bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real world outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-PSMA-vipivotide tetraxetan (Lu177-PVT).
Authors: Bergstrom Colin P , Song Hong , Ruiz Shann Mika , Chien Joanne , Moore Kaidi , Parikh Divya Ahuja , Shah Sumit , Fan Alice C. , Srinivas Sandy , Iagaru Andrei , Khaki Ali Raza 
Published: January 2024

86 Background: Lu177-PVT is a novel radioligand, which was recently approved by the FDA to treat mCRPC. Real world data on its use and efficacy is limited. We aimed to build a new retrospective cohort of patients with mCRPC treated with 177Lu PSMA-617 in order to investigate clinical and pathological variables associated with treatment responses. Methods: We identified patients with a confirmed diagnosis of prostate cancer and were treated at Stanford University Medical Center with at least one dose of Lu177-PVT including trial patients. Data collection included demographic, clinicopathological and outcome variables. Statistical analysis was performed using Chi-squared and log-rank Kaplan-Meier analysis. Results: We identified 85 patients who met study criteria and were treated between March 2021 and June 2023, the median age was 66, 33% were non-white, median PSA at treatment initiation was 60, and 94% had osseous metastasis. Patients were pretreated with a median of six lines (range: 1-10) of prior therapy including local therapies; prostatectomy (28%), radiation (61%), brachytherapy (11%), taxane (78%), immunotherapy including checkpoint inhibitor and Sipuleucel-T (24%), PARP inhibitor (6%), and Radium-223 (15%). A majority of patients also received prior germline or somatic genetic testing (79%), with homologous recombination germline and somatic deficiencies present in 13% of patients. Of the identified cohort, 19 patients were still undergoing active treatment with Lu177-PVT at the time of data collection. Of the 66 patients not currently undergoing active Lu177-PVT treatment, 29 patients discontinued treatment due to progressive disease (44%) and 14 (21%) to toxicity related to 177Lu PSMA-617, completing a median of 4 cycles. 47 patients (71%) had an overall decline in their PSA from baseline, with 32 patients (49%) experiencing a decrease greater than fifty percent. Median overall survival of patients not actively receiving 177Lu PSMA-617 treatment was 366 days. Age, previous lines of therapy, and median time from diagnosis were not predictive of PSA treatment response (greater than fifty-percent reduction from baseline PSA). Conclusions: Lu177-PVT is a promising treatment for mCRPC in patients. Our results confirm ‘real-world’ activity of Lu177-PVT and align well with VISION study results, though real-world overall survival was comparatively shorter (12 months vs 15 months in VISION trial). Further investigation is warranted into predictors of response and toxicity.
Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC).
Authors: Choueiri Toni K. , Tomczak Piotr , Park Se Hoon , Venugopal Balaji , Ferguson Thomas , Symeonides Stefan N. , Hajek Jaroslav , Chang Yen-Hwa , Lee Jae-Lyun , Sarwar Naveed , Gurney Howard , Gross-Goupil Marine , Mahave Mauricio , Haas Naomi B. , Sawrycki Piotr , Zhang Tian , Cornell Jerry , Elfiky Aymen , Burgents Joseph E. , Powles Thomas 
Published: January 2024

