tbuckley/cabot-search huggingface dataset:
Prognostic assessment of simple hysterectomy versus radical/modified radical hysterectomy in clinically apparent stage II endometrial cancer: A multi-center cohort study.
Authors: Yuliang Chen, Penglin Liu, Hualei Bu, Kun Song, Beihua Kong
Journal: Journal of Clinical Oncology (2024)

5611 Background: The extent of hysterectomy for endometrial cancer (EC) patients with suspected or gross cervical involvement remains controversial. This study aimed to compare the effect of simple hysterectomy (SH) and radical or modified radical hysterectomy (RH/mRH) on the prognosis in clinically apparent stage II endometrial cancer, stratified by aggressive and non-aggressive histological types. Methods: This multi-center retrospective study enrolled patients with clinically apparent stage II (macroscopically cervical involvement without pelvic extension based on the preoperative imaging examination and intraoperative exploration) from the largest endometrial cancer database in China between 2000 and 2019. The primary and secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS), respectively. The prognostic difference was assessed using Kaplan-Meier analysis and Cox regression analysis, in total cohort and stratified by aggressive and non-aggressive histological subtypes. Propensity score matching (PSM) algorithm were applied. Results: A total of eligible 725 participants were enrolled, including 245 patients with aggressive histological types and 480 with non-aggressive subtypes. The Kaplan-Meier showed better CSS and DFS in the RH/mRH group than the SH group both in the before ( P=0.0014 and P=0.0038, respectively) and after PSM cohorts ( P=0.042 and P=0.046, respectively) among patients with aggressive histological types. Nevertheless, no significant difference was found (P&gt;0.05) among the patients with the non-aggressive subtypes. Similarly, the multivariate COX analysis revealed that hysterectomy type was an independent prognostic factor for CSS (hazard ratio [HR] RH/mRH vs SH : 0.36, 95% confidence interval [CI] 0.14–0.95, P=0.039) and DFS (HR RH/mRH vs SH : 0.47, 95% CI 0.24–0.93, P=0.030) in patients with aggressive histological types. Conclusions: Compared to SH, RH/mRH were associated with better CSS and DFS in patients with aggressive histological types, but not in the non-aggressive histological types. Despite guidelines recommend SH as first-line treatment for patients with suspected or gross cervical involvement, RH/mRH might be a more reasonable and individualized choice for those with aggressive histological subtypes.
Time course of adverse events in primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy in the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial.
Authors: Elizabeth Lokich, Trine Lembrecht Jørgensen, Destin Black, David Cibula, Lucy Gilbert, Antonella Savarese, Matthew A. Powell, Rebecca Herbertson, Sarah Gill, Bradley J. Monk, Nicole Nevadunsky, Kari L. Ring, Noelle Cloven, Iwona Podzielinski, Tashanna K. N. Myers, Christine Dabrowski, Shadi Stevens, Lyndsay Willmott, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2024)

5607 Background: Dostarlimab (DOST)+carboplatin-paclitaxel (CP) significantly improved PFS and OS vs CP alone in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) in the phase 3RUBY trial (NCT03981796). Safety has been reported for immunotherapy+chemotherapy combinations in EC, though timing of adverse events (AEs) and the longer-term AE profile is not yet clear. This analysis examines the time course of AEs related to any study treatment (TRAEs) during the RUBY trial. Methods: Pts with pA/rEC were randomized 1:1 to DOST+CP or placebo (PBO)+CP Q3W (6 cycles), followed by DOST or PBO monotherapy Q6W for up to 3 years. AEs were assessed according to CTCAE v4.03 and summarized by quarter. Results: The safety population included 487 pts who received ≥1 dose of treatment (241 DOST+CP; 246 PBO+CP). TRAEs were experienced by 97.9% of pts in the DOST+CP arm and 98.8% of pts in the PBO+CP arm. In both arms, the majority of the most common TRAEs (≥30%) and grade ≥3 TRAEs (≥10%) occurred within the first 3 to 6 months of treatment (Table). The timing of immune-related AEs (irAEs) was generally consistent with this finding. Conclusions: The majority of TRAEs seen in the RUBY trial occurred within the first 3 to 6 months, with limited differences between arms. This timing is consistent with the pts’ receipt of chemotherapy. Few pts experienced an onset of new TRAEs in the DOST+CP arm after 12 months. These safety data further support a favorable long-term benefit-risk profile of dostarlimab+CP in pts with primary advanced or recurrent EC. Clinical trial information: NCT03981796 . [Table: see text]
The efficacy of recombinant human adenovirus type 5 (H101) intra-tumor therapy in persistent/recurrent/metastatic gynecological cancer and the exploration of changes in tumor microenvironment.
