Dataset Information

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study.

ABSTRACT:

Introduction

Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status.

Material and methods

Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin.

Results

Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16- tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures.

Conclusion

Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.

SUBMITTER: Kristensen MH

PROVIDER: S-EPMC11002542 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

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Publications

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study.

Kristensen Morten Horsholt MH Holm Anne Ivalu Sander AIS Hansen Christian Rønn CR Zukauskaite Ruta R Samsøe Eva E Maare Christian C Johansen Jørgen J Primdahl Hanne H Bratland Åse Å Kristensen Claus Andrup CA Andersen Maria M Overgaard Jens J Eriksen Jesper Grau JG

Clinical and translational radiation oncology 20240330

<h4>Introduction</h4>Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status.<h4>Material and methods</h4>Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 a ...[more]

PMID: 38596816

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Project description:Determination of human papillomavirus (HPV) status has become clinically relevant for head and neck squamous cell carcinoma (HNSCC) patients. p16 immunohistochemistry is one of the recommended methods for classifying HPV status. However, long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks linked to different p16-status HNSCC are still absent. In the present study, The Cancer Genome Atlas database provided RNA profiles as well as clinical information from 26 p16-positive HNSCC samples, 71 p16-negative HNSCC samples, and 44 adjacent normal control samples. Differentially expressed RNAs (DERNAs) between HNSCC samples and normal samples were identified by limma package in R. Functional enrichment analysis of differentially expressed mRNAs was performed using Clusterprofiler package in R. Survival analysis of DERNAs was carried out by survival package in R. The ceRNA network was constructed using GDCRNATools package in R. A total of 102 lncRNAs, 196 microRNAs (miRNAs), and 2282 mRNAs were identified as p16-positive-specific DERNAs. There were 90 lncRNAs, 153 miRNAs, and 2038 mRNAs were identified as p16-negative-specific DERNAs. Functional enrichment analysis revealed that the differentially expressed mRNAs in the p16-positive and the p16-negative group were mainly enriched in the "DNA replication" and "extracellular matrix -receptor interaction" pathway, respectively. Among the top 25 DERNAs, there were 1 key lncRNA, 1 key miRNA, and 1 key messenger RNA in the p16-positive group and 2 key lncRNAs, 1 key miRNA, and 2 key mRNAs in the p16-negative group were significantly related to the overall survival. Then the ceRNA network in the p16-positive and p16-negative group was constructed. There were 5 lncRNAs, 16 miRNAs, and 66 mRNAs included in the p16-positive group ceRNA network and 1 lncRNA, 4 miRNAs, and 28 mRNAs included in the p16-negative group ceRNA network. Among the RNAs in the ceRNA network, 5 mRNAs were