bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim PSMA PET/CT for response evaluation during LuPSMA treatment in mCRPC (INTERIM PET): An explorative, multicenter study.
Authors: Gafita Andrei , Rauscher Isabel , Weber Manuel , Hadaschik Boris A. , Wang Hui , Armstrong Wesley R , Tauber Robert , Czernin Johannes , Rettig Matthew , Herrmann Ken , Calais Jeremie , Weber Wolfgang A , Benz Matthias R. , Fendler Wolfgang Peter , Eiber Matthias 
Published: June 2021

5066 Background: The aim of this analysis was to evaluate the prognostic value of interim PSMA PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA and to develop a novel framework for Response Evaluation Criteria In PSMA-imaging (RECIP). Methods: This was an explorative, multicenter, retrospective study; 124 men with mCRPC who underwent 177Lu-PSMA treatment and received PSMA-PET/CT at baseline (bPET) and at interim after two cycles of treatment (iPET) met the eligibility criteria and were included in this analysis. The primary endpoint was overall survival (OS). Pairs of bPET and iPET were interpreted by three independent readers for appearance of new lesions. Whole-body tumor lesions were segmented using qPSMA software and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Changes in PSMA-VOL on iPET relative to bPET were calculated. After being tested separately for associations with OS, appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP. Results: The median OS was 13.5 months (95%CI, 11.6-15.4). Appearance of at least one new lesion on iPET was observed in 73 (59%) patients and was associated with poor OS (hazard ratio [HR] 2.23; 95%CI, 1.51-3.28; P <.001). Based on the current data, RECIP were defined as: partial response (PSMA-PR) as a decline ≥20% in PSMA-VOL and no appearance of new lesions; progressive disease (PSMA-PD) as an increase ≥20% in PSMA-VOL and appearance of new lesions; stable disease (PSMA-SD) was defined as any condition but not PSMA-PR or PSMA-PD. The OS of men with PSMA-PD (n = 41) was significantly worse compared to men with PSMA-SD (n = 47; HR 2.52; 95%CI, 1.61–3.93; P <.001) and PSMA-PR (n = 36; HR 4.16; 95%CI, 2.54–6.78; P <.001). PSMA-SD was associated with significantly worse OS compared to PSMA-PR (HR 1.65; 95%CI, 1.02–2.65; P =.039). The time dependent C-index of associations with OS for response according to RECIP was 0.68 (95%CI, 0.63-0.72). Conclusions: Interim staging using PSMA-PET/CT and response classification by RECIP is prognostic for survival of men with mCRPC treated with 177Lu-PSMA. Validation of these findings in clinical trials is warranted.
A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).
Authors: Roque Dana M , Bellone Stefania , Siegel Eric R. , Buza Natalia , Bonazzoli Elena , Guglielmi Adele , Zammataro Luca , Nagarkatti Nupur , Zaidi Samir , Lee Jungsoo , Schwartz Peter E. , Ratner Elena , Alexandrov Ludmil B. , Iwasaki Akiko , Kong Yong , Song Eric , Dong Weilai , Elvin Julia Andrea , Choi Jungmin , Santin Alessandro 
Published: June 2021

5523 Background: Microsatellite instability (MSI-H) is a biomarker for response to immune-checkpoint inhibitors (ICIs); however, these neoplasms are heterogenous including Lynch (germline), Lynch-like (somatic) and sporadic ( MLH1-methylated) tumors. Whether mechanisms underlying MSI alter responses to ICIs is unclear. We report data from a phase II pilot study (NCT02899793) of pembrolizumab in recurrent MSI-H endometrial cancer (EC) patients and potential mechanisms of primary/secondary ICI resistance. Methods: Patients with measurable, MSI-H EC confirmed by immunohistochemistry and polymerase chain reaction were evaluated by next-generation sequencing and received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: Twenty-five patients (24 evaluable) were treated. Six (25%) patients harbored Lynch/Lynch-like tumors while 18 (75%) had sporadic EC. Tumor mutational burden (TMB) was higher in Lynch-like (median 2939, IQR:867-5108) versus sporadic tumors (median 604, IQR:411-798) ( P= 0.0076). Median follow-up was 25.8 months with an ORR of 58% (95% CI, 36.6-77.9%). ORR was 100% in Lynch/Lynch-like patients but only 44% in sporadic patients ( P= 0.024). The 3-year progression-free (PFS) and overall survival (OS) proportions were 100% versus 30% ( P= 0.017) and 100% versus 43% ( P= 0.043), respectively. Grade 3/4 treatment-related adverse events (6.8%) occurred in 12 patients. Defective antigen processing/presentation and deranged induction in interferon responses served as mechanisms of resistance in sporadic MSI-H EC. Conclusions: Our study demonstrated prognostic significance of Lynch-like versus sporadic MSI-H EC on ORR, PFS and OS when treated with pembrolizumab. Clinical studies evaluating separate subtypes of MSI-H EC treated with ICIs are warranted. Clinical trial information: NCT02899793.
