bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: A multicenter study by the Turkish Oncology Group (TOG).
Authors: Akyildiz Arif , Gultekin Melis , Yigit Ecem , Demir Ecem , Ismayilov Rashad , Ahmed Melin Aydan , Buyukkor Mustafa , Yıldırım Hasan Çağrı , Yildirim Nilgun , Algin Efnan , Orman Seval , Çolak Rumeysa , Özen Engin Esra , Beyaz Havva , Ibis Kamuran , Ergen Şefika Arzu , Sari Sezin Yuce , Tezcan Yilmaz , Yildiz Ferah , Arik Zafer 
Published: July 2024

e17534 Background: This multicentric study aimed to investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy (CRT). Methods: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive CRT. Radiotherapy (RT) was applied as external beam pelvic with or without para-aortic RT and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3-weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were employed to assess factors influencing progression-free survival (PFS) and overall survival (OS). Results: The median cumulative cisplatin dose was 210 mg (range, 40-320 mg), and it was ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months. The 5-year PFS and OS rates were 66.9% and 77.1%, respectively. Multivariate analysis (MVA) identified poor performance status, non-squamous cell histology, presence of lymph node metastasis and hemoglobin <10 g/dl before CRT were poor prognostic factors for both PFS and OS in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose below 200 mg was also found to be a significant poor prognostic factor in OS (HR 1.79, 95% CI, 1.1 to 3.0, p=0.031). Conclusions: The study revealed that a cumulative cisplatin dose exceeding 200 mg, particularly in patients with lymph node metastasis, significantly improved OS. Factors such as anemia, toxicity-related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the delicate balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer. [Table: see text]
Measuring COVID-19's impact on diagnosis of cervical cancer by race/ethnicity, age, and region of the United States.
Authors: Stewart Chelsea , Chan Joshua Elbridge , Tran Nathan , Johnson Caitlin Ruth , Darcy Kathleen M. , Tian Chunqiao , Kapp Daniel Stuart , Liao Cheng-I 
Published: July 2024

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race, stage at presentation, and regions of the US. Methods: Data on cervical cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 to calculate estimated and actual incidence rates per 100,000 women. We compared actual cervical cancer incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 245,618 cases of cervical cancer were identified. In 2019, prior to the pandemic, the incidence was 7.64 per 100,000 women. From 2001-2019, cervical cancer incidence decreased by 0.96% per year (p=0.023). Based on this trend, we expected the incidence to be 7.57 per 100,000 women in 2020, but the reported incidence was only 6.83 per 100,000, therefore, there were 9.8% less cervical cancer cases (1,189 cases) in 2020 than expected. This was most noticeable at the lower and upper ends of the age distribution, with 17.6% less cases than expected in the year 2020among 25-29 year-olds and 18.4% less cases than expected among 85+ year-olds. This is in comparison to the median age group for cervical cancer (50-54 year-olds) in whom there were 14.5% (193) less cases than expected in 2020. Based on stage of disease, for local, regional, and distant disease there were 16.3%, 2.8%, and 1.9%, less cases than expected in 2020, respectively. Within racial and ethnic groups, we found that Non-Hispanic Black (NHB) and Hispanic patients had 15.0% and 13.9% less cases than expected, versus 8.7% among Non-Hispanic White (NHW) and 5.8% among Non-Hispanic Asian and Pacific Islander (NHAPI) patients. Comparing U.S. regions, the Midwest, Northeast, West, and South had 14.6%, 10.2%, 10.2%, and 9.0% less cases than expected for 2020, respectively. Conclusions: Our data suggest that the reported cervical cancer cases were significantly less than predicted based on past trends during the COVID-19 pandemic.. Older age, NHB and Hispanic patients, and those residing in Midwest states had the greatest number of possible missed diagnoses of cervical cancer during this time. Mitigating strategies are needed to reinstate screening programs, particularly in these at-risk groups to prevent increased rates of advanced stage disease and mortality.
