Chemoradiation Treatment Research Articles

Retrospective Evaluation of the Efficacy of Total Neoadjuvant Therapy and Chemoradiotherapy Neoadjuvant Treatment in Relation to Surgery in Patients with Rectal Cancer.

Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.

Pretreatment multiparametric MRI radiomics-integrated clinical hematological biomarkers can predict early rapid metastasis in patients with nasopharyngeal carcinoma

BackgroundTo establish and validate a predictive model combining pretreatment multiparametric MRI-based radiomic signatures and clinical characteristics for the risk evaluation of early rapid metastasis in nasopharyngeal carcinoma (NPC) patients.MethodsThe cutoff time was used to randomly assign 219 consecutive patients who underwent chemoradiation treatment to the training group (n = 154) or the validation group (n = 65). Pretreatment multiparametric magnetic resonance (MR) images of individuals with NPC were employed to extract 428 radiomic features. LASSO regression analysis was used to select radiomic features related to early rapid metastasis and develop the Rad-score. Blood indicators were collected within 1 week of pretreatment. To identify independent risk variables for early rapid metastasis, univariate and multivariate logistic regression analyses were employed. Finally, multivariate logistic regression analysis was applied to construct a radiomics and clinical prediction nomogram that integrated radiomic features and clinical and blood inflammatory predictors.ResultsThe NLR, T classification and N classification were found to be independent risk indicators for early rapid metastasis by multivariate logistic regression analysis. Twelve features associated with early rapid metastasis were selected by LASSO regression analysis, and the Rad-score was calculated. The AUC of the Rad-score was 0.773. Finally, we constructed and validated a prediction model in combination with the NLR, T classification, N classification and Rad-score. The area under the curve (AUC) was 0.936 (95% confidence interval (95% CI): 0.901–0.971), and in the validation cohort, the AUC was 0.796 (95% CI: 0.686–0.905).ConclusionsA predictive model that integrates the NLR, T classification, N classification and MR-based radiomics for distinguishing early rapid metastasis may serve as a clinical risk stratification tool for effectively guiding individual management.

Molecular Profiling to Understand Treatment Resistance and Response in Glioblastoma

INTRODUCTION: Patients with glioblastoma experience a wide variation in response to standard treatment, with nearly 30% experiencing tumour progression during treatment, and nearly 6% surviving more than 5 years. To date, there are few non-invasive clinical biomarkers to predict response to firstline treatment. Chemical exchange saturation transfer (CEST) MRI may have the potential to fill this gap. CEST MRI is sensitive to treatment-induced changes and changes in tumor metabolism1. Our team has obtained CEST data for patients before, during and after standard chemoradiation treatment, and found that CEST provides markers of early response and can identify early, standard and late progressors before treatment initiation.2 METHODS: Patients (n = 104) with primary, IDH wild-type glioblastoma were imaged with CEST-MRI at multiple time points throughout standard chemoradiation treatment. DNA and RNA were co-extracted from matched normal and tumour pairs and processed for whole genome sequencing and gene expression analysis using Nanostring. Clinical variables such as age, extent of resection, sex, ECOG status and MGMT promoter methylated were also collected. A survival analysis was conducted using the Kaplan-Meier method with log-rank tests. Univariate and multi-variate hazard ratios for clinical variables were calculated by fitting Cox Proportional Hazards Models. RESULTS: Early progressors reported a median progression-free survival (PFS) of 142 days compared to 296.5 in standard and 832 days in late progressors (p < 0.0001). Early progressors also harbored distinct and statistically significant differences in gene expression and genomic alterations, namely in DNA damage repair, glucose transport and arginine metabolism pathways. A gene signature was prognostic of PFS and overall survival in a Cox proportional hazards model. CONCLUSIONS: This data may serve as a radiogenomic biomarker to assess treatment response within early phases of treatment and allow for a personalized treatment plan.

Serum HSP70 and VEGF levels are effective predictive factors of chemoradiosensitivity and prognosis of pancreatic cancer patients.