LBA359 Background: The randomized, multicenter, double-blind, phase 3 KEYNOTE-564 study (NCT03142334) showed that adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo following nephrectomy in participants (pts) with ccRCC at an increased risk of recurrence. We report results from the third prespecified interim analysis with a median follow-up of ~57 months. Methods: Pts were aged ≥18 years and had histologically confirmed ccRCC with or without sarcomatoid features, increased risk of recurrence, ECOG PS of 0 or 1, nephrectomy and/or metastasectomy ≤12 weeks before randomization, and no prior systemic therapy for RCC. Pts were randomly allocated 1:1 to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≥17 cycles (~1 year) or until disease recurrence, intolerable toxicity, or withdrawal of consent. DFS by investigator assessment was the primary end point. Overall survival (OS) was a key secondary end point. Safety was a secondary end point. Results: 994 pts were randomized 1:1 to pembrolizumab (n=496) or placebo (n=498). The median time from randomization to data cut-off date of September 15, 2023, was 57.2 months (range, 47.9−74.5). Statistically significant improvement in OS was observed with pembrolizumab vs placebo (medians not reached, HR 0.62, 95% CI 0.44−0.87; P=.0024). A total of 55 OS events were observed in the pembrolizumab arm and 86 in the placebo arm. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86.0% with placebo. OS benefit was observed across key subgroups, including in pts with M0 disease (HR 0.63, 95% CI 0.44−0.90) or M1 NED (HR 0.51, 95% CI 0.15−1.75), with PD-L1 CPS <1 (HR 0.65, 95% CI 0.31−1.38) or CPS ≥1 (HR 0.62, 95% CI 0.42−0.91), and with presence (HR 0.69, 95% CI 0.28−1.70) or absence (HR 0.57, 95% CI 0.39−0.84) of sarcomatoid features. The observed DFS benefit with pembrolizumab vs placebo was consistent with prior interim analyses (HR 0.72; 95% CI 0.59−0.87). No new safety signals were observed. Conclusions: After a median of ~57 months of follow-up, adjuvant pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in overall survival versus placebo in participants with RCC at increased risk of recurrence post surgery. KEYNOTE-564 is the first phase 3 study to show improved survival with any adjuvant therapy in RCC. These results continue to support adjuvant pembrolizumab as a standard of care. Clinical trial information: NCT03142334 .
LORIKEET: A phase 2, randomized, open-label study of lorigerlimab plus docetaxel versus docetaxel alone in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Subudhi Sumit Kumar , Hauke Ralph J. , Call Justin A , Sun Jichao , Casey Denise , Wei Xiao X. 
Published: January 2024

TPS242 Background: Lorigerlimab is an investigational bispecific, Fc-bearing (IgG4) DART molecule that binds PD-1 and CTLA-4. Lorigerlimab is engineered to enhance CTLA-4 binding in the tumor microenvironment (TME) while minimizing off-tumor CTLA-4 binding in normal tissue.2 A phase 1 study of lorigerlimab monotherapy in 162 patients with advanced solid tumors (NCT03761017) demonstrated a manageable safety profile. The objective response rate (ORR) among 35 patients with heavily pretreated mCRPC and measurable disease was 25.7%.1 Chemoimmunotherapy combination regimens have demonstrated improved outcomes over chemotherapy or immune checkpoint inhibitors given alone in multiple cancers. Although recent data showed lack of survival improvement when anti-PD-1 antibody was combined with docetaxel in mCRPC,3 dual blockade of PD-1 and CTLA-4 with lorigerlimab may be an effective strategy to potentiate host immune responses in the TME with limited CTLA-4-associated toxicities. In addition to direct antitumor activity, docetaxel may stimulate antitumor immunity and enhance the immunomodulating effects of lorigerlimab. The phase 2 LORIKEET study will compare the combination of lorigerlimab plus docetaxel versus docetaxel alone in patients with mCRPC. Methods: Approximately 150 patients will be randomized 2:1 to lorigerlimab (6mg/kg Q3W) combined with docetaxel (75 mg/m2 Q3W) and prednisone (5mg BID) versus docetaxel and prednisone alone. Patients are stratified by the presence of visceral disease (yes vs no) and geographic region (North America vs other). Key eligibility criteria include age ³ 18; ECOG performance status 0 or 1; disease progression by PCWG3 criteria following prior androgen receptor axis-targeted therapy (e.g., abiraterone, enzalutamide, apalutamide); no prior taxane chemotherapy for mCRPC;immune checkpoint inhibitors. The primary endpoint is radiographic progression free survival (rPFS) per PCWG3 criteria. Secondary endpoints include ORR, duration of response, PSA response, safety, overall survival, and HRQOL measures including change in pain severity and time to first symptomatic skeletal events. Eligible patients randomized to receive docetaxel and prednisone alone who experience radiographic progression may remain on study and receive lorigerlimab monotherapy. Enrollment is ongoing. 1. Luke, ASCO-GU 2023, Abstract 155. 2. Berezhnoy, PMID 33377134. 3. Petrylak, ASCO-GU 2023, Abstract 19. Clinical trial information: NCT05848011 .
A multicohort phase 2 trial of ADT, docetaxel plus nivolumab in patients with de novo metastatic hormone-sensitive prostate cancer enriched for inflamed tumors and DNA damage repair defects.
Authors: Wei Xiao X. , Xie Wanling , Chahoud Jad , Emamekhoo Hamid , McKay Rana R. , Marshall Catherine Handy , Einstein David Johnson , Lang Joshua Michael , Raymond Sarah , Roberts Daniel Aaron , Sunkara Rajitha , Ravi Praful , Tewari Alok , Pomerantz Mark , Dong Fei , Siegmund Stephanie , Rodig Scott J. , Pfaff Kathleen L. , Sweeney Christopher , Taplin Mary-Ellen 
Published: January 2024

