bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypofractionated radiotherapy compared with conventionally fractionated radiotherapy to treat initial distant metastases in nasopharyngeal carcinoma: A multicenter, prospective, randomized, phase II trial.
Authors: Jiang Wei , Liu Jian , Zhang Bin , Su Yixin , Qin Guanjie , Kong XiangYun , Mo Yunyan , Zhang Rongjun
Published: June 2023

e18019

Background: To investigate the safety and efficacy of hypofractionated plus chemotherapy in patients with initially distant metastatic nasopharyngeal carcinoma (mNPC). Methods: Between May 2014 and June 2020, 35 patients initially diagnosed with mNPC were enrolled on prospective trial. The enrolled patients were assigned randomly to receive either hypofractionated plus chemotherapy (HFRT) or conventionally fractionated radiotherapy plus chemotherapy (CFRT). 60 Gy over 25 fractions was administered to the HFRT group (n = 17) and 69.96 Gy over 33 fractions was administered to the CFRT group (n = 18), both groups five times each week. Progression free survival (PFS) comprised the primary endpoint. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and acute and late toxicity comprised the secondary endpoints. Results: Twenty-eight patients (seven were excluded) were enrolled. The 2-year PFS was 33.3% (HFRT group) versus 30.0% (CFRT group) (stratified hazard ratio (HR):1.09; 95% confidence interval (CI): 0.45–2.65, P = .843). The 2-year OS was 66.7% (HFRT group) versus 62.5% (CFRT group) (stratified HR, 0.88; 95% CI; 0.31–2.51, P= .806). All patients experienced acute grade 1 or 2, skin toxicity, oral mucositis, dysphagia, dry mouth, but no acute grade 3 or 4 toxicities. All patients had grade 1 late xerostomia. Two patients experienced hearing loss (one grade 1 and one grade 3). One patient developed mucosal necrosis. Conclusions: The two groups had similar outcomes. Improving the balance between severe late toxicities and local control by appropriately reducing the total dose but increasing the fractionated dose has marked clinical significance for patients with initially diagnosed mNPC. The trial has been registered with clinicaltrials.gov (NCT03598218). Clinical trial information: NCT03598218 . [Table: see text]
Intratumoral heterogeneity as a predictive biomarker in immunotherapy for advanced head and neck squamous cell carcinoma.
Authors: Liu Juying
Published: June 2023

e18028

Background: Intratumoral heterogeneity (ITH) is associated with the poor prognosis in a variety of solid tumors, because of the therapeutic failure and drug resistance. However, we still lack understanding of the relationship between ITH and immunotherapy for advanced head and neck squamous cell carcinoma (HNSCC). Methods: We used the Bioconductor R package Maftools to analyze somatic variants of HNSCC from MSK-IMPACT-1611 study cohort (PMID: 30643254) with data from 68 patients. Then, a mutant-allele tumor heterogeneity (MATH) algorithm was used to measure ITH score. Finally, we analyzed the difference in the genomes, and the association with tumor mutational burden (TMB) between the ITH score high (ITH-H) and ITH score low (ITH-L) groups, and the effect of ITH on the prognosis of immunotherapy. Results: There was no significant difference in the high frequency mutated genes between the high ITH and low ITH groups. The genes with the highest mutation frequency in ITH-H group were TP53 (90.48%), TERT (47.62%), CDKN2A (38.1%), FAT1 (33.33%), NOTCH1 (28.57%), KMT2D (19.05%), APC (14.29%), and ASXL1 (14.29%), while the genes with the highest mutation frequency in ITH-L group were TP53 (44.68%), PIK3CA (38.3%), TRET (36.17%), FAT1 (21.28%), NOTCH1 (19.15%), KMT2C (17.02%), KMT2D (17.02%), and CDKN2A (14.89%). The median overall survival (mOS) of ITH-L group was significantly higher than that of ITH-H group (not reach versus 10 months, hazard ratio (HR) = 2.15, 95%CI 1.05−4.4, P = 0.032). There was no significant difference in median TMB levels between ITH-L and ITH-H groups (P = 0.55). The TMB high (TMB-H) patients had no significantly better mOS than the TMB low (TMB-L) group (HR = 0.54, 95%CI 0.25−1.16, P = 0.11). A pooled analysis of ITH and TMB show that the ITH-L+TMB-H group had significantly better improvement mOS than that in the ITH-L+TMB-L, ITH-H+TMB-H, and ITH-H+TMB-L group (HR = 0.71, 95%CI 0.13−1.35, P = 0.048). Conclusions: ITH may serve as a positive predictor of immunotherapy in patients with advanced HNSCC and is independent of TMB.
Atypical new metastatic sites after immunotherapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M H&NSCC).
Authors: Deeken John F. , Ahmadi Mahsa , Johnston Laura , Heyer David M. , Lee Patty , Niknia Katherine , Bajaj Gopal Krishna
Published: June 2023