To evaluate the value of serum HSP70 and VEGF levels for predicting the chemoradiosensitivity of the pancreatic cancer patients. A total of 255 patients with pancreatic cancer and 60 healthy subjects were enrolled in this study. Serum levels of HSP70 and VEGF were measured using enzyme-linked immunosorbent assay (ELISA) for the pre-treatment, during-treatment and post- chemoradiotherapy time-points. The results were analyzed to evaluate the potential of serum HSP70 and VEGF levels for predicting the chemoradiosensitivity of pancreatic cancer patients. The serum levels of both HSP70 and VEGF were found to be elevated in pancreatic cancer patients as compared to healthy subjects. After chemoradiotherapy treatment, 179 patients showed effective clinical response [complete response (CR) + partial response (PR)] while 76 patients showed ineffective clinical response [stable disease (SD) + progressive disease (PD)]. Compared with the pre-treatment levels, serum levels of HSP70 and VEGF were higher during chemoradiotherapy, and lower post-treatment in the effective group. However, serum levels of HSP70 and VEGF were higher during and after treatment in the ineffective group. At any given timepoint, serum levels of HSP70 and VEGF were higher in the ineffective group as compared to those of the effective group. The overall survival (OS) and progression free survival (PFS) trends were: HSP70 High/VEGFHigh < HSP70High/VEGFLow or HSP70Low/VEGFHigh < HSP70Low/VEGFLow. Serum levels of HSP70 and VEGF were individually effective, and their combination was even more effective in predicting the chemoradiosensitivity of pancreatic cancer patients. HSP70 and VEGF expression were independent risk factors for OS and PFS of pancreatic cancer patients. Higher levels of serum HSP70 and VEGF were associated with lower radiosensitivity and worse prognosis, while lower levels of serum HSP70 and VEGF were associated with improved radiosensitivity and better prognosis of pancreatic cancer patients.

Abstract 1190: NK cell subsets as potential correlates of antitumor immunity in HPV+ cancers

Abstract High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of head and neck squamous cell cancers is fast increasing in the USA and worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) chemoradiation treatment (CRT). Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. Antitumor immunity comprises of adaptive and innate immune effectors. The immediate innate immune response by natural killer (NK) cells is a critical component for antitumor efficacy. The effector function of NK cells is modulated by various receptors via a wide array of activation or inhibitory signals. Among these receptors is HLA-DR, a recognized activation marker on CD8 T and NK cells. Literature studies refer to HLA-DR+ NK cells as pre-mNK. Preclinical data demonstrated therapeutic vaccine mediated induction of pre-mNK equivalent to contribute to tumor-free long-term survival. In our studies with clinical samples from HPV+ cancer patients, we’ve observed a dysfunctional phenotype of circulating pre-mNK when compared to healthy donors, demonstrated by flow cytometry methods. The correlates for dysfunction include increased PD-1 expression, a known inhibitory receptor, and reduced CD16, an NK receptor for Antibody Dependent Cellular Cytotoxicity (ADCC). Further, we observed circulating pre-mNK cells in HPV+ head and neck patients gain functionality post-treatment, as shown by significant increases in granzyme B and CD16, both known contributors for NK cytotoxicity. In cervical cancer patients, we had the opportunity to analyze the tumor microenvironment (TME). Interestingly, we found a significant increased frequency of cytotoxic pre-mNK cells, shown by granzyme B, in the TME that was not present in circulation. Overall, pre-mNK represent a uniquely activated immune subset for antiviral and antitumor immunity. Citation Format: Madison O'Hara, Jagannadha Sastry. NK cell subsets as potential correlates of antitumor immunity in HPV+ cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1190.

