bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients (pts) with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who progressed to metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TRUMPET registry.
Authors: Shevrin Daniel H. , Symanowski James Thomas , Shore Neal D. , Lin Daniel W. , Russell David , Kral Pavol , Song Yi , El-Chaar Nader N. , Karsh Lawrence Ivan 
Published: June 2023

e17085 Background: Significant lack of treatment (Tx) intensification is seen in clinical practice for pts with mHSPC until progression to mCRPC. The TRUMPET registry enabled a post-hoc analysis of clinical outcomes in pts with mCRPC, initially diagnosed with de novo mHSPC vs nmHSPC. Methods: TRUMPET, a prospective, observational study of US pts with CRPC, enrolled male adults (03/2015-09/2018) who began first or second-line Tx for M0/M1 CRPC. For this post hoc, pts with M1 CRPC at enrollment initially diagnosed with de novo mHSPC (clinical TNM1 stage) were compared to M1 CRPC pts initially diagnosed with nmHSPC (clinical TNM0 stage). Clinical outcomes (radiographic progression-free survival [rPFS], prostate specific antigen [PSA] progression, time to opiate initiation [OI], mortality) were analysed with Kaplan–Meier and Cox proportional hazards models. An exploratory subanalysis investigated outcomes in de novo mHSPC pts who received Tx intensification (docetaxel or abiraterone) with androgen-deprivation therapy (ADT) as primary Tx prior to mCRPC vs pts who did not. Results: M1 CRPC pts initially diagnosed with de novo mHSPC (n = 199) or nmHSPC (n = 254) were included; median age: 70.0 vs 73.0 years, duration from initial PC diagnosis to baseline mCRPC visit: 1.62 vs 6.72 years, PSA at PC diagnosis: 113.1 vs 10.1 ng/mL, Gleason score: 9.0 vs 8.0, respectively. In the de novo mHSPC and nmHSPC groups, initial CRPC Tx was chemotherapy in 9.0% vs 5.9% of pts, novel hormonal therapy (enzalutamide or abiraterone) in 55.3% vs 59.1%, immunotherapy in 35.2% vs 42.9%, respectively. No differences were seen in rPFS or PSA progression (table). The de novo mHSPC group showed a trend toward shorter time to OI and significantly increased risk of mortality (37%) with 6.6 months shorter median survival vs nmHSPC. The subanalysis included 44 (22.1%) de novo mHSPC pts who received Tx intensification with ADT at initial diagnosis. A trend towards improved survival was seen in the Tx-intensified vs nonintensified subgroup (median time to death [95%CI]; 47.7 months [22.18, NE] vs 37.3 months [28.35, 43.01]). Conclusions: At mCRPC diagnosis, pts with de novo mHSPC have significantly higher mortality risk than pts with nmHSPC, indicating a need to delay progression of de novo mHSPC to mCRPC. The trend for improved survival benefit in pts with Tx-intensified de novo mHSPC further underlines the need for early Tx intensification. [Table: see text]
Biochemical recurrence after salvage prostate bed radiotherapy captured on PSMA-PET: Patient characteristics and distribution of recurrent disease.
Authors: Hsu Miles , Shan Xinhe , Vapiwala Neha , Zhang Rebecca , Pantel Austin , Berlin Eva , Narayan Vivek , Takvorian Samuel U , Vaughn David J. , Haas Naomi B. 