Use of Gynecologic Cancer Intergroup (GCIG) CA125 criteria to evaluate cell cycle checkpoint kinase 1 inhibitor (CHK1i) prexasertib response and disease progression (PD) in recurrent high-grade serous ovarian cancer (HGSOC).
Authors: Ibanez Kristen , Donohue Duncan , Malys Tyler , Lee Jung-Min 
Published: July 2024

e17536 Background: Data suggest discordance between serum biomarker CA125 and Response Evaluation Criteria in Solid Tumors (RECIST) response and/or PD in chemotherapies and PARP inhibitors. Here, we investigated the impact of CA125 on prognosis and its relationship with RECIST response/PD in HGSOC patients treated with a CHK1i, prexasertib. Methods: All relapsed HGSOC patients in this post-hoc analysis were treated with prexasertib at 105 mg/m2 IV every 14 days in a 28-day cycle until RECIST v1.1 PD, unacceptable toxicity, or consent withdrawal (NCT02203513). CA125 was assessed every cycle and CT scans obtained every two cycles. GCIG CA125 response was defined as >50% reduction confirmed after 28 days and PD as > 2X upper limit of normal (ULN) if baseline was normal or doubling of nadir if baseline was elevated. Patients with baseline CA125 < 2X ULN or nadir > 750 units/mL were not eligible for analysis. Clinical benefit rate (CBR; CR + PR + SD ≥ 6 months) was analyzed by Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves and univariate (UV) and multivariate (MV) hazard ratios by Cox regression models. Positive predictive value (PPV) and negative predictive value (NPV) confidence intervals (CI) were estimated by the Wilson-Brown method. Results: Eighty-one patients received at least two cycles of prexasertib between January 2015 and November 2020, out of which 72 were evaluable by both RECIST and GCIG CA125 response criteria. CBR in the CA125 response (CA125-R) group (24/32; 75%) was significantly higher than the CA125 non-responder (CA125-N) group (12/40; 30%; p<0.001). CA125 response tended to occur prior to RECIST response (median: 28 days; IQR: 28, 30). PFS was improved in CA125-R at 8.0 months vs. CA125-N at 3.5 months (UV HR: 0.34, 95% CI: 0.21-0.56; MV HR: 0.35, 95% CI: 0.20-0.59). OS was improved in CA125-R at 19.8 months vs. CA125-N at 10.3 months (HR: 0.43, 95% CI: 0.26-0.71; MV HR: 0.45, 95% CI: 0.27-0.75). No significant differences in PFS or OS were observed between subgroups by BRCA mutation status, platinum-sensitivity, FIGO stage, baseline CA125 value, or previous PARP inhibitor therapy in MV analysis. Out of 70 patients evaluable by RECIST and CA125 PD criteria, 43 patients had CA125 PD and 24 of those had RECIST PD occur within one cycle of CA125 PD (PPV: 59%; 95% CI: 43-72). Of the 27 patients without a CA125 PD, 9 patients also did not have a RECIST PD (NPV: 33%; 95% CI: 19-52). Conclusions: GCIG CA125 response is an independent predictor of response to CHK1i in HGSOC prior to the first restaging scans and is associated with a higher CBR and improved PFS and OS. However, GCIG CA125 PD has poor PPV and NPV within a one cycle window, indicating that CA125 alone is not sufficient in monitoring for PD in HGSOC treated with CHK1i.
Multiomic analysis in ovarian clear cell carcinoma to gain insight into biology and therapeutic opportunities.
