Mengting Shi, Xueyuan Chen, Tingting Liu, Shasha Yin, Zhixiong Lin
Publicatie 31-12-2024
Signe Bergliot Nielsen, Mikkel Hjordt Holm Larsen, Hani Ibrahim Channir, Katalin Kiss, Benedicte Parm Ulhøi, Christian Godballe, Jesper Grau Eriksen, Niclas Rubek, Thomas Kjaergaard, Christian von Buchwald
Publicatie 30-12-2024
Shi-Tong Yu, Da Huang, Chengfeng Xiong, Rong Xie, Jichun Yu
Publicatie 19-12-2024
Locally advanced papillary thyroid carcinoma (PTC) with RET fusion-positive poses significant challenges for surgical resection due to tumor invasion into critical structures. Neoadjuvant targeted therapies are a promising approach to reduce the tumor burden and improve the resectability. Selperctinib, a RET kinase inhibitor, has been approved for the treatment of advanced or metastatic RET-altered thyroid cancer. However, the efficacy of selperctinib as a neoadjuvant treatment for locally advanced RET-altered thyroid cancer is unclear. We report two cases of RET fusion-positive PTC that received neoadjuvant treatment with selperctinib (160 mg twice daily) to reduce the tumor size and enable for radical resection. Tumor sizes were reduced after neoadjuvant treatment with selperctinib. Patients successfully underwent R0 resection with no major surgical complications. Selperctinib isa potential neoadjuvant treatment for PTC with RET fusion-positive.
Pubmed PDF WebGian Marco Pace, Andrea Costantino, Armando De Virgilio
Publicatie 19-12-2024
Lucas Alves da Mota Santana, Bernardo Ferreira Brasileiro, Rajiv Gandhi Gopalsamy, Gina Délia Roque-Torres, Dalmo Correia-Filho, Lysandro Pinto Borges, Cleverson Luciano Trento, Leandro Napier de Souza
Publicatie 19-12-2024
Shihong Xu, Jiagang He, Zheran Liu, Yiyan Pei, Junyou Ge, Yan Qing, Youneng Wei, Ye Chen, Xingchen Peng
Publicatie 03-01-2025
Immune-related adverse events (irAEs) have been associated with better therapeutic outcomes in patients receiving immune checkpoint inhibitors (ICIs) across various cancers. This study investigates the association between irAEs and ICI outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). A post hoc analysis was performed on 153 patients with R/M NPC who received anti-PD-L1 inhibitors between February 26, 2019, and January 13, 2021. These patients were enrolled in a multicenter, single-arm, phase 2 clinical trial, which represents the largest study to date evaluating anti-PD-L1 therapy in previously treated R/M NPC. Patients who experienced irAEs had significantly higher overall response rates (ORR) and diseade control rates (DCR) compared to those without irAEs (31.2 % vs. 17.1 %, p = 0.039; 66.7 % vs. 44.8 %, p = 0.017). Additionally, the median progression-free survival (PFS) was longer in patients with irAEs (129 days vs. 56 days, p = 0.007). Patients with endocrine-related irAEs exhibited higher DCR (71.8 % vs. 46.2 %, p = 0.012), and longer PFS (144 days vs. 69 days, p = 0.02) and overall survival (OS: 746 days vs. 438 days, p = 0.02). In contrast, patients with grade ≥ 3 irAEs or thoserequiring systemic steroid therapy had shorter median OS (179 days vs. 466 days, p = 0.03; 166 days vs. 462 days, p = 0.02). The occurrence of irAEs, particularly those involving the endocrine system, is associated with enhanced efficacy of anti-PD-L1 therapy and extended survival in patients with R/M NPC, highlighting their potential as prognostic biomarkers.