Published: June 2023

e17088 Background: The SPPORT trial demonstrated that salvage whole pelvic radiotherapy (sWPRT) after radical prostatectomy (RP) reduced prostate cancer progression compared to salvage prostate bed radiotherapy (sPBRT), at the expense of greater toxicity. To identify pts most appropriate for sWPRT, we studied the incidence of and risk factors associated with radiologic relapse after sPBRT on 18F-DCFPyL PET, a sensitive new imaging modality. Methods: We analyzed 538 18F-DCFPyL PET/CTs performed at our large academic institution and screened for pts who had biochemical recurrence (BCR), defined as PSA > 0.2 ng/mL, after receiving sPBRT for persistent or recurrent PSA. Risk factors including pathologic T stage (pT), pathologic Gleason score (pGS), seminal vesicle invasion (SVI), positive margins, perineural invasion (PNI), PSA at RP (PSA1), prior to RT (PSA2), and at time of scan (PSA3), and PSA doubling time after sPBRT (PSADT) were obtained. Associations between risk factors and radiographic relapse were quantified with logistic regression, with a p < 0.05 defined as significant. Results: 38 pts with BCR after sPBRT were identified. Median values were: pt age = 69.5 years (interquartile range 64 – 74), PSA1 = 7.83 ng/mL (4.7 – 11.5), PSA2 = 0.26 (0.1 – 0.8), PSA3 = 0.71 (0.5 – 2.2), PSA DT = 9.8 (5.3 – 18.2). Pt characteristics were: pT (pT2, 46% of pts; pT3a/b, 54%), pGS ( < 7, 11%; 3+4, 32%; 4+3, 39%; > 7, 18%), 19% w/ SVI, 68% w/ positive margins, 93% w/ PNI and 80% (of evaluable pts) w/ high-risk decipher score. 42% of pts received salvage ADT with sPBRT. 68% of pts had detectable disease on 18F-DCFPyL PET. Radiologic relapse in pelvic LNs was present in 47% of all pts, and 32% of pts had relapse only in the pelvic nodes. 26% of pts had distant metastases (DM) on imaging. Only 13% of pts had DM without pelvic LN involvement. Between pts with pelvic LN only relapse (n = 12) and pts without radiographic disease (n = 12), age, pT, pGS, SVI, margins, ADT, PSA1-3 and PSADT did not differ on univariate or multivariate analyses. On the univariate analysis between pts with DM (n = 10) and without DM (n = 28), only PSA3 (p < 0.05) was associated with radiographic relapse, and pT trended toward a negative association (p< 0.10) with DM. Only PSA3 (p < 0.10) trended toward association with DM in a multivariate analysis using age, pT, margins, ADT, and PSA2-3. Conclusions: Pts with biochemical relapse after sPBRT had frequent high-risk pathology. Aside from PSA3, no risk factors were predictive of detectable pelvic nodal or DM disease. However, most pts with detectable disease had pelvic LN involvement, suggesting that a substantial portion of these high-risk pts may have benefited from whole-pelvic RT. Further data on risk factors will help inform selection of pts appropriate for salvage whole pelvic RT.
Results of digital patient-reported outcomes measures (PROMs) data collection for patients with localized prostate cancer at diagnosis.
Authors: Knipper Sophie , Dewulf Karel , Branger Nicolas , Rybikowski Stanislas , Maubon Thomas , Salem Naji , Guerin Mathilde , Vicier Cecile , Gravis Gwenaelle , Walz Jochen , Pignot Geraldine 
Published: June 2023

e17103 Background: Patient-reported outcomes measures (PROMs) allow optimal evaluation of side effects of treatments and their impact on quality of life. Therefore, the objective of our study was to analyze the functional outcomes at different timepoints for urinary continence and erectile function in patients treated with active surveillance (AS), brachytherapy (BT), radiotherapy (RT, +/- hormonal treatment (HT)) and radical prostatectomy (RP). Methods: Since May 2019, all patients treated for localized prostate cancer in our center have been offered inclusion in a digital prospective program, with automated sending of PROMs questionnaires via a dedicated digital application, before treatment (baseline), at 1 (M1), 3 (M3), 6 (M6) and 12 months (M12). Data were analyzed for urinary continence and erectile function (EPIC-26 HRQOL Domain Summary Score of Urinary Incontinence (UI) and Sexuality) according to treatment strategy. Results: Overall, 552 patients answered questionnaires (05/2019-12/2022), including 97 AS patients, 23 patients treated by BT, 9 patients treated by RT, 37 patients treated by RT with HT and 386 patients treated by RP. Regarding continence, the median UI score at M12 (compared to baseline) was 88 (vs. 100) for AS, 100 (vs. 100) for BT, 100 (vs. 100) for RT, 93 (vs. 100) for RT with HT and 100 (vs. 100) for RP. Regarding erectile function, the median sexuality score at M12 (compared to baseline) was 100 (vs. 73) for AS, 40 (vs. 61) for BT, 40 (vs. 47) for RT, 17 (vs. 54) for RT with HT, 32 (vs. 67) for RP. Conclusions: Surgical treatment transiently affects continence but with almost complete recovery at one year in the majority of cases. However, erectile dysfunction remains a critical issue with an important deterioration for surgery as well as radiotherapy with combined HT. [Table: see text]
3D open-top light-sheet microscopy and 3D microdissection of neuoadjuvant-treated primary prostate cancer reveals latent subclonal mutations.