Authors: Qiying Zhang, Zi Liu, Jing Zhang, Fei Wang, Shi Fan, Juan Wang, Tao Wang, Jin Su
Journal: Journal of Clinical Oncology (2024)

5536 Background: Previous small sample retrospective study has showed that H101 has promising efficacy and favorable safety in patients with persistent /recurrent/metastatic (P/R/M) gynecological cancer. To further assess the effecacy and safety of H101 in P/R/M gynecological cancer, we conducted this prospective Phase II study and further explore the tumor microenvironment (TME) through Cell DIVE multiplexed imaging solution. Methods: This was a prospective, open-label, single-arm study (clinicaltrials.gov number NCT05051696). P/R/M gynecological cancer patients who had at least one injectable lesion and had received at least one line of systemic therapy or could not tolerate chemotherapy were eligible. H101 (0.5-1.5×10 12 viral particles) was injected into the target lesion once a day for 5 consecutive days, with a cycle of 3 weeks and a maximum of 4 cycles. Whether added other medications was at the physician’s discretion. Cell DIVE multiplexing of 15 immune cell markers were performed in 6 paired pre- and post-H101 injected tumors. Results: From September 2021 to February 2024, 116 P/R/M patients received H101 intro-tumor injection, of which 16 patients did not evaluate for the efficacy endpoint. At the data cut-off of February 2024 for the primary analysis, overall median follow-up time was 10 months. The best complete response was achieved in 30 patients, 34 patients achieved partial response and 15 patients had stable disease, yielding an objective response rate of 64%. The disease control rate was 79% by RECIST1.1, and the median duration of time was 7.1 months. The median progression-free survival was 8.7 months, and the median overall survival was currently not reached. Furthermore, 83% of the patients experienced treatment-related adverse events and the major adverse events were fever (64%), fatigue (31%) and pain at the injection site (25%). Compared with baseline, the number of B cells, T regulatory cells and Ki 67+ tumor cells decreased in the injected lesions, while the number of M1 macrophage, monocytes, CD4 and CD8 T cells were increased. Additionally, B cells and CD68+CD163- tumor associated macrophage (M1 TAM) were higher in response patients. Conclusions: This was the first reported large sample size prospective study regarding H101 in gynecological cancer. These results indicated that H101 as second line or later therapy for P/R/M gynecological cancer patients was efficacious and safe. Cell DIVE multiplexing of immune cell markers suggested that the H101 efficiently reshaped the TME and the response of H101 oncolytic virotherapy may associated with increased B cells and M1 TAM in the TME. Clinical trial information: NCT05051696 .
Real-world treatment patterns and outcomes by mismatch repair/microsatellite instability (MMR/MSI) status in patients (pts) with advanced endometrial cancer (aEC), 2018-2023.