Abstract 4845: Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity

Abstract Introduction: In recent years, immune checkpoint inhibitors (ICI) have revolutionized the landscape of treatment across a variety of cancers. Potential concerns regarding racial disparities in ICI access and therapeutic efficacy have been well documented. Recent studies have indicated improved ICI access and response outcomes in White patients compared to minority groups with head and neck cancer (HNC) and melanoma patients. In contrast, patients diagnosed with lung cancer have been mixed, with some research suggesting black patients may fare better with ICI therapy. Existing literature is largely limited to retrospective studies with small population sizes, and lacks comparisons of racial disparities across malignancies. We aim to describe and compare racial inequities in ICI outcomes in HNC, melanoma, and lung cancer. Methods: The TriNetX US Collaborative Network database was queried for patients &amp;gt;18 years-old with a diagnosis of head and neck cancer, melanoma or lung cancer that were treated with ICIs. Malignancy cohorts were defined by race: non-Hispanic White (NHW) and Black. Race cohorts were 1:1 propensity score matched (PSM) for comorbidities, oncologic stage, and chemoradiation treatment. Demographic differences in cohorts were evaluated prior to matching. Following PSM, overall survival and rates of autoimmunity were assessed at 5 years. Results: 19,443 NHW and 2,827 Black patients treated with ICI were identified. At a baseline, the Black patient cohorts had significantly higher rates of comorbidies (p&amp;lt;0.02). Across all malignancies, the geographic distribution of NHW patients was more equally distributed compared to Black patients (majority south). With PSM, black HNC patients had significantly lower survival rates compared to NHW [HR: 1.4 (1.2, 1.6), p=0.0002]. In melanoma, the same trend was present, though not significant [HR: 1.3 (0.95, 1.7), p=0.1]. In contrast, in lung cancer, Black patients had significantly higher survival rates compared to NHW patients [HR 0.78 (0.70, 0.86), p&amp;lt;0.0001]. In HN and lung cancer, NHW patients had significantly higher rates of autoimmune conditions after ICI therapy compared to Black [OR: 2.0 (1.4,2.8), 1.2 (1.0, 1.4), respectively]. Conclusion: This study represents the most extensive analysis of racial disparities on ICI outcomes across malignancies. This study found that black patients treated with ICIs had decreased survival rates at 5 years compared to NHW patients in HNC and melanoma, but increased survival rate in lung cancer. This disparity persisted following PSM, matching cohorts for comorbidities, oncologic stage and adjuvant therapy. Black patients also had significantly lower rates of autoimmunity in HN and lung cancer. Noted differences in survival may be a reflection of geographic practice differences, access to care and/or socioeconomic status. Further investigation is required to elucidate the underlying etiologies of these trends. Citation Format: Kathryn L. Nunes, Pablo Llerena, Praneet Kaki, Shreya Mandloi, Annie Moroco, Eric Mastrolonardo, David M. Cognetti, Adam J. Luginbuhl, Joseph M. Curry. Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4845.

Abstract 1192: Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients

Abstract Background: Chemoradiotherapy (CRT) followed by Durvalumab consolidation has been the standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients. This study aimed to evaluate how CRT changes TCR repertoire on peripheral CD8+PD-1+ T-cells, and the change affects the clinical outcomes of CRT followed by durvalumab treatment. Methods: This was a prospective cohort study conducted from November 2019 to May 2021 in three institutes (National Cancer Center Hospital, Kansai Medical University Hospital, and Aichi Cancer Center Hospital) in Japan. We revealed the diversity of TCR repertoire (diversity evenness 50 [DE50]) on PD-1+CD8+ T cells, and CD8+ T cell phenotype in PBMCs before and after CRT treatment. Results: A total of 40 patients treated with CRT were included. Of these patients, 32 patients received durvalumab consolidation treatment after CRT (Durva cohort). The diversity and usage of T cell Receptor Beta Variable (TRBV) and T-cell receptor beta joining gene (TRBJ) usage were significantly positively correlated before and after CRT (TRBV usage: r=0.62, p&amp;lt;0.001, TRBJ usage: r=0.55, p&amp;lt;0.001). Regarding the association of TCR repertoire diversity with CD8+ T cell phenotype, DE50 and frequencies of CD8 naive were significantly positively correlated before CRT (p=0.049), while there was no correlation between PD-L1 expression and TCR repertoire before CRT (r=0.03, p=0.89) In Durva cohort, DE50 in patients with non-recurrence was higher than those with recurrence both before and after CRT (Before CRT: 0.0032 vs. 0.0019, p=0.13, After CRT: 0.0026 vs. 0.0014, p=0.06). The progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than those with DE50Low (NR vs. 14.3 months; p=0.01). Moreover, when the patients were exploratory classified based on the PD-L1 expression status and the diversity of TCR repertoire, the PFS of the CRT followed by durvalumab apparently differed (DE50High, PD-L1 TPS≥1%, NR, and DE50Low, PD-L1 TPS&amp;lt;1%, 5.9 (4.6-7.3) months, p=0.001). Conclusions: TCR diversity of peripheral CD8+PD-1+ T-cell predicted the recurrence in unresectable locally advanced NSCLC patients treated with chemoradiotherapy followed by durvalumab maintenance. Additionally, the TCR diversity combined with PD-L1 expression status could more accurately predict the efficacy of the CRT followed by durvalumab. Citation Format: Masayuki Shirasawa, Tatsuya Yoshida, Yuki Takeyasu, Takaji Matsutani, Shigehiro Yagishita, Shigehisa Kitano, Hiroaki Kuroda, Toyoaki Hida, Takayasu Kurata, Yuichiro Ohe. Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1192.