Pubmed PDF WebZhaohong An, Xiwei Zhang, Zhaoyang Wang, Dilinaer Wusiman, Xiaohui Zhao, Lin Li, Lei Guo, Minghui Wei, Wenbin Li, Changming An
Publicatie 03-01-2025
Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT). HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC). The populations of CD4 The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3
Pubmed PDF WebNivedita Kaorey, Kyle Dickinson, Venkata Ramana Agnihotram, Anthony Zeitouni, Nader Sadeghi, Julia V. Burnier
Publicatie 02-01-2025
The incidence of head and neck cancer (HNC) is on the rise, making it a significant clinical challenge. Human papillomavirus (HPV)-related and HPV-negative HNC exhibit distinct etiopathogenesis and prognoses, requiring targeted approaches for effective management. Conventional tissue biopsies are essential for confirming the diagnosis and locating solid tumors. However, they have limitations in detecting microscopic disease, tracking treatment response, and capturing the dynamic heterogeneity of the mutational profile within the tumor. Liquid biopsy using circulating tumor DNA (ctDNA) analysis has emerged as a promising non-invasive tool to overcome the drawbacks of conventional biopsy for comprehensive molecular profiling. This meta-analysis aims to colligate available evidence on the clinical utility of ctDNA analysis in predicting survival outcomes, specifically in HPV-negative HNC. Our systematic search of six electronic databases identified eight publications (N = 886 patients) meeting the inclusion criteria. The included studies reported data from HPV-negative HNC patients, employing ctDNA analysis to report survival outcomes. Our findings reveal a significant association between mutation or methylation in ctDNA and worsened survival outcomes in HPV-negative HNC cases. The presence of ctDNA mutations in TP53 and methylation of SEPT9 and SHOX2 was linked to reduced overall survival, disease-free survival, and progression-free survival. Subgroup analyses demonstrated consistent associations across different survival outcomes, ctDNA detection methods, and blood collection tubes used. Our study underscores the need for future research endeavors prioritizing larger, well-designed prospective studies with standardized methodologies to further elucidate the role of ctDNA analysis in guiding personalized treatment approaches and optimizing patient care in this specific HNC cohort.
Pubmed PDF WebNicholas Dietrich, Erin Watson, Tony Tadic, Rosemary Martino, Scott Bratman, John Cho, John de Almeida, Lawson Eng, David Goldstein, Ezra Hahn, Andrew Hope, Ali Hosni, John Kim, Nauman Malik, Brian O’Sullivan, Enrique Sanz Garcia, Lillian Siu, Anna Spreafico, Susie Su, Jillian Tsai
Publicatie 28-12-2024
This study aimed to develop a prediction model for feeding tube dependence in a large homogenous cohort of HPV-associated oropharyngeal squamous cell carcinoma (HPV + OPSCC) patients receiving chemoradiotherapy (CRT). We further aimed to externally validate three previously published feeding tube prediction models on this cohort. p16-confirmed HPV + OPSCC patients treated with definitive CRT at a tertiary cancer centre between April 2017 and February 2022 were identified. The primary endpoint was G-tube dependence, defined as enteral feeding for ≥ 4 weeks following CRT. Clinical and dosimetric data were extracted from electronic patient records. Multivariable analyses (MVA) assessed the associations of potential predictors with G-tube dependence. The discriminatory performance of three previously published models was assessed on this cohort using the area under the receiver operating curve (AUC), and calibration was evaluated with calibration plots. A total of 291 patients were included (TNM8 stage I: 129; II:67; III: 95). MVA identified Dmean to the superior pharyngeal constrictor muscle, D70% to the middle pharyngeal constrictor muscle, and modified diet texture at baseline as predictive for G-tube dependence, with the AUC of 0.68. External validation of three existing models yielded an AUC of 0.60, 0.63, and 0.67, with no evidence of good calibration. Despite a sizable cohort and comprehensive capture of dosimetric information, our prediction model, and external validation of previously published models, showed moderate performance. This suggests that additional factors beyond disease and treatment may need to be considered in future models to refine nutrition support decisions.
Pubmed PDF WebKrishna S. Hanubal, Logesvar Balaguru, David Rengifo, Alexander Simko, Zhanna Galochkina, Reordan DeJesus, Zhongyue Zhang, Cristina Benites, Ji-Hyun Lee, Dustin Conrad, William Mendenhall, Peter T. Dziegielewski
Publicatie 26-12-2024
Osteoradionecrosis (ORN) following radiation therapy (RT) is a serious complication for patients undergoing head and neck cancer treatment. Recent literature has found an association between ipsilateral external carotid artery (ECA) diameter and the development of ORN. This study evaluates microvascular free-flap arterial anastomosis diameter and the development of ORN. Sixty-six patients underwent fibular free-flap reconstruction followed by RT between 2012-2019 at the University of Florida. Anastomosis and ECA diameters pre- and post-RT were measured from computed tomography images. Multivariate regression analysis identified significant factors in the development of ORN. Incidence of ORN was 33.3 % (N = 22/66). Mean post-RT anastomosis diameters were 2.3 and 2.2 for the ORN group and no-ORN group, respectively (p = 0.548). Mean post-RT ipsilateral ECA diameters were 4.7 and 4.2 for the ORN group and no-ORN groups, respectively (p = 0.040). The change in pre-RT versus post-RT ipsilateral ECA diameters was different in patients with RT dose above and below 55 Gy (p = 0.041). Neither post-RT anastomosis (OR = 1.78, 95% CI: 0.43, 8.65, p = 0.434), nor ECA (OR = 1.44, 95% CI: 0.78, 2.83, p = 0.250) diameters were associated with development of ORN while controlling RT dose (OR = 1.15, 95% CI: 1.04, 1.28, p = 0.006), post-operative fistula (OR = 9.11, 95% CI: 1.65, 93.7, p = 0.010), and post-operative infection (OR = 3.48. 95% CI = 1.01, 12.7, p = 0.048), and CCI (OR = 0.61, 95 % CI: 0.36, 0.96, p = 0.031). A higher degree of narrowing in ipsilateral ECA following RT may be linked to development of ORN. RT doses ≥ 55 Gy were associated with a high risk of ORN.
