bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved germline screening for patients with pancreatic cancer through provider driven testing.
Authors: Frazier Heather , Toyon Sewanu Anjolaoluwa , Coleman DeJuana , Thomas Martha , Kunk Paul Raymond , Le Tri Minh , Rehman Muneeb , Reilley Matthew 
Published: July 2024

e16366 Background: National guidelines recommend germline genetic screening for all pancreatic cancer patients. Results provide meaningful insights into pathogenic variants and impacts both treatment selection and family screening recommendations. We previously reported on current state and the need to improve germline screening rates. Since implementing a provider-driven approach, we have seen a significant increase in testing. Our findings demonstrate the feasibility and ongoing need for novel approaches to germline screening. Methods: This is a retrospective review of 223 patients with pancreatic adenocarcinoma evaluated at the University of Virginia Health System within the calendar year of 2022 compared to the 2021 calendar year. Primary endpoints include the rate of genetic counseling referral placement, the rate of attendance of outpatient genetic counseling, and the rate of individuals who completed germline screening. Our primary data points will be compared with outcomes obtained from a prior study evaluating 210 patients with pancreatic adenocarcinoma in the calendar year of 2021 at the same academic medical center. Results: Of the 223 patients with pancreatic adenocarcinoma, only 30% (69/223) had genetic counseling referrals present in the electronic health record system (EHR). This was an improvement from the 2021 calendar year, where 19% (39/210) had referrals present in the EHR. Of those with referrals present, an improvement in the rate of genetic counseling attendance was found, from 51% (20/39) in 2021 to 58% (40/69) in 2022. There was also an improvement in the rate of germline screening completion rates; 38% (85/223) of patients evaluated in 2022 completed testing, compared to 21% (44/210) in 2021. Six percent (5/85) of tested patients in 2022 had pathogenic findings, consistent with historical incidence rates. The main provider barriers were time and testing logistics. Conclusions: Our data shows an improvement in the rates of genetic counseling referrals, the rates of genetic counseling attendance, and the rates of germline screening completion. This modest improvement is primarily related to increased awareness by our providers. We acknowledge the need for further improvements and are developing a prospective clinical trial to better educate and empower patients to understand the need and results of germline testing.
Emergency treatment for primary intracranial germ cell tumours (PICGCTs).
Authors: Murphy Ravindhi , Russell Jodie , Talbot Thomas , Lythgoe Mark , Sherpa Gina , Xing Eunice Yun , Khanna Sanjay , Li Ling , Tin Terry , Kalam Sabrina , Singh-Curry Victoria , Ghorani Ehsan , Caldwell Reece , Sarwar Naveed , Seckl Michael , Gonzalez Michael 
Published: July 2024

e17020 Background: PICGCTs arise de novo in children and young adults, most frequently in the pineal or suprasellar regions. Here, we evaluate the acute pathway for patients (pts) with PICGCTs managed at our Emergency Cancer Treatment Centre. Methods: Retrospective observational study from 1984-2022 at a single institution. Data was collected from paper and electronic patient records for all PICGCT pts, including pts treated with our intracranial regimen EP-OMB (Etoposide-Cisplatin alternating every week with Vincristine-Methotrexate-Bleomycin) administered with and without intrathecal Methotrexate. Results: To date, we have identified 43 pts with intracranial disease treated at our Centre over 38 years: 25 pts (58%) with PICGCT, 18pts (42%) with germ cell tumour brain metastases treated with EP-OMB and excluded from analysis. Most PICGCT pts are male (92%, n=23) with a median age 25 (range 17-50). The majority present with symptomatic disease (88%, n=22) confined to the pineal gland (72%, n=18), with hormone dysfunction in 24% ( n=6). Only two female pts (8%) have presented with suprasellar and pituitary midline lesions causing headache, progressive visual loss and hypothalamic failure including cranial diabetes insipidus. Eloquent areas in the brain cannot be biopsied so only 60% PICGCTs ( n=15) were confirmed histologically, 47% as germinoma ( n=7), 27% dysgerminoma ( n=4), 27% unclassified ( n=4). Tumour markers (TM) were elevated in all pts with cerebrospinal fluid (CSF) evaluation ( n=5) compared to elevated serum TM in under half (44%, n=12). 68% pts required emergency treatment for a new cancer diagnosis ( n=17): neurosurgery (59%, n=10), chemotherapy (35%, n=6) or radiotherapy (6%, n=1). 88% PICGCT pts received EP-OMB ( n=22) with intrathecal Methotrexate in 63% ( n=14). For all PICGCT pts, 72% pts remain alive ( n=18) with median follow-up 3.8 years (range 0.2-27.3). For 36% pts with TM relapse or radiological progression despite treatment ( n=9), 44.4% remain alive ( n=4) with median overall survival at 6.8 years (range 1.1-18.6). Conclusions: PICGCT pts frequently require emergency surgical treatment for a new cancer diagnosis. Although rare, accurate diagnosis will affect management and prognosis in this young patient group. CSF rather than serum TM analysis is crucial for diagnostic work-up. Consensus on optimal management is warranted given the potential toxicity from multiple therapeutic interventions administered with curative intent.
Impact of hospital volume on outcomes of autologous stem cell transplant (ASCT) in patients with testicular cancer.
Authors: Singh Paramveer , Kaur Jasmeet , Mir Tanveer , Qureshi Waqas 
Published: July 2024