e18032

Background: Immunotherapy with PD-1 inhibitors (PD-1Is) nivolumab (N) or pembrolizumab (P) has led to significant improvements in overall survival in pts with R/M H&NSCC. Common metastatic (met) sites for R/M H&NSCC are locoregional in the H&N area (LR), lung (L) and liver (LV). We investigated where patients developed met sites after successful treatment with PD-1Is. Methods: Eligible pts were treated with N or P for at least 3 months in the 1st or 2nd line setting and with at least stable disease as best response. Records were reviewed for initial sites of disease and whether metastatic sites developed after PD-1 therapies, including during subsequent lines of therapy. Patients could have more than one initial or progressive metastatic/recurrent sites of disease. Results: 26 eligible pts treated between 2016-2022 were identified with demographics as follows: 20 males/6 females; average age 65.3 yrs; primary diseases were 13 oropharynx (12 HPV+), 10 oral cavity, 1 larynx, and 2 nasopharynx; 8 received N and 18 got P (4 with chemotherapy); 22 were treated in 1st line and 4 in 2nd line. The median time on PD-1I therapy was 51.7 weeks (range 19 – 100). Best response was stable disease in 9 (35%), partial response in 15 (58%), and complete response in 2 (8%). Initial sites of disease were: LR 16 (62%), L 16 (62%), LV 2 (8%) and bone 2 (8%). In the 16 pts who developed new sites of disease, these included L in 5 (31%), LV in 4 (25%), bone in 7 (44%), abdomen/mesentery in 7 (44%), lower extremities in 4 (25%), and brain in 3 (19%). All 3 who developed CNS mets had HPV+ oropharynx cancer. Conclusions: Pts successfully treated with PD-1Is had uncommon sites of new metastatic disease, including in the lower extremities, abdomen, and brain. This has important ramifications for restaging scan requirements in these patients while on treatment. These results also raise the possibility of disease site sanctuaries resistant to immunotherapy, including in the abdomen, bone, and brain. Larger patient series should be investigated.
Patients characteristics, treatment patterns and clinical outcomes in patients with head and neck squamous cell carcinoma (aHNSCC) receiving immunotherapy in advanced setting: Retrospective cohort analysis of real-world data in Spain.
Authors: Ortega Granados Ana Laura , Vinueza German Paolo , Lopez Lopez Jose Antonio , García Verdejo Francisco José , Montosa Fernando Gálvez , Luque Caro Natalia , Ruiz Sanjuan María , Beltran Leticia Diaz , de la Torre Cabrera Capilla , Fernández Navarro Mónica , Cárdenas Quesada Nuria , Moreno Jimenez Miguel Angel , Marin Pozo Juan Francisco , Sanchez Rovira Pedro
Published: June 2023

e18033

Background: This retrospective cohort analysis looked at real-world data from Spain to better understand the characteristics, treatment patterns and clinical outcomes of patients with aHNSCC who received immunotherapy in an advanced setting. In aHNSCC, the standard of care was platinum-based chemotherapy. However, this treatment modality is associated with significant toxicity and only a minority of patients achieve long-term disease control. As a result, there was an unmet need for effective and well-tolerated treatment till immunotherapy has shown efficacy in some clinical trials. However, data on the use of immunotherapy in routine clinical practice are limited. The aim of this study was to characterize the real-world safety and effectiveness of immunotherapy in patients with aHNSCC in real practice. Methods: This was a retrospective cohort study that included data from our database, a tertiary hospital in Spain. Patients with a diagnosis of aHNSCC who received immunotherapy between 2017 and 2022 were included, excluding those in clinical trials. Clinical outcomes assessed were overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity profile. 97 patients were included in the analysis. The most common histological subtype was oral cavity cancer (43%), followed by laryngeal cancer (29%). Results: The majority of patients had stage IVA-B disease at diagnosis (62%). A 53% of patients received first line nivolumab as monotherapy, or pembrolizumab as monotherapy or combined with platinum chemotherapy, and a 58% of patients received second or third line nivolumab as monotherapy.With a median age of 64 years (range: 45-86), most patients received it as second-line or later treatment (70%). The overall response rate was 29%, with durable responses seen in some patients (28% longer than 1 y). The median overall survival was 13.9 months in first-line setting (3-24 mo), and the 1-year survival rate was 36%. In second-line setting, the median OS was 11.1 mo (3-89 mo), and 1-year survival rate was 33%. More frequent toxicities were skin (26%) and endocrine (21%). We had 8 cases of hyperprogressive disease (8.2%) and treatment was interrupted due toxicity in 6 patients. Conclusions: These results are very close to results found in clinical trials (KEYNOTE-048, CheckMate 141) and confirm that immunotherapy is safe and impacts on survival of aHNSCC patients. We need to identify predictive biomarkers for response and toxicity.
Effect of GNA13 on the alteration of tumor microenvironmental components through exosomes to promote the development of head and neck tumors.
Authors: Zhu Weili , Zhao Miaoqing , Li Xiaoming , Ma Yuting , Yao Zhi-Gang , Ru Kun
Published: June 2023