Pubmed PDF WebQigen Fang, Junhui Yuan, Xu Zhang, Liyuan Dai, Ruihua Luo, Tao Huang
Publicatie 25-12-2024
To examine the distribution of non-sentinel lymph nodes (SLNs) and to determine the feasibility of omitting elective neck dissection (END) in cases of cT1/2N0 oral cancer presenting with SLN metastasis. A prospective cohort of patients with cT1/2N0 oral cancer underwent SLN biopsy using a γ-probe alongside methylene blue staining, followed by subsequent END. The primary outcome variable was non-SLN metastasis, with its predictors evaluated through logistic regression analysis. A total of 200 patients with detectable SLNs were analyzed. Logistic regression revealed a significant odds ratio of 4.28 [95 % confidence interval: 2.11-14.56] for predicting non-SLN metastasis when comparing a depth of invasion greater than 4.0 mm to a DOI of 4.0 mm or less. Among the six cases of non-SLN metastasis, three patients with negative SLN biopsy results exhibited metastasis; one was found in ipsilateral level V and two in contralateral level Ib. In contrast, all three patients with positive SLN biopsy results had a DOI surpassing 4.0 mm, presenting with at least two positive SLNs. Non-SLN metastasis was detected in ipsilateral level III for one patient and at level IV for two others. END may be judiciously omitted in cases where only one positive SLN is identified in early-stage oral cancer with a depth of invasion of ≤ 4.0 mm.
Pubmed PDF WebJ.M. Price, K. Garcez, C. Hughes, L.W. Lee, H.M. Mistry, G. Motamedi-Ghahfarokhi, G.J. Price, C.M. West, D.J. Thomson
Publicatie 22-12-2024
Studies reported inferior outcomes when radiotherapy starts >6-8 weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6-8 weeks post-surgery. Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted. 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44 days (IQR: 14 days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95 % CI 0.99-1.02; p = 0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95 % CI 0.99-1.03; p = 0.5). Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6-8 weeks post-surgery and that no threshold is considered for patient selection.
Pubmed PDF WebUchechukwu C. Megwalu, Yifei Ma, Vasu Divi
Publicatie 20-12-2024
There are significant racial disparities in head and neck cancer (HNC) outcomes. Racial differences in survival may be explained by differential access to high-quality care. The goal of this study was to evaluate the association of race and ethnicity with the quality of the treating hospital, and receipt of guideline-compliant care among HNC patients. Retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics. The study cohort included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Outcome measures included the quality of treating hospital, and NCCN guideline-compliant care. Black (OR 0.76, 95 % CI 0.67 to 0.85) and Hispanic (OR 0.68, 95 % CI 0.63 to 0.74) patients were less likely to be treated in top-quality hospitals compared with non-Hispanic White patients, after adjusting for demographic, and clinical factors. This association disappeared for Black patients, but persisted for Hispanic patients, after additionally adjusting for socioeconomic status and insurance status. Black patients with advanced-stage disease were less likely to be treated with dual-modality therapy (OR 0.82, 95 % CI 0.70 to 0.96), however, this association disappeared after adjusting for demographic, and clinical factors, and hospital quality. There are significant racial and ethnic disparities in quality of care for patients with HNC. Our findings suggest that differential access to high-quality care may account for some of the racial disparities in HNC survival, and highlight the need for continued investigation into the drivers of racial disparities in HNC outcomes.