e17021 Background: ASCT has a potential to achieve cure in relapsed refractory testicular cancers (TC). A large volume hospital (LVH) is generally recommended but the impact of hospital volume on the outcomes of this therapy is not clearly known. Methods: We included 39435 adult (>18 years) patients with TC from national inpatient sample database from 2016 – 2018. Patients were stratified based on hospital volume. Based on the weighted number of ASCT performed annually, LVH were defined as >45 annual cases, and small volume hospitals (SVH) were defined <25 annual cases. Subgroup analysis was performed for the patients with brain metastasis. Results: A total of 1,225 patients (3.1%) with TC underwent ASCTs between 2016 and 2020. Baseline characteristics are summarized in the table. Patients treated at LVH exhibited a significantly higher median age (p < 0.01), had more proportion with private insurance (p =0.003). Patients treated at SVH experienced significantly higher rates of pneumonia (p < 0.01), vtach (p = 0.02), and neurologic complications (p = 0.02) compared to those at medium volume (MVH) or LVH. Length of stay exceeding 18 days (LOS18) was significantly longer in SVH compared to LVH (p = 0.02). No significant differences in in-hospital mortality were observed based on hospital volume (p = 0.86), even among patients with brain metastases (p = 0.78). LVH had a significantly higher proportion of patients with private insurance compared to MVH and SVH (p = 0.003). Health care costs were significantly higher in SVH and MVH for patients with brain metastases undergoing ASCT compared to LVH (p < 0.01). In adjusted analysis, significant predictors for mortality included liver disease (OR: 6.12, (95% CI: 4.1 to 266); p < 0.01), and electrolyte imbalance (OR: 19, 95% CI (1.6 to 233); p = 0.02). Predictors for LOS18 included AKI (IRR: 1.8, 95% CI (1.17 to 3.05); p = 0.009) and vtach (IRR: 1.04, (1.28 to 8.3); p < 0.01). In LVH, LOS18 was significantly lower (IRR: 0.40, (0.20 to 0.78); p = 0.008). Conclusions: ASCT-related complication rates and length of stay were higher in small volume hospitals that treated testicular cancer which also correlated with higher costs. The study suggests that ASCT should be considered in large volume hospitals. [Table: see text]
The role of TROP-2 in the progression and target therapy in penile squamous cell carcinoma.
Authors: Tang Yi , Tan Xingliang , Liu Zhicheng , Zhou Qianghua , Wei Wensu , Yuan Gangjun , Yao Kai 
Published: July 2024

e17023 Background: Penile squamous cell carcinoma(PSCC) is a devastating malignancy of urogenitary system. However, current chemotherapy treatments including TIP regimen has showed limited effects but strong side effects in advanced PSCC. Trophoblast cell-surface antigen-2 (Trop-2) is a novel target for Antibody-drug conjugates (ADC) drugs and is proved to be effective in several human cancers, but its role in PSCC has not been clearly certified. Methods: 198 PSCC tumor tissue specimens and clinicopathological data were collected. TROP-2 expression was detected by IHC experiments and the correlation between TROP-2 expression and clinicopathological data of patients was analyzed through statistical methods. Then a series of in vivo and in vitro experiments were conducted to investigate the mechanism that how TROP-2 promote PSCC cell proliferation. Results: IHC results showed that TROP-2 was highly expressed in 60.2% of tumor specimens, and statistical analysis revealed a positive association of TROP-2 expression with advanced pT, pN stages and extranodal extension (ENE), as well as poor prognosis. Knockdown of TROP-2 expression inhibited the proliferation of PSCC cells both in vivo and in vitro. Further experiments identified that TROP-2 promoted PSCC cell proliferation via AKT-mediated PKCα signaling pathway. TROP-2 ADC drugs could inhibited PSCC cell proliferation both in vitro and in vivo. Conclusions: TROP-2 promotes PSCC cell proliferation, and TROP-2 targeted ADC-drug is a promising agent for PSCC treatment in future.
Impact of treatment approaches in patients with advance penile cancer: An analysis from a nationwide study.
Authors: Ganiyani Mohammad Arfat , Khosla Atulya Aman , Ahmad Shahzaib , Jatwani Karan , Rubens Muni , Roy Mukesh , Bastos Bruno R. , Ozambela Manuel , Eldefrawy Ahmed , Manoharan Murugesan , Garje Rohan 
Published: July 2024