Authors: Bhavana Pothuri, Premal H. Thaker, Olga Tymejczyk, Samantha Reiss, Giovanni Nitti, Theresa Cain, Manila Hada
Journal: Journal of Clinical Oncology (2024)

5601 Background: Over the past decade, progress has been made in treating aEC, with newer therapies introduced in the first-line (1L) and second-line (2L) setting. Molecular profiling of MMR/MSI has emerged as a valuable tool for guiding treatment decisions, but real-world evidence on the shifting treatment paradigm is limited. Thus, this study aims to assess molecular profiling uptake, treatment patterns, and outcomes among aEC pts. Methods: This retrospective study included pts from the nationwide Flatiron Health electronic health record-derived deidentified database who were diagnosed with aEC (stage III/IV or recurrent) and initiated 1L therapy between 1/1/2018 and 6/30/2023. Patient characteristics, treatment patterns, and real-world time to next treatment (rwTTNT) were examined across MMR/MSI status: deficient (dMMR), proficient (pMMR), and never tested (NT). Kaplan-Meier methods were used to generate unadjusted time to event estimates. Results: A total of 1,441 pts met study criteria. Median age at aEC diagnosis was 68 years (range: 26-85), 1,056 (73%) were treated in the community setting, and 1,199 (83%) received MMR/MSI testing. Endometrioid carcinoma occurred in 619 (43%) overall and was the predominant histology (231/293; 79%) in dMMR. Approximately 15% had record of another cancer diagnosis at any point. NT pts were more likely than those tested to be Black or African American (26% vs 18%) and diagnosed with stage IV disease (55% vs 48%). The table presents select therapies and rwTTNT estimates. pMMR pts often received platinum-based chemotherapy (PBCtx) in 1L (67%) and immune checkpoint inhibitor (CPI) + vascular endothelial growth factor (VEGF) inhibitor therapies in 2L (23%), while dMMR pts were more likely than others to receive other CPI regimens (mono, combo + chemo) in 1L (23%) and 2L (44%). Median rwTTNT was similar across subgroups in 1L but was markedly longer among dMMR pts (10.8 vs 5-6 months) in 2L. Conclusions: While MMR/MSI testing was common, use of 2L immunotherapy for dMMR (51%) and CPI + VEGF for pMMR (23%) was lower than expected and may reflect slow uptake of recently approved, molecular profile-specific therapies. MMR/MSI testing gaps remain, especially in underrepresented pts, and may be a barrier to adoption of new therapies. Future analyses will be critical to assess changes in outcomes over a longer timeframe. Continued education is needed to increase access to newer FDA approved treatments. [Table: see text]
Maximizing cervical cancer prevention in safety-net settings of care: Resources from the Federal Cervical Cancer Collaborative for provider and patient engagement.
Authors: Jane Segebrecht, Ellen Hendrix, Veronica Chollette, Jennifer K. K. McGee-Avila, Jennifer K. Loukissas, Elise Tookmanian, Nicolas Wentzensen, Sarah M. Temkin
Journal: Journal of Clinical Oncology (2024)

5542 Background: Uneven administration of cervical cancer prevention, screening, and management, and changing guidelines prompted the Health Resources and Services Administration (HRSA) Office of Women’s Health and federal partners to develop the Federal Cervical Cancer Collaborative (FCCC). The FCCC aims to achieve the vision of the Cancer Moonshot in safety-net settings, reduce disparities in cervical cancer, and bridge the U.S. government’s priorities of cancer research and health care delivery. The FCCC supported: i) a survey of NCI-Designated Cancer Centers on barriers and opportunities that influence how Cancer Centers partner and engage with HRSA-supported and other safety-net settings of care; ii) the development of resources for providers in safety-net settings of care to support equitable cervical cancer prevention, screening, and management; and iii) the development of health communications materials to foster patient engagement for improved access to preventive health services. Methods: From January-February 2022, the FCCC conducted a multiple-choice and open-ended survey of 72.3% of Cancer Centers (n = 47) to identify opportunities to strengthen collaborations with safety-net settings. From February 2022-June 2023, the FCCC convened nine roundtables, with stakeholders across U.S. territories and freely associated states, national organizations, academia, and federal agencies, to inform provider technical assistance and patient outreach materials. Results: Cancer Centers reported patient-level barriers as the most challenging, compared with clinician-level, organizational-level, and systems-level barriers. The most common barriers to management of abnormal cancer screening included: transportation/travel (98%), health literacy (96%), and caregiving responsibilities (95%). The roundtable series informed the development of two resources: a primary care provider toolkit and patient outreach materials to strengthen cervical cancer prevention, screening, and management of abnormal results in safety-net settings of care. Conclusions: Roundtables and survey findings can inform needed structural and public health interventions to overcome patient level barriers and strengthen partnerships between Cancer Centers and safety-net settings. The findings also guide the FCCC’s long-term commitments to support equitable cervical cancer prevention in safety-net settings. The toolkit offers practical tools and guidance to primary care providers to improve quality of care, train staff, and communicate with patients. Patient outreach materials can support patient engagement in care and access to care. Both freely available resources will be used in a national remote tele-mentoring initiative for providers in safety-net settings of care.