e18035

Background: Guanine nucleotide-binding protein alpha subunit 13 (GNA13) is closely related to tumor development, but the effect of GNA13 on the biological behavior of head and neck tumors is unknown. The aim of this study was to investigate whether GNA13 can influence the alteration of tumor microenvironment components through exosomes, which in turn promotes the development of head and neck squamous carcinoma (HNSCC). Methods: Using the Gene Expression Omnibus database, the differentially expressed gene GNA13 was screened. Immunohistochemistry and western blotting were used to detect the expression of GNA13 in HNSCC tissues and control tissues. GNA13 expression was down-regulated in tumor cell lines using transfection techniques. The effect of GNA13 downregulation on tumor cell growth was examined by in vitro experiments. RT-PCR and dual luciferase reporter gene assays were used to validate GNA13-regulated miRNAs and their target genes. Clonogenesis assays were used to examine the effect of target gene expression on fibroblasts, and the HNSCC xenograft mouse model was used to verify the role of GNA13 in tumor growth in vivo. The peripheral blood from patients with different stages of HNSCC was collected to determine the expression level of GNA13 in serum exosomes and to analyze its relationship with metastasis and postoperative recurrence. Results: GNA13 expression was elevated in HNSCC tissues and cells. The growth capacity of HNSCC cells was significantly reduced after downregulation of GNA13, which induced fibroblast conversion to MAF via exosomes and promoted their proliferation and migration. Meanwhile, GNA13 was able to regulate miR-26a-5p/STRADB expression in fibroblasts via exosomes. The overexpression of STRADB promoted the proliferation and migration of fibroblasts and induced their conversion to MAF. More importantly, in the conditioned medium of STRADB overexpressing fibroblasts, the proliferation and migration of HNSCC cells were promoted. Furthermore, knockdown of GNA13 expression inhibited the tumor growth in nude mice. It appeared that high expression of GNA13 in serum exosomes of patients with HNSCC was associated with poor prognosis. Conclusions: GNA13 regulates the miR-26a-5p/STRADB axis in fibroblasts via exosomes to create a metastasis-friendly microenvironment for tumor cells, ultimately promoting the progression of HNSCC. Meanwhile, the expression of GNA13 was positively correlated with the pathological grade and clinical stage of HNSCC, which seems to be a reliable indicator of tumor recurrence. Targeting this signaling pathway would be a promising therapeutic strategy for HNSCC.
Association of molecular profiles of head and neck squamous cell carcinoma with heterogeneity across racial/ethnic groups in the United States.
Authors: Bhayani Mihir K , Jaeger Ellen B. , Al-Khudari Samer , Stenson Kerstin , Joshi Nikhil , Godden Jen , Stoppler Melissa Conrad , Jelinek Michael J.
Published: June 2023

e18036

Background: Significant disparities exist across the head and neck cancer (HNC) care continuum in presentation, treatment, and survival. Along with demographic factors such as race or ethnicity, tumor-specific molecular signatures may play a role in these differences. In the United States, the current body of literature mainly highlights molecular contrasts between Black and White patients. Here, we further investigate the molecular profiles of Black and White patients with HNC and add to the literature by comparing additional racial/ethnic groups in a large, real-world cohort. Methods: De-identified records of patients with a primary diagnosis of HNC who underwent Tempus xT testing (Tempus Labs, Chicago, IL) were selected from the Tempus Database. Those with squamous cell histology and self-reported race were selected for retrospective analysis. Briefly, Tempus xT is a targeted, tumor/normal-matched panel that detects single-nucleotide variants, insertions and/or deletions, and copy number variants in 648 genes, as well as chromosomal rearrangements in 22 genes with high sensitivity and specificity. Tumor mutational burden (TMB) was calculated by dividing the number of nonsynonymous mutations by the megabase size of the panel. Results: Among the 749 patients included, most identified as Non-Hispanic/Latino (NHL) White (n = 570), while 62 identified as NHL Black, 44 as NHL Asian/Pacific Islander (API), 21 as NHL of other races, and 52 as Hispanic/Latino of any race. Age at diagnosis differed between races ( P= 0.009). Oral cavity was the most common subsite in our cohort (N = 306, 41%). TMB also differed among races ( P= 0.018), with Black patients demonstrating the highest TMB (median = 4.6 mut/Mb [3.0-6.2]) and API the lowest (median = 2.3 mut/Mb [1.5-4.2]). Black patients had higher proportions of TP53 (76%), KMT2D (24%), and CTTN (15%) alterations (not significant across races). There were differences in the frequencies of OR4G11P (q = 0.031) and OR4F5 (q = 0.014) aberrations between races, with Black patients showing the highest frequencies (16% and 15%, respectively). The API population demonstrated higher frequencies of RASA1 (16%), MTAP (11%), CDKN2B (32%), and ERCC3 (11%) mutations (not significant across races). Additionally, there were differences in TERT mutations between races (q = 0.01), with API harboring the highest proportion of TERT co-mutations (52%). Conclusions: Overall, these results demonstrate that molecular profiles are heterogeneous across multiple racial/ethnic groups. Many of the alterations described here have been previously associated with outcomes in HNC. Accordingly, future investigations should aim to understand the effects of the activated pathways for clinical utility and investigate biomarkers to drive individualized treatment plans that result in equitable care.
Rapid establishment of patient-derived organoids from treatment-naive head and neck cancer patients for drug and radiosensitivity screening.
Authors: Tinhofer Inge , Fisch Anne-Sophie , Pestana Ana , Doll Christian , Heiland Max , Dommerich Steffen , Obermüller Theresa , Hofmann Veit Maria , Klinghammer Konrad Friedrich , Piwonski Iris , Schallenberg Simon , Zips Daniel
Published: June 2023