e17024 Background: Advance penile cancer (APC) is a rare and aggressive malignancy, characterized by the presence of metastases to lymph nodes and/or distant organs. The rarity of patients with APC poses challenges in conducting comprehensive studies, with most existing evidence being small-scale, retrospective analyses from single institutions. Additionally, the absence of large clinical trials limits the evidence to compare the survival rates with different treatment approaches in patients with APC. Methods: Our study utilized the national cancer database (NCDB) from 2004 to 2021. Our primary analytic cohort included patients diagnosed with advance penile cancer based on the AJCC 8 th classification (T4 or N3 or M1). Treatment modalities comprised perioperative systemic therapy combined with definitive surgery (PST), concurrent chemoradiation (CCR), surgery only (S), and systemic therapy only (ST). We used Kaplan-Meier analysis and the cox proportional regression to evaluate the impact of these treatment modalities on survival outcomes. Results: We identified 1342 patients with advance penile cancer. The median overall survival (OS) was 22.24 months (CI: 15.87-27.86, P <0.001) for patients who received PST, 16.99 months (CI: 13.86-27.4) for those who underwent CCR, 11.99 months (CI: 9.2-15.01) for patients managed with surgery only, and 10.94 months (CI: 9.95-14.09) for those who received only ST. Our multivariate analysis revealed combining PST with surgery was associated with 27% reduction in the risk of death (HR: 0.73, P = 0.037) compared to systemic therapy after adjusting for age, race, tumor grade, comorbidities, distant metastasis and socioeconomic factors. Conclusions: Treatment approach with systemic therapy along with definitive penile surgery is associated with improved survival in patients with advanced penile cancer compared to other treatment modalities. Whenever feasible, this treatment approach should be considered as a management strategy in patients with APC. Further prospective studies are needed to validate our observations. [Table: see text]
A systematic literature review and indirect treatment comparison of PARP inhibitors in combination with next-generation hormonal agents in BRCA-mutated metastatic castration-resistant prostate cancer.
Authors: Shore Neal D. , Williams Jack , Clouthier Derek L. , Swift Stephanie L. , Tatman Sophie , Lang Shona , Hettle Robert 
Published: July 2024

e17029 Background: In the USA, several poly(ADP-ribose) polymerase inhibitors (PARPi) are approved in combination with next-generation hormonal agents (NHAs) for metastatic castration resistant-prostate cancer (mCRPC), including olaparib plus abiraterone acetate with prednisone/prednisolone (OLA+AA/P) and niraparib plus AA/P (NIRA+AA/P) for mCRPC with BRCA1 and/or BRCA2 mutations (BRCAm), and talazoparib plus enzalutamide (TALA+ENZ) for mCRPC with homologous recombination repair mutations, including BRCAm. All approvals were based on placebo (PBO)-controlled Phase III trials. To support clinical decision-making, we performed a systematic literature review and indirect treatment comparison (ITC) to assess the comparative efficacy and safety of regimens. Methods: Published clinical trials were identified by searching Embase, MEDLINE, Evidence-Based Medicine Reviews database, conferences and registries up to September 2023. Studies reporting radiographic progression-free survival (rPFS), overall survival (OS), and/or safety outcomes for mCRPC were included. The feasibility of performing anchored or unanchored ITCs using BRCAm subgroup data was assessed. Where feasible, Bayesian ITCs were performed using BRCAm subgroup hazard ratios (HRs) for investigator-assessed rPFS, blinded independent central review (BICR) rPFS, and OS. Safety ITCs were performed using overall study data and reported as risk differences (RD) for adverse events (AEs). Results: Thirty-nine studies were identified, of which three reported BRCAm-specific data, including PBO-controlled studies for OLA+AA/P, NIRA+AA/P, and TALA+ENZ. An anchored ITC was feasible for OLA+AA/P and NIRA+AA/P using PBO+AA/P as a common comparator. ITC results showed a significant improvement in rPFS and OS, and a numerical reduction in AE risk for OLA+AA/P vs NIRA+AA/P (Table). TALA+ENZ was excluded from the ITC as it was not possible to form a network with OLA+AA/P or NIRA+AA/P due to differences in NHA use (ENZ vs AA/P) in PBO-control arms, whilst data limitations prevented unanchored ITCs. Conclusions: In BRCAm mCRPC, ITC results suggest that OLA+AA/P has improved efficacy and a favorable safety profile vs NIRA+AA/P. Current evidence does not allow for a robust comparison of OLA+AA/P or NIRA+AA/P with TALA+ENZ in BRCAm mCRPC. [Table: see text]
Association of baseline characteristics with adverse events (AEs) in the PROpel trial of olaparib (ola) plus abiraterone (abi) as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Armstrong Andrew J. , Saad Fred , Oya Mototsugu , Shore Neal D. , Procopio Giuseppe , Vianna Karina , Mehra Niven , Özgüroğlu Mustafa , Gedye Craig , Brown Emma , Schlürmann Friederike , Lee Ji Youl , Joung Jae Young , Sugimoto Mikio , Emmenegger Urban , Oscroft Emma , Shaw Bob , Winter Maria , Hosius Christian , Clarke Noel 
Published: July 2024