Authors: Reder Nicholas , Pritchard Colin C. , Konnick Eric Q , Huang Hongyi , Lerma Angelica , Glaser Adam K , True Lawrence D , Liu Jonathan T.C. , Schweizer Michael Thomas 
Published: June 2023

e17109 Background: Intratumoral molecular heterogeneity is a well described phenomenon in primary prostate cancer. Increased genomic heterogeneity is associated with more aggressive clinical behavior, including recurrence and metastasis. However, current methods to characterize heterogeneity suffer from tradeoffs between generating high quality morphologic information, correlating morphology with genomic alterations, and workflow considerations. We describe a technology to image prostate samples in 3D, perform 3D microdissection of regions of interest (ROIs), and preserve nucleic acids for DNA sequencing. Methods: Samples (N = 18) were obtained from patients (N = 12) enrolled in an open-label, single-site, Phase II neoadjuvant trial in men with NCCN high to very-high risk PC. Patients received 12 weeks of apalutamide, abiraterone acetate plus prednisone, degarelix, and indomethacin followed by radical prostatectomy (RP). Fresh frozen prostate samples (~2x2x0.4cm) were obtained from RP specimens. Frozen samples were fixed in an ethanol-based fixative, stained with nuclear (TOPRO-3) and general protein (eosin) fluorescent dyes, cleared with ethyl cinnamate, and imaged using 3D open-top light-sheet (OTLS) fluorescence microscopy. Image-guided 3D microdissection was performed on ROIs with distinct morphologies. Microdissected ROIs measured 0.5x0.5x2mm. Microdissected samples were sent for DNA extraction and sequencing using the comprehensive clinically-validated UW-OncoPlex NGS assay. Results: The tissue from neoadjuvant-treated patients contained sparse carcinoma, with cancer volumes ranging from 0.01-0.3 cm2 and cellularity ranging from 2%-30%. Molecular alterations were detected in a sample with only 0.07 cm2 volume of carcinoma with 5% cellularity. The read depth of 3D microdissected samples was 3.9 times greater than the read depth of FFPE samples from the same patients. At least two morphologically distinct ROIs were 3D microdissected from 11 of 12 patients. Four of the 18 samples had molecular alterations that differed between ROIs, i.e. intra-sample molecular heterogeneity. For example, one sample with three microdissected ROIs had a PTEN alteration exclusive to a single ROI. Conclusions: The findings show the potential for 3D microdissection of morphologically distinct subclones in samples from neoadjuvant-treated patient, to enable sequencing of specific cellular populations. The sparsity of carcinoma necessitated a spatially targeted approach for extracting material for sequencing. The increased yield from avoiding FFPE processing and carcinoma enrichment from targeted 3D microdissection of carcinoma ROIs enabled the detection of spatially distinct molecular subclones. Future work will include the analysis of additional samples and implementation of AI-guided ROI detection to streamline workflows.
Socioeconomic and demographic patterns associated with treatment delay in prostate cancer: An analysis of the National Cancer Database.
Authors: Abodunrin Faith , Adeoye Oluwatayo , Nelson Nick , Amadi Nwonuwkuru I , Silberstein Peter T. , Tupper Connor 
Published: June 2023

e17122 Background: Prostate cancer is the second leading cause of cancer related deaths in men. In 2023, about 288,300 new cases of prostate cancer are expected . Delays in cancer treatment can impact patients’ outcomes. In our study, we sought to describe socioeconomic and demographic factors influencing time to treatment in prostate cancer. We also studied the trend in time to treatment through the years. Methods: Using the National Cancer Database, we identified 1,605,396 patients diagnosed with prostate cancer between 2004 and 2019. Variables used for assessment include age at diagnosis, race, Charlson-Deyo score, stage at diagnosis, insurance status, median household income in patient’s zip code and year of treatment. We separated patients into two groups: those who started treatment < 60 days and patients who started treatment > 60 days using statistical analyses. We used Chi-square test to assess for differences within these groups and multivariable analysis to determine relationships between time to treatment and the socioeconomic and demographic variables. All tests were performed with a significance level of a = 0.05. Results: Out of 1,605,396 patients included in this study, 806,576 patients began treatment 60 days or less after diagnosis and 798,820 began treatment over 60 days after diagnosis. Older patients (age > 71) were less likely to be treated later than younger patients aged < 60 years (OR 0.530). Black and Hispanic patients were significantly more likely to start treatment later than white patients (OR 1.231; OR 1.086 p < 0.001). Compared to uninsured patients, those with private and other government coverage were more significantly likely to begin treatment later (OR 1.144; OR 1.469 p < 0.001). Patients with advanced stage prostate cancer were at lower risk for delayed treatment compared to those with localized disease (OR 0.218 P < 0.001). Compared to community programs, patients at academic/research programs were significantly more likely to begin treatment later (OR 2.097 p < 0.0001). In 2004, 40.5% patients began treatment over 60 days from diagnosis compared to 55.1% in 2019 (p < 0.001). We found that patients diagnosed between 2016 and 2019 were more likely to be treated later than those diagnosed between 2004-2007 (OR 1.717 p < 0.001). Conclusions: Increased rate of later time to treatment were seen in younger patients, minority groups, staging at diagnosis less than stage IV, patients treated at academic or research programs, and patients diagnosed between 2016-2019. This is likely due to the rise of active surveillance rather than immediate treatment as a management strategy in prostate cancer. Black men are at increased risk for advanced disease, hence, treatment delays should be avoided in these patients. Institution-level studies should be done to determine the pattern of treatment and address treatment delays.