Abstract 2294: Monitoring glioma treatment response through longitudinal analysis of cell-free DNA in cerebrospinal fluid: Insights from a comprehensive study using next-generation sequencing

Abstract Background: Assessing treatment response in gliomas with high fidelity remains challenging. Cell-free DNA (cfDNA) is increasingly recognized as a liquid biomarker in plasma and cerebrospinal fluid (CSF), showing promise in optimizing therapeutic regimens for various cancers. While CSF has been explored as a source of cfDNA for gliomas, understanding the dynamics of cfDNA abundance and sequencing changes during treatment and recurrence is essential. Leveraging our biobank of longitudinal CSF specimens obtained through CSF access devices, we aimed to determine the potential utility of CSF cfDNA as a monitoring tool for treatment response in glioma patients. Materials and methods: Longitudinal CSF specimens were collected through Ommaya reservoirs (NCT04692337) or ventriculoperitoneal shunts (NCT04692324) from patients with brain tumors, including gliomas. cfDNA was extracted from 1-5 mL of CSF based on available sample volumes and quantified using Qubit. Next-Generation sequencing using PredicineCARE or PredicineSCORE low-pass whole genome sequencing (LPWGS) was performed based on the available cfDNA. Results: CSF collected before versus after resection showed an increase in quantified cfDNA (2.97x, range: 1.58-5.26x), indicating the impact of increased parenchymal disruption and closer contact with CSF. Subsequently, CSF cfDNA decreased during chemoradiation and adjuvant treatment and increased at recurrence, even in patients co-enrolled in immunotherapy trials for IL-7 agonists and pembrolizumab. Notably, copy number burden (CNB) increased at recurrence in three patients with known disease progression and decreased throughout immunotherapy treatment in one patient despite concerns of pseudoprogression. In a patient with a hypermutated glioblastoma, CSF cfDNA revealed over 59 genomic alterations, including MAP2K1, KIT, and PDGFRA. Another patient with a progressing EGFR-amplified GBM showed over 200 new variants in the final sample, with EGFR copy number increasing from 2 to over 30. Conclusion: Analysis of cfDNA throughout a patient’s disease course, encompassing resection and treatment with standard-of-care and experimental therapies, may aid in disease monitoring and treatment response. Further evaluation in a larger patient cohort is needed to determine the sensitivity of changes in mutations, CNB, and cfDNA quantity for glioma disease burden. Citation Format: Riviere-Cazaux Cecile, Xiaoxi Dong, Chao Dai, Wei Mo, Pan Du, Shidong Jia, Terence Burns. Monitoring glioma treatment response through longitudinal analysis of cell-free DNA in cerebrospinal fluid: Insights from a comprehensive study using next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2294.

Abstract 6171: Evolution of the spatial myeloid-lymphoid engagement in glioblastoma under temozolomide treatment

Abstract The current standard of care for glioblastoma (GBM), encompassing surgery, chemotherapy, and radiation, fails to extend patient survival beyond ~12-15 months. Even advanced immunotherapies, such as checkpoint blockade and chimeric antigen receptor-armored T-cell therapies, are ineffective in GBM due to tissue-specific niche-dependent escape strategies employed by glioma cells. Immune effectiveness, a finely regulated spatial and context-dependent process, underpins such a dismal state of the present therapeutic options. Herein, we applied CO-Detection by indEXing (CODEX), a state-of-the-art multiplex imaging platform, to elucidate the immune cell networks of the tumor microenvironment. By harnessing computational tools on multiplexed regions of interest across whole-slide images, we characterize the immune repertoire of GBMs by studying intratumor heterogeneity across space-histological territories- and time, matching pre- and post-treatment tissue sections of GBMs from seven patients under treatment (Stupp protocol). We aimed to assess changes in the interactions between the two main compartments of the immune system, myeloid and lymphoid, pre- and post-treatment using spatial statistics. We designed a computational workflow for the georeferencing, classification, and phenotyping individual cells of CODEX images across 105 regions of interest, representative of a mosaic of histologically defined cellular tumor (CT) or infiltrating tumor. We defined six major immune phenotypes and evaluated their spatial association with Cd45-Nestin+Olig2+ glioma cells. We modeled the GBM ecosystem and the cells’ spatial coexistence as spatial point processes that allowed the projection of coexistence networks. After stringent quality control, we detected and phenotyped 2.3M cells. Despite interpatient heterogeneity, some patients maintained an even immune composition, while others showed an enrichment in microglia, particularly in CT. Spatial network analyses revealed an increased coexistence between myeloid and lymphoid cells after treatments despite T cells being canonically considered moderately abundant. Quantitatively, the immune meta-network displayed higher edge density and lower modularity post-treatment compared with pre-treatment, reflecting increased lymphoid-myeloid engagement. In summary, we detected an increased spatial myeloid-lymphoid engagement in GBM undergoing chemo-radiation treatments. Spatiotemporal rearrangement of tumor-immune interactions indicates mechanisms implicated in disease recurrence and resistance to standard treatment, opening the frontiers for developing new targeted immunotherapies. Citation Format: Simon P. Castillo, Afrooz Jahedi, Pravesh Gupta, Jason T. Huse, Kasthuri Kannan, Yinyin Yuan, Krishna P. Bhat. Evolution of the spatial myeloid-lymphoid engagement in glioblastoma under temozolomide treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6171.

