tbuckley/cabot-search huggingface dataset:
GOG 3088: A randomized phase II study of letrozole versus observation in patients with newly diagnosed uterine leiomyosarcoma.
Authors: Bradley Corr, Michael Sill, Jennifer Klein, Thomas J. Herzog, Robert L. Coleman, Brian M. Slomovitz
Journal: Journal of Clinical Oncology (2024)

TPS5643 Background: Uterine leiomyosarcomas (uLMS) are rare, accounting for less than five percent of all malignant uterine neoplasms. Approximately 85% of women present with clinical stage I disease (i.e., disease limited to the uterus and cervix). NCCN guidelines for stage I uterine confined disease currently recommend observation; however, recurrence risk of uLMS overall is quite high at 50-70% within the first two years. The estrogen receptor (ER) is expressed in 40-87% of leiomyosarcomas. Because of this high expression, estrogen may act as a growth factor that stimulates cell proliferation and tumor growth. Subsequently, there have been several evaluations for the use of aromatase inhibitors as single agent therapy for uLMS. These trials have each shown varying degrees of clinical activity. We hypothesize that by decreasing systemic estrogen using an aromatase inhibitor we will prolong the time to recurrence for patients with this disease. Methods: This is a GOG Foundation led phase II randomized controlled trial comparing letrozole (2.5mg PO daily) to observation in newly diagnosed patients with uterine confined stage I uLMS. Forty patients will be randomized 1:1. Patients will be eligible post operatively if they have no measurable disease and will be required to be estrogen receptor (ER) positive, as defined by ³ 10% expression by immunohistochemistry (IHC). No stratification methods will be applied. The primary endpoint of the trial is investigator-assessed progression free survival. Exploratory translational evaluation will occur to 1) correlate response to letrozole based on IHC hormone receptor status, 2) evaluate gene expression signatures of hormone receptor activity, tumor biology, and tumor microenvironment in relation to response to letrozole, and 3) evaluate the contribution of single nucleotide polymorphism rs3820282 to tumor biology and response to letrozole. GOG 3088 activated in January of 2024 and expects to enroll across 20 US sites. Clinicaltrials.gov Identifier: NCT05649956. Clinical trial information: NCT05649956 .
Phase II/III study of paclitaxel/carboplatin alone or combined with either trastuzumab and hyaluronidase-oysk or pertuzumab, trastuzumab, and hyaluronidase-zzxf in HER2 positive, stage I-IV endometrial serous carcinoma or carcinosarcoma (NRG-GY026).
Authors: Britt Kristina Erickson, Danielle Enserro, Heather A. Lankes, Lauren E. Dockery, sharad A. ghamande, Matthew T. Oliver, Gregory M. Gressel, Tara Castellano, Elena Ratner, Amy Deery, Erin Bishop, Leslie Siriya Bradford, Jessica Thomes Pepin, Elizabeth Burton, Stephanie V. Blank, Alessandro Santin, Laura J Havrilesky, Carol Aghajanian, Amanda Nickles Fader, Matthew A. Powell
Journal: Journal of Clinical Oncology (2024)

TPS5641 Background: Uterine serous carcinoma and uterine carcinosarcoma are rare, high-risk uterine cancer subtypes that overexpress HER2 in up to 40% and 10% of cases, respectively. Phase II data demonstrated a benefit in adding trastuzumab in HER2 positive advanced and recurrent uterine serous carcinoma. Dual anti-HER2 therapy has the potential for further improvement in survival. Methods: This is a non-blinded, three-arm randomized phase II/III study. The primary objective is to evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) or a fixed dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive uterine serous carcinoma or carcinosarcoma. The primary outcome of the phase II component is PFS. Depending on the phase II results, the study will progress to a phase III study of either two or three study arms. Patients in the control arm (Arm 1) receive carboplatin and paclitaxel every 3 weeks for 6 cycles. Patients on Arm 2 receive carboplatin and paclitaxel with trastuzumab and hyaluronidase-oysk every 3 weeks for 6 cycles plus one year of maintenance trastuzumab and hyaluronidase-oysk. Patients enrolled on Arm 3 receive carboplatin and paclitaxel with trastuzumab, pertuzumab, and hyaluronidase-zzxf every 3 weeks for 6 cycles plus one year of maintenance trastuzumab, pertuzumab, and hyaluronidase-zzxf . Those with an ongoing partial response may continue maintenance therapy for up to three years. Patients are eligible if they are diagnosed with chemo-naïve, non-recurrent stage IA-IVB myoinvasive uterine serous or carcinosarcoma. All tumors must be HER2 positive as defined by the ASCO/CAP Breast Cancer 2018 guidelines (testing performed locally). Tumors may also be HER2 positive based on next generation sequencing testing. Patients may have measurable, non-measurable, or no measurable disease and may have a plan for vaginal brachytherapy . Key exclusion criteria include severe heart disease or interstitial lung disease. The phase II portion of this study is open and enrolling. Clinical trial information: NCT05256225 .
Somatic tissue testing in prostate cancer using the Oncomine V3 panel: A single-institution retrospective analysis.
Authors: Lilian Hanna, Nicole Park, Xin Wang, Larissa Waldman, Yael Silberman, Urban Emmenegger, Michelle R. Downes, Martin Smoragiewicz
Journal: Journal of Clinical Oncology (2024)