e18043

Background: Patient-derived organoids (PDOs) have been shown to be powerful tools for modeling disease and patient-individualized drug sensitivity screening, opening a novel avenue to precision medicine. A major challenge for guidance of clinical decisions is the extended time frame for establishing these models. Here, we report the feasibility of a refined protocol for PDO generation from head neck squamous cell carcinoma (HNSCC) tumors, suitable to guide personalized treatment decisions in the curative setting. Methods: After informed consent, tumor tissue specimens from 145 newly diagnosed HNSCC patients were collected during diagnostic biopsy or curative surgery. Following mechanic / enzymatic dissociation and initial expansion in 2D cultures, tumor cells were seeded in extracellular matrix (Matrigel) to form PDOs. Primary endpoint of the study was the PDO engraftment rate. In additio, the time needed for ex vivo expansion of PDO cultures for personalized drug/radiosensitivity testing was determined. Interference of patient and tumor characteristics with PDO engraftment was analyzed using SPSS version 27. Results: The PDO engraftment rate in the entire cohort was 51% (n = 74 of 145 patients). Neither tumor stage, grading, anatomical sublocalisation, HPV status nor sample type (biopsy vs. surgical specimen) were significantly associated with PDO establishment. Of note, Kaplan-Meier analysis revealed a trend between successful ex vivo engraftment and reduced overall survival (log-rank: p = 0.09), suggesting preferential engraftment of aggressive poor prognosis tumors. Engraftment rate in the subgroup of patients with recommendation for adjuvant chemoradiation was 58%. Time for expansion of PDO cultures for subsequent drug/radiation screening was 18.5 ± 9.6 days (median ± SD). Expansion was completed before start of adjuvant chemoradiation in all but one cases. Conclusions: Our study suggests feasibility of PDO generation for locally advanced aggressive HNSCC within a timeframe suitable for guiding treatment decisions for adjuvant therapy. Planned future directions include clinical validation of drug testing results for individual patients and clinical study cohorts.
Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.
Authors: Lu Hsueh-Ju , Chiu Yu-Wei , Peng Chih-Yu , Tseng Hsien-Chun , Hsin Chung-Han , Chuang Chun-Yi , Chen Chun-Chia , Wu Ming-Fang , Huang Wei-Shiou , Yang Sung-Fa
Published: June 2023

e18052

Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P < 0.001), histologic grade ( P < 0.001), and pathologic features (depth of invasion [DOI] > 4mm, P < 0.001; perineural invasion, P < 0.001) than those without. Positive margin and advanced DOI ( > 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.
Association of patient and tumor characteristics with outcomes in young patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Hsieh Ronan Wenhan , Gooding William E. , Nilsen Marci Lee , Kubik Mark , Kelly Zahra Rahman , Sridharan Shaum , Skinner Heath Devin , Iheagwara Uzoma K. , Zevallos Jose , Duvvuri Umamaheswar , Kim Seungwon , Ferris Robert L. , Zandberg Dan Paul
Published: June 2023

e18054

Background: HNSCC is increasingly being diagnosed in a younger population, with a variable prognosis. While studies have evaluated outcomes in young compared to older patients, evaluation of prognostic factors specifically in younger patients, that may help guide treatment decisions, is needed. Therefore, we conducted a retrospective study to investigate the association of patient and tumor characteristics with disease specific survival (DSS) in HNSCC patients ≤45 years old (yo). Methods: Patients treated at the University of Pittsburgh Medical Center from January 1, 2007 to June 30, 2020, that were ≤45 yo at time of diagnosis with HNSCC without distant metastatic disease, were included. Those who received treatments at other institutions and who had no follow-up after index treatments were excluded. Patient demographics, social history, tumor pathology and treatment course were collected. The primary endpoint of DSS was defined as the interval between the time of pathologic diagnosis and the time of cancer-related death. Proportional hazards regression was applied separately for surgically and non-surgically treated patients. A multivariate analysis was conducted for surgically treated patients only. Results: 230 patients were included. Median age was 42, 73% male, 45% oral cavity primary, 35% oropharynx (89% Human papillomavirus positive), 14% larynx, 69% were smokers, and 73% received combined modality therapy. 35% of patients had a recurrence with the majority locoregional only (61%). Median DSS was not reached. The 5 year DSS was 73% (95% CI 67% to 80%). There was no difference in DSS between surgically treated (n = 169) and non-surgically treated (n = 61, p = 0.94) patients. For surgically treated patients, univariate analysis showed significantly worse DSS in those with higher pathologic T and N stages, positive margins, perineural invasion (PNI), extranodal extension (ENE), and negative HPV status. For non-surgically treated patients, only negative HPV status was associated with significantly worse DSS (p = 0.034). In the multivariate analysis for surgical treated patients, which included all significant characteristics from univariate analysis, pathologic T and N stage, positive margins, (HR 4.92, 95% CI 1.98-12.25, p = 0.006) and PNI (HR 2.66, 95% CI 1.17-6.08, p = 0.02) were significantly associated with worse DSS. Conclusions: Pathologic T and N stage, positive margins, and PNI are independently associated with significantly worse DSS in surgically treated HNSCC patients aged ≤45. Compared with classic prognostic factors seen in the overall population with HNSCC, PNI may be a uniquely strong prognostic factor in younger-aged HNSCC patients.
Efficacy and safety of immunonutrition in preventing oral mucositis during concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.
Authors: Qin Yating , Yang Chaolin , Yang Dong , Meng Zhen , Dong Huan , Li Pian , Huang Heqing , Hu Xueying , Zhang Tingting , Shen Meizhu , Liu Kang , Fang Yeying , Wang Rensheng , Kang Min
Published: June 2023