Tumor-informed ctDNA as an objective marker for postoperative residual disease in epithelial ovarian cancer.
Authors: Valentina Paspalj, Christoph Grimm, Magdalena Postl, Christina Viktoria Tauber, Nuria Segui, Christian Brueffer, Miguel Alcaide, Lucia Oton, Yilun Chen, Lao H. Saal, Gerda Hofstetter, Leonhard Muellauer, Mirjana Kessler, Fabian Trillsch
Journal: Journal of Clinical Oncology (2024)

5544 Background: The most important predictor of prognosis in patients with high-grade serous ovarian cancer (HGSOC) is complete tumor resection after primary surgery. The current practice for classifying postoperative residual disease is the subjective assessment by the physician at the end of surgery. To date, an accurate objective marker for postoperative tumor residuals is lacking. In this study we are evaluating circulating tumor DNA (ctDNA) as a predictive marker for postoperative minimum residual disease (MRD). Methods: In this prospective multi-center feasibility study, we included 52 patients with advanced HGSOC who underwent primary debulking surgery between July 2021 and December 2023. Intraoperatively, tumor tissue from several tumor locations was evaluated. Blood samples were examined preoperatively, on day two, and day ten postoperatively. Whole genome sequencing (WGS) was used to identify structural variants (SVs), single nucleotide variants (SNVs) and indels in fresh frozen or FFPE tumor tissue to develop personalized multiplex digital polymerase chain reaction (dPCR) fingerprint assays. Results: A high burden of SVs was detected (median 90 SVs, range 24-287) and dPCR assays successfully designed and orthogonally validated in all tumor samples. A unique dPCR fingerprint was generated for every patient, tracking one to eight biomarkers per patient (median 8). In a subset of 10 patients tissue biopsy samples from multiple tumor localizations were available. The personalized fingerprint was validated across all locations and shown to be consistent. In the overall cohort, ctDNA was positive in 96% (n=46/48) of patients preoperatively and in 87% (n=39/45) at postoperative day 10 (d10), when a plasma sample was available. Compared to patients without macroscopic residual disease, patients with postoperative tumor residuals expressed significantly higher ctDNA levels at d10 (p &lt;0.001). Furthermore, for patients with macroscopic tumor residuals, ctDNA levels at d10 (% variant allele fraction (VAF)) remained comparable to preoperative ctDNA levels (4% decrease in median ctDNA levels). In contrast, patients with macroscopic complete resection were noted to have a 97% decrease in median ctDNA levels between pre-operative and d10 detection. Conclusions: The present tumor-informed dPCR SV fingerprint ctDNA approach demonstrated feasibility with remarkably high detection rates pre- and postoperatively. Postoperative ctDNA levels differed substantially based on postoperative tumor residuals. These findings suggest that this personalized approach could be used to develop a dPCR SV detection assay and may have clinical utility for postoperative MRD evaluation in patients with primary advanced HGSOC.
Safety and tolerability of durvalumab + carboplatin/paclitaxel followed by durvalumab ± olaparib in patients with newly diagnosed advanced or recurrent endometrial cancer (EC) in the DUO-E/GOG-3041/ENGOT-EN10 trial.
