bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic literature review of the real-world burden and use of chemotherapies for treatment of advanced or recurrent endometrial carcinoma.
Authors: Zhao Qi , Hughes Rachel , Altaf-Haroon Ishaaq , Schiller Emma , Kadambi Ananth 
Published: June 2021

e17571 Background: Women diagnosed with advanced or recurrent endometrial cancer (EC) have a poor prognosis, with a 5-year survival of only 15% to 17%. While a multi-modality approach is often used for newly diagnosed EC including platinum-based chemotherapy, there are no definitively approved standard treatment options for advanced or recurrent EC following prior systemic therapy (FPST). The real-world evidence surrounding the effectiveness of chemotherapies in this setting is not well characterized. We conducted a systematic literature review to attempt to fill this evidence gap. Methods: Systematic searches were run in Embase, MEDLINE, and the Cochrane Library to identify English-language publications from January 2000 to July 2020. Additional hand searches of 5 key conferences held from 2018 to 2020 were also conducted. The review included observational studies reporting the clinical effectiveness, safety, or treatment patterns of pharmacological treatments in adult women with advanced or recurrent EC. Results: Seventy-seven observational studies met the inclusion criteria, of these 63 studies reported on the effectiveness of chemotherapies. While 57 studies described adjuvant chemotherapy use, 6 described use of chemotherapies FPST, including 1 study in the second line or later. Only one of these 6 studies reported a sample size greater than 100 patients. Chemotherapy FPST included paclitaxel/carboplatin (3 studies), doxorubicin (2 studies), etoposide (1 study), or any platinum-based chemotherapy (1 study). Shorter median overall survival (OS) was observed in patients with treatment-free intervals (TFI) < 6 months from prior systemic therapy (5.5-11.3 months; 2 studies) compared to those with TFI > 6 months (13.0-27.0 months; 3 studies). Similarly, shorter median progression-free survival (PFS) was seen in patients with TFI < 6 months from prior systemic therapy (2.0-3.2 months; 2 studies) vs. those with TFI > 6 months (6.0-10.0 months; 3 studies). Conclusions: Women with advanced or recurrent EC have poor OS and PFS with current chemotherapy regimens, especially for those with TFI < 6 months. The time at recurrence from prior systemic therapy seems to correlate with the outcomes of subsequent treatment. Novel efficacious treatment strategies are required to improve patients’ outcomes in the FPST setting. While extensive real-world evidence exists for patients with EC receiving adjuvant chemotherapy, real world data is limited for use of chemotherapy in advanced or recurrent setting, warranting further research in larger samples of patients.
Vaginal biocenosis in patients with gynecological cancers.
Authors: Nikitina Vera P. , Zykova Tatiana A. , Shevyakova Elena A. , Zhenilo Oksana E. , Verenikina Ekaterina V. , Ivanova Viktoria A. , Kruze Polina A. 
Published: June 2021

e17574 Background: The purpose of the study was to assess vaginal biocenosis in patients with gynecological cancers (GCs) and in non-cancer women. Methods: The study included 50 patients aged 52.3+2 years with histologically verified GCs (cervical cancer – 23, endometrial cancer – 27) – group 1, and 22 non-cancer women aged 42.4+2.3 – group 2. Vaginal swabs were taken prior to antitumor treatment. Real-time PCR was used to determine the total bacteria mass (TBM) and DNAs of 16 groups of microorganisms: Lactobacillus spp., Enterobacteriaceae, Streptococcus spp., Staphylococcus spp., Gardnerella vaginalis+Prevotella bivia+Porphyromonas spp., Eubacterium spp., Sneathia spp.+Leptotrichia spp.+Fusobacterium spp., Megasphaera spp.+Veillonella spp.+Dialister spp., Lachnobacterium spp.+Clostridium spp., Mobiluncus spp.+Corynebacterium spp., Peptostreptococcus spp., Atopobium vaginae, Candida spp., Mycoplasma hominis, Ureaplasma (urealyticum+ parvum), Mycoplasma genitalium. Results: Vaginal biocenosis was assessed as normocenosis in 12 (24%) women in group 1 and 12 (54.5%, p = 0.012) women in group 2; conditional normocenosis - 2 (4%) and 3 (13.6%, p > 0.05); dysbiosis - 36 (72%) and 7 (31.8%, p = 0.0017), respectively. Anaerobic bacteria prevailed in women with dysbiosis in both groups (46% and 22.7%, p = 0.005); aerobic dysbiosis was registered in 16% and 4.5% (p > 0.05), mixed dysbiosis – in 10% and 4.5% (p > 0.05) of women of groups 1 and 2, respectively. Normal flora ( Lactobacillus spp.) was observed in 23 (46.0%) in group 1 and 17 (77.3%, p = 0.02) in group 2. Streptococcus spp. >10% of TBM were found in 9 (21.9%) women in group 1 and not found in group 2 (p = 0.049). Gardnerella vaginalis+Prevotella bivia+Porphyromonas spp. >10% of TBM were found in 27 (54.0%) in group 1 and 6 (27.3%, p = 0.031) in group 2; Staphylococcus spp. - 13 (26.0%) in group 1 and 12 (54.5%, p = 0.031) in group 2. Conclusions: Development of gynecological tumors was accompanied by a sharp decrease in Lactobacillus spp., a significant increase in Gardnerella vaginalis+ Prevotella bivia+ Porphyromonas spp. and Streptococcus spp., vaginal dysbiosis with a predominance of anaerobic and mixed microflora.