e18056

Background: To assess the efficacy of immunonutrition on severe radiotherapy-induced mucositis (RIOM) during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC). Methods: In total, 30 patients with NPC undergoing CCRT were enrolled in our study. Patients in immunonutrition group (n = 15) receive an immunonutrient formula containing omega-3-fatty acids, arginine, nucleotides from five days before radiotherapy until the end of radiotherapy. Patients in control group (n = 15) receive isocaloric isonitrogenous product. The incidence of grade 3 or 4 RIOM was compared between two groups. Results: Although there was no difference of the incidence of grade 3-4 oral mucositis between the two groups (p = 0.050), the rate of severe mucositis were 13.3% (2/15) in immunonutrients, which was much lower than 53.33% (8/15) in control group. A significant improvement in body fat mass was observed in immunonutrition group than that in control group during the CCRT (3.476, 95CI% 0.015~6.937, P = 0.049) and at the end of CCRT (4.115, 95%CI 0.872~7.359, p = 0.015). And the levels of interleukin 6 (-6.765, 95%CI -16.104~2.573, p = 0.148) and C-reactive protein (CRP) (-7.937, 95%CI -20.395~4.520, p = 0.201) at the end of radiotherapy were lower in immunonutritions even though no statistical difference was reached. In addition, immunonutrition has the potential to improve the life of the patient in the EORTC QLQ-H&N35 scales in painkillers (-13.332, 95%CI -22.612~-4.052, p = 0.007), pain (-15.873, 95%CI -32.131~0.384, p = 0.055), dysphagia (-15.516, 95%CI -34.136~3.104, p = 0.099) and dry mouth (-12.860, 95%CI -31.135~5.415, p = 0.160) at the end of radiotherapy. No patients died of treatment-related causes. Conclusions: Our study indicates that immunonutrition may reduce severe oral mucositis and improved quality of life for patients with NPC during CCRT. Further studies with a larger sample size on the role of immunonutrition in oral mucositis are required to substantiate the result of the study.
Radiation-induced nasopharyngeal necrosis in locally-recurrent nasopharyngeal carcinoma patients after re-radiotherapy.
Authors: Huang Runda , Miao Jingjing , Zhang Lu , Peng Yinglin , Huang Shaomin , Han Fei , Wang Lin , Deng Xiao-Wu , Zhao Chong
Published: June 2023

e18063

Background: Re-radiotherapy (re-RT) is the main treatment for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and commonly led to radiation-induced nasopharyngeal (NP) necrosis, which was lethal but rare study has focused on it. The aim of this study was to evaluate the cause and impact of radiation-induced NP necrosis in lrNPC patients who received re-RT. Methods: Totally 252 lrNPC patients who received re-RT between January 2013 and December 2020 were retrospectively collected. The inclusion criteria were as follows: (1) no NP necrosis before re-RT; (2) complete medical records, including treatment, clinical and dosimetric information; (3) conventional fractionated radiotherapy. All patients received intensity-modulated radiotherapy ± chemotherapy. Radiation-induced NP necrosis was diagnosed by magnetic resonance imaging and/or electronic nasopharyngoscopy. Dosimetric factors of the planning target volume of primary tumor (PTVp) were extracted from the dose-volume histogram (DVH), which was rescaled to an equivalent dose of 2 Gy per fraction (EQD 2 Gy) using a linear quadratic model. Logistic regression was used to identify the independent prognostic factors for generating the nomogram. Results: With a median follow-up of 44.63 months (inter-quartile range [IQR], 27.70 – 69.20 months), 47.6% of patients (120/252) occurred radiation-induced NP necrosis, which mostly happened within 1 year post re-RT (median [IQR], 5.83 [3.37 – 11.57] months). The 3-year overall survival was 83.0% vs 39.7% ( P＜0.001) in lrNPC patients with or without radiation-induced NP necrosis. Except for the fractionated dose, other dosimetric factors of PTVp were not significantly different between two groups, including D98 (dose to 98% of PTVp), D50, D2 and homogeneity index (Table). Furthermore, multivariate analysis showed that continuous variable age (HR [95%CI]: 1.04 [1.02 – 1.07], P = 0.003) and tumor volume (HR [95%CI]: 1.02 [1.01 – 1.03], P＜0.001), and fractionated dose > 2.22 Gy (HR [95%CI]: 2.36 [1.32 – 4.21], P = 0.004) were independent factors in predicting radiation-induced NP necrosis, which yielded a C-index of 0.742 (95% CI, 0.682 - 0.803) for OS in the nomogram. Conclusions: The incidence of radiation-induced NP necrosis was high in lrNPC patients who received re-RT. Patients with older age, larger tumor volume or receiving fractionated dose over 2.22 Gy were more easily to suffer NP necrosis, which need to explore novel treatment strategies to improve patients’ survivals. [Table: see text]
Occult lymph node metastasis in cN0 tongue squamous cell carcinoma: A prospective observational study.
Authors: Huang Sanqian , Li Feiping , Wang Sunbin , Wu Zheng , Li Yiting , Zhou Yujuan , Huang Wenxiao , Wang Hui , Han Yaqian , Zhang Hailin
Published: June 2023

