tbuckley/cabot-search huggingface dataset:
Beyond margins: TIME-infused insights into recurrence in surgically treated oral squamous cell carcinoma (OSCC).
Authors: Parvathy Reghunadhan, Vishal Uchila Shishir Rao, Shalini Thakur, Anand Subash, Abhijith George, Anamika Sharma
Journal: Journal of Clinical Oncology (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, &amp; 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, &amp; 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 &amp; OS obtained. TIME score was derived. A standard equation for RFS &amp; 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 &amp; 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)), &gt;0.5 the score is 0 : RFS (&lt; 23+/-7 M), OS (&lt;47+/-8 M) &lt;0.5 the score is 1 : RFS (&gt;23+/-7 M), OS (&gt;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 &amp; OS are 23+/-6 &amp; 47+/-8 M respectively.
Prospective monitoring for immunotherapy by liquid biopsy and signal pathway alterations in head and neck cancers.
Authors: Yoshihito Kano, Rika Noji, Takahiro Naito, Shun Fujiwara, Sadakatsu Ikeda, Takehiko Mori, Hiroyuki Harada, Mitsukuni Suenaga
Journal: Journal of Clinical Oncology (2024)

e18000 Background: Clinical biomarkers that predict response or prognosis to immune checkpoint inhibitors (ICIs) are unclear in head and neck squamous cell carcinoma (HNSCC). Comprehensive genome profiling (CGP) testing including liquid biopsy using cell-free DNA (cfDNA) has become clinically available; however, CGP testing is approved only once per patient under the Japanese health insurance system. Therefore, whether liquid biopsy is useful for detecting sequential genetic change and disease progression as a real-time monitoring tool is still unknown. This study aims to analyze the cfDNA in the plasm of recurrent or metastatic (R/M) HNSCC patients during ICI therapy. This study was prospectively conducted to examine the relationship between sequential genetic changes and treatment response. Methods: In this prospective study, we examined ten evaluable R/M HNSCC cases treated with ICI monotherapy (nivolumab or pembrolizumab) from October 2020 to December 2023. Blood samples were collected and analyzed using Guardant360 at differing three-time points (0, 4, and 24 weeks or at progressive disease, PD). Results: The ten cases consisted of 5 males and 5 females, with a median age of 71 years old (52-92 years old). Seven patients received pembrolizumab as a first line and three received nivolumab as the second line treatment. The best response to ICI was partial response (PR) in 3 cases , stable disease (SD) in 1 and PD in 6. Three cases discontinued the study at the second point because of the rapid disease progression. Microsatellite status is stable in all cases. Eight of the ten cases had at least one pathogenic mutation, one case had only variants of unknown significance, and one case that had target lesions at lung metastases had none of them through a series of liquid biopsies. The most frequent gene alterations observed were TP53 (60%), TERT promoter (20%), GNAS (20%), and EGFR amplification (20%). In particular, EGFR amplification had emerged at the second point in two PD cases and these patients showed the sensitivity to cetuximab-based therapy at the following treatment line. In all PD cases, the highest variant allele fraction (VAF) was increased at the second point, which might help predict the response to ICI therapy. In one case achieving PR, BRAF mutation had emerged at the second point. Then it was undetectable at the third point with PD, and GNAS mutation was newly detected. In another case, APC inactivation had disappeared at the second point with PR, even though GNAS mutation emerged, and this case maintained the response to ICI. These results suggest that switching the signals in the MAPK or Wnt pathway could impact the response to ICI therapy. Conclusions: The findings of this prospective study demonstrated that the highest VAF alterations and genetic mutations detected by cfDNA analysis could reflect and predict the response to ICI.
Trends on treatment patterns in patients with newly diagnosed AML: Preliminary findings from a real-world analysis.
Authors: Ester Rita Alessandrini, Jeverson Moreira, Virginie Simon, Oscar Mallet, Rihab Gamaoun, Romane Péan, Gauvain Hamkoung, Yue Zuo, Théophile Reppelin, Mehdi Kertous, Alexandre Templier, Nadjat Mounedji
Journal: Journal of Clinical Oncology (2024)