Cachexia in treatment-naïve gynecological cancer patients: Prevalence, predictors, and clinical associations.
Authors: O'Donoghue Niamh , Sullivan Charlie , Thompson Claire , Abu Saadeh Feras , Kamran Waseem , D’Arcy Tom , Gleeson Noreen 
Published: June 2021

e17576 Background: Cancer cachexia is associated with considerable morbidity and mortality, yet its prevalence in gynaecological malignancy is unknown. Prevalence of cachexia in de novo gynaecological cancer patients and the impact of cachexia on clinical parameters and patient-reported outcomes were investigated. Methods: A prospective, exploratory study of newly diagnosed gynaecological cancer patients was conducted at St. James’s Hospital, the largest treatment provider for gynaecological malignancy in the Republic of Ireland. Patients recently diagnosed with a gynaecological cancer were eligible. Demographics, oncological history, Clavien Dindo Classification and length of stay were collected from participants’ medical record. A questionnaire completed by participants on 3 consecutive days collected data on height, weight, weight history, recent dietary intake, nutritional impact symptoms and functional status. Cachexia was defined using the criteria established in 2011 (Fearon and Strasser et al, 2011). Participants’ staging computed tomography scans were utilised for body composition analysis. Descriptive statistics, Mann Whitney U tests and Chi-square were used to summarise and identify significant associations between variables. Logistic regression was used to model predictors of cachexia. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire in conjunction with EORTC gynaecological cancer-specific modules assessed quality of life. Results: A total of 94 participants were recruited. All five gynaecological cancers were represented. Prevalence of cachexia was 21.4% and was highest in patients with cervical cancer. Any weight loss in the previous month was predictive of developing cachexia. Low albumin and anorexia were associated with cachexia, although neither reached significance. Median post-operative length of stay for cachectic patients was 5 days (range 1-57) compared to 4 days (range 0-27) for non-cachectic patients (p = 0.682). 60% of cachectic patients had some post-operative complication. Cachectic patients were more symptomatic and had lower functional status in all quality of life categories, with the exception of emotional function. Conclusions: As prevalence of cachexia in this population is at least 22%, we strongly recommend screening for cachexia at all clinical assessments. Although weight loss and body mass index can identify the majority of cachectic patients, skeletal muscle mass index should also be included where possible. Its incorporation into standard radiology assessment of cancer patients would be optimal. Further research is warranted in a larger population to fully elucidate the predictors of cachexia. Quality of life is a useful means to monitor symptoms and functional status which may contribute to or exacerbate cachexia.
Real-world outcomes for patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with nivolumab: A Galician multicentric study (Spain).