e17002 Background: Approximately 20-30% of prostate cancer (PC) patients have a mutation in the homologous recombination repair or mismatch repair genes, 50% of which are somatic. These mutations have prognostic and predictive implications. Somatic tissue testing (STT) was implemented at Sunnybrook Health Sciences Centre using the Oncomine V3 panel, which includes 161 genes, but only four genes (BRCA1/2, ATM, PALB2) are reported due to funding restrictions. We describe our centre’s testing experience and the utility of reporting beyond these four genes. Methods: Sixty-two PC patients between May 1, 2021 - January 31, 2023 were included. Clinical characteristics were gathered via chart review. Somatic variants of genes of interest (GOI) within the Oncomine V3 panel were extracted by an annotation specialist. Results: STT was ordered at diagnosis in 69.4% of cases (n=42) vs. at progression in 27.4% (n=17), 3 cases were external and lacked clinical context. Tests were ordered in the locoregional disease setting in 46.8% (n=29), 37.1% (n=23) in the metastatic castrate-sensitive setting, 8.1% (n=5) in the metastatic castrate-resistant (CR) setting and 3.2% (n=2) in the non-metastatic CR setting. Tests were ordered by Urology or Pathology (reflex testing) in 64.5% (n=40), by Medical Oncology in 16% (n=10), by Radiation Oncology in 13% (n=8) and by others in 6.5% (n=4). Fifty-one samples (82.2%) were of the prostate and 11 (17.7%) were of metastatic sites. The median sample age was 8 days (range 0-5781). The median test turn-around time was 28.5 days (range 5-57). There were 378 variants within the GOI and meeting the limit of detection [1] , of which 63 (16.7%) were tier 1 or 2 and are listed by gene in the table. Eight of 63 variants (12.7%) were within the four funded genes whereas 55/63 (87.3%) were within unfunded genes of clinical significance. CDK12, FANCA, NBN (n=7, 11.2%) are investigated in poly (ADP-ribose) polymerase inhibitor trials and PMS2 deficiency (n=1, 1.6%) can select for immune checkpoint inhibitors. PIK3R1/PIK3CA/AKT1-mutated tumors (n=11, 17.7%) have shown response to AKT-inhibitors. SPOP-mutated tumors (n=6, 9.7%) are associated with prolonged response to androgen receptor blockade whereas PTEN/TP53/RB1-negative tumors (n=12, 19.4%) are associated with anti-androgen resistance and worse prognosis. Conclusions: The majority of STT variants identified were beyond the currently funded genes in Ontario, and many have important prognostic and predictive implications. This highlights that STT early in the disease course using expanded gene panels may help in delivering personalized PC care. [Table: see text]
Lutetium-177–PSMA-617 experience in Appalachian patients with advanced prostate cancer at West Virginia University Health Science Center.
Authors: Stephen Lee Yu, Seth Holler, Sijin Wen, Xiaofei Wang, Thomas F. Hogan
Journal: Journal of Clinical Oncology (2024)