Parametrial evaluation in cervical cancer by magnetic resonance imaging and clinical examination: Analysis of data from the prospective Leipzig School MMR study.
Authors: Wolf Benjamin , Sodeikat Paulina , Lia Massimiliano , Martin Mireille , Horn Lars-Christian , Höckel Michael , Aktas Bahriye 
Published: June 2021

5525 Parametrial evaluation in cervical cancer by magnetic resonance imaging and clinical examination Background: In cervical cancer patients, assessment of parametrial tumor extension is important for staging and treatment planning. The 2019 cervical cancer guideline published by the Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) for the first time includes recommendations for usage of magnetic resonance imaging (MRI) in this setting. However, valid data regarding the accuracy of this method, especially in patients with advanced disease, are sparce. The objective of this investigation was to compare the accuracy of parametrial assessment in cervical cancer patients using MRI and clinical examination under general anesthesia. Methods: A retrospective cohort study based on data from the prospective monocentric observational Leipzig School Mesometrial Resection study was conducted. Cervical cancer patients staged FIGO IB1 to FIGO IVA who underwent primary surgery between 1999 and 2017 were included. Data from pathological specimen of these patients was compared to the MRI findings and the results from clinical examination under general anesthesia. The gynecological oncologist had access to the MR images during clinical assessment. We calculated sensitivities, specificities, and predictive values for both examination methods. We performed logistic regression modelling to determine factors influencing the accuracy of either method. Results: 400 women were included. Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. Examination under anesthesia augmented by intraoperative display of MR images exhibited a higher accuracy (83%) as compared to MRI alone (76%; McNemar’s odds ratio = 2.0, 95%CI 1.25 – 3.27, p = 0.003). While accuracy was not affected by tumor size in clinical examination, MRI was associated with a significant drop in accuracy in tumors ≥ 2.5 cm (univariable logistic regression, OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). This association remained significant in a multivariable model. There was also a significant decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥ 2.5 cm in diameter (p < 0.0001). Body mass index had no influence on performance of either method. Accuracy was significantly higher when test results were concordant (OR 7.5 and 6.0 on univariable and multivariable regression modelling, respectively, p < 0.0001 in both cases). Conclusions: Clinical evaluation of the parametrium by pelvic examination under anesthesia in conjunction with intraoperative presentation of MR images leads to more accurate staging in cervical cancer patients as compared to magnetic resonance imaging alone. Clinical examination should therefore remain an integral part of parametrial assessment in cervical cancer patients.
An international, multicenter, real-world analysis of epithelial ovarian cancer treatment and outcomes.