Pubmed PDF WebGeorge B. Sankar, Ghazal S. Daher, Lazaro R. Peraza, Eric J. Moore, Daniel L. Price, Kendall K. Tasche, Linda X. Yin, Toby N. Weingarten, Kathryn M. Van Abel
Publicatie 22-12-2024
Ann-Kristin Struckmeier, Martin Gosau, Ralf Smeets
Publicatie 21-12-2024
Head and neck squamous cell carcinoma (HNSCC) poses a considerable challenge due to its high incidence and mortality rates. Immunotherapy targeting PD-(L)1 emerges as a promising approach for HNSCC, as it has the potential to trigger a broad and long-lasting anti-tumor response. Nevertheless, the effectiveness of immunotherapy encounters hurdles, and only a small proportion of patients benefit, with many eventually experiencing relapse. Consequently, there is a pursuit of strategies to enhance overall treatment outcomes. Understanding the mechanisms driving resistance to PD-(L)1 inhibition and devising strategies to overcome these challenges are vital for advancing more effective treatments. Furthermore, gaining insights into the mechanisms of action and safety profiles of novel combination therapies is critical for their successful adoption in clinical practice. As a result, current research is dedicated to investigating various immunotherapeutic agents beyond the PD-1/PD-L1 axis. This review offers a comprehensive overview of the existing immunotherapy strategies in HNSCC with a focus on TIM-3, TIGIT, LAG-3, and VISTA. The aim is to lay a strong foundation for the continual advancement of therapies for HNSCC.
Pubmed PDF WebJin Wang, Hong Chen, Shuang Fu, Zhen-Ming Xu, Kai-Lai Sun, Wei-Neng Fu
Publicatie 02-12-2024
Carlos M. Ardila, Pradeep Kumar Yadalam
Publicatie 16-12-2024
Lucas Alves da Mota Santana, Marina dos Santos Barreto, Gilmagno Amado Santos, Rajiv Gandhi Gopalsamy, Bernardo Ferreira Brasileiro, Cleverson Luciano Trento, Lysandro Pinto Borges
Publicatie 11-12-2024
Xuan Xiao, Yajia Xie, Zhaocheng Shi, Zhifeng Song
Publicatie 08-12-2024
Flávia Sirotheau Corrêa Pontes, Emilie Christina Teixeira de Barros, Thaís da Silva Fonseca, Igor Mesquita Lameira, Anderson Maurício Paiva e Costa, Douglas Fabrício da Silva Farias, Hélder Antônio Rebelo Pontes
Publicatie 01-12-2024
Eric L. Wu, Fendi Obuekwe, Joshua D. Smith, Mario G. Solari, Arturo A. Eguia, Tonge Enoh, Anthony Tang, Marci L. Nilsen, Jonas T. Johnson, Seungwon Kim, Kevin J. Contrera, Shaum S. Sridharan, Matthew E. Spector
Publicatie 28-11-2024
Gnanaprakash Jeyaraj
Publicatie 28-11-2024
Carlos M. Ardila, Pradeep Kumar Yadalam
Publicatie 23-11-2024
Neil D. Almeida, Han Yu, Austin J. Iovoli, Mengyu Fang, Tyler V. Schrand, Abigail Pepin, Vishal Gupta, Kimberly E. Wooten, Michael R. Markiewicz, Ryan P. McSpadden, Wesley L. Hicks, Mark K. Farrugia, Anurag K. Singh
Publicatie 14-12-2024
The role of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement in head and neck cancer (HNC) patients treated with chemoradiation remains controversial and varies by center. To evaluate the impact of prophylactic PEG tube placement in patients undergoing chemoradiation for HNC PEG tube use for more than 6 months and weight loss. This single-institution retrospective study included 502 patients with head and neck cancer. Concurrent Chemoradiation (CCRT) and prophylactic PEG tube placement. Univariate analyses were performed to determine risk factors for long term PEG tube and weight loss. Outcomes that were significantly associated with prophylactic PEG were selected for a multivariate analysis. The Kaplan-Meier method was used to estimate survival and the time to PEG removal, with comparisons between groups analyzed by log-rank tests. The global health status score from the EORTC QLQ30 was utilized to assess impact on quality of life. Significantly higher weight loss was seen with the following variables: 1) omitting prophylactic PEG tube (p < 0.00001), 2) younger age (p = 0.0032), and 3) adjuvant CCRT (p = 0.0005). There was significantly higher risk of feeding tube duration longer than 6 months in those who: received prophylactic PEG tube (p < 0.0001) and were older than the median age of 60.8 years (p = 0.0165) on multivariate analysis. Prophylactic PEG tube was not associated with improved global health status, overall survival, or progression-free survival on univariate analysis. Prophylactic feeding tubes significantly decreased weight loss during treatment. Prophylactic PEG tube and older than median age was significantly associated with higher risk of feeding tube duration longer than 6 months.