Authors: Kong Ben , Stommel Jayne , Emerson Jenna , Munro Elizabeth G. , Corless Christopher L. , Mills Gordon B. , Pejovic Tanja ,   SMMART Clinical Trial Program
Published: July 2024

e17540 Background: Ovarian clear cell carcinoma (OCCC) is a rare subtype with distinct histologic and molecular features. The prognosis of advanced/recurrent OCCC treated with standard of care surgery and platinum-based chemotherapy remains poor due to inherent chemoresistance. Therefore, there is an urgent need to identify novel biological insights and personalized treatment approaches to improve outcomes. Methods: Participants were referred to the SMMART Program at the OHSU Knight Cancer Institute. Archival or fresh tissue was obtained from metastatic sites and processed through a multiomics platform that included immunohistochemistry (Ki67, HER2, CD4, CD8, PD-L1), fluorescent in-situ hybridization, targeted next-generation sequencing panel (225 genes), whole transcriptomic sequencing, chromosomal microarray, and multiplexed analysis of 67 key cancer proteins and phosphoproteins on the Nanostring GeoMx Digital Spatial Profiler. Results: 5 participants were enrolled with an average age of 62 years (range 52-72). Therapeutically relevant findings included detectable HER2 expression by IHC (2+, N=2; 3+, N=2), HER2 amplification by FISH (N=2), and high HER2 and phospho-HER2 protein expression compared to a breast cancer cohort (phospho-HER2 supports active HER2 signaling in the tumor cells). Additional findings include TMB <10 muts/Mb (N=5), microsatellite stable (N=5), Ki67 40-60% (N=4), mild to moderate CD4 and/or CD8 infiltration (N=4), PD-L1 >1% (N=3), low homologous recombination deficiency score (N=4), chromosomal losses including ATM, SMAD4, RB1, and TP53, and single nucleotide variations in ARID1A (N=4). Two participants with HER2 expression were treated with off-label trastuzumab deruxtecan for 6 or 7 cycles yielding significant clinical benefit. Participant A (HER2 = 3+, FISH negative) had an exceptional response while Participant B (HER2 = 2+, FISH amplified) had stable disease. The toxicity profile was consistent with literature. Conclusions: Our OCCC cohort revealed elevated HER2 expression with or without genomic amplification in 4/5 cases. Two participants experienced clinical benefit when treated with trastuzumab deruxtecan, supporting further exploration of HER2 antibody drug conjugates in this aggressive disease. More study is needed to determine the frequency of HER2 overexpression and amplification in OCCC, the importance of HER2 on OCCC pathophysiology, and the therapeutic benefit of targeting HER2 in this population.
Homologous recombination deficiency score for predicting efficacy of platinum-based chemotherapy and PARPi maintenance therapy in ovarian cancer.
Authors: Wang Jinhua , Shen Jing , Zhang Zhe , Ye Lei , Lu Jin , Xiao Ziyi , Zhang Lihua , Liu Xiaojian , Zhu Chan , Wang Xiaoxuan , Zhang Chao , Zhang Xing , Chen Dong-sheng , Xu Xinyu 
Published: July 2024

e17543 Background: Currently, homologous recombination deficiency (HRD) has been confirmed to be a predictive biomarker for poly-ADP-ribose-polymerase inhibitors (PARPi) in ovarian cancer, while its effects on the clinical outcomes of platinum-based chemotherapy and PARPi maintenance therapy are not assessed rigorously in ovarian cancer. We developed an HRD assay to evaluate the effect of HRD scores on the platinum-based chemotherapy and PARPi maintenance therapy in Chinese patients with ovarian cancer. Methods: HRD testing was performed on the samples obtained at primary cytoreductive surgery. The progression-free survival (PFS) was observed among the BRCA-mutated/HRD-positive and BRCA wild-type/HRD-negative patients. Univariate and multivariate COX analyses were performed to test the association of PFS with different variables, and hazards ratios (HR) and 95% confidence interval (CI) were calculated. The two-tailed p value less than 0.05 was considered statistically significant. Results: Totally 74 patients who received platinum-based chemotherapy were eligible for the study, among whom 81.1% responded to the initial platinum-based chemotherapy, 33.8% harbored BRCA1/2 mutations and 74.3% were HRD-positive. The median HRD score of platinum-sensitive patients (n=60) was 48.5, significantly higher than the 31 of platinum-resistant patients (n=14, p=0.0035). Analysis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) between platinum-sensitive and platinum-resistant patients showed significant differences in TAI ( p=0.0012) and LST ( p=0.004). Compared with HRD-negative patients, HRD-positive patients had a significantly longer median PFS (10 vs. 15 months, p=0.017), and multivariate analysis further indicated that HRD-positive status (HR, 0.423, 95%CI: 0.191-0.939, p=0.035) was a significant predictor for the improvement of PFS. Conclusions: The HRD assay developed in our study can accurately predict the response to platinum-based chemotherapy and PARPi efficacy in patients with ovarian cancer, providing powerful evidence for implementation of genetic testing and guidance of clinical treatment in ovarian cancer.