TPS244 Background: Intensification of upfront treatment with the addition of docetaxel chemotherapy and/or a novel androgen signaling inhibitor to androgen deprivation therapy (ADT) have improved clinical outcomes for patients with de novo metastatic hormone sensitive prostate cancer (mHSPC). However, most patients develop castration resistance, the lethal form of disease. ADT early in the hormone-sensitive setting and docetaxel may have immunostimulatory effects which sensitize tumors to immune checkpoint blockade. Immunotherapy may be most effective in patients with pre-existing antitumor immunity or DNA damage repair defects (DDRD). Methods: We are conducting a multicenter, multicohort, phase 2 clinical trial of ADT, docetaxel, plus nivolumab in patients with de novo mHSPC. Cohort allocation is assigned based on tumor PD-L1 and CD8 staining by a multiplexed immunofluorescence platform (ImmunoProfile), and DDRD status on a targeted cancer next-generation sequencing panel (OncoPanel). Planned enrollment goal is 60 patients (20 patients per cohort; Table). Eligible patients must have newly diagnosed metastatic prostate cancer on conventional imaging, ECOG performance status 0-2 (ECOG 2 allowed if attributed to metastatic disease), PSA >4.0 ng/mL before ADT initiation, adequate organ function, and be candidates for docetaxel chemotherapy. Patients are allowed to receive up to 140 days of ADT prior to C1D1 study treatment. All patients receive continuous ADT, docetaxel 75 mg/m2 plus nivolumab 360mg IV Q3W for 6 cycles, followed by nivolumab 480mg IV Q4W for up to 2 years. After January 2022, the addition of standard of care abiraterone/prednisone was allowed after 7 months of study treatment at investigator discretion. The primary endpoint is PSA ≤ 0.2 ng/mL at 7 months from initiation of chemoimmunotherapy. Key secondary endpoints include PSA ≤ 0.2 ng/mL during chemoimmunotherapy, time to castration resistance, time to clinical progression, time to PSA progression, objective response rate, overall survival, and safety. Planned exploratory analysis include profiling circulating tumor cell (CTC) enumeration and analysis of PD-L1 and HLA I expression on CTCs. The first patient was enrolled on 5/4/2020, and 45/60 patients have been enrolled to date (N=7 in Cohort 1, N=18 in Cohort 2, and N=20 in Cohort 3). Study enrollment is ongoing. Clinical trial information: NCT04126070 . [Table: see text]
CaboLu: A phase 1b study of cabozantinib (cabo) in combination with lutetium (Lu 177) vipivotide tetraxetan (LVT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Galarza Fortuna Gliceida , Moynier Colin , Boucher Kenneth M. , Nordblad Blake , Covington Matthew , Fine Gabriel , Clement Susan , Esplin Michelle , Kohli Manish , Gupta Sumati , Maughan Benjamin L. , Agarwal Neeraj , Swami Umang 
Published: January 2024