Pubmed PDF WebS. Hasan Pracha, Suvekshya Shrestha, Nathan Ryan, Puja Upadhaya, Felipe F. Lamenza, Sushmitha Jagadeesha, Pete Jordanides, Peyton Roth, Anna Springer, Steve Oghumu
Publicatie 08-12-2024
Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer globally with a 40-50 % survival rate. Although macrophage migration inhibitory factor (MIF) is overexpressed in most solid tumors and promotes tumor growth and invasion, the therapeutic potential of MIF inhibition in HNSCC is yet to be explored. In this study, we investigated the efficacy of CPSI-1306, a small-molecule MIF inhibitor, on HNSCC cell growth and cancer associated signaling pathways in vitro, as well as its impact on T cells in the HNSCC tumor microenvironment in vivo. CPSI-1306 did not reduce HNSCC cell proliferation in vitro, and mildly decreased VEGF and EGFR expression. However, CPSI-1306 significantly reduced tumor development in two orthotopic mouse oral cancer (MOC-2 and MOC-1) HNSCC models. Interestingly, CPSI-1306 treatment increased T cell infiltration to the tumor microenvironment and completely abrogated immunosuppressive checkpoint markers TIGIT, TIM3, and CTLA-4, but not PD-1 on tumor infiltrating CD8
Pubmed PDF WebHui Li, Liming Lou, Juan Du, Mei Li, Xianhui Wen, Yuan Zhang, Songran Liu, Zi-Qi Zheng, Xu Liu
Publicatie 07-12-2024
Nasopharyngeal carcinoma (NPC), historically termed 'lymphoepithelioma-like carcinoma' due to its rich lymphocyte infiltration, benefit from PD-1 blockade treatment. However, a comprehensive understanding of its tumor microenvironment (TME) remains elusive, hindering the identification of effective biomarkers for immunotherapy. We leveraged multimodal profiling data, including gene expression, immunohistochemistry, and multiplex immunohistochemistry, from three independent cohorts of NPC patients with a total of 327 patients to dissect the TME in NPC. Unsupervised hierarchical clustering of TME cell populations in the discovery cohort revealed two novel subtypes with distinct prognosis: 'Immune Inflamed' and 'Immune Deficient'. Intriguingly, the most significant differences between the two subtypes were the abundance of B cells and tertiary lymphoid structures (TLS), with a nearly two-fold increase in TLS presence in the Immune Inflamed subtype. The prognostic significance of TLS was confirmed in three independent NPC cohorts, surpassing the prognostic value of individual immune cell subsets. Mechanistically, TLS enhanced anti-tumor immunity by increasing T and B cell receptor repertoire diversity, promoting infiltration of plasma cells, macrophages, and natural killer cells, and consequently increasing antibody-dependent cell-mediated cytotoxicity and antibody-dependent phagocytosis. Finally, TLS status robustly predicted prognosis in a cohort of NPC patients treated with PD-1 blockade, and its prognostic value was consistent across a pan-cancer immunotherapy cohort of 10 tumors and 1158 patients, although with context-specific effects depending on cancer type and immunotherapy modality. In conclusion, this study provides compelling evidence that TLS is a robust indicator of overall immune response within TME and have great potential to guide individualized immunotherapy.
Pubmed PDF WebAkira Ohkoshi, Ryo Ishii, Kenjiro Higashi, Tadahisa Shishido, Satoshi Kano, Takahiro Kusaka, Daisuke Matsushita, Kosuke Murayama, Yuya Miyakura, Satoshi Kubota, Ryosuke Sato, Shino Godo, Hiroki Tomizawa, Satoshi Toyoma, Ai Tagawa, Akina Shirotori, Yukio Katori
Publicatie 03-12-2024
Salivary gland cancer is a rare disease composed of more than 20 histological types with different grades of malignancy. The aim of this multicenter, retrospective study was to identify the most important predictors affecting recurrence and survival after surgery. A total of 543 patients with salivary gland cancers that underwent curative surgery between 2012 and 2022 in 13 institutions in northern Japan were evaluated in this study. Predictors affecting recurrence and survival were identified by univariate and multivariate Cox regression analyses. Age, sex, primary site, histological type, pathological T status, surgical margin, lymph node metastasis, extranodal extension, and postoperative radiotherapy were the variables evaluated. Multivariate Cox regression analysis showed that increasing age, submandibular cancer, pathological T status 3 or 4, positive surgical margin, and lymph node metastasis, especially with extranodal extension, were independent risk factors for both recurrence and survival. Sublingual cancer was an independent risk factor for recurrence. Postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis, and adenoid cystic carcinoma was associated with a good prognosis. Lymph node metastasis with extranodal extension was the most important prognostic factor affecting both recurrence and survival after surgery, adenoid cystic carcinoma was associated with a good prognosis, and postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis.