Clinical outcomes after adjuvant anti-PD1 therapy for high-risk resectable melanoma and predictors of response.
Authors: Marsiglio John , Bingjian Feng , Kovacsovics Magdalena , Gibson Berit , Zhou Qin , Swami Umang , Russell Jeffery Scott , Erickson-Wayman Alyssa , Asare Elliot Amponsah , Monroe Marcus , Bowles Tawnya Lynn , Nix David , Williams Matthew , Tan Aik-choon , Hyngstrom John Robert , Hu-Lieskovan Siwen 
Published: July 2024

e21502 Background: Adjuvant anti-PD1 is the standard of care for high-risk resectable melanoma but many still suffer recurrence. We report a single institution observational study of patients who received adjuvant anti-PD1 with a particular focus on those who recurred. Methods: Through an approved protocol by Huntsman Cancer Institute IRB, patients with resected high-risk melanoma who first received anti-PD1 in the adjuvant setting were consented and followed. Clinical outcomes were assessed per RECIST 1.1, progression free survival (PFS), and overall survival (OS). Results: 186 eligible patients were included, 105 male and 81 females, median age at C1D1 58 (22-93), 12/161/7 at stage II/III/IV and 5 unstageable. Subtypes included 79 (43%) superficial spreading, 50 (27%) nodular, 16 (9%) lentigo/nevoid, 13 (7%) non-acral skin (NOS), 10 (5%) acral, 4 (2%) mucosal, and 14 (7%) others. With median follow up of 708 days (23-9599), 66 (35.5%) had progressive disease (PD), including 33 (50%) early PD and 33 (50%) late PD. Statistically significant predictors of worse outcome included age > 50 (OS p = 0.043), acral subtype (PFS p = 0.023), PD-L1 IHC < = 1% (OS p = 0.052, PFS p = 0.002), duration of treatment < 3 months (OS p = 0.005, PFS p = 1.8E-07), early PD (OS p = 0.003, PFS p = 1.5E-6) and distant recurrence (OS p = 0.002). Trends that were not significant included: male gender (worse OS), BRAF mutation (better PFS), NF1 mutation (better PFS). No correlation between outcomes and TMB, NRAS, TERT mutation, and primary location. In the early/late PD groups, median age was 57/55 (range 28-79 / 25-84), 64/61% male, 1/0, 29/31, 3/2 stage II, III, IV. 17/13 were superficial spreading, 6/10 nodular, 2/5 acral, 2/2 lentigo, 1/0 mucosal and 4/3 other non-acral skin. Primary site was 12/12 head/neck, 9/5 trunk, 4/7 upper limb, 8/9 lower limb. BRAF was 9/11 wildtype, 15/9 mutant and 9/13 unknown. PD-L1 > = 1% by IHC was 4/2. TMB mut/mb > 10 was 6/5. Sites of recurrence included 6/12 local, 7/7 regional LN, 20/14 distal (3/1 in brain) relapses. For unresectable PD (13/13 early/late) response to next line systemic therapy is shown in Table 1. Conclusions: One third of patients developed PD after adjuvant anti-PD1 for high-risk melanoma. PD-L1 negativity and short duration of treatment was associated with worse outcome. Early PD corresponded to more distant metastasis, poorer OS and response to subsequent systemic therapy. Importantly most late PD can still have a favorable response by resuming anti-PD1 therapy. Further molecular study is ongoing to investigate mechanisms of resistance. [Table: see text]
Real world experience of bispecific fusion protein in patients with metastatic uveal melanoma: Can we deliver?