e17045 Background: Lutetium Lu-177 vipivotide tetraxetan (Lu-177) allowed for improved biochemical and radiographic response rate with relatively low toxicity for metastatic castration-resistant prostate cancer (PC) after multiple lines of therapy. In the 2021 VISION study (DOI: 10.1056/NEJMoa2107322), Lu-177 was reported to have a median overall survival (OS) of 15.3 months in patients (pts) with advanced prostate cancer (PC). We reviewed the result with Lu-177 for the treatment of advanced PC at a rural tertiary academic center at West Virginia University Health Science Center (WVU-HSC). Methods: All PC pts receiving one or more doses of Lu-177 at WVU-HSC were retrospectively reviewed. Pts were followed until death or the last clinic visit. All pts were established patients at WVU-HSC for management of the advanced PC between July 2022 and February 2024. Data was tabulated with descriptive statistics and median survival was calculated from Kaplan-Meier method. Results: Over an eighteen months period 34 pts received 126 doses of Lu-177. 26 pts were referred from outside the WVU-HSC specifically for Lu-177. Demographics from data collection showed predominantly Caucasian pts (91% Caucasian). The time from the initial PC diagnosis to the first dose of Lu-177 was a median of 67 months (range: 10 months-367 months). The median age at the first dose of Lu-177 was 65 years (range: 45-80). 18 patients (53%) remain alive as of Feb 2024. 14 pts (41%) completed 6 cycles of Lu-177 and 11 pts (32%) remain alive. The Kaplan-Meier median OS for these 34 pts starting from the first cycle of Lu-177 was 10 months. Conclusions: A 2022 estimated cost for Lu-177 was $42,500 per dose (excludes administration) so “payors” may have been charged more than $5,000,000 for the Lu-177 for these patients. Lu-177 may be of more benefit earlier in the PC disease spectrum, or perhaps pre-treatment PSMA imaging can better target patients who will benefit from Lu-177. Our observed median OS of 10 months did not match the 15.3 reported in the VISION study (DOI: 10.1056/NEJMoa2107322). Further data evaluation and collection are warranted from different communities to investigate the differences observed in the survival data reported in the literature and observed in the clinic setting. [Table: see text]
Genomic profile of Japanese patients with rare ductal adenocarcinoma of the prostate has high grade and poor prognostic aspects.
Authors: Takeo Kosaka, Hiroaki Kobayashi, Kohei Nakamura, Yuto Baba, Yota Yasumizu, Kazuhiro Matsumoto, Keiichi Ito, Hiroshi Nishihara, Mototsugu Oya
Journal: Journal of Clinical Oncology (2024)

e17046 Background: Ductal adenocarcinoma (DAC) is a rare subtype of prostate cancer with unknown etiology and poor prognosis. Genomic profile analysis using next-generation sequencing has the potential to elucidate the pathogenesis of rare cancers. To date, some studies have investigated the genetic profile of the DAC genotype; however, no definitive findings have been obtained due to the small number of patients and limited geographic coverage. The discovery of novel prognostic biomarkers and identification of new pharmacotherapeutic targets for DAC are currently of research interest. The aim of this study is to analyze the genomic profile of DAC in a Japanese population and to summarize its features. Methods: Clinical and histopathological records from our three hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens containing a DAC component in the past 10 years. Twenty-eight patients diagnosed with DAC of the prostate were identified, of whom 15 were eligible for genomic profile analysis and 10 patients (66.7%) had the pure type. Genomic evaluation was performed using either the FoundationOne CDx or PleSSision testing platform. Results: At least one genomic alteration occurred in 14 patients (93.3%), and the most frequently mutated gene was tumor suppressor protein p53 ( TP53), which was found in seven cases (46.7%). Additionally, five cases (33.3%) had mutations in retinoblastoma transcriptional corepressor 1 ( RB1), and all these patients had the pure type. Four cases had both TP53 and RB1 alterations, and most of these possessed the pure type and had PSA levels of less than 4.0. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 20.0%) and Wnt-β/catenin pathway (n = 6; 40.0%) was comparable, but alterations in the DNA damage repair (DDR) pathway were few (n=1; 6.7%). None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions: We found that the Japanese cohort with DAC has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1, and few DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of DAC, and further accumulation of cases is considered important.
Urinary-based detection of MSL, HE4, and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.
Authors: Pauline Wimberger, Franziska Maria Schwarz, Daniel Klotz, Jan Dominik Kuhlmann
Journal: Journal of Clinical Oncology (2024)

