bluuebunny/crossref_metadata_2025_split huggingface dataset:
High pre-treatment NLR and PLR predict poor prognosis of patients with recurrent/metastatic head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.
Authors: Anile Giuseppe , Gottardi Chiara , Micheletto Ilaria , Nicolai Piero , El Khouzai Badr , Ferrari Marco , Ghirelli Angelica , Pretto Greta , Guarneri Valentina , Ghi Maria Grazia 
Published: June 2024

e18001 Background: The treatment landscape of unresectable recurrent and/or metastatic (R/M) Head and Neck Squamous cell Carcinoma (HNSCC) has profoundly changed with the introduction of Immune checkpoint inhibitors (ICIs). High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with poor outcome in several tumor types. The aim of the present study was to investigate the role of pre-treatment NLR and PLR in predicting overall survival (OS) of patients treated with ICIs. Materials and Methods: We retrospectively reviewed the clinical records of 106 consecutive patients with R/M-HNSCC who received ICIs (single-agent or ICIs-based treatment) between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Patients were grouped into platinum-refractory (patients progressed within 6 months from the last platinum dose) and platinum-sensitive. The cut-off values of pre-treatment NLR and PLR were determined based on percentile distribution (75th percentile). OS was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to compare survival outcomes. Results: A total of 102 patients were analyzed. Four patients were excluded because of incomplete data. Primary tumor sites were oropharynx (37%), oral cavity (24%), hypopharynx (19%), larynx (15%), nasopharynx (5%) and nasal cavity (1%). 63 patients (62%) with platinum-refractory disease received nivolumab single-agent. All 39 patients (38%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab-based treatment. Median OS was 8.0 months (95% CI 5.8-10.1) in the platinum-refractory cohort and 13.3 months (95% CI 7.3-19.3) in the platinum-sensitive cohort. At the univariate analysis high NLR (≥7) and PLR (≥345) correlated with poor OS in the overall population and in both the platinum-refractory and the platinum-sensitive cohorts (Table1). At the multivariate analysis PLR was an independent predictor of OS. Conclusions: The efficacy results reported in this retrospective series were in line with the literature data. High PLR was an independent predictor of poor outcome regardless of the platinum sensitivity. Prospective studies are needed to better explore the predictive role of easily obtainable blood biomarkers in this poor prognostic population. Univariate analysis for OS [Table: see text]
Comparative efficacy of pembrolizumab with carboplatin and paclitaxel as first-line (1L) therapy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A network meta-analysis (NMA) with matching-adjusted indirect comparison (MAIC).
Authors: Zheng Dandan , Mojebi Ali , Black Christopher M. , Giezek Hilde , Naicker Niroshini , Vanetta Chiara , Keeping Sam , Merchant Sanjay , Dzienis Marcin Radoslaw 
Published: June 2024

e18006 Background: The single-arm, phase IV, KEYNOTE-B10 (KNB10) trial demonstrated the antitumor effect of the KNB10 regimen for 1L treatment of R/M HNSCC. It is critical to understand the comparative efficacy of the KNB10 regimen versus other recommended interventions in 1L R/M HNSCC, using advanced evidence synthesis methodologies, to inform clinical decision making. Methods: A systematic literature review, conducted on October 31, 2023, identified 25 randomized controlled trials evaluating 1L interventions in R/M HNSCC, of which six evaluated recommended interventions and formed a connected network. Of these, KEYNOTE-048 was determined to be the most similar study to the disconnected, single-arm, KEYNOTE-B10 trial. Therefore, individual patient-level data from KEYNOTE-B10 final analysis were reweighted and matched to KEYNOTE-048 via a MAIC in terms of metastatic disease, PD-L1 Combined Positive Score, ECOG performance status, primary tumor location as well as HPV status, sex, race, age, and smoking status. KEYNOTE-B10 was then considered an additional treatment arm of KEYNOTE-048 and was incorporated in the network. Fixed-effect NMA models in Bayesian framework were then used to estimate odds ratios of objective response rate (ORR), with 95% credible intervals, for comparisons between KNB10 and other interventions recommended for 1L R/M HNSCC. Results: Results from the fixed-effects NMA are summarized in the table. For ORR, the KNB10 regimen was more efficacious compared to pembrolizumab+platinum+5-FU, cetuximab+platinum+5-FU, platinum+5-FU, cisplatin+paclitaxel, cisplatin, 5-FU, and methotrexate ( p < 0.05). There was no statistically significant difference in ORR between the KNB10 regimen and cetuximab+cisplatin+docetaxel. Conclusions: This NMA with MAIC suggests patients treated with the KNB10 regimen had improved or comparable ORR outcomes versus other recommended 1L interventions for R/M HNSCC, which further reinforces the combination therapy of pembrolizumab+platinum+taxane as an acceptable alternative 1L treatment option for R/M HNSCC. Future analyses should additionally compare survival outcomes between the KNB10 regimen and other recognized interventions in this patient population. [Table: see text]
Survival outcomes of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy.