Machine Learning-Based Algorithms for Enhanced Prediction of Local Recurrence and Metastasis in Low Rectal Adenocarcinoma Using Imaging, Surgical, and Pathological Data.

(1) Background: Numerous variables could influence the risk of rectal cancer recurrence or metastasis, and machine learning (ML)-based algorithms can help us refine the risk stratification process of these patients and choose the best therapeutic approach. The aim of this study was to assess the predictive performance of 4 ML-based models for the prediction of local recurrence or distant metastasis in patients with locally advanced low rectal adenocarcinomas who underwent neoadjuvant chemoradiotherapy and surgical treatment; (2) Methods: Patients who were admitted at the first Oncologic Surgical Clinic from the Regional Institute of Oncology, Iasi, Romania were retrospectively included in this study between November 2019 and July 2023. Decision tree (DT), naïve Bayes (NB), support vector machine (SVM), and random forest (RF) were used to analyze imagistic, surgical, and pathological data retrieved from the medical files, and their predictive performance was assessed; (3) Results: The best predictive performance was achieved by RF when used to predict disease recurrence (accuracy: 90.85%) or distant metastasis (accuracy: 89.63%). RF was closely followed by SVM (accuracy for recurrence 87.8%; accuracy for metastasis: 87.2%) in terms of predictive performance. NB and DT achieved moderate predictive power for the evaluated outcomes; (4) Conclusions: Complex algorithms such as RF and SVM could be useful for improving the prediction of adverse oncological outcomes in patients with low rectal adenocarcinoma.

Evaluation of the safety and effectiveness of robot-assisted neck dissections.

Robot-assisted neck dissection (RAND) for the management of the regional lymphatic basin offers the potential for improved cosmesis and reduced lymphedema. While RAND has been previously described, functional outcome and oncologic control rates need further elucidation. A retrospective, matched cohort study of neck dissections completed at UPMC from 2017 to 2021 was conducted. RAND was identified and matched to open neck dissections (open) in a 1:2 ratio. Matching characteristics included primary cancer site, pre-operative clinical N-stage, age at time of surgery, HPV status, and previous chemoradiation treatment (salvage vs. nonsalvage procedure). Additional information was collected on patient demographics, surgery characteristics, and outcomes. Comparisons were made using t-test, chi-square test, Fisher's exact test, and Kaplan-Meier Wilcoxon (KMW) test with p < 0.05 indicating significance. Overall, RAND and open groups had similar distributions of age, gender, BMI, primary site of cancer, HPV status, clinical N-stage, clinical T-stage, known neck disease prior to procedure, prior chemoradiation therapy, and level(s) of neck dissection. Surgically, RAND procedures yielded less drainage on average (124 mL in RAND vs. 220 mL in open approaches; p = 0.01). There was no difference in the rates of complications, estimated blood loss, or number of lymph nodes obtained. There were also no differences in the rates of adjuvant therapy. Long term, there were no differences in the rates of local, locoregional, and distant recurrence of primary disease between RAND and open procedures. There were also no differences in postprocedure disease-free survival time (KMW p-value = 0.32; HR [of RAND compared with open] = 0.62). Similarly, there were no statistical differences in the overall survival of RAND patients when compared with the open group (75 vs. 58.9 months; HR = 0.11, p = 0.87). This study is the first to report the long-term effectiveness of robot-assisted surgery compared with the traditional, open approach. In addition to well-known cosmetic benefits, robot-assisted surgery may also offer patients a reduction in uncomfortable drains and improved effects from lymphedema. Overall, this study provides initial data that the RAND may be considered as an alternative approach to open surgery.