e18066

Background: Tongue squamous cell carcinoma (TSCC) is prone to occult lymph node metastasis, and preoperative evaluation of cervical nodes is critical for determining treatment strategies. There is scarce report of detecting occult lymph node metastasis in TSCC by using multi-parameter magnetic resonance imaging (mpMRI), spectral computed tomography (spectral CT) or other diagnostic functional imaging. In this study, we aimed to analyze the incidence and risk factors of occult lymph node metastasis in cN0 TSCC by comparing preoperative imaging with postoperative pathology results. Methods: This study prospectively enrolled newly-diagnosed cN0 TSCC patients admitted to the Hunan Cancer Hospital between May, 2022 and December, 2022. All patients underwent primary resection and selective dissection of cervical lymph nodes. MpMRI and spectral CT scan of oral cavity and neck were performed prior to surgery. Preoperative evaluation of lymph node metastasis was conducted by two senior radiologist independently. The location of cervical lymph nodes was assigned based on the 2013 consensus guidelines. Results: A total of 26 cN0 TSCC patients (6 cT1 stage, 13 cT2 stage, and 7 cT3 stage) were enrolled. The median age was 53 (range, 36-64), and there were 25 males. Among all patients, 13 patients underwent unilateral cervical lymph node dissection, while 13 patients underwent bilateral cervical lymph node dissection. A total of 208 lymphatic drainage areas were resected, and 1003 lymph nodes were removed. There were 7 of pT1, 12 of pT2, 7 of pT3 based on postoperative pathological stages. Besides, there are 21 cases staged pN0, 2 cases staged pN1, 2 cases staged pN2, and 1 case staged pN3. Among the 26 patients, 5 (19.23%) cases had occult lymph node metastasis. A total of 8 metastatic lymph nodes (4 in ipsilateral Ib level, 1 in contralateral Ib level, 3 in IIa level ipsilateral side) were detected in the whole group. No lymph node metastasis was detected in level IIb, III and IV. The median maximum diameter of metastatic lymph nodes was 12 mm (range 5 to 15 mm), and 1 extra-nodal extension was observed. Moreover, all occult lymph node metastases occurred in patients with a primary invasion depth of ≥ 5 mm (29.41%, 5/17). Conclusions: The incidence of occult lymph node metastasis in cN0 TSCC remains high under functional imaging diagnostic technology. Preventive neck dissection is necessary for patients with cN0 disease, especially those with primary tumor invasion depth exceeding 5 mm.
Hearing loss related outcomes post-lateral temporal bone resection and other oncologic treatment.
Authors: Jivani Shirin , Hutcheson Kate A. , Nader Marc-Elie , Pratihar Rajarshi , White Claudia Karina , Gidley Paul
Published: June 2023

e18069

Background: Lateral temporal bone resection (LTBR) is used to treat malignancies originating from the auricle, periauricular skin, external auditory canal, parotid gland, or temporal bone. LTBR is the workhorse of otologic cancer surgery; however, few studies have described audiologic outcomes in a large sample of patients. The current literature focuses on overall survival rates post-surgery; however, hearing loss-related outcomes after surgery and adjuvant therapy are lacking in the literature. Following surgery, patients are expected to have maximal conductive hearing loss in the affected ear which can be augmented by ototoxic effects of adjuvant treatment such as radiation and systemic therapy. This type of hearing loss significantly impacts quality of life, making it difficult to understand speech directed to the surgically closed ear, localize sounds, and understand conversational speech in noisy environments. Less is known about the rate and severity of sensorineural hearing loss (SNHL) following LTBR. Methods: A retrospective chart review was conducted among 252 patients who underwent LTBR at single tertiary care center from 2010 to 2020. We evaluated changes in ipsilateral bone conduction (BC) hearing thresholds after LTBR ± adjuvant therapy, including head and neck radiation, chemotherapy, and immunotherapy. Patients who completed at least 1 preoperative and 1 postoperative audiogram within 2 years of surgery were included. Patients who had preoperative chemotherapy, immunotherapy, or temporal bone radiation were excluded. Of 252 patients reviewed, 94 met the eligibility criteria. Audiometric data included pure tone average (PTA) for BC thresholds. A significant decline in hearing was defined as an increase in PTA ≥ 10 decibels (American Academy of Otolaryngology-Head and Neck Surgery). Three treatment subgroups were analyzed, including LTBR only, LTBR and radiation therapy, and LTBR with radiation and systemic therapy. Results: Among all patients, BC PTA increased on average by 7dB after treatment (p<0.001); 30% of patients had ≥ 10dB shift. Patients undergoing LTBR with adjuvant therapy had a higher rate of hearing loss compared to patients undergoing LTBR alone (22/69, 32% vs. 5/25, 20%, respectively). Conclusions: LTBR can cause significant long-term decline in BC hearing that is worsened with the addition of adjuvant therapy. Therefore, it is critical to systematically obtain preoperative and post-treatment audiologic testing to monitor and rehabilitate hearing loss over time. The findings of this study may help patients understand realistic expectations of long-term treatment outcomes related to hearing loss, as an initial step to help improve quality of life with hearing rehabilitation such as osseointegrated bone conduction devices.
Incidence and survival of oropharyngeal carcinoma patients and the development of HPV-testing prevalence in North Rhine-Westphalia: A Cancer Registry analysis from 2008-2018.
Authors: Teichler Valentin , Kajüter Hiltraud , Wellmann Ina , Pogorzelski Michael , Lang Stephan , Klussmann Jens Peter , Stang Andreas , Grünwald Viktor
Published: June 2023