Authors: Burkitt Kyunghee , Fu Pingfu , Margevicius Seunghee 
Published: June 2024

e18010 Background: There have been reports of higher than expected objective response rate (ORR) to platinum-based combinations following immunotherapy failure in a number of metastatic solid and hematological malignancies. In light of these intriguing results and the fact that the optimal second line regimen for R/M HNSCC after immunotherapy remains unclear, we conducted a prospective cohort study of patients with R/M HNSCC treated with platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy to investigate survival outcomes. Methods: This is a single institutional prospective cohort study which has a total of 12 patients with R/M HNSCC. Within 2 weeks after confirmation of progression from anti-PD-1 monotherapy (pembrolizumab or nivolumab), platinum-based chemotherapy (cisplatin 80mg/m2 or carboplatin AUC=5) plus paclitaxel 175mg/m2 every 21 day cycle were initiated and continued for a total of 3-9 cycles. The best overall response (BOR) was assessed by RECIST v1.1. ORR was determined based on binomial distribution theory and Wilson’s method. Progressive-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method. The association between ORR and HPV status, PD-L1 score were determined by the chi-square test. Blood samples were collected prior to the start of chemotherapy and also at the time of restaging scans (every 3 cycles of chemotherapy) for RNA sequencing. Results: Patients were treated from May 2021 to June 2023. There were 10 men and 2 women, median age of 63 years (range, 51-73) and ECOG 0-1. Oropharynx (9, 75%) was the most common primary site (oral cavity: 1, larynx: 1). Eleven (92%) had distant metastatic disease. 45% of patients (5 out of 11) had PD-L1 CPS <50. 58% of patients (7 out of 12) had HPV positive HNSCC. The median follow up of the study was 15.6 (range: 4.9-23.9) months. The ORR was 75% with 95% CI: 0.47- 0.91. The median OS was 17.9 months and median PFS was 6.74 months. The median OS for PDL1 >= 50 is longer than 23.9 months vs 15 months in patients with PD-L1 CPS <50. Compared to HPV negative patients, HPV positive patients had a superior median PFS (8.75 vs 3.9 months, p= 0.069). The ORR by HPV status was higher in HPV positive than HPV negative patients (85.7% vs 60%, p=0.311), and the ORR by PDL1 score was higher in PDL1 ≥ 50 than PDL1 <50 (100% vs 66.7%, p=0.154), but neither ORR by HPV status nor PDL1 was significant. Conclusions: Platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy showed dramatically higher ORR and more favorable median OS compared to the historical data from the pre-anti PD-1 era (ORR: 75% vs 26%, median OS: 17.9 vs 8.1 months), which warrants a larger prospective study for validation. Our ongoing analysis of RNA sequencing may reveal mechanism for immunotherapy induced chemosensitization effect.
Impact of tertiary lymphoid structures in response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma.