e17030 Background: The PROpel trial (NCT03732820) met its primary endpoint and showed a statistically significant radiographic progression-free survival benefit (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.0001) with ola + abi vs placebo + abi in 1L mCRPC; whilst not statistically significant, overall survival (OS) was numerically prolonged (median 42.1 vs 34.7 months; HR 0.81, 95% CI 0.67–1.00; P=0.0544). To further inform clinical decision making, we provide exploratory post hoc analysis investigating the relationship between selected patient baseline characteristics and AEs for ola + abi. Methods: Anemia and venous thromboembolism events (VTEs) were identified as the only grade (Gr) ≥3 AEs or AEs of special interest reported in >20 (>5.0%) patients (pts) in the ola + abi arm (data cutoff 12 Oct 2022). Baseline characteristics were correlated with AEs using Cox regression by backwards elimination and analysis with AEs as dependent variables. Baseline characteristics assessed included: age (<70 or ≥70 y), time since diagnosis (<median or ≥median) , ECOG status (0 or 1), metastatic sites (visceral [yes or no], bone only [yes or no]), number of bone metastases (0, 1–4, 5‒9, 10‒20 or >20), Gleason score (<9 or 9–10), homologous recombination repair mutation status (HRRm, non-HRRm or unknown), race (white or non-white), prior docetaxel at metastatic hormone-sensitive prostate cancer (yes or no), pain (symptomatic or asymptomatic/mildly symptomatic), type of progression (prostate-specific antigen [PSA], radiographic or both), prior radiotherapy (yes or no) and albumin, creatinine, lactate dehydrogenase, alkaline phosphatase (ALP), hemoglobin (10<12 or ≥12) and log PSA levels. Results: 398 pts received ola + abi. 64 (16.1%) had Gr ≥3 anemia and 34 (8.5%) a VTE. Baseline characteristics correlated significantly with increased risk of these AEs as shown (Table); characteristics not shown were not associated with AEs. Conclusions: These results provide insight into which baseline characteristics correlate with the risk of Gr ≥3 anemia. Pts with abnormal ALP, pre-existing anemia, ECOG PS 1 or age ≥70 years could be at higher risk and the development of Gr ≥3 anemia during treatment with ola + abi should be monitored. Clinical trial information: NCT03732820 . [Table: see text]
Dosimetry of lutetium-177 PSMA-targeted radiopharmaceutical therapies for prostate cancer patients: A comparative systematic review and meta-analysis.
Authors: Ells Zachary , Dahlbom Magnus , Czernin Johannes , Grogan Tristan , Calais Jeremie 
Published: July 2024