Authors: Hall Geoff , Cheeseman Sue , Levick Bethany , Nam Eun Ji , Lim Subin , Classe Jean-Marc , Martin Elodie , Kubelac Paul , Achimaș-Cadariu Patriciu , Savva-Bordalo Joana , Borges Marina , Becker Sven , Shaid Shabnam , Niklas Nicolas , Guergova-Kuras Mariana 
Published: June 2021

5531 Background: Few major studies have examined and compared the management and outcomes of patients from diagnosis to death between countries. We have established an international collaboration across Europe and South Korea to compare treatment and outcomes in Epithelial Ovarian Cancer (EOC). Methods: Patients diagnosed with EOC between January 2012 and December 2018 (age ≥18), were included for analysis. Data from medical records from five European and a single South Korean treatment centre were extracted, standardised to a common data model and analysed at each centre using a common script developed in R. Time to each progression/recurrence event (defined as time to next treatment) and overall survival have been estimated using Kaplan Meier methodology and outcomes stratified by categories of interest. Changes in the use of anti-cancer therapies over time and the incidence of BRCA mutations and incidence/timing of second breast cancers have also been examined. Results: A total cohort of 2925 patients was identified with a median age at each centre of 53 to 67 years. Advanced disease (FIGO stage III - IV) (range 57% to 84%) and high-grade serous morphology (38% to 70%) were most common at each centre. The timing of surgery (primary, interval debulking or delayed) and the proportion of patients undergoing surgery varied with stage. Patients with stage I disease where most likely to undergo surgery (range 73% to 100%) and stage IV the least (range 39% to 84%). Median overall survival for high grade serous cancers ranged from 1.9 to 4.9 years, and for the whole cohort from 2.1 to 5.5 years. Median time to next treatment at first relapse for the whole cohort ranged from 14 to 22 months. Second breast cancers were noted in 6 to 17% of patients and the majority of these occurred before the diagnosis of EOC at a median time of 96 to 118 months prior to diagnosis of EOC. Additional data on treatment pathways, BRCA status and outcomes by line of therapy for each centre will be presented. Conclusions: Preliminary analysis of results across this network suggests a variation in patient populations between sites and substantial differences in both treatments and outcomes. The establishment of a common data model and the use of a common analytic script between sites across six different countries allows for detailed exploration of the factors influencing differences in patient management and treatment outcomes in ovarian cancer patients.
Clinicopathologic features of breast cancers diagnosed in females treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.
Authors: Wong Stephanie M , Ajjamada Lissa , Weiss Anna , Prakash Ipshita , Skamene Sonia , Boileau Jean-Francois , Pollak Michael N. , Basik Mark 
Published: June 2021

567 Background: Childhood and young adult survivors of Hodgkin Lymphoma are at an increased risk of developing breast cancer, although little data exist on the characteristics and biologic subtype of breast cancers that develop in this high-risk population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all histologically confirmed breast cancers diagnosed between 1990-2016 in women treated with prior radiation therapy for Hodgkin Lymphoma ≤ 30 years of age. Clinicopathologic features of subsequent breast cancers (BC-HL) were examined and compared to breast cancers diagnosed in women with no prior malignancy (BC-NPM). The association between prior chemotherapy use and biologic subtype of BC-HL was evaluated. Results: We identified 321 breast cancers diagnosed in 257 women with a history of radiation therapy for Hodgkin Lymphoma. The median age at Hodgkin Lymphoma diagnosis was 22 years (range, 12-30 years), and nearly all BC-HL (97.9%) were diagnosed 8 or more years after radiation therapy. Overall, 56 (21.8%) BC-HL patients developed bilateral breast cancer, of which 28 (50%) were synchronous. When compared to women with BC-NPM, women with BC-HL were significantly younger at time of diagnosis (median age, 43 years vs. 60 years, p<0.001) and less likely to present with ductal carcinoma in situ (8.4% vs. 14.9%, p=0.001). Patients with invasive BC-HL were more likely to have high grade (43.8% vs. 32.9%, p<0.001), estrogen receptor (ER) negative breast cancer (27.7% vs. 18.2%, p<0.001), although pathologic tumor size, nodal status, and stage were not significantly different from those with BC-NPM. Compared to women with BC-NPM, the majority of operable BC-HL patients underwent surgical management with mastectomy (86.5% vs. 42.5%, p<0.001). In subset analysis of 102 women for which HER2 status was available, BC-HL were HER2+ in 18.7% of patients. Distribution of biologic subtype between BC-HL and BC-NPM are shown in the table below. In BC-HL patients, prior chemotherapy exposure was not associated with substantial differences in the proportion of ER+HER2- breast cancers (65.8% vs. 63.5%, p=0.82). Conclusions: Breast cancers in women treated with radiation therapy for Hodgkin Lymphoma are characterized by earlier onset and more aggressive biologic features, although the majority remain estrogen sensitive and early stage at presentation. Further studies are warranted to evaluate the use of preventive strategies in this high-risk patient population.[Table: see text]
Independent validation of simbiosys tumorscope to predict response to neoadjuvant chemotherapy (NACT) in early breast cancer (EBC).