Authors: Ruiz Torres Daniel A. , Hirayama Shun , Merkin Ross D. , Roberts Thomas J. , Patel Manisha Jayandra , Park Jong Chul , Wirth Lori J. , Sadow Peter , Sade-Feldman Moshe , Stott Shannon , Faden Daniel 
Published: June 2024

e18021 Background: Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yetefficacy remains low. Current assessment for tumor response relies on a single proportional biomarker expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with improved ICB response than PD-L1. However, their exact composition, size, and spatial biology in HNSCC remain understudied, and there is a need for a deeper examination of TLS biology in HNSCC and its link with clinical response to ICB. Methods: Pre-ICB tumor tissue sections (formalin-fixed, paraffin-embedded) were obtained from 10 responders (complete response, partial response, or stable disease) and 10 non-responders to ICB (progressive disease). A custom multi-immunofluorescence (mIF) staining assay was designed, optimized, and applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblast (alpha Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). Following imaging and tissue classification using machine learning techniques, spatial profiling was performed, including proximity, density, and infiltration analysis. Response status was assessed via RECIST 1.1. Spatial metrics were compared among groups based on response to ICB. An unpaired t-test was used to compare mean densities. Multivariable logistic regression was used to measure the effect of TLS size on achieving response to ICB (CR, PR or SD). Results: A higher density of dendritic cells (LAMP3) was found in responders compared to non-responders to ICB (p=0.0415). A positive correlation was observed between mIF and pathologist identification of TLS (r2=0.51; p=0.0039). TLS trended toward more prevalent in responders to ICB (p=0.0906). There was no association of high CPS (>20) with improved PFS (HR=0.91; p-value=0.8538 C.I.= 0.3538-2.369). Multivariate logistic regression analysis showed that total TLS area > 5.8 (mm²) (mean TLS size in this cohort) in pretreatment tissue biopsies was associated with 2.4 increased odds of achieving objective response (OR= 2.4, p=0.05, 95% C.I.=1.2-275.1) independent of CPS score. Conclusions: Tertiary Lymphoid Structures play a critical role in the immune response to HNSCC, are quantifiable through histopathologic assessment by a pathologist, and may potentially outperform CPS as a predictor of ICB response.
Role of induction chemotherapy in locally advanced oropharyngeal carcinoma in Indian population.
Authors: Moorthy Vijay , Naik Radheshyam , Bj Srinivasa , Patil Shekar , Thungappa Satheesh Chiradoni , Kumar Delvin , T P Sharafudheen , Adadi Srinivasa Naidu 
Published: June 2024

e18026 Background: Head and neck cancer is the third most frequent cancer in Indian men, it is a growing public health problem. Given the numerous disparities in head and neck cancer biology, etiologic and demography between the developing world and the developed world, management guidelines should be based on Indian literature rather than western data. This study aims to define role of Induction chemotherapy in locally advanced oropharyngeal cancer In Indian population by comparing the outcomes which are Overall response rate (O.R.R), Progression free survival (P.F.S), overall survival (O.S) between patients who received Induction chemotherapy followed by CTRT vs CTRT. Methods: Patients who were registered for treatment between jan-2018 to dec-2022 who met the selection criteria were included for the study. Selection criteria: Patients who were diagnosed with Stage III OR IV (a & b, non-metastatic) oropharyngeal squamous cell carcinoma from age group of 20 to 70 who were HPV negative or unknown status were included for study. Total of 50 patients were chosen for the study after stringent selection criteria. Out of 50 ,23 patients received Induction chemotherapy and 27 patients received only CTRT. Results: Overall response rate was analysed using Interim PET CT after Induction chemotherapy and PET CT after 3 to 6 months of CTRT. Complete response and partial response is considered as ORR. It was observed that ORR in sequential therapy arm is 42% and only CTRT arm is 36%, however this is not statistically significant with p value of 0.54. Median PFS for CTRT arm is 8 months and median PFS for IC +CTRT arm is 12 months with p value = 0.97(>0.05) (Log rank test) which is not statistically significant. Median OS for CTRT is 60 months and IC+ CTRT is 18 months. The log rank test has been used for comparing the overall survival outcomes of both the groups , and thus the p-value obtained is 0.56(>0.05), which shows that there is no statistically significant difference in the survival outcome of the two groups. Conclusions: In conclusion, our study on induction chemotherapy in locally advanced head and neck cancer did not identify statistically significant differences in O.R.R, PFS and OS between the two treatment arms which is concordant with MACH- NC updated 2021 data. Several factors, including patient heterogeneity, sample size, treatment protocol, follow-up, duration, may have contributed to these results, it is essential to interpret these results in the context of the study's limitations. [Table: see text]
Beyond margins: TIME-infused insights into recurrence in surgically treated oral squamous cell carcinoma (OSCC).