Authors: Iglesias Rey Leticia , Vilchez Simo Rocio , Aguin Losada Santiago , Garcia Arroyo Francisco Ramon , Pena Carolina , Carral Maseda Alberto , Huidobro Vence Gerardo , Molina Díaz Aurea , García-Gómez Jesus , Covela Rúa Marta , Costa Rivas Marinha , Medina Ana 
Published: June 2021

e18002 Background: Nivolumab has demonstrated efficacy in clinical trials of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). These results have been corroborated in real world studies in different populations. We describe the outcomes of 116 patients with R/M SCCHN in our clinical practice treated with Nivolumab in the main hospitals of the Galician health network (Spain). Methods: This multicenter study was carried out in nine hospitals that belong to the Galician Group of Head and Neck Cancer (GGCC). A total of 116 patients with R/M SCCHN who received nivolumab were recruited between January 2017 and June 2019. These patients were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS) and the disease control rate (DCR) of the overall patient and specifically in the first, second and third lines, as well as toxicity, were evaluated. Results: Data from 116 patients were available. Most of them were males (91.37%) with a median age of 60 years (41-84 years). The primary tumor sites were oral cavity, oropharynx, hypopharynx and larynx. At first diagnosis, the majority of the patients had advanced disease (stage IV a/b/c 74.12%) and a performance status (PS ECOG) rate of 1 (64.65%). Owing to the real-world nature of the study, patients with poor performance status were also included (ECOG 2: 13.79% and ECOG 3: 0.86%). HPV and PDL1 status were not available for the majority of patients. The use of nivolumab in the first, second and third line was carried out in 20 (17.24%), 76 (65.52%) and 20 (17.24%) patients respectively. With a median follow-up of 14 months (1-69), in all patients (n = 116) the median progression-free survival (mPFS) was 2.30 months (95% CI 1.45 – 3.14) and the median overall survival (mOS) was 8.08 months (95% CI 5.93 – 10.23). DCR was 43% with 5% complete response (CR), 25% partial response (PR) and 15% stable disease (EE). The mPFS of the patients who received nivolumab in the first, second and third line was 3.9 (IC 95%1.01- 6.93), 3.6 (IC 95% 0.82-6.47) and 2.3 months (IC 95% 0.72-3.87) and the mOS was 6.8 (IC 95% 2.36-11.43), 8.5 (IC 95% 5,9 - 11.62) and 7.2 months (IC 95% 4.51-10.07) respectively. Drug-related adverse effects (grade 3/4) were observed in 21.27% and were controlled with steroid treatment. Conclusions: in this real-life study, the population is broader than the represented in the phase III CheckMate 141 trial, including patients with higher ECOG PS (0-3). These concordant results in the real-world setting in both efficacy and safety, support the use of nivolumab in this group of patients with R/M SCCHN.
Novel biomarkers for head and neck squamous cell carcinoma: A retrospective study.
Authors: Dou Shengjin , Zhang Lin , Li Rongrong , Sun Debin , Wu Lijia , Zhu Guopei 
Published: June 2021

e18010 Background: PDL-1 and tumor mutation burden are only useful to select a small portion of patients with head and neck squamous cell carcinoma for immunotherapy, more biomarkers are in an urgent need for the majority. Methods: Ninety-nine recurrent/metastatic patients were analyzed. PD-1 cohort including 78 patients; Non-PD-1(NPD-1) cohort including 28 patients received anti-EGFR antibody and harbored at least one of EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations (including 7 patients received with both treatment). Patients were evaluated as no clinical benefit (NCB) if experiencing progressive disease or stable disease lasting < 6 months and were discontinued from immunotherapy within 3 months; otherwise, patients were evaluated as clinical benefit (CB). Tumor genomic DNA was isolated from formalin-fixed paraffin-embedded tissue for the targeted sequencing by a 769-gene panel. R package was used for fisher test to evaluate the variants. p < 0.05 was set as significant. Results: With median age of 57 years old, this study included 75 (75.8%) oral squamous cell carcinoma patients,17 (17.2%) oropharyngeal carcinoma patients and 7 others. Sixty-nine (69.7%) patients have PD-L1 CPS≥1, 27 (27.3%) patients have CPS＜1 and 3 (3.0%) have an unknown CPS. The estimated 10-month progression-free survival of the NPD-1 cohort and PD-1cohort were 60.0%and 47.6% (p = 0.06) respectively. In NPD-1 cohort, 23 patients were evaluated as CB (78.3%), and in PD-1 cohort, 41 were evaluated as CB (52.6%) (p = 0.00682), indicating EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations may be negatively correlated with immunotherapies. There were 14 patients who harbored either EGFR amplification or SNV mutation. Of the 8 patients who received NPD-1 treatment, 7 were CB (87.5%); Of the 8 patients who received PD-1 treatment, 2 were CB (25%) Statistically, the difference between NPD-1 treatment group and PD-1 treatment group was significant with a p value of 0.04056. There were 16 patients who harbored CCND1 amplification, or FGF3/4/19 amplification. Of the 12 patients who received NPD-1 treatment, 10 were evaluated as CB (83.3%); Of the 7 patients who received PD-1 treatment, 1 was evaluated as CB (14.3%). The difference was significant with a p value of 0.00627. There were 44 patients who obtained CDKN2A/B mutations. Of the 12 patients who received NPD-1 treatment, 11 acquired CB (81.7%); Of the 33 patients who received PD-1 treatment, 18 acquired CB (54.5%). The difference was significant with a p value of 0.03325. Conclusions: We for the first time showed that genetic-altered EGFR, FGF3/4/19, CCND1 and CDKN2A/B were negatively correlated with anti-PD-1 therapy in clinical cohorts retrospectively and these genetic aberrations may serve as novel immune-negative biomarkers for immunotherapies.
