportunities in ATM-altered mCRPC without standard-of-care approaches.
Prostate cancer intensive, non-cross reactive therapy (PRINT) for CRPC: Interim analysis of efficacy endpoints.
Authors: Liaw Bobby Chi-Hung , Zhong Xiaobo , Tsao Che-Kai , Bakst Richard Lorne , Stewart Robert , Stock Richard , Galsky Matt D. , Oh William K. 
Published: June 2021

e17027 Background: The standard mCRPC treatment paradigm, with sequential single agents administered until resistance, may be limited due to heterogenous tumors comprised of clones differentially sensitive to available therapies. An alternative approach involves rapid cycling of non-cross resistant therapies in an attempt to efficiently eradicate sensitive clones, mitigate resistance, and minimize toxicity. Methods: Patients with mCRPC received 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month study regimen, patients continued ADT alone. The primary endpoint is time to progression (TTP). A sample size of 33 patients will provide 90% power for a one-sided test at the 5% level to detect increase in TTP compared with historical control. Secondary endpoints include PSA response (>90%, >50%) with each module, and changes to alkaline phosphatase levels. Results: From 3/2017 to 11/2020, 40 mCRPC patients were enrolled. As of the data cut-off of 1/03/2021, 31 patients have completed the 9-month study regimen and are evaluable for TTP analysis. With a median follow up of 20.7 months, the median time to PSA progression is 3.8 months (95%CI; 2.1-6.3 mo). PSA declines >90% from baseline was achieved in 35.5% after module 1, 41.9% after module 2, 58.1% after module 3. Of the patients with bone metastasis and elevated alkaline phosphatase levels at baseline (9/31), 78% had normalization of alkaline phosphatase upon completion of study regimen. Five of 31 patients (16%) were able to be maintained on ADT alone for over a year during the post-study surveillance period: three patients were subsequently restarted on a mCRPC agent at time of disease progression (14.4 mo, 17.0 mo, 24.8 mo), two patients demonstrate sustained disease control and remain on ADT alone (16.3+ mo, 21.5+ mo). Shared baseline clinical features of the 5 patients with prolonged control include PSA of <10 ng/mL and normal alkaline phosphatase levels (< 126 IU/L); Gleason score and presence of bone and nodal metastases varied. Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross resistant regimen is feasible and a subset of patients achieve prolonged disease control on ADT alone after completion of study treatment. Rapid cycling of available CRPC therapies may eliminate castration-resistant clones in a subset of patients, a concept warranting further preclinical and clinical evaluation. Clinical trial information: NCT02903160. [Table: see text]
Effect of immunotherapy on survival outcomes in prostate cancer: Systematic review and meta-analysis.
Authors: solipuram Vinod , Pokharel Kishor , Venkatesulu Bhanu Prasad , Samanapally Harideep 
Published: June 2021