e17567 Background: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified by Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio). In total, this study was based on 1080 biomarker detection runs from 188 serum and 172 urine samples from 192 ovarian cancer patients. Results: While absolute concentrations of MSL and CA125 were higher in serum than in urine, serum HE4 concentrations were considerably lower than urinary HE4 concentrations. Nonetheless, relative intra-patient levels of all three biomarkers strongly correlated between matched serum vs. urinary samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity in predicting surgical outcome and relapse/death among both body fluid types (urinary HE4: AUC=0.854; AUC=0.750, respectively). All clinically relevant findings of urinary MSL, HE4 and CA125 were reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis. Conclusions: We report that the capacity of MSL, HE4 and CA125 for predicting surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.
Patient characteristics, treatment patterns and early trends of lutetium Lu 177 vipivotide tetraxetan (<sup>177</sup>Lu-PSMA-617) use by US urologists and oncologists.
Authors: Jennifer Nguyen, Jeetvan Patel, Barinder Kang, Channing Yu, Amrita Sawhney, Mark Fallick, Magdaliz Gorritz, Chi-Chang Chen, Queenie Paltanwale, Kainan Sun, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

e17048 Background: 177 Lu-PSMA-617 was approved by the US Food and Drug Administration in March 2022 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This study describes characteristics of patients treated with 177 Lu-PSMA-617, treatment patterns and early trends in 177 Lu-PSMA-617 utilization by US urologists (URO) and medical oncologists (ONC). Methods: This retrospective cohort study identified adult patients with ≥1 claim for 177 Lu-PSMA-617 between 3/1/22 and 6/30/23 (first claim = index date) from the IQVIA open-source pharmacy and medical claims database. Patients were grouped by the physician specialty of the treating/referring physician. Patient characteristics were assessed within the 6 months prior to 177 Lu-PSMA-617 initiation. Prior prostate cancer treatments were assessed over all available pre-index data. Results: Overall 1,394 patientstreated with 177 Lu-PSMA-617 were identified during the first 16 months post-approval; 76.9% treated by an ONC and 23.1% treated by a URO. The mean age overall was 72.1 years; most patients were aged 65 and older (ONC, 83.3%; URO, 84.8%). Most patients had bone metastases (ONC, 88.0%; URO, 86.3%) and over one-third had visceral metastases (ONC, 34.6%; URO 35.7%). URO treated a higher proportion of patients with only lymph node metastases (5.9%) than oncologists (2.6%). Prior to 177 Lu-PSMA-617, the vast majority of patients received ARPI and/or taxanes (ONC, 88.2%; URO, 89.4%). Use of 177 Lu-PSMA-617 has steadily increased over the 16 months since approval with over five times as many patients being treated by ONC and URO in the first half of 2023. Conclusions: This is the first large-scale study describing 177 Lu-PSMA-617 patient characteristics, prostatic cancer metastatic distribution, treatment patterns, and utilization trends by prescriber type (ONC and URO). This study highlights how URO are playing a pivotal role in management of post-taxane mCRPC patients receiving 177 Lu-PSMA-617. As additional data with 177 Lu-PSMA-617 becomes available, we anticipate the role of URO to significantly evolve with the potential for earlier use of 177 Lu-PSMA-617 for pre-taxane mCRPC patients.
Positive psychology interventions in patients with prostate cancer: A systematic review.
Authors: Eleanor Xu, Quan Phung, Karie Runcie, Michael A. Liu
Journal: Journal of Clinical Oncology (2024)