Authors: He Gong , Howard Frederick , Pandey Tushar , Abe Hiroyuki , Nanda Rita 
Published: June 2021

582 Background: Despite substantial advances in the understanding of breast cancer biology, the decision to use NACT for EBC is based on tumor size, lymph node status, and subtype. Even with aggressive therapy, the majority of women will not achieve a pathologic complete response (pCR). Investigational treatment regimens, including immunotherapy, can increase pCR rates, but are associated with irreversible immune-related toxicities. Being able to accurately predict pCR could identify candidates for intensification or de-escalation of NACT, allowing for personalized medicine. SimBioSys TumorScope (TS) is a biophysical model that utilizes baseline MRI, receptor status, and planned treatment regimen to simulate response to NACT over time. TS has demonstrated accurate prediction of pCR in prior studies. Here, we describe an independent external validation of TS. Methods: We conducted a retrospective study of University of Chicago patients (pts) who received NACT for EBC from Jan 2010 - March 2020. Pts must have had a pretreatment breast MRI. Tumors were analyzed using TS by investigators who were blinded to response data. TS predicted pCR was predefined as a residual tumor volume < 0.01 cm3 or a 99.9% or greater reduction in tumor volume. Performance metrics of TS were calculated. Results: 144 tumors from 141 pts were analyzed. Average age was 52 yrs; 65% had stage II and 19% had stage III disease. Sensitivity and specificity of TS for predicting pCR were 90.4% and 92.4%, respectively. Of the 7 patients who were predicted to achieve a pCR but did not, 5 had a tumor cellularity < 5%. With a median follow-up of 4.7 yrs, the 4-yr distant disease free survival (DDFS) was 100% for patients predicted to achieve pCR, versus 81.5% for those predicted to have residual disease. Results were generally robust for all subgroups analyzed (Table). Conclusions: TS accurately predicts pCR and DDFS from baseline MRI and clinicopathologic data. Given the high sensitivity and specificity of this assay across breast cancer subtypes, TS can be used to aid in escalation/de-escalation strategies for EBC.[Table: see text]
Impact of comprehensive geriatric assesment (CGA) in the treatment decision and outcome of older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Authors: Llop Serna Sandra , Ejarque Martinez Clara , Brenes Castro Jesús , Honorato Macarena , Vilajosana Altamis M. Esther , Melero Mireia , Bermejo Oriol , Gomez Garcia Victoria , Fulla Marta , Goma Montse , Linares Isabel , Lozano Alicia , Taberna Miren , Mesia Ricard , Plana Maria , Rebollo Maite Antonio , Oliva Bernal Marc 
Published: June 2021

6057 Background: Up to 24% of patients (pts) newly-diagnosed with LA-HNSCC are 70 years old (yo). NCCN guidelines recommend a geriatric assessment to guide treatment decisions in this pts population. Comprehensive geriatric assessment (CGA) of older HNSCC pts was implemented at our institution in 2018. We evaluated the impact of CGA in treatment decision and outcome and compare it to a control cohort with no CGA treated within the same institution. Methods: Retrospective single-institution analysis of two consecutively-treated cohorts of newly-diagnosed elderly LA-HNSCC pts treated at the Catalan Institute of Oncology: a cohort treated based on CGA between 2018-2020; and a control cohort with no CGA treated based on physician criteria following tumor board decision between 2016-2018. Pts demographics and disease characteristics were obtained from our in-site prospective database. Treatment received (standard, adjusted, palliative-intent, best supportive care [BSC]), treatment completion rate (TCR) an overall response rate (ORR) after conservative treatment were collected and compared for both cohorts using chi-square. Results: A total of 197 pts were included: CGA cohort =81; Control cohort=96. Baseline characteristics were similar between cohorts (Table). Pts in CGA cohort were classified as fit (F) 35 (34.7%), medium-fit (MF) 51 (50.5%) and unfit (UF) 15 (14.9%) according to CGA results. CGA changed final treatment decision following tumor board in 31 % of the cases. Pts were more likely to receive standard treatment in the CGA cohort when compared control (36 vs 21%; p = 0.048), with no differences observed in TCR (84% vs 86%; p = 0.805). In pts who underwent conservative treatment, ORR was similar between CGA and control cohort (73.9% vs 66.7 %; p = 0.082), respectively. Tumor progression was the major cause of death in both groups. Conclusions: Older pts with LA-HNSCC who underwent CGA were more likely to receive standard treatment than those who did not, supporting the relevance of CGA for clinical decision-making in this pt population. No differences were observed in CRR, TCR or death cause. In-deep survival analysis are on-going.[Table: see text]
The association of sexual orientation with cancer screening and diagnosis.