Network meta-analysis (NMA) of pembrolizumab for first-line (1L) treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Ramakrishnan Karthik , Mojebi Ali , Ayers Dieter , Chirovsky Diana Romana , Borse Rebekah , Keeping Sam 
Published: June 2021

e18012 Background: In the KEYNOTE-048 trial, pembrolizumab as monotherapy (P) and in combination with platinum+5FU chemotherapy (P+C) versus cetuximab+platinum+5FU (EXTREME regimen) significantly improved overall survival (OS) in the combined positive score (CPS) ≥1 (hazard ratio: 0.74; 95% confidence interval: 0.61-0.90) and total (0.72; 0.60-0.87) R/M HNSCC populations, respectively, and was approved by the FDA in these patient populations. While the EXTREME regimen is considered standard of care in 1L R/M HNSCC, other systemic treatment options including cetuximab+platinum+docetaxel (TPEx regimen), platinum+paclitaxel/taxane (Pt+T), and platinum+5FU (Pt+F) are also commonly used. Due to lack of head-to-head comparisons with pembrolizumab, an NMA was conducted to estimate the comparative efficacy of P and P+C versus these interventions in 1L R/M HNSCC. Methods: A systematic literature review (SLR) was conducted on November 13, 2019 to identify randomized controlled trials for the relavant interventions. Data were extracted for the OS and progression-free survival (PFS) outcomes. NMA analyses were conducted for the total population and for the CPS ≥1 and CPS ≥20 subgroups in a Bayesian framework using proportional hazards (base case) and time-varying (sensitivity analysis) treatment-effect models. The deviance information criterion was used to compare the goodness-of-fit of the alternative survival models. Results: The SLR identified 28 trials, of which six trials matched the trial eligibility criteria of KEYNOTE-048 and were included in the NMA. Results from the fixed-effects NMA for P and P+C are summarized in table below for the FDA indicated population. Improvement in OS was noted for P and P+C versus EXTREME, Pt+T, and Pt+F, and a trend in improved OS versus TPEx was observed. The sensitivity analysis showed improved OS over time across all comparisons. PFS was improved with P and P+C versus Pt+F and comparable versus other interventions. These results were generally consistent for P and P+C in the CPS (CPS ≥1 or CPS ≥20) patient subgroups. Additionally, NMA results versus EXTREME were consistent with the KEYNOTE-048 trial results. Conclusions: Pembrolizumab (P or P+C), showed improved OS and comparable PFS outcomes versus alternative 1L R/M HNSCC interventions, consistent with the efficacy results versus EXTREME observed in the KEYNOTE-048 trial. [Table: see text]
Treatment patterns for patients with metastatic or recurrent head and neck cancer in a large integrated health-care system.