Authors: Reghunadhan Parvathy , Rao Vishal Uchila Shishir , Thakur Shalini , Subash Anand , George Abhijith , Sharma Anamika 
Published: June 2024

e18036 Background: Surgical margins are considered negative if the tumor is 3-5mm away from margins. At times patients with clear margins report back with a recurrence. There are factors beyond the margins that needs to be analyzed. The tumor immune microenvironment (TIME) plays a critical role in cancer development, progression, & control. Aim: To assess the TIME at different surgical margins and derive scoring criteria for the prognostication of recurrence in OSCC. Objective: 1) Derive a TIME score that prognosticates the recurrence-free survival (RFS) and overall survival (OS) of the patients 2) Determine the most significant margin at which TIME score can be estimated. Methods: A retrospective cohort study between 2016 to 2023. Slides of the OSCC patients who had local recurrence were evaluated for TIME parameters: a) Tumor infiltrating lymphocytes (TILS)-(CD3, CD4, CD8, FOXP3, CD57) b) Tumor associated macrophages (TAMS)-(CD68, CD163) c) Programmed death Ligand(PDL-1) d) P53 and d) Desmoplasia at - Interphase, 1mm, 3mm, 5mm, & periphery of the surgical specimen. 30 patients were included. Logistic Regression Equation (LRE) was derived for all the variables of TIME at 5 different margins. Significant margin and average RFS & OS obtained. TIME score was derived. A standard equation for RFS & OS was obtained using the TIME score. Results: Total = 30 patients. 19 were 40-60 years. Tongue was common site(36.66%). The predicted RFS = 23+/- 7 Months (M). OS = 47+/-8M. Regression model with the highest accuracy was found at 3mm margins (83.33%) for all the variables. LRE were fitted for all the variables to find the RFS & OS. LRE for RFS for each parameter at 3mm: TILS:12.4211-0.0190*CD3-0.1222*CD4-0.0979*CD8-0.0744*FXOP3-0.1809*CD57 TAMS: -0.6635+0.0768*CD68 +0.0241*CD163 PDL1: -0.4055+0.5878*PDL1+TC +2.1972*PDL1+2.1972*PDL1 DESMOPLASIA: 0.4055+0.4418* DESMOPLASIA GRADE P53: 0.4700+0.4055*P53 LRE for OS for each parameter at 3mm: TILS:0.5784+0.0262*CD3-0.0233*CD4-0.0132*CD8-0.0233*FXOP3-0.0036*CD57 TAMS: -2.8158+0.1307*CD68 + 0.0451*CD163 PDL-1: -1.3860+1.9460*PDL1 + 1.0990*PDL1 + 0.4700*PDL1 DESMOPLASIA: -0.4055* DESMOPLASIA P53: -0.8109+0.9287*P53 Value (V) From the above equations substituted in : Probability=1/1+exp(-V)), >0.5 the score is 0 : RFS (< 23+/-7 M), OS (<47+/-8 M) <0.5 the score is 1 : RFS (>23+/-7 M), OS (>47+/-8 M) Summing the score from each equation= TIME score (Max. score =5) RFS = 15.621+3.030*TIME score (p Value significant) OS = 11.481+10.699*TIME score(p Value significant) Conclusions: The TIME score can be the real-time estimator of the recurrence in surgically treated OSCC. 3mm margins have best accuracy in evaluating the RFS and OS. Average RFS & OS are 23+/-6 & 47+/-8 M respectively.
Quantifying the financial impact of treatment intolerance in chronic myeloid leukemia on oncology clinical practices: A mixed methods study.