Chemoradiation to the submental muscles alters hyoid movement during swallowing in a rat model.

Hyolaryngeal dysfunction is a commonly reported swallowing problem after chemoradiation treatment for head and neck cancer. The displacement of the hyolaryngeal complex during swallowing protects the airway and assists in opening the upper esophageal sphincter. Activation of the submental muscles, specifically the mylohyoid and geniohyoid muscles, is thought to facilitate movement of the hyoid. The purpose of this study was to determine if targeted radiation to the submental muscles given concurrently with chemotherapy alters hyolaryngeal displacement 1 mo after treatment. We hypothesized that chemoradiation treatment would result in abnormal patterns of hyoid movement compared with controls. Furthermore, we propose that these changes are associated with alterations in bolus size and discoordination of the jaw during drinking. Eighteen rats underwent either chemoradiation, radiation, or no treatment. Radiation treatment was targeted to submental muscles using a clinical linear accelerator given in 12 fractions of 4 Gy (3 days per week). Cycles of 1 mg/kg of cisplatin were administered concurrently each week of radiation. One month posttreatment, videofluoroscopy swallow studies (VFSS) were performed in self-drinking rats using a fluoroscope customized with a high-speed camera. The hyoid, jaw, and hard palate were tracked during swallowing from VFSS. Hyoid kinematics were analyzed from the start to the end of hyoid movement, and parameters were compared with bolus size and jaw movement. Significant differences in hyoid retraction parameters were found postchemoradiation. Alterations in the trajectory of hyoid motion during swallowing were observed. The findings demonstrate early changes in hyoid motion during swallowing associated with chemoradiation treatment.NEW & NOTEWORTHY Chemoradiation treatment for head and neck cancer can cause functional impairments in swallowing, which can adversely affect quality of life. This study provides new evidence that chemoradiation targeted to the submental muscles provokes early adaptations in hyoid movement during swallowing, which correlate with changes in bolus size. We also demonstrate a method for tracking the hyoid during swallowing in a rat model of chemoradiation injury.

Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.

CT-perfusion in the diagnosis of oropharyngeal cancer and monitoring of chemoradiotherapy.

Purpose of the study: to identify diagnostic effectiveness of the CT perfusion method in diagnosing squamous cell carcinoma of the oropharynx and in assessing dynamic changes in the affected area after chemoradiotherapy.Materials and methods. The results of CT perfusion and CT with intravenous contrast were analyzed in 27 patients aged 40 to 76 years, who were divided into three groups: 1) a control group of patients with suspected oropharyngeal tumors – 9 people (33.4%); 2) group of primary (untreated) patients – 8 people. (29.6%) with a verified diagnosis of squamous cell carcinoma; 3) a group of patients with this diagnosis only after chemoradiotherapy – 10 people (37.0%).Results. Our own algorithm for CT perfusion of the oropharynx region was developed. Digital indicators characterizing the presence of tumor tissue in the tissues of the oropharynx were determined: arterial blood flow (AF) and blood volume (BV). When studying CT perfusion indicators, the following was established: in the group of untreated patients, in contrast to the control group of patients, the values of equivalent blood volume (BV), arterial blood flow velocity (AF) and permeability (FE) were statistically significantly increased. Whereas in patients after chemoradiation treatment, compared with the group of untreated patients, CT perfusion indices were statistically significantly reduced in the following parameters: equivalent blood volume (BV), arterial blood flow velocity (AF). The vascular permeability indicator (FE) is only of secondary importance in identifying the tumor process. Analysis of the results of CT perfusion in patients after chemoradiation treatment revealed an almost complete restoration of tissue perfusion indices in terms of AF and BV relative to perfusion indices in patients in the control group.Conclusion. The results of our study indicate the diagnostic effectiveness of CT perfusion in detecting oropharyngeal cancer and in assessing the corresponding changes in the affected area that occur after chemoradiotherapy. Changes in CT perfusion parameters are associated with microcirculation in the tumor area, which is confirmed by a statistically significant decrease in BV and AF parameters after chemoradiotherapy.