Authors: Seto Tiffany , Samant Navendu D. , Shah Nina , Shirazi Aida , Colevas A. Dimitrios , Katzel Jed Abraham 
Published: June 2021

e18015 Background: Since publication of the landmark KEYNOTE-048 Trial, pembrolizumab alone or with platinum-based chemotherapy and 5-fluorouracil (5FU) was established as a standard of care for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC), replacing the EXTREME regimen of Cetuximab with platinum and 5FU. In clinical practice, some clinicians modify the KEYNOTE-048 regimen by substituting a taxane for 5FU (i.e., Paclitaxel + Carboplatin + Pembrolizumab, PCT). Within the Kaiser Permanente Northern California (KPNCAL) network, we identified a cohort of 123 patients who received palliative first-line therapy for metastatic HNSCC to identify practice patterns in a real-world setting within a large health care delivery system. Methods: This is a data-only cohort study of all adult KPNCAL members diagnosed with metastatic HNSCC treated with palliative combination chemotherapy and/or immunotherapy between January 1, 2018 and July 31, 2020. Results: Among a cohort of 123 patients, 28 patients received the EXTREME regimen (platinum + 5FU + cetuximab), 10 received modified EXTREME (platinum + taxane + cetuximab), 14 received platinum + 5FU + pembrolizumab, 9 received platinum + taxane + pembrolizumab and 62 received single agent immunotherapy. From 2018 through mid-2020, there was an apparent shift away from cetuximab based regimens and a concurrent rise in immunotherapy-based regimens. By mid-2020, the majority of patients received an immunotherapy-based regimen (28 patients), while only 5 patients received a cetuximab based regimen (Table). Conclusions: Data from our cohort reported clinical practice patterns within a large multispecialty integrated health-care system in Northern California. Our findings highlight the marked variability in practice patterns within a single health care system for first-line metastatic therapy. While we identified trends away from cetuximab based therapy and toward immunotherapy-based therapy in clinical practice there remained wide practice variations among clinical oncologist treating patients with newly diagnosed metastatic HNSCC. This further emphasizes the need for prospective clinical trials to identify the optimal regimen or to confirm clinical equipoise between regimens among patients with metastatic or recurrent head and neck cancer. [Table: see text]
Association of HLA loss of heterozygosity with allele-specific neoantigen expansion in response to immunotherapy.
Authors: Pyke Rachel Marty , Abbott Charles , Dea Steven , Bedi Nikita , Colevas A. Dimitrios , Levy Eric , Zhang Simo V. , Snyder Michael , Mellacheruvu Datta , Sunwoo John B. , Chen Richard , Boyle Sean Michael 
Published: June 2021

e18030 Background: Human leukocyte antigen loss of heterozygosity (HLA LOH) restricts immune recognition of tumors by limiting the major histocompatibility complex (MHC) presentation of neoantigens to T cells and correlates with reduced response to immune checkpoint blockade therapy (ICB) in non-small cell lung cancer. To explore the mechanism behind the impairment of HLA LOH on ICB, we analyzed the relationship between the antigen presentation pathway, neoantigen presentation and response to ICB in a head and neck squamous cell carcinoma (HNSCC) cohort. Methods: Following baseline sample collection, a cohort of 14 HNSCC patients recieved a single dose of PD-1 inhibitor. The primary tumor mass was definitively resected approximately one month later. If resection was impractical, a second biopsy was taken. Response to therapy was evaluated using RECIST criteria. Each pre- and post-intervention tumor sample and normal PBMC sample were profiled using Personalis’ ImmunoID NeXT Platform, an HLA-enhanced exome/transcriptome platform. HLA LOH was detected using a digital PCR validated machine learning algorithm (DASH). Neoantigen presentation was computationally predicted using a machine learning algorithm (SHERPATM) trained on mono-allelic immunopeptidomics data. Results: We found that 50% of the HNSCC cohort had HLA LOH, a larger percentage than in a large pan-cancer cohort (23%, n=611) and a distinct HNSCC cohort (40%, n=20). Further, two patients had B2M LOH and one patient had a deleterious mutation in an HLA allele. Despite the high frequency of somatic alteration in the antigen presentation pathway, we did not find an association between HLA LOH and ICB response. However, if HLA LOH was still shaping tumor evolution in response to ICB, we would expect to see immune pressure against subclonal tumor populations with neoantigens presentable by the retained HLA alleles but not the deleted HLA alleles. Indeed, we found that significantly more novel post-treatment neoantigens were predicted to bind to deleted HLA alleles compared to their homologous alleles (p=0.045). Conclusions: Given the high prevalence of HLA LOH across tumor types, a greater understanding is needed regarding the impact of HLA LOH on tumor evolution during ICB treatment. Though HLA LOH does not correlate with response to ICB, the consistent shift in neoantigen composition suggests that it acts as an evolutionary force in resistance to response during immunotherapy.