e18506 Background: In the last two decades, new therapeutic options have emerged to complement traditional intensive chemotherapy (IC) regimens in the treatment of Acute myeloid leukemia (AML). Hypomethylating agents (HMAs), the B-cell lymphoma 2 (BCL-2) protein inhibitor Venetoclax, and other targeted therapies are examples. Guideline-based treatment decisions are intricate, considering both patient fitness to IC and disease characteristics. AML real-word studies on treatment patterns typically focus on specific subpopulations (e.g., elderly or unfit patients), and few studies analyze broader populations. We analyzed an US electronic health records (EHR) database to describe AML treatment patterns. Methods: Study was designed as retrospective, descriptive analysis of deidentified secondary data from COTA database in the US. Data was abstracted for AML patients diagnosed for the first time between January 2017 and September 2022. Follow-up period (FP) was defined as the period starting at the diagnosis until the last information available for: death, or last contact, or the emergence of other malignancies. To improve descriptive analysis, treatment categories were classified accordingly: IC and non-IC. We conducted descriptive statistics (expressed as counts, percentages or means and medians [with SD or IQR]) for the different assessed features. Results: From the 3,500 patients included on the database, 1,436 were eligible for the analysis with a newly diagnosed AML disease after January 2017. Individuals’ age at diagnosis falls between 60 and 74 years old for 41% of the cohort with mean age of 64[15] years and 60% were followed on community centers. Male patients slightly outnumber female patients (53% and 47%, respectively). Primary AML accounted for 41% of the population and secondary for 28%. Mean time to first treatment after diagnosis was 14[42] days for the overall cohort, the main reason for the end of follow-up was death for 58% of individuals and 47% of the patients had a follow-up inferior to one year. While analyzing treatment patterns according to line of therapies (LoT) sequences, IC only was predominant for 30% of the population, followed by non-IC only for 28%. Remaining counts (42%) correspond to association of both categories. Most prevalent regimen on IC only group was High-dose Cytarabine monotherapy (HIDAC) (12%), and HMA (Azacitidine)+Venetoclax (27%) for the non-IC only group. Conclusions: Our preliminary and recent findings demonstrate that incidence of AML remains high in elderly groups. Despite the introduction of novel therapies, IC remains the predominant treatment approach for newly diagnosed AML patients. Our ongoing real-world analysis aims to assess a more detailed description of LoT sequences in AML population.
Quantifying the financial impact of treatment intolerance in chronic myeloid leukemia on oncology clinical practices: A mixed methods study.
Authors: Jason Shafrin, Kehal Jadhav, Cheryl Warren, Sabiha Quddus, Nadine Zawadzki, Daisy Yang, Andrea Damon, Kathryn Spurrier, Katharine Batt, David Wei
Journal: Journal of Clinical Oncology (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]
Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with <i>NPM1</i> mutated de novo acute myeloid leukemia.
Authors: Yiyi Yao, Nanfang Zhuo, Yile Zhou, Liping Mao, Min Yang, Yinjun Lou, Hongyan Tong, Jie Jin, Huafeng Wang
Journal: Journal of Clinical Oncology (2024)

e18505 Background: 25-35% of adult patients with acute myeloid leukemia (AML) carries NPM1 mutation, characterized by aberrant cytoplasmic dislocation of NPM1 protein, which is generally associated with a favorable outcome in the absence of FLT3-ITD mutation. Indeed, for NPM1-mutated AML patients with different co-mutation profiles, identification of specific co-mutation combinations other than FLT3-ITD mutation is necessary for accurate risk stratification and contributes to identify the optimal population who may benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) during post-remission therapy. Methods: Eligible patients included newly diagnosed adult patients (≥18 years old) with NPM1 mutated de novo AML (M3 excluded) treated at the First Affiliated Hospital of Zhejiang University School of Medicine for at least one complete course of induction therapy from October 2018 to December 2022. All patients received next generation sequencing (NGS) detection for diagnosis before treatment. Response was evaluated within two courses of induction chemotherapy. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were collected for endpoint analysis. Results: 178 patients were analyzed. Median age was 59 years old (IQR, 51-68). The co-mutated genes with a detection rate of ≥ 10% included FLT3, DNMT3A, TET2, IDH2, IDH1, PTPN11, NRAS, and WT1. The median follow-up was 26.2 months. Our results showed that in NPM1 mutated AML, co-mutations of IDH1, IDH2, and PTPN11-PTP domain were associated with favorable prognosis, while co-mutations of FLT3-ITD and DNMT3A were associated with poor prognosis. Interestingly, the adverse outcome trends brought by FLT3-ITD and DNMT3A co-mutations could be reversed by IDH mutation and PTPN11 mutations, respectively (Table). Besides, for NPM1 mutated AML patients combined with FLT3-ITD/ DNMT3A mutations, allo-HSCT after remission could significantly improve outcome ( P &lt; 0.05), while similar results were not found in FLT3-ITD/ DNMT3A wild type patients. Conclusions: This study demonstrated that NPM1-mutated AML with different co-mutation profiles led to heterogeneous outcomes. For NPM1-mutated AML patients with adverse prognosis-related co-mutation combinations, allo-HSCT after remission may be a recommended strategy to improve outcome. [Table: see text]
Role of induction chemotherapy in locally advanced oropharyngeal carcinoma in Indian population.
Authors: Vijay Moorthy, Radheshyam Naik, Srinivasa Bj, Shekar Patil, Satheesh Chiradoni Thungappa, Delvin Kumar, Sharafudheen T P, Srinivasa Naidu Adadi
Journal: Journal of Clinical Oncology (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 &amp; 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(&gt;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(&gt;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]
A call for improved anemia treatments in myelofibrosis: A single-center retrospective study.
Authors: John Yan, Josette Mary Kamel, Swati Goel, Amit Verma
Journal: Journal of Clinical Oncology (2024)