e17033 Background: Novel theranostic approaches using radiopharmaceuticals targeting PSMA have emerged for treating metastatic castrate resistant prostate cancer (mCRPC). The physical properties and commercial availability of Lutetium-177 (Lu177) makes it one of the most used radionuclides for radiopharmaceutical therapy (RPT). In this review we aimed at comparing the dosimetry of the most used Lu177-PSMA RPT compounds. Methods: This is a systematic review and meta-analysis of Lu177-PSMA RPT (617, I&T, and J591) dosimetry for prostate cancer. Absorbed doses in Gy/GBq for each organ (kidney, parotid and submandibular glands, bone marrow, liver, lacrimal glands) and for tumor lesions (bone and non- bone lesions) were extracted. These were used to estimate the pooled average absorbed dose of each RPT, and normalize each to the respective injected activity (Gy/cycle) as determined by the dose per cycles used in VISION (7.4 GBq), SPLASH (6.8 GBq), and PROSTACT Trials (5.8 GBq). Results: 29 published manuscripts comprising 535 patients were included in the meta-analysis. The pooled dose was calculated for kidney based on (28 studies, 485 patients), parotid (20, 309), submandibular (7, 100) and lacrimal glands (9, 174), bone marrow (18, 293), and liver (14, 245) were 4.04 and 4.70, 5.85 and 2.62, 5.15 and 4.35, 11.03 and 19.23, 0.24 and 0.19 and 1.11 and 0.56 Gy respectively for Lu177-PSMA-617 and Lu177-PSMA-I&T. Lu177-PSMA-J591 reported absorbed doses to the kidney, bone marrow and liver were 3.95, 0.90, and 5.88 Gy respectively. There was no significant difference between Lu177-PSMA-I&T and Lu177-PSMA-617 for the dose to kidneys (p=0.10), submandibular glands (p=0.56), bone marrow (p=0.31), lacrimal glands (p=0.20), or tumors (p=0.16). However, parotid dose from Lu177-PSMA-617 was higher than that of Lu177-PSMA-I&T (p=<0.01). Average tumor doses tended to be higher for Lu177-PSMA-617 than for Lu177-PSMA-I&T, (27.94 vs. 21.31 Gy); p=0.16. Lu177-PSMA-J591 exposed the bone marrow and liver, to a significantly higher dose while resulting in a lower dose to the kidney than either of the two small molecule compounds. Absorbed doses to the salivary glands, lacrimal glands, and tumors after the treatment with Lu177-PSMA-J591 have not been published yet. Conclusions: The clinical impact of higher tumor to kidney dose ratio for Lu177-PSMA-617 than Lu177-PSMA-I&T has yet to be determined. Data for Lu177-PSMA-J591 are thus far too limited to draw firm conclusions.
Prevalence of HER-2 expression and correlation with clinicopathological features in gynecological cancer: A single-center retrospective study in China.
Authors: Chen Rui , Dong Juanhui , Li Guangxin , Peng Yi , Lei Haike , Yuan Li , Long Xingtao , Zhou Qi 
Published: July 2024

e17500 Background: Targeted therapy for human epidermal growth factor receptor 2 (HER2) has become a standard of care in several HER2-expressing solid tumors. Nonetheless, there remains an unmet need for effective treatment, for instance, anti-HER2 antibody-drug conjugates (ADCs), in advanced stage gynecological cancer. In this context, we presented a retrospective study on the incidence of HER2 expression in primary gynecological cancer based on a single-center data from southwestern China. Methods: Paraffin-embedded tumor tissue blocks, clinicopathological, and survival data of gynecological cancer patients were collected from Chongqing University Cancer Hospital. HER2 IHC scoring was carried out according to the updated ASCO/CAP guidelines for breast and gastroesophageal adenocarcinoma by two pathologists independently. Data analysis was performed using SPSS v.24. Results: A total of 104 cases of cervical cancer, 102 cases of endometrial cancer and 103 cases of ovarian cancer were included between 2019 and 2023. HER2 expression was detected in 31.7% samples, with scores of 1+, 2+, and 3+ in 23.9% (74/309: 36/104, 16/102, 22/103), 5.8% (18/309: 7/104, 7/102, 4/103), and 1.9% (6/309: 2/104, 1/102, 3/103) of patients, respectively. Notably, ultra-low HER2 expression with incomplete and faint staining in ≤10% of tumor cells was observed in 41.1% (127/309: 37/104, 53/102, 37/103) of patients. Metastasis and lymphovascular invasion were associated with elevated HER2 expression in endometrial cancer (p=0.037, 0.040, respectively), while a larger tumor size was associated with elevated HER2 expression in cervical cancer (p=0.004). However, no positive association between HER2 status and overall survival (OS) was found in cervical, endometrial or ovarian cancer. In our cohort, metastasis was the only risk factor related to reduced OS of gynecological cancer patients by COX regression analysis (HR=14.00, 95%CI=1.32-148.21, p=0.028). Conclusions: Our data revealed a considerable number of patients with HER2-low and ultra-low gynecological cancer. It might represent a significant portion in real-world scenarios and warrant more consideration in selecting candidates for HER2-targeted ADCs, especially for those with relapsed or refractory conditions. Given the inherent challenge in interpretation, the study highlights the necessity for a consensus on evaluating HER2 immuno-staining results in gynecological cancer. Clinical trial information: MR-50-23-019676 . [Table: see text]