Robot-Assisted Free Flap Reconstruction for Oropharyngeal Cancer: A Systematic Review

Management of oropharyngeal cancer is undergoing a shift due to different profiles of patients, who tend to be younger and show better prognosis. Transoral robotic surgery is being established as the first-line approach as the procedure has shown minimal invasiveness and good oncological and functional outcomes, while avoiding extensive open surgery approaches and intensive chemoradiotherapy treatments. Naturally, the next step in the management of oropharyngeal cancer would be using the same technology for reconstruction to preserve the function and anatomy of the oropharynx. Free flaps, especially the radial forearm free flap and the anterolateral thigh flap, proved to be ideal for oropharyngeal reconstruction, and robotic assistance in these cases is yet to be explored. A limited number of studies have reported robot-assisted oropharyngeal reconstruction, so this review summarizes the currently available data and explores the feasibility, safety, and functional outcomes of this novel technique.

The Impact of Immunotherapy Use in Stage IIIA (T1-2N2) NSCLC: A Nationwide Analysis

IntroductionMultiple clinical trials have revealed the benefit of immunotherapy (IO) for NSCLC, including unresectable stage III disease. Our aim was to investigate the impact of IO use on treatment and outcomes of potentially resectable stage IIIA NSCLC in a broader nationwide patient cohort. MethodsWe queried the National Cancer Database (2004–2019) for patients with stage IIIA (T1-2N2) NSCLC. Treatment and survival were evaluated with descriptive statistics, logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling. ResultsOverall, 5.5% (3777 of 68,335) of patients received IO. IO use was uncommon until 2017, but by 2019, it was given to 40.1% (1544 of 2308) of stage IIIA patients. The increased use of IO after 2017 was associated with increased definitive chemoradiation treatment (54.2% [6800 of 12,535] from years 2017 to 2019 versus 46.9% [26,251 of 55,914] from 2004 to 2016, p < 0.001) and less use of surgery (18.1% [2266 of 12,535] from years 2017 to 2019 versus 22.0% [12,300 of 55,914] from 2004 to 2016, p < 0.001). IO treatment was associated with significantly better 5-year survival in the entire cohort (36.9% versus 23.4%, p < 0.001) and the subsets of patients treated with chemoradiation (37.2% versus 22.7%, p < 0.001) and surgery (48.6% versus 44.3%, p < 0.001). Pneumonectomy use decreased with increased IO treatment (5.1% of surgical patients [116 of 2266] from years 2017 to 2019 versus 9.2% [1127 of 12,300] from 2004 to 2016, p < 0.001). ConclusionsIncreased use of IO was associated with a change in treatment patterns and improved survival for patients with stage IIIA(N2) NSCLC.

Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.

High-risk human papillomaviruses (HPVs) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing in the USA and worldwide. Survival rates for patients with locally advanced disease are poor after standard-of-care chemoradiation treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential. We reported earlier that in a syngeneic immunocompetent preclinical HPV tumor mouse model, intranasal immunization with an HPV peptide therapeutic vaccine containing the combination of aGalCer and CpG-ODN adjuvants (TVAC) promoted clearance of HPV vaginal tumors via induction of a strong cytotoxic T cell response. However, TVAC was insufficient in the clearance of HPV oral tumors. To overcome this deficiency, we tested substituting aGalCer with a clinically relevant adjuvant QS21 (TVQC) and observed sustained, complete regression of over 70% of oral and 80% of vaginal HPV tumors. The TVQC-mediated protection in the oral tumor model correlated with not only strong total and HPV-antigen-specific CD8 T cells, but also natural killer dendritic cells (NKDCs), a novel subset of NK cells expressing the DC marker CD11c. Notably, we observed induction of significantly higher overall innate NK effector responses by TVQC relative to TVAC. Furthermore, in mice treated with TVQC, the frequencies of total and functional CD11c+ NK cell populations were significantly higher than the CD11c- subset, highlighting the importance of the contributions of NKDCs to the vaccine response. These results emphasize the importance of NK-mediated innate immune effector responses in total antitumor immunity to treat HPV+ cancers.

Endoscopic resection vs. endoscopic resection plus chemoradiation for T1 stage colorectal cancer: a real-world retrospective cohort study.