Treatment patterns and outcomes among locally advanced cervical cancer patients receiving concurrent chemoradiotherapy.
Authors: Coutinho Francesca , Gokhale Mugdha , Doran Charlotte , Monberg Matthew , Yamada Karin Sayuri , Chen Lei 
Published: June 2023

e17511 Background: Concurrent chemoradiotherapy (CCRT) is standard treatment for patients with locally advanced cervical cancer (LACC). However, little is known on the real-world treatment patterns and outcomes among LACC patients. This study evaluated patient characteristics and treatment patterns of LACC patients, and real-world outcomes among patients receiving CCRT as the first treatment after diagnosis (CCRT-first) in US academic and community settings. Methods: Data were drawn from the ConcertAI Oncology Dataset, a US-based electronic medical record dataset. We included adult patients diagnosed between 2010-2018 with LACC, defined as stage IB2-IIB with node involvement or stage III-IVA cervical cancer, with squamous cell carcinoma (excl. verrucous), adenocarcinoma (excl. clear cell and endometroid), or adenosquamous carcinoma. Patients with prior immunotherapy or a second primary cancer (other than in situ or non-melanoma skin cancer) were excluded. Patients were followed from initial diagnosis through end of the second regimen of systemic anti-cancer therapy, end of record, or death, whichever occurred first. Patient characteristics and treatments were reported overall and in CCRT-first patients. Among CCRT-first patients, real-world time on CCRT treatment (rwTOT), recurrence-free survival (rwRFS), and progression-free survival (rwPFS) among patients with persistent disease were estimated using Kaplan-Meier methods. Results: Overall, 300 patients with LACC were included. At LACC diagnosis, median age of patients was 51 years, 53.7% were White, 30.0% were Black, 48.0% were peri/postmenopausal, 89.3% had squamous cell histology, 75.3% had stage III disease, 92.7% had no evidence of performance status impairment, 50.3% were treated in community settings, and 21.7% had only public insurance (11.0% Medicaid, 10.7% Medicare; 56.3% had no documentation of insurance). Distributions were similar among CCRT-first patients. First treatment after diagnosis included CCRT (N=229), surgery (N=28), systemic therapy (N=11), and radiation therapy alone (N=5). 27 were untreated, and 29 patients received CCRT after another therapy. Of the 229 CCRT-first patients, median (95% CI) rwTOT was 1.6 (1.4-1.7) months; 78.2% received cisplatin within CCRT, and median duration of cisplatin treatment was 35 days; 28.4% received a systemic therapy after CCRT, and 11.8% further initiated a second systemic therapy. 27 patients had recurrent disease after complete response (median rwRFS not reached). 179 patients had persistent disease after CCRT, among whom median (95% CI) rwPFS was 29.7 (16.9-59.3) months from CCRT start. Conclusions: In US clinical practice during 2010-2018, most LACC patients received CCRT as the first treatment after diagnosis. The high proportion of patients who develop persistent disease after CCRT indicates a need for improved first treatment options.
Response and re-treatment response to immune checkpoint inhibitor treatment in advanced cervical cancer: A follow up study.