Pubmed PDF WebGrégoire Marret, Constance Lamy, Sophie Vacher, Luc Cabel, Mathieu Séné, Ladidi Ahmanache, Laura Courtois, Zakhia El Beaino, Jerzy Klijanienko, Charlotte Martinat, Nicolas Servant, Choumouss Kamoun, Maral Halladjian, Thierry Bronzini, Cédric Balsat, Jean-François Laes, Aubray Prévot, Sébastien Sauvage, Maxime Lienard, Emmanuel Martin
Publicatie 30-11-2024
Head and neck squamous cell carcinoma (HNSCC) is characterized by significant genetic intra-tumor heterogeneity (ITH), which may hinder precision medicine strategies that depend on results from single tumor-biopsy specimens. Treatment response assessment relies on radiologic imaging, which cannot detect minimal residual disease (MRD). We assessed the relevance of circulating tumor DNA (ctDNA) as a biomarker for ITH and MRD in HNSCC. We recruited 41 non-metastatic resectable HNSCC patients treated with upfront curative-intent surgery in the prospective biobanking SCANDARE study (NCT03017573). Thirty-one patients (76 %) showed recurrent disease at a median follow-up of 41 months. Targeted next-generation sequencing was performed on resected tumor tissues, as well as on serial blood samples obtained at surgery, within 14 weeks after surgery, at six months and at recurrence. ctDNA was detected in 21/41 patients at surgery (sensitivity: 51 %; 95 % CI, 35-67 %) and 15/22 patients at recurrence (sensitivity: 68 %; 95 % confidence interval [CI], 45-86 %). Among patients with mutations identified in longitudinal plasma samples, additional mutations missed in tumor tissues were reported in 3/21 patients (14 %), while emerging mutations were reported in 9/21 patients (43 %). In the postoperative surveillance setting, ctDNA-based MRD detection anticipated clinical recurrence with a median lead-time of 9.9 months (interquartile range, 8.0-14.5 months) in 17/27 patients (63 %). When detected within 14 weeks after surgery, MRD correlated with disease recurrence after adjusting for classical prognostic variables (HR = 3.0; 95 % CI, 1.1-7.9; p = 0.03). ctDNA detection is a useful biomarker for ITH and MRD in resectable HNSCC patients.
Pubmed PDF WebChang Yan, Runzhi Wang, Chaojun Zhang, Guoxiang Lin, Youqing Du, Meiwen Chen, Fushuang Liu, Ling Li, Song Qu, XiaoDong Zhu
Publicatie 26-11-2024
Gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin plus fluorouracil (TPF) are induction chemotherapy (IC) regimens for locally advanced nasopharyngeal carcinoma (LA-NPC). The oral convenience of capecitabine presents its potential as a fluorouracil substitute in the TPF regimen, which has yet to be thoroughly investigated. This study aims to compare the efficacy and safety of the docetaxel, cisplatin, and capecitabine (TPC) with GP and TPF in LA-NPC. A retrospective analysis was conducted on newly diagnosed stage III-IVa nasopharyngeal carcinoma patients who received GP, TPC, or TPF induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) between February 2019 and December 2021. A comparison of the prognostic outcomes and associated adverse reactions among patients receiving different IC regimens. Multivariate Cox regression was applied to analyze independent prognostic factors, and subgroup survival analyses were conducted based on these factors. A total of 291 LA-NPC patients were included, with 70 receiving TPC, 119 receiving GP, and 102 receiving TPF. Kaplan-Meier survival analysis indicated no significant differences in OS, PFS, LRFS, and DMFS among the 3 groups. Multivariate Cox regression identified T classification and clinical stage as independent prognostic factors. Subgroup analyses revealed no significant differences in OS and PFS between the 3 groups across T1-2 and T3-4 classifications or III and IVa stages.The TPC group exhibited lower incidence rates of treatment-related acute toxicity reactions, including grade 3-4 toxicities. The TPC induction chemotherapy regimen demonstrates comparable efficacy to GP and TPF, while maintaining a favorable safety profile.