Authors: Joseph Liz , Herbert Christopher , Taylor Hannah , Winter Helen , Howe Adrienne 
Published: July 2024

e21504 Background: Effective treatments for patients with metastatic uveal melanoma has remained a longstanding unmet need. Poor response rates to checkpoint inhibitors has increased the need for patients to access new ways of targeting this disease. Tebentafusp is a first in class T Cell receptor bispecific fusion protein that has demonstrated an overall survival benefit. However although licensed it has yet to be approved in the UK for wider use. Methods: Prospective data collection on five patients receiving tebentafusp through the Managed Access Programme at a cancer centre that had not taken part in any trials of this therapy before. Patients were permitted with metastatic uveal melanoma; ECOG performance status 0-1 and were HLA-A*02:01 positive. Protocols were disseminated across the wider cancer teams for the management of side effects including cytokine release syndrome. Patients received extended monitoring for at least 16 hours, and vital signs (blood pressure, heart rate, temperature and pulse oximetry) taken every 2-4 hours. Drop in systolic BP < 20mmHg treated with IV fluids. Results: Five patients with advanced uveal melanoma participated in the Access Programme at one cancer site to assess efficacy, tolerability and workforce upskilling and capability with a first in class bispecific fusion protein therapy. All patients were HLA-A*02:01 positive. The patients commenced therapy between November 2021 and July 2023. All were male; median age 66. Four patients developed cytokine release syndrome commencing at cycle one. These patients required intravenous fluids for CRS grade 2, no patients required vasopressors. One patient required IV hydrocortisone. Four patients developed skin toxicity. These were managed with antihistamines and steroids. Three patients stopped due to confirmed disease progression, receiving 2-7 cycles; one made an informed decision to stop due to grade 3 skin toxicity. One patient continues on tebentafusp and has received 32 cycles to date. They recently had treatment paused for ablation and resection of oligometastatic disease that found residual uveal melanoma and have restarted. Conclusions: Real-world data suggests that using a gp100-targeting TCR/anti-CD3 bispecific fusion protein is tolerated and deliverable in new settings. Tebentafusp was delivered without any medical emergencies and CRS was successfully managed with proactive fluid management and steroids. The rate and grading of side effects reflects that described in the large randomised controlled trial. Patients with uveal melanoma can derive ongoing clinical benefit - including one patient who has received 32 cycles and proceeded to surgical resection of oligometastatic disease. Through workplace education and upskilling, the proactive management of the side effects including cytokine release syndrome can be managed in the oncology inpatients and seamlessly moved to outpatient settings.
First-line therapy for metastatic uveal melanoma: Experience from a single reference center.
Authors: Nazarova Valery V. , Magomedova Zakhra R. , Orlova Kristina V. , Unguryan Vladimir , Romanov Denis , Yarovaya Vera , Yarovoy Andrey , Trofimova Oxana , Demidov Lev V. 
Published: July 2024

e21514 Background: Metastatic uveal melanoma (mUM) continues to have a poor prognosis with distinct biology from cutaneous melanoma and limited effective treatment options. The main options include immunotherapy (IT, anti-PD-1+/- anti-CTLA-4, tebentafusp), chemotherapy, targeted therapy and local treatment methods for patients with isolated liver metastasis (isolated hepatic perfusion, transarterial chemoembolization, percutaneous hepatic perfusion, radiofrequency ablation). Methods: We conducted a single-center retrospective observation IRB-approved study of first-line therapy for pts age 18 and older with mUM treated at the N.N. Blokhin National Medical Research Center of Oncology from 2020 to 2023. Our objectives were to evaluate clinical outcomes in real-world settings, as well as treatment patterns, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 125 pts included. The mean age was 54 yrs (range: 20-74), and the median time to metastasis from primary tumor was 2 years (range: 0-21). Liver metastases were diagnosed in 92% of patients, lung metastases in 20%, bone metastases in 17%, and soft tissue metastases in 9%. Conclusions: Our data suggest that the combination of systemic and local liver-directed treatment methods may be associated with a survival benefit and higher treatment response to IT in patients with mUM. [Table: see text]