TPS251 Background: LVT is a β-emitting radioligand approved for pts with prostate-specific membrane antigen (PSMA)-positive mCRPC with prior treatment with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. However, in the VISION trial, 50% of pts with measurable disease didn’t respond (PMID: 34161051). Prior studies have shown a significant correlation between PSMA and VEGF expression (p<0.001) in LNCaP tumors and locally recurrent PCa after radiotherapy. Cabo is an oral, small-molecule tyrosine kinase inhibitor with potent activity against multiple receptor tyrosine kinases including VEGFR2. Therefore, the combination of cabo with LVT may be synergistic. We initiated a phase 1b dose-scalation study of cabo in combination with standard of care (SOC) LVT in pts with mCRPC. Methods: This is an IRB-approved, investigator-initiated, single-arm, single-center, dose-escalation (DEsc) and dose-expansion (DExp) study. The primary hypothesis is that Cabo+LVT will be safe and effective in mCRPC pts. Key inclusion criteria: ≥18 years of age, mCRPC with histologically/cytologically confirmed adenocarcinoma without small cell histology, ECOG performance status ≤2, prior treatment with ≥2 cycles of taxane and at least 1 ARPI, adequate organ function and eligible for SOC LVT. Key exclusion criteria: Prior treatment with cabo or PSMA-targeted radioligand therapy. DEsc part will follow traditional 3+3 design to evaluate SOC LVT in combination with 3 dose levels (DL) of daily oral cabo: 40 mg (DL 1), 60 mg (DL 2) and 20 mg (DL -1). Primary objective: to determine maximal tolerated dose (MTD), and recommended dose and schedule for DExp phase. Secondary objective: To assess safety and tolerability of cabo with LVT. Expected enrollment 9 pts (range 4-18). DExp part will enroll 24 evaluable pts. Primary objective: to evaluate preliminary efficacy by estimating the progression-free survival (PFS) at 24 weeks (PFS24w) as assessed by PCWG3-modified RECIST v1.1. 2-sided 80% and 60% confidence intervals will be constructed for PFS24w via exponential Greenwood’s formula for Kaplan-Meier survival estimate, providing 90% and 80% 1-sided confidence for 30 pts at DExp dose (6 DEsc+24 DExp). Secondary objective: (1) To assess safety and tolerability cabo+LVT (2) assess objective response rate, duration of response, radiographic PFS, PFS at 38 weeks, PSA PFS, PSA 50% response rate, and OS. 1 patient has been enrolled. Clinical trial information: NCT05613894 .
P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for individuals aged 11-45 years with intermediate and poor-risk metastatic germ cell tumours (GCTs).
Authors: Mak Blossom , Tran Ben , Pashankar Farzana D. , Mazhar Danish , Huddart Robert A , Wheater Matthew , Walpole Euan Thomas , Feldman Darren R. , Dunwoodie Elaine , Lawrence Nicola Jane , Birtle Alison Jane , Wyld David , Stevanovic Amanda Gwendolyn , Balagtas Jay Michael S. , Stockler Martin R. , Davis Ian D. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: January 2024

TPS524 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard first-line chemotherapy for intermediate and poor-risk metastatic GCT. Accelerating standard chemotherapy regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. It aims to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2 stages. The primary endpoint for stage 1 (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival at 2 years (PFS2y). These sample sizes provide > 80% power with a two-sided type I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF 6mg D6 or filgrastim daily. Study assessments occur at 30 days after completing chemotherapy, 6 months from randomization, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of 24 August 2023, 274 participants have been recruited from 23 ANZ sites, 17 UK sites (led by Cambridge Clinical Trials Unit), and 150 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage 1 analysis of safety and activity (response rate) for the 1st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .
Adjuvant Therapy After Upfront Resection of Resectable Pancreatic Cancer: Patterns of Omission and Use—A Prospective Real-Life Study
Authors: Paiella Salvatore , Malleo Giuseppe , Lionetto Gabriella , Cattelani Alice , Casciani Fabio , Secchettin Erica , De Pastena Matteo , Bassi Claudio , Salvia Roberto 
Published: January 2024

Abstract
Background
Little is known about adjuvant therapy (AT) omission and use outside of randomized trials. We aimed to assess the patterns of AT omission and use in a cohort of upfront resected pancreatic cancer patients in a real-life scenario.

Methods
From January 2019 to July 2022, 317 patients with resected pancreatic cancer and operated upfront were prospectively enrolled in this prospective observational trial according to the previously calculated sample size. The association between perioperative variables and the risk of AT omission and AT delay was analyzed using multivariable logistic regression.

Results
Eighty patients (25.2%) did not receive AT. The main reasons for AT omission were postoperative complications (38.8%), oncologist’s choice (21.2%), baseline comorbidities (20%), patient’s choice (10%), and early recurrence (10%). At the multivariable analysis, the odds of not receiving AT increased significantly for older patients (odds ratio [OR] 1.1, p < 0.001), those having an American Society of Anesthesiologists score ≥II (OR 2.03, p = 0.015), or developing postoperative pancreatic fistula (OR 2.5, p = 0.019). The likelihood of not receiving FOLFIRINOX as AT increased for older patients (OR 1.1, p < 0.001), in the presence of early-stage disease (stage I–IIa vs. IIb–III, OR 2.82, p =0.031; N0 vs. N+, OR 3, p = 0.03), and for patients who experienced postoperative major complications (OR 4.7, p = 0.009). A twofold increased likelihood of delay in AT was found in patients experiencing postoperative complications (OR 3.86, p = 0.011).