Authors: Shafrin Jason , Jadhav Kehal , Warren Cheryl , Quddus Sabiha , Zawadzki Nadine , Yang Daisy , Damon Andrea , Spurrier Kathryn , Batt Katharine , Wei David 
Published: June 2024

e18520 Background: Tyrosine kinase inhibitors (TKIs) have changed the prognosis for patients with chronic myeloid leukemia (CML) to a chronic disease. However, adverse events related to TKI treatment intolerance frequently occur. While the impact of CML treatment intolerance on patient quality of life and cost to health insurers has previously been measured, the time and cost impact to oncology practices is unknown. This mixed methods study aimed to estimate the average time and cost to oncology practices per CML treatment intolerance episode. Methods: The study combined interviews of oncology practice staff with economic modeling. A convenience sample of oncology practice managers was interviewed between October 2023 - January 2024. Interviews aimed to identify and quantify the cost dimensions of addressing treatment intolerance in CML patients. Time impacts reported by respondents were converted into monetary terms using hourly compensation rates of staff needed to complete the identified task. Results: A total of 10 academic oncology practice managers participated in the study. Eight cost dimensions were identified including time spent on prior authorization for medication switch, patient communication, follow-up visits, and care coordination after inpatient stays. Estimated practice time and cost per treatment intolerance episode requiring hospitalization were 34 hours and $3,413 (Table), which were largely attributable to navigating payer prior authorization for medication switch (10 hours, $871), additional follow-up visits (8 hours, $858) and care coordination with inpatient team (9 hours, $782). Activities that could be coded for reimbursement represented only 31.9% of incurred cost. The time and cost per treatment intolerance episode requiring no hospitalization were 17 hours and $1,772. Other burdens not explicitly quantified included negative impact on patient satisfaction, staff morale and care continuity. Conclusions: CML treatment intolerance imposes additional resource and economic burden on oncology practices, and most of these activities are not reimbursed in the current healthcare system. [Table: see text]
In-hospital outcomes of patients with myelodysplastic syndromes and rheumatic heart disease: A National Inpatient Sample study (2018-2020).
Authors: Iqbal Rabia , Gaddam Mrunanjali , Bajwa Ahmad Taimoor , Colon Ramos Ana , Sinha Samridhi , Singh Surbhi , Singh Surbhi , Clement Jincy 
Published: June 2024

e18525 Background: Autoimmune conditions are relatively uncommon in patients with Myelodysplastic syndromes (MDS), with only a small proportion of patients affected. Among these autoimmune conditions, rheumatic heart disease (RHD) is the most commonly associated with MDS. Very few cases have been reported in literature that show the impact of RHD on patients diagnosed with MDS. In this study, we aimed to investigate the impact of RHD on the patients with myelodysplastic syndrome who were admitted in hospitals from 2018-2020. Methods: We utilized National Inpatient Sample (NIS) 2018-2020 to identify hospitalizations of patients with Myelodysplastic syndromes with a secondary diagnosis of Rheumatic heart disease. The primary outcomes examined were In-patient mortality and average length of stay, All the patients with MDS were divided into two cohorts based on the presence of rheumatic heart disease. Multivariable regression analyses were conducted, taking into account demographics, hospital-level characteristics, and pertinent comorbidities as adjusting factors. Results: Using the NIS dataset from 2018 to 2020, we identified 222,364 patients admitted with MDS during this period. Among them, 4.57% (10,162 patients) also had a diagnosis of rheumatic heart disease (RHD). The average age of patients with MDS and RHD was 80 years. Among these patients, 50.1% were male and 49.9% were female. The mortality rate among patients admitted with MDS and coexisting RHD was 7.7%. Multivariate regression analysis indicated that the presence of RHD increased the likelihood of mortality with an odds ratio (OR) of 1.2 (95% confidence interval [CI]: 1.0-1.4, p-value <0.05). Additionally, RHD was associated with a higher incidence of arrhythmias (OR: 2.9) and congestive heart failure (OR: 5.0) among MDS patients. The total hospital charges were more in patients with RHD than those without RHD ($80108 vs $82843). However, there was no significant difference in the length of stay (LOS) between patients with MDS alone and those with MDS and RHD. Conclusions: Rheumatic heart disease (RHD) cases in patients with MDS are rare in clinical practice, leading to uncertainty regarding the effects of RHD on admitted MDS patients. Our study sheds light on the influence of RHD on mortality and other outcomes in this patient population. The efficacy of timely RHD treatment in reducing mortality and improving outcomes among hospitalized MDS patients remains to be verified in future investigations. [Table: see text]