e18070

Background: Oropharyngeal cancer (OPC) is caused by tobacco and alcohol or by HPV infection, which is associated with a better overall survival. A growing incidence of OPC with a decrease in other risk factors suggests a rising proportion of HPV-associated oropharyngeal carcinomas. However, regional differences exist and require further analyses. Therefore we analysed the incidence and the survival of OPC-patients and the test-rate for HPV in the largest European cancer registry in North-Rhine Westphalia (NRW), Germany. Methods: All patients diagnosed with oropharyngeal cancer (ICD-10: C01; C02.4; C05.1; C05.2; C09.0-9; C10.0-9) during 2008-2018 were included in the study. We assumed a carcinoma to be HPV-associated if either p16-IHC-test and/or HPV-DNA-PCR test was positive. In this retrospective study we analysed pseudonymized individual pathology and incidence reports collected by the cancer registry to extract our data. Five-year survival was calculated with the Kaplan-Meier Estimator. Results: A total of 10.652 cases of oropharyngeal cancer were reported in the study period. Age standardized incidence rate was 4.1 (SE 0.041) and constant over time. The majority (M:71.9%;n = 7663/W:28.1%n = 2989) of all cases were men, which is comparable to the distribution for HPV-associated OPC (M:70,3%;n = 786/W:29,7%;n = 332). 1,866 (17.5%) of OPC were tested for HPV. (M:70,4%;1314/W29,6%;552) In 2008 the test rate was 2.3% (n = 20), which increased steadily to 49.3% (n = 490) in 2018. HPV detection rate was 59,9% (n = 1118) in tested cases, which remained stable during the observation period.(M:59,8%; W:60,1%) Five-year survival was better for HPV-associated OPC (0.656; SE 0.023) than for non-HPV-associated OPC (0.430; SE 0.026) and not-HPV-tested OPC (0.468; SE 0.006). Five-year survival was slightly worse for men with OPC (0.466; SE 0.007) than for women (0.531; SE 0.011). The mean age was 63.0 (n = 10,652; HPV+Ø = 62,5; HPV-Ø = 62,7). Conclusions: In line with existing data, HPV-associated OPC achieved a better prognosis in NRW. HPV test rate increased in OPC recently, however, about 50% were still not tested. With relatively constant fractions of HPV-positive OPC in the tested group over the timespan our data does not suggest a rise in the fraction of HPV-associated OPC, which is in contrast to published data. The retrospective analyses, variance in HPV testing as well as the lack of occupational or behavioural hazards captured in the registry limit the interpretation of our data.
Neoadjuvant chemotherapy followed by definitive chemoradiation in technically unresectable oral cavity squamous cancers.
Authors: Trikha Mehak , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Singh Ajaykumar Chandrabhan , Dhanawat Aditya , Chaturvedi Pankaj , Pai Prathamesh S , Chaukar Devendra A , Laskar Sarbani Ghosh , Prabash Kumar
Published: June 2023

e18073

Background: Definitive Chemoradiation has dismal outcomes in very advanced oral cavity cancers. Surgical resection is the preferred modality of treatment . NACT followed by assessment for surgery is the standard algorithm used in technically unresectable oral cavity squamous cancers. Patients who are not amenable for surgery or not willing for the same are subjected to definitive Chemoradiation. There is very limited data about the outcomes of these patients and hence we have performed this analysis. Methods: This is an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable oral cavity squamous patients who received NACT. Adults patients with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who were deemed as technically unresectable in a multi-disciplinary clinic (MDC) were included. These patients received 2-3 cycles of NACT (3-weekly) and underwent a response assessment. Depending on response and general condition, they were re-assessed in MDC and further therapy was decided. Patients who were not amenable to surgery and not willing for the and considered for definitive Chemoradiation were included in this analysis. Overall survival (OS) was calculated from date of diagnosis to date of death. Kaplan-meier method was used for estimation of 5 years OS. Impact of response to neoadjuvant chemotherapy on overall survival was calculated using log-rank method. Results: A total of 429 patients were analysed of which 387 (90.2%) were males The median age was 40 years (IQR; 40-54 years). The baseline ECOG PS was 0 in 163 (38%), 1 in 257 (59.9%) and 2 in 9 (2.1%) patients. The clinical stage at presentation was IVA in 257 (59.9%) patients and IVB in 172 (40.1%). The neoadjuvant regimen received were TPF regimen in 162 (37.8%) patients and two drug Taxane- Platinum regimen in the rest. The response rate to neoadjuvant therapy was 35.9% (N=154). Three thirty nine patients had an event with a median survival of 10 months (95%CI-;8.6-11.4). The five year survival was 15.6 % (Standard error 2%), while the 10 year OS was 9.6% (standard error 2.6%). On multivariate analysis, the only factor impacting the OS was response to neoadjuvant chemotherapy (HR: 0.54, 95% CI; 0.43-0.69; P=0.000). Conclusions: Neoadjuvant Chemotherapy followed by definitive Chemoradiation (who are not amenable for surgical resection or not willing) leads to dismal outcomes and further strategies to improve the outcomes are warranted.
Concurrent EGFR wild-type tongue squamous cell carcinoma and EGFR-mutant lung adenocarcinoma and response to osimertinib.
Authors: Wu Fang , Hu Chunhong , Zhang Sujuan , Wang Shuxing , Pan Yue , He Fengjiao , Lu Can , Fu Yucheng , Zeng Yue , Liu Junqi , Shi Shenghao , Peng Yurong , Xiao Chaoyue
Published: June 2023