Conclusions
AT is not delivered in about one-quarter of upfront resected pancreatic cancer patients. Age, comorbidities, and postoperative complications are the main drivers of AT omission and mFOLFIRINOX non-use.
ClinicalTrials registration: NCT03788382.
Ultra-compact, low-loss,TE0- and TE1-compatible mode waveguide bends
Authors: Gao Mingyang , Fei Yedeng , Xu Yin , Ni Yi 
Published: January 2024

Waveguide bends have become an interesting research direction because they allow highly curved light transmission in a limited space. Here, we propose waveguide bends supporting two TE modes by etching slots and adding germanium arcs in the inner side of a waveguide bend. Simulations show that the bending radius of our proposed base-mode TE0 waveguide bend drops to 500 nm and its insertion loss (IL) is reduced to 0.13 dB with footprints as small as 0.75µm×0.75µm. For the higher-order TE1 mode waveguide bend, we adjust the introduced structure in combination with the light field distribution. The IL of the waveguide bend is also reduced to 0.18 dB with footprints as small as 1.85µm×1.85µm. TE0 mode has 410 nm bandwidth in the optical communication band while TE1 mode has 330 nm bandwidth by keeping IL<0.5dB. Through the analysis of these structural characteristics, we believe that this method still has great potential in higher-order mode transmission.
Raman lidar at 355  nm using low dead time photon counting for atmospheric aerosol measurements
Authors: Chen Feitong , Wu Lingyun , Chen Chuxiao , Wan Xueping , Chen Wentai , Chen Xiaolong , Zhou Jianfeng , Cheng Miao , Fu Zhewei , Ding Naiying , Deng Zhiji , Shen Yibing , Liu Chong , Bai Jian , Wu Lan , Sun Wenbo , Liu Dong 
Published: January 2024

Photon counting is an effective way to enhance the dynamic range of the data acquisition system (DAQ) in Raman lidars. However, there exists a deficiency of relatively high dead times among current options, which necessitates an additional calibration procedure for the nonlinearity of the photon counting signal, thus leading to unanticipated errors. A field programmable gate array (FPGA)-based photon counting module has been proposed and implemented in a Raman lidar, offering two operational channels. Through observational experiments, it was determined that this module has an overall dead time of 1.13 ns taking advantage of the high-speed amplifier/discriminator pair and the logic design, a significant improvement compared to the 4.35 ns of a commercially used Licel transient recorder within the same counting rate range. This notably low dead time implies that its output maintains sufficient linearity even at substantially high counting rates. As a result, the need for a dead time calibration procedure prior to signal integration with the analog signal is eliminated, reducing uncertainty in the final integrated signal, and even in the retrieval result. The backscattering result of the comparison between this module and a transient recorder indicates that a more precise performance can be acquired benefiting from this hardware upgrading.
Preparation of convex edges in fused silica by single pass perforation with a 2D Airy–Gaussian beam
Authors: Cai Libin , Chen Yan , Lv Yongjie , Ye Fangcheng , Ye Yunxia , Ren Yunpeng 
Published: January 2024

Following ultrafast laser machining of fused silica, post-processing such as polishing and honing are typically required for edges. In this study, we employed a spatial light modulator (SLM) to generate the 2D Airy–Gaussian beam to prepare the convex edges in fused silica by using a single pass of a picosecond laser. It is found that, if the speed exceeds 5 mm/s, there would be plasma interference which is unfavorable for the separation process. A filament effect was observed when the internal laser peak power exceeds the damage threshold of fused silica. The shape of the convex edges was consistent with the propagation path of the 2D Airy–Gaussian beam inside the fused silica before separation. The inclination angle was 17° and 13°, respectively, on the upper and lower end of the edges. The results of this study provide a new, to our knowledge, method for the preparation of curved structures with different curvatures in transparent materials.