Authors: Herriges Michael Joseph , Pinkhasov Ruben , Lehavot Keren , Shapiro Oleg , Jacob Joseph M , Sanford Thomas , Liu Nick , Bratslavsky Gennady , Goldberg Hanan 
Published: June 2021

6506 Background: Data on heterogeneity in cancer screening and diagnosis rates among sexual minorities (SMs) is lacking. Recent studies have shown SMs are more likely to engage in risky health behavior and have decreased healthcare utilization compared to heterosexual counterparts. However, few studies have examined how sexual orientation (SO) impacts cancer screening and prevalence. We therefore investigated whether SO affects prevalent gender-specific cancer screening and prevalence, including prostate (PCa), breast (BC), and cervical cancer (CC). Methods: This was a cross-sectional survey-based US study, including men and women aged 18+ from the Health Information National Trends Survey (HINTS) database (part of the National Cancer Institute’s division of cancer control and population sciences) between 2017-2019. The primary endpoint was individual-reported PCa, BC, and CC screening and prevalence rates among heterosexual and SM men and women. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. Results: Overall, 4,441 (95.18%) men and 6,333 (96.75%) women reported a SO of heterosexual whereas 167 (3.6%) and 58 (1.2%) men and 105 (1.6%) and 108 (1.6%) women reported a SO of gay and bisexual, respectively. Mean age was higher in the heterosexual group compared to the gay and bisexual groups in both men (57.7 [±16.0] vs. 52.4 [±14.5] and 51.9 [±18.0] years, p = < 0.001) and women (56.2 [±16.7] vs. 49.0 [±17.1] and 40.0 [±14.8] years, p = < 0.001). Homosexuals and bisexuals were less likely to be screened for PCa (30.53% and 27.58% vs 41.27%, p = < 0.001), BC (63.81% and 45.37% vs 80.74%, p = < 0.001), and CC (90.48% and 86.11% vs 95.36%, p = < 0.001) than their heterosexual counterparts. While rates of PCa and BC diagnoses were similar across SO, more homosexual and bisexual women were diagnosed with CC compared to their heterosexual counterparts (4.76% and 3.70% vs 1.85%, p = 0.039). Multivariable logistic regression models showed that SMs were less likely to be screened for cancer with ORs of 0.61 (95% CI 0.39-0.95, p = 0.030) for PCa, 0.52 (95% CI 0.30-0.92, p = 0.025) for BC, and 0.21 (95% CI 0.09-0.46, p = < 0.001) for CC. Although multivariable models did not show that SMs were more likely to be diagnosed with PC, BC, or CC, SMs were more likely to be diagnosed with any cancer with ORs of 1.64 (95% CI 1.06-2.54, p = 0.026) in women only and 1.50 (95% CI 1.11-2.03, p = 0.009) in men and women combined. Conclusions: These data suggest that in addition to other established and known specific socio-economic risk factors, SMs may be less likely to undergo screening of prevalent malignancies such as PCa, BC, and CC. This provides more evidence of ongoing healthcare inequality, urging our healthcare system to invest more in cancer screening of this vulnerable population.