Pubmed PDF WebYanan Liu, Nantao Fu, Haitao Liu, Shanshan Su, Tingting Yang, Ping Long, Wei Zhong, Xiang Min
Publicatie 26-11-2024
To analyze the clinicopathological features and predictors of lymph node metastasis (LNM) in the diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and compare these findings with conventional papillary thyroid carcinoma (C-PTC) in pediatric populations. Patients aged 18 years or younger who were preoperatively diagnosed with PTC and underwent thyroidectomy at the First Affiliated Hospitals of Nanchang University from January 2017 to May 2024 were included in this study. Demographic and clinicopathological characteristics were retrospectively analyzed. Univariate and multivariate analyses were performed to identify risk factors for lymph node metastasis. Clinical outcomes, including nerve injury, hypocalcemia, and recurrence, were also recorded and evaluated. A total of 119 children were enrolled in this study, with a median age of 15.6 years. Of these, 89 (74.8 %) were female, and 18 (15.1 %) were diagnosed with DSV-PTC. Central lymph node metastasis (CLNM) was observed in 94 (79 %) patients, while 60 (50.4 %) had lateral lymph node metastasis (LLNM). DSV-PTC was associated with a higher incidence of CLNM and LLNM compared to C-PTC (p = 0.039, p < 0.001). Multifocality and bilateral tumors were also more common in DSV-PTC (p < 0.001). Cox regression analysis identified tumor size as an independent predictive factor for CLNM in pediatric C-PTC patients. Tumor size, ETE and the presence of CLNM were independent predictive factors for LLNM. After a mean follow-up of 32.8 months, no patient died from the disease, but four C-PTC patients (4.0 %) developed local recurrences, which were managed surgically. Lung metastasis occurred in 2 (11.1 %) DSV-PTC and 1(1.0 %)C-PTC patients, respectively. Permanent injuries included one case of unilateral recurrent laryngeal nerve(RLN) injury and two cases of bilateral RLN injury. Four patients (4.0 %) experienced temporary hypocalcemia, which resolved after 6 months of calcium therapy. DSV-PTC presents unique characteristics of lymph node metastasis and may be more aggressive than conventional PTC in pediatric populations. The presence of CLNM, tumor size and ETE were identified as independent predictors of LLNM in pediatric patients with conventional PTC. Evaluating these prognostic factors may help in customizing individualized surgical approaches for children, thereby reducing unnecessary surgical complications.
Pubmed PDF WebRoosmarijn S. Tellman, Dominique N.V. Donders, Rutger Mahieu, Ellen M. Van Cann, Robert J.J. van Es, Gerben E. Breimer, Bart de Keizer, Remco de Bree
Publicatie 22-11-2024
Sentinel lymph node biopsy (SLNB) has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). The 10%-rule, used to define sentinel lymph nodes (SLN) intraoperatively, states that an SLN is defined by gamma counts that are at least 10% of the hottest harvested lymph node (LN). However, this intraoperative rule has not yet been adequately evaluated for early-stage OSCC. This study aims to evaluate the 10%-rule intraoperatively and explore possibilities for redefining this criterion. A single center retrospective study was performed between 2014 and 2023. Patients (n = 66) with clinically node-negative OSCC (cT1-3N0) and positive SLNB were included in this study. Radioactivity of all harvested LNs were measured ex-vivo. Metastatic LNs were assessed for complying with the 10 %-rule. The accuracy of alternative thresholds was evaluated. If multiple positive SLNs on one side of the neck were found, the hottest positive SLN on that side was considered the LN accountable for upstaging the corresponding neck side from N0 to N+. A total of 233 LNs were harvested, of which 98 contained metastases and 190 met the 10%-rule. Of these metastatic LNs, 70 were accountable for upstaging the side of the neck. The 10%-rule correctly staged 69 of 70 metastatic sides of the neck. By increasing the intraoperative cut-off point to 20%, 68 of 70 metastatic sides of the neck were correctly staged and 18 LNs (172 vs. 190) were not defined as SLN. Applying the 10%-rule to each side of the neck increased detection of one metastatic LN. However, this LN was not accountable for upstaging that side of the neck. The 10%-rule in SLNB applies to patients with OSCC and effectively identifies metastatic SLNs intraoperatively. Applying the 10%-rule per neck side must be considered. Increasing the threshold percentage is not advisable.
Pubmed PDF WebTan Mai Nguyen, Pauline Quilhot, Isabelle Brochériou, Guillaume Rougier, Philippe Maingon, Chloé Bertolus, Jean-Philippe Foy
Publicatie 30-11-2024
Oral squamous cell carcinoma (OSCC) is associated with an important mortality and morbidity related to surgery and radiotherapy. In particular, radiation-induced xerostomia has a major impact on patient's quality of life. Although intensity-modulated radiation therapy allowed mean dose reduction to the spared submandibular gland (SMG) in patients with head and neck squamous cell carcinoma, xerostomia is still an important sequela for patients treated for an OSCC. SMG surgical transfer into anatomical subsite receiving very low radiation doses is a promising approach to prevent xerostomia. Based on a literature review and data from our institutional cohort, we analyzed the oncological safety of SMG preservation. Then, we discussed the feasibility and relevance of SMG transfer into the temporal fossa, in order to prevent radiation-induced xerostomia in patients with OSCC.
Pubmed PDF WebSarah Mortaja, Francesca Angela Chiumenti, Deepak M. Kalaskar, Raghav C. Dwivedi
Publicatie 02-12-2024
Pedicled, fasciocutaneous and visceral flaps are all widely adopted for reconstruction after ablative surgery for advanced laryngeal, hypopharyngeal and cervical oesophageal cancers. With multiple options available, the choice depends on type and extent of the defect, patient's general conditions and institution expertise or preference. Since its first description in 1959, the use of jejunal free flap (JFF) has been refined thanks to the introduction of microvascular anastomoses, progressively allowing to achieve low mortality and morbidity rates. Both swallowing and speech outcomes are also positively reported across studies. A systematic review of English literature on JFF in H&N cancer reconstruction published after 2000 was carried out on Medline and Embase. Thirty-six studies were included in the analysis with a total of 3191 JFF reconstructions. Primary outcomes were surgical complications and functional outcomes (quality of speech and oral alimentation). A cumulative review was created pooling complication rates reported in single studies, and overall rates were obtained for fistulas (11.39%), strictures (14.17%), total and partial flap failure (4.79 and 6.15% respectively) and perioperative mortality (3.1%). Functional outcomes were variably reported, with different qualitative and quantitative assessment methods showing overall positive results. When reported, we've included impact of adjuvant radiotherapy and the ability of JFF to tolerate it has been widely confirmed. Above results have also been compared with same outcomes registered for different flaps. Overall, studies over the past 20 years demonstrate good clinical and functional outcomes, proving JFF to be a reliable and safe method for reconstructing circumferential pharyngoesophageal defects.
Pubmed PDF WebNoémie Villemure-Poliquin, Rui Fu, Karolina Gaebe, Jin Kwon, Marc Cohen, Marianne Ruel, Kennedy Ayoo, Andrew Bailey, Madette Galapin, Julie Hallet, Antoine Eskander
Publicatie 23-11-2024
Delayed diagnosis to treatment interval (DTI) in head and neck cancers (HNC) can significantly impact patient outcomes. The need for multimodal treatment in HNC may cause delays in initiation of treatment. This systematic review aims to provide a comprehensive understanding of the consequences of delayed DTI on both oncologic and QoL outcomes, proposing a new quality benchmark along the treatment continuum of HNC patients. We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases for trials and cohort studies evaluating the impact of delayed DTI in patients with HNC. Outcomes included overall survival (OS), disease-free survival (DFS), locoregional (LRR) and local recurrences (LR) and distant metastasis. Our search strategy initially identified 10,779 titles and abstracts, of which 63 articles met inclusion criteria for a total of 873,718 patients. The pooled analysis showed that treatment initiation within 30 days improved OS by 9 % compared to longer intervals (aHR: 1.09 [1.06-1.13]; I While adherence to a 30-day DTI may be associated with improved survival in some HNC patients, significant heterogeneity in the data limits the generalizability of this finding. Further research with more refined analyses, including adjustments for treatment modality and cancer stage, is necessary. Additionally, gaps remain in the literature, particularly in the methodological limitations related to DTI classification.
Pubmed PDF WebGJ Fan-Yuan,S Wang
Publicatie 02-01-2025
A novel continuous-variable quantum passive optical network is proposed in which a user can increase their key rate by trusting other users. This is because the keys, which would be discarded to remove correlations with untrusted users, can be retained when the users are trusted. It provides a new perspective for enhancing network performance.
Pubmed PDF WebYanan Liu, Nantao Fu, Haitao Liu, Shanshan Su, Tingting Yang, Ping Long, Wei Zhong, Xiang Min
Publicatie 01-01-2025