Early-stage colorectal cancer (CRC) patients treated with either endoscopic resection (ER) alone or combined ER with chemoradiotherapy (CRT) have unknown survival rates. A national descriptive epidemiological study was conducted to compare the long-term survival of patients with T1 stage CRC with or without the two different treatment options. Our study identified the records of patients with T1-stage CRC between 2010 and 2018 by searching the Surveillance, Epidemiology, and End Results (SEER) database. Long-term survival was compared using Kaplan-Meier methods and Cox proportional hazard models based on patient demographic and cancer parameters. After propensity score matching (PSM), 825 T1-stage CRC patients were finally enrolled in this study, with 718 patients treated with ER and 107 patients treated with ER + CRT. The overall survival (OS) and cancer specific survival (CSS) rates were similar between the two treatment options (OS: P=0.47; CSS: P=0.28). According to subgroup analysis, older patients and patients with rectal tumor locations exhibited significantly higher OS and CSS rates in the ER + CRT group than in the ER group (OS: P<0.0001; CSS: P<0.0001). The findings from the SEER database showed that OS and CSS rates were similar between the ER and ER + CRT treated groups. Older patients and patients with rectal cancer benefited the most from ER + CRT treatment.

Effectiveness of neoadjuvant chemoradiotherapy in the treatment of rectal cancer: A comprehensive study

This study addresses the global health challenge of rectal cancer, aiming to assess the effectiveness of neoadjuvant chemoradiotherapy and its implications for treatment outcomes in 100 retrospectively analyzed patients. The cohort underwent neoadjuvant chemoradiotherapy followed by sphincter-sparing surgery, with recorded parameters including demographics, tumor stage, treatment protocol, and surgical outcomes. Results indicated tumor reduction in 80% of patients, with a 15% complication rate for sphincter-sparing surgery. Pathological examination underscored neoadjuvant treatment’s impact on tumor regression and reduced lymph node metastasis. In conclusion, the study emphasizes the demonstrated efficacy of neoadjuvant chemoradiotherapy in rectal cancer treatment, advocating for a comprehensive approach to managing this condition.

Adjuvant chemoradiotherapy (CRT) plus pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC) with high risk of recurrence after neoadjuvant CRT plus surgery: A single-arm phase II study.

320 Background: Adjuvant anti-PD-1 therapy with nivolumab has shown efficacy in reducing recurrence rates in patients with locoregional esophageal cancer including squamous cell carcinoma who achieved R0 resection but harboring pathologic residual disease following neoadjuvant CRT. However, the efficacy of adjuvant anti-PD-1 therapy in improving outcomes for patients at higher risk of recurrence, especially those with involved or close resection margin (≤1 mm), remains unclear. Methods: We conducted a phase II trial of adjuvant cisplatin (30mg/m2 IV every week for 2 cycles)-based CRT (180-200cGy per fraction for 10-13 fractions) followed by pembrolizumab (200mg IV every 3 weeks for 18 cycles) in patients with locally advanced ESCC who had high-risk recurrence features in esophagectomy tumor tissues, including involved or close margin (≤1 mm), extranodal extension (ENE) of involved lymph node, and ypN2-3, following neoadjuvant CRT (ClinicalTrials.gov Identifier: NCT03322267). Primary endpoint was 1-year relapse-free survival (RFS) rate in comparison with a historical control of 32%.1 Secondary endpoints included RFS, overall survival (OS), and toxicity. Results: Between Nov 2018 and Dec 2022, we enrolled a total of 25 patients with high risk recurrence features, including margin ≤1 mm (18 patients), ENE of involved lymph node (9), and ypN2-3 (9). Majority of patients were male (88%) and current smokers (84%). The median follow-up duration was 16.5 months (95% CI 10.6-27.1). One-year RFS rate was 63.3% (95% CI 44.5-79.8). Median RFS and OS were 15.3 months (95% CI 10.2-20.4) and 38.3 months (95% CI 10.2-66.3), respectively. Any grade treatment emergent adverse events (TEAEs) occurred in 56% and 75% of patients during cisplatin-based CRT and pembrolizumab treatment, respectively. Grade 3 TEAEs were infrequent, including leukopenia (4%), pancreatitis (4%), infection (8%), and colitis (4%). There was no grade 4 TRAE. Conclusions: Adjuvant cisplatin-based CRT followed by 1-year treatment of pembrolizumab was well-tolerated, and was associated with an improved 1-year RFS rate in patients with pathologic residual disease and high risk for recurrence following trimodality therapy for locally advanced ESCC. 1. Guo JC et al: J Thorac Oncol 2015;10:1481-9. Clinical trial information: NCT03322267 .