e17005 Background: Prostate cancer is the most common malignancy in men and often results in psychiatric symptoms due to the direct disease effects, hormonal treatments, functional losses, and psychological responses of patients to the cancer. Positive psychology interventions have shown promise in alleviating psychological symptoms in patients with chronic diseases but are infrequently studied in patients with prostate cancer. Therefore, our systematic review aimed to examine the benefits of positive psychology interventions for patients with prostate cancer. Methods: Using PRISMA guidelines, a systematic literature search was conducted using the Medline, PubMed/Medline, and PsycInfo databases using a combination of MeSH terms and free text words, including publications up to November 2023. Studies were eligible if they included at least one positive psychology therapy intervention and the title or abstract mentioned the inclusion of patients with prostate cancer. Two individuals independently reviewed reports identified by the search to meet the above criteria and performed a quality assessment scale of studies based on standardized criteria that were adapted from those used in prior systematic reviews. The study was pre-registered on the Open Science Framework (OSF) repository. Results: The database searches yielded 1244 initial studies, 10 of which met inclusion criteria. Of the 10 included studies, 2 were randomized clinical trials, 2 were pilot feasibility trials, 3 were single-arm interventional studies, and 3 were cross-sectional studies. Manuscripts focused on older adults, with reported mean ages ranging from 54.5 to 72.0. Positive psychology interventions consisted of mindfulness-based therapies, meditation, hope and resilience therapies, and well-being therapies. Most studies showed a positive effect on improving outcomes for patients with early to advanced stage prostate cancers, including psychological distress, mood disorders, anxiety, quality of life, happiness, and life satisfaction. However, most of the studies were limited by small sample size, qualitative findings, loss to follow-up, and observational data. Most studies also excluded patients with severe psychiatric disorders, who may potentially benefit most from these interventions. Conclusions: This systematic review demonstrates that positive psychology approaches may have benefit in patients with prostate cancer. However, further larger prospective studies and clinical trials are needed to determine whether these interventions have proven benefit in this understudied population.
Quality metrics analysis in patients who received Lutetium-177 PSMA-617 (<sup>177</sup>Lu–PSMA) therapy in a real-world practice setting.
Authors: Omid Yazdanpanah, Sami Dwabe, Brian Warnecke, David Joseph Benjamin, Shyam M. Srinivas, Arash Rezazadeh, Nataliya Mar
Journal: Journal of Clinical Oncology (2024)

e17049 Background: 177Lu–PSMA is a radiolabeled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA). It has been approved for use in metastatic castration-resistant prostate cancer (mCPRC) in 3/2022, based on VISION study. The Food and Drug Administration (FDA) label for 177Lu–PSMA requires prior therapy with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy as well as presence of at least one PSMA-positive tumor with uptake greater than normal liver and no PSMA-negative lesions on a PSMA positron emission tomography (PET) scan. In the VISION study, PSMA PET was performed within 4 weeks of therapy start. Further, patient received either 177Lu–PSMA plus protocol permitted standard of care (SOC), including ARPI, or SOC alone. Given the relatively recent approval of this therapy, real-world familiarity with administration of this agent may not be optimal. Methods: A retrospective analysis of 25 patients with mCRPC who received 177Lu–PSMA therapy since 3/2022 at the University of California Irvine (24/25) and Hoag Hospital (1/25) was performed. Multiple variables were analyzed and compared to the FDA label for this agent as well as design of the VISION study. Results: All patients in this study had received an ARPI and at least one taxane chemotherapy prior to 177Lu–PSMA. A PSMA-PET scan was obtained prior to 177Lu–PSMA therapy in all patients. The timing of the scan was within 4 weeks of starting 177Lu–PSMA therapy in only 5/25 (20.0%) patients. The average time from PSMA PET scan to 177Lu–PSMA therapy start was 66 days [range: 18 - 326 days]. None of the PSMA PET scan reports included a baseline liver standardized uptake value (SUV) or mentioned whether any lesions were non PSMA-avid. All reports provided SUV values for some, but not all, PSMA-avid lesions. The average maximum SUV of the most PSMA-avid lesion noted on the reports was 34.7. All PSMA PET scans were retrospectively reviewed by a nuclear medicine specialist and the average maximum SUV of the most PSMA-avid lesion on re-review was 42.0 (p &lt;0.05). During 177Lu–PSMA therapy, co-administration of ARPI occurred in 10/24 (23.8%) of patients. Conclusions: This study highlights the differences in quality metrics between patients who received 177Lu–PSMA therapy in a real-world practice setting compared to the FDA label for this agent and VISION study design. Differences included lack of uniform PSMA PET scan reporting, timing of obtaining pre-treatment PSMA PET imaging, and co-administration of ARPI. Development of institutional algorithms around administration of 177Lu–PSMA therapy may be needed.