e18531 Background: Anemia in myelofibrosis (MF) is associated with poor prognosis and decreased quality of life. Effective treatments are limited, posing a significant challenge in clinical management. This study aims to provide insights into the treatment of anemia in MF patients from an underserved urban tertiary care center. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Demographic data, presence of anemia (hemoglobin ≦10 g/dl) at time of diagnosis or referral (TODR), transfusion dependence ( ≥ 2 units on ≥2 occasions within 8 weeks), anemia treatments, disease modifying treatment, and anemia response to treatments (as defined by the IWG-MRT and ELN consensus report) were assessed via non-parametric tests and univariate cox regression. Events were defined as death from any cause or development of anemia. Patients with missing data were excluded. Results: Among 88 patients analyzed, 77 (87.5%) experienced anemia during the study period. Overall survival (OS) for anemic patients was 7.7 years with 31 deaths, versus only 1 death in the non-anemic group. 51 (60%) of patients were anemic at TODR. For patients not anemic at TODR, median time to anemia (TTA) was 31 months. Patients with HMR (n=24) had faster median TTA than those without (22 vs. 49 months, p = 0.1). All triple-negative (TN) patients (n=8) were anemic at TODR and had statistically lower initial hemoglobin compared to patients with driver mutations (7.4 g/dl vs. 9.9 g/dl, p = 0.0023). Among anemic patients (n=77), age &gt; 65 was associated with poorer OS (HR 2.293, CI 1.076 - 4.887, p=.0315), while transfusion dependency (HR 2.093, CI 0.4777 - 0.9422, p=0.0697) and Ruxolitinib use (HR 2.843, CI 0.9912 - 8.155, HR 0.052) approached significance. Secondary anemia treatments did not impact OS (HR 0.9346, CI 0.4537 - 1.925, p=.854) and are summarized in the table. Most patients received Ruxolitinib (68.8%) and hydroxyurea (35.06%), while fewer received Momelotinib (N = 4), Pacritinib (N = 6), or Fedratinib (N = 4). Conclusions: Our findings highlight the limited effectiveness of current treatments in reducing transfusion burden and anemia in MF, and that patients of higher genetic risk may be more susceptible to developing anemia. Transfusion dependency and treatment non-response are marginally associated with poorer outcomes, emphasizing the need for newer therapies. [Table: see text]
Myelofibrosis prognostic models validated in an underserved minority population: A retrospective analysis.
Authors: Josette Mary Kamel, John Yan, Mendel Goldfinger, Eric J. Feldman, Marina Konopleva, Ioannis Mantzaris, Aditi Shastri, Noah Kornblum, Kira Gritsman, Alejandro R. Sica, Nishi Shah, Dennis Cooper, Amit Verma, Swati Goel
Journal: Journal of Clinical Oncology (2024)

e18529 Background: Contemporary prognostic models for myelofibrosis (MF) risk stratify patients using a heterogeneous composition of clinical and genetic factors. Little is known regarding how these scores perform in underserved populations. Our study assesses how well current models stratify risk at an inner-city tertiary care center which carries unique challenges including increased diversity, later disease presentation, and less access to healthcare resources. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Clinical and genetic data were used to calculate prognostic scoring for DIPSS, DIPSS plus, MIPSS70, MIPSSV2, and GIPSS. Overall survival (OS) was calculated from the time of diagnosis and non-deceased patients were censored at last follow-up. Patients with missing clinical or genetic data were excluded from individual analysis. Models were assessed via univariate and multivariate cox proportional hazards analysis followed by concordance analysis. Results: Mean age of the cohort was 66 years (range 29-88) with median survival of 7.7 years. Ethnicities included non-hispanic white (NHW) [30 (34.1%)], NH black [23 (26.1%)], NH asian [6 (6.8%)], and hispanics of all races [22 (25%)] (unknown n=7). DIPSS (n= 88, HR 1.77, CI 1.22 - 2.41, p-value = 0.0001), DIPSS plus (n=83, HR 1.54, 1.15-2.07, p = 0.0033), MIPSS70V2 (n=68, HR 2.06, CI 1.23 - 3.61, p = 0.0088), and GIPSS (n=69, HR 2.73, CI 1.24 - 3.78, p = 0.0063) were significantly associated with OS based on univariate analyses. Both DIPSS and GIPSS were significant even upon adjustment for each other (p=.009 and p=.043 respectively). MIPSS70 (n=73, HR 1.87, CI .93 - 3.88, p = 0.0842) did not meet significance. In terms of predictive accuracy based on C-index scores, DIPSS and GIPSS combined analysis scored highest (0.773), followed by GIPSS (.7226), DIPSS (0.719), MIPSSV2 (0.717), DIPSS Plus (0.6495), then MIPSS70 (0.6414). Conclusions: Our study shows that GIPSS, DIPSS, DIPSS plus, MIPSSV2 all function as valid prognostic models in the inner-city setting and that integrating both clinical and genetic models may have higher predictive value than either individual model alone. Additionally, GIPSS predicted superior survival outcomes to what was observed in our cohort for higher risk categories, prompting the need for further investigation. [Table: see text]