e17030 Background: Prostate cancer is one of the leading cancers in men with an estimated 191,930 new cases in 2020 in the USA alone. Treatment options for metastatic castration resistant prostate cancer (mCRPC) have evolved in recent years. Immunotherapy involving vaccines like sipuleucel-T, PROSTVAC and immune checkpoint inhibitors have been evaluated in these patients. We present a systematic review and meta-analysis of the randomized controlled trials (RCTs) testing the effect of immunotherapy in mCRPC. Methods: A systematic search was performed using PubMed, Embase and the Cochrane library without language limitations from inception to January 3, 2021. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), prostate specific antigen (PSA) reduction ≥ 50% and incidence of grade 3-4 adverse events. The analysis of OS, PFS was done using random effects hazard ratio (HR) by generic inverse variance method and analysis of PSA reduction ≥ 50% and grade 3-4 adverse events was done using random effects risk ratio (RR) by the Mantel-Haenszel method. Results: 12 RCTs comprising 4109 patients were included in the analysis. There was a statistically significant improvement in OS (HR 0.89; 95% CI (0.81, 0.97)) and PFS (HR 0.83; 95% CI (0.76, 0.92)) in the immunotherapy arm compared to placebo or standard treatment arms with moderate quality of evidence. Patients in the immunotherapy group had significant reduction in PSA ≥ 50% (RR 1.71; 95% CI (1.09, 2.68)) but also had statistically significant increased risk of grade 3-4 adverse events (RR (1.25; 95% CI (1.02, 1.54)) when compared to placebo and the standard treatment group. Subgroup analysis showed that the use of vaccine therapy in prostate cancer leads to significant improvement in OS (HR 0.83; 95% CI (0.74, 0.93)) and PFS (HR 0.80; 95% CI (0.67, 0.95)) compared to placebo and standard treatment. The use of immune checkpoint inhibitors was not associated with statistically significant improvement in OS (HR 0.98; 95% CI (0.88, 1.09)) but is associated with improvement in PFS (HR 0.87; 95%CI (0.81, 0.94)). Conclusions: This meta-analysis showed that immunotherapy led to significant improvement in OS, PFS and PSA reduction of ≥ 50%. However, there is an increased incidence of grade 3-4 adverse events with the use of immunotherapy when compared to other standard therapies and placebo. The improvement in overall survival is limited to the use of vaccine therapy and not to immune checkpoint inhibitors. Careful use of selective forms of immunotherapy in mCRPC can lead to greater improvement in survival.
The impact of COVID-19 on delivery of systemic anti-cancer treatment in urological cancer patients: A comparison with 2019 data from Guy’s Cancer Center.
Authors: Karampera Christina , Khan Muhammad , Russell Beth , Moss Charlotte , Monroy-Iglesias Maria J , Dolly Saoirse , Thillai Kiruthikah , Josephs Debra Hannah , Pintus Elias , Rudman Sarah , Van Hemelrijck Mieke , Enting Deborah 
Published: June 2021

e17057 Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats approximately 8,800 patients annually and is one of the largest Comprehensive Cancer Centres in the UK. When dealing with the second wave of COVID-19, it is important to further evaluate the safety of cancer treatments whilst balancing the risks of COVID-19 infection and complications. Here, we report on the patient/tumour characteristics of those patients undergoing SACT for a urological cancer diagnosis during the first wave, so as to help establish clinical guidelines for the management of these patients in a SARS-CoV-2 epidemic. Methods: All urological cancer patients receiving at least one SACT between 1st March- 31st May 2020 (COVID-19 period) were compared to the same timeframe in 2019. SARS-CoV2 infection was defined as a positive RT-PCR test; patients with symptoms or radiological changes alone were excluded. As part of Guy’s Cancer Cohort, we collected information on demographics, and cancer type, stage, and treatment. Results: A total of 455 patients (305 prostate, 102 renal, 38 bladder, and 10 testicular) received SACT in 2020 as compared to 535 (353 prostate, 129 renal, 37 bladder, and 15 testicular) in 2019 (15% overall decline). Patient characteristics in terms of demographics were fairly comparable, with 10% female patients in 2019 and 9% in 2020; 49% aged 70+ vs 45%; and 77% in the low socio-economic category vs 78%. There was an increase in patients with stage 4 (89% vs 95% in 2020) and a slight change in distribution of SACT types (2019 vs 2020): chemotherapy (18% vs 14%), immunotherapy (7% vs 10%), biological or targeted (63% vs 66%), combination of biological/targeted (6% vs 5%), other combinations (5% vs 5%). The proportion of SACT delivered as part of radical treatment declined from 3% to 0.2% in 2020. A total of 5 patients (1%) developed COVID-19 (2 prostate, 2 renal, and 1 bladder). All were male and aged 60+; three had 2+ comorbidities. One patient was on immunotherapy and four on biological or targeted treatment. Four patients had severe pneumonia and one died of their COVID-19 (bladder cancer). Conclusions: Whilst there was a decline of number of patients receiving SACT during COVID-19, we were still able to provide a safe high-quality urological cancer SACT pathway during the peak of the COVID-19 pandemic, with very few COVID-19 positive patients. In a next step we will evaluate oncological outcomes at 6 months follow-up