Authors: Jessica Thomes Pepin, Hye Sook Chon, Michael J. Sundborg, Michael A. Gold, Byoung-Gie Kim, Stephanie V. Blank, Ji-Hong Liu, Michael McCollum, Masahiko Mori, Kathleen N. Moore, Julian Rivera Diaz, Charles Andreé Joseph de Padua, Jerónimo Martínez-García, Christos Papadimitriou, Karin Gri an, Róbert Póka, Matthew Kowgier, Emma Oscroft, Els Van Nieuwenhuysen, Shannon Neville Westin
Journal: Journal of Clinical Oncology (2024)

5599 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival improvement with addition of durvalumab (D) to carboplatin/paclitaxel (CP) followed by D ± olaparib (O) vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). We describe safety and tolerability, focusing on the most common adverse events (AEs). Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to systemic treatment were randomized 1:1:1 to CP (CP + D placebo [pbo; 6 cycles] followed by D pbo + O pbo), CP+D (CP + D [1120 mg IV q3w; 6 cycles] followed by D [1500 mg IV q4w] + O pbo), or CP+D+O (CP + D [6 cycles] followed by D + O [300 mg tablets bid]). Safety was assessed through AEs. Results: 709 pts (19.3% mismatch repair deficient [dMMR], 80.7% MMR proficient [pMMR]) received treatment (CP: n=236; CP+D: n=235; CP+D+O: n=238). Total median treatment duration with D/pbo was 9.0, 9.9 and 13.1 months in the CP, CP+D and CP+D+O arms and 5.7, 7.6 and 9.2 months withO/pbo, respectively. 18.6%, 20.9% and 24.4% of pts in the CP, CP+D and CP+D+O arm, respectively, had AEs leading to treatment discontinuations, 50.0%, 54.5% and 68.9% had AEs leading to dose interruptions, and 56.4%, 54.9% and 67.2% had grade ≥3 AEs. There was no increase in immune-mediated AEs or AEs of special interest for O with CP+D+O. There were 3 cases of pure red-cell aplasia with CP+D+O (all grade 3) and 3 of autoimmune hemolytic anemia (1 with CP+D, 2 with CP+D+O; all grade 3). The most common AEs were mostly low grade, with grade 3/4 in few pts (anemia [14%, 16%, 24% in the CP, CP+D, CP+D+O arms, respectively], alopecia [0%, 0%, 0%], nausea [1%, &lt;1%, 3%], fatigue [2%, 2%, 2%]), and led to few treatment discontinuations and interruptions (Table). AE profiles were generally consistent across MMR subgroups. Conclusions: In DUO-E, safety findings were generally consistent with the known safety profiles of CP, D and O. The addition of D to CP followed by D or by D + O resulted in expected and manageable safety profiles compared with CP alone, with the most common AEs being low grade and leading to few discontinuations or dose modifications/interruptions of D/pbo or O/pbo. Clinical trial information: NCT04269200 . [Table: see text]
Automated Lugano Metabolic Response Assessment in <sup>18</sup> F-Fluorodeoxyglucose–Avid Non-Hodgkin Lymphoma With Deep Learning on <sup>18</sup> F-Fluorodeoxyglucose–Positron Emission Tomography
Authors: Skander Jemaa, Souhila Ounadjela, Xiaoyong Wang, Tarec C. El-Galaly, Lale Kostakoglu, Andrea Knapp, Grace Ku, Lisa Musick, Denis Sahin, Michael C. Wei, Shen Yin, Thomas Bengtsson, Alex De Crespigny, Richard A.D. Carano
Journal: Journal of Clinical Oncology (2024)

PURPOSE Artificial intelligence can reduce the time used by physicians on radiological assessments. For 18 F-fluorodeoxyglucose–avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic. METHODS Here, we present a deep learning–based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier: NCT01287741 ) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers NCT02257567 , NCT02500407 ; 20% holdout in ClinicalTrials.gov identifier NCT01287741 ), outputs the detected lesions at baseline and follow-up to enable focused radiologist review. RESULTS The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers NCT01287741 , NCT02500407 , and NCT02257567 , respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers NCT01287741 , NCT02500407 , and NCT02257567 , compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses. CONCLUSION These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.