Authors: Wolf Jennifer , Xu Yiqing 
Published: June 2023

e17516 Background: Single agent checkpoint inhibitor immunotherapy (CII) was approved in June 2018 for second line treatment for metastatic cervical cancer after failure of platinum-based chemotherapy. Clinical trials recommended 2 years of treatment, however the optimal duration of treatment, outcome after stopping treatment and response after re-initiation of immunotherapy is still largely unclear. Methods: A cohort of 10 patients who were started on CII before September 31, 2019, with an initial analysis published in July 2021 were eligible. We performed an updated review of the duration of response, outcome off treatment after 2 years, and outcome after re-initiation of CII. Results: The current median follow up is 40 months (range, 2.0-50.8 months), 4 patients did not respond to treatment and have passed away, while six patients remain alive. The previous report showed 7 responders, with 3 complete responses (CR) at a median follow up of 20.7 m. With prolonged treatment, 6 patients achieved CR or stable minimal disease. After more than 2 years of treatment, 2 continued treatment for 39m and 50 m. Among the 4 patients who stopped treatment, 2 of them are 18 m and 20 m off treatment and remain no evidence of disease. Another 2 patients developed asymptomatic recurrence detected on surveillance CT (at 9 m and 12 m respectively), both with small volume of disease in the retroperitoneal and pelvic lymph nodes. They were both re-initiated on CII, and showed a CR and partial response (PR) respectively, on 3-6 month follow up CT scans, now 11.7 m and 3.5 m on treatment. A median PD-L1 combined expression score (CPS) was similar between responders (n=6) (20) and non-responders (26) (n=4) in the entire cohort overall, and was 83 in the group of patients who discontinued treatment after 2 years and have been without evidence of disease since (n=2). Conclusions: Patients who respond to immune checkpoint inhibitors may have durable response off treatment and may respond again to re-treatment in the event of recurrent disease. Our limited data suggest that providers can use CPS to aid in decision making. [Table: see text]
Circulating tumor DNA–based detection of molecular residual disease as a biomarker for recurrence monitoring predict disease recurrence in patients with ovarian cancer.
Authors: Lv Tianjiao , Shi Xinyi , Zhao Dan , Sun Jing , Wang Bo , Lu Kai , Zou ShiPing , Wang Jing , Wang Qiang , Feng Weiwei 
Published: June 2023

e17542 Background: Despite recent advances in cancer diagnostics and treatments, nearly 75% ovarian cancer patients relapse within two years of primary therapy and become candidates for treatment of recurrent diseases. A novel approach to post-surgical risk stratification for molecular residual disease (MRD) detection and treatment monitoring is needed to improve patient outcomes. Methods: We analyzed a cohort of 22 stage Ⅰ-Ⅳ ovarian cancer patients which were followed up at median 6 (range,3-15) times between July 2017 and December 2020. Among the 22 patients, stage I, II, III and Ⅳ comprised 9%, 5%, 50% and 36%, respectively. Tumor tissue and blood samples of all subjects were collected at Ruijin Hospital, Shanghai Jiao Tong University.Somatic mutations were identified by whole exome sequencing and assessed from plasma collected during treatment using personalized tumor-informed MRDtect assays with a median of 25（range,17-30） amplicons/assay targeting tumor-specific variants unique to each patient, sequenced at mean 200,000X depth. Plasma samples with ≥2 variants detected were considered MRD-positive and ctDNA levels were reported in mean tumor molecules per mL (MTM/mL) of plasma. Sequencing data were analyzed using PiVAT secondary analysis software and MRD positive was concluded when at least two variants were detected in plasma. Results: CtDNA was preoperatively detectable in 18 (85.7%) patients, and the positive rate became 38.8% (7/18) after surgery. Serial ctDNA analysis during surveillance after definitive treatment of the 22 patients with longitudinal collected plasma samples identified relapse with 100% sensitivity and 100% specificity. The median lead time from ctDNA detection in plasma to relapse detection by standard-of-care computed tomography was 135 days (range,45-387days). Variants from a total of 526 genes were selected from the WES results of these 22 patients. Among these 526 genes, 96% (505 genes) were selected for only one patient, 3.4% (18 genes) were selected for two patients and 0.2% (one gene) were selected for three patients. Compared with tumor-agnostic assay, tumor-informed assay is a more accurate route that is more consistent with the heterogeneity of tumor and can maximize the ability to reflect the real situation of each patient. Conclusions: Sensitive methods for risk stratification, therapeutic efficacy monitoring, and early relapse detection may have a major impact on treatment decisions and patient management for ovarian cancer patients. MRD can be used as an effective biomarker to prompt prognosis and recurrence risk, providing powerful assistance for accurate diagnosis and treatment for patients.