e18074

Background: Epidermal growth factor receptor (EGFR) mutation is most commonly oncogenic driver in lung adenocarcinoma with 50% incidence in Asians.Osimertinib is the third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which has been widely used in metastatic EGFR-mutant non-small cell lung cancer (NSCLC) and has significantly improved outcomes. At present, the treatment of HNSCC mainly relies on surgery or chemoradiotherapy. EGFR is overexpressed in more than 90% of head and neck squamous cell carcinoma (HNSCC). Targeted therapy for HNSCC is mainly monoclonal antibodies, while the application of small molecule inhibitors is limited. The EGFR-TKI can only be applied in subsequent-line, when disease progression on or after platinum therapy. However, the efficacy of EGFR-TKI in patients with both NSCLC and HNSCC remains unclear. Methods: We searched all patients with EGFR-mutation metastatic non-small cell lung cancer and HNSCC who used EGFR-TKI in the Second Xiangya Hospital. Tumor sections were assessed immunohistochemically using PD-L1 and EGFR expression. EGFR amplification was detected by fluorescence in situ hybridization (FISH). We collected clinical characteristics and treatment histories for all patients including time to progression on EGFR-TKI. Time to progression on EGFR-TKI was defined as time from start of EGFR-TKI to time of radiographic RECIST progression. The efficacy and prognosis were evaluated based on the RECIST (version 1.1). Results: We found an advanced lung adenocarcinoma patient who harbored an EGFR-mutation and concurrently had tongue squamous cell carcinoma with EGFR wild-type.The tongue tumor tissue sample for EGFR expression was positive by immunohistochemistry and EGFR amplification was negative by FISH. NGS showed inactive mutation of patched1 (PTCH1) and EGFR wild-type.PET-CT scans demonstrated a partial response (PR) of the lung tumor and tongue cancer after two months of treatment of osimertinib. The lung tumor maintian partial response until now (nearly 30 months). And the tongue tumor reached the first progression- free survival (PFS) at 21 months. Conclusions: The patient with NSCLC and tongue cancer who exhibited objective response to EGFR-TKI, osimertinib monotherapy. The result indicates a clear response of tongue cancer to osimertinib and the potential for the use of osimertinib in tongue cancer. However, with the specific mechanism largely unknown, it is necessary to study further the effect of osimertinib on HNSCC.
Treatment patterns and clinical outcomes of newly diagnosed locally advanced head and neck squamous cell carcinoma (LA HNSCC): A retrospective cohort analysis of national real-world data in England.
Authors: Black Chris M. , Kong Anthony , Chiu Gavin , Bolodeoku John , Massey Olivia , Patel Amisha , Ford Alexander , Holbrook Tim
Published: June 2023

e18075

Background: LA HNSCC (stage III-IVb) is a potentially curable disease. However, many patients experience recurrence and metastasis, resulting in poorer prognoses. The multimodal approach to treating LA HNSCC makes the evaluation of treatment regimens difficult. This study aimed to describe the real-world treatment patterns, clinical outcomes and HCRU of LA HNSCC patients in England. Methods: This retrospective cohort study involved the use of data from the National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset). Adults with a first record of primary LA HNSCC between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to 31st December 2020. Results: 12,790 patients were included within the cohort. 52.1% (n = 6,665) received chemotherapy at some point during follow-up as part of their combination treatment with surgery and/or radiotherapy. Within the chemotherapy receiving cohort, 21.2% (n = 1,413) received induction chemotherapy prior to surgery or radiotherapy, 92.2% (n = 6,145) received concurrent chemo-radiotherapy and 11.8% (n = 787) received chemotherapy following surgery or radiotherapy, suggesting palliative treatment. The majority of chemotherapy regimens used were platinum-based. Of those receiving surgery (n = 5,292), the most common type of surgery was transoral surgery, occurring in 51.3% of the resectable patients. 40.2% of the overall cohort received salvage surgery during follow-up. 50.1% and 12.4% of patients experienced locoregional or distant metastatic progression, respectively and 39.2% of the cohort died. The 5-year overall survival (OS) was ~59% and ~55% for resected and unresected patients respectively. For event free survival (EFS), the 5-year median survival time post event free state index for the overall cohort was 12.32 months. Median survival time for the different tumour sites ranged from 19.4 and 2.6 months, with the nasopharynx and ‘other’ site group representing these range ends respectively. The highest HCRU/costs were incurred within the first 3 months following diagnosis; mean number of HNSCC-related inpatient stays were 2.93 (SD = 4.05), costing a total of £57,781,497 (per patient: £4,855.18 [£5872.05], mean[SD]). Conclusions: This is the first real world study using the UK NCRAS datasets to assess the treatment pathway and outcomes of the LA HNSCC population in England. Survival outcomes varied across site of primary tumour and patients diagnosed at stage 4 experienced poorer outcomes, highlighting the need for improved treatment plans and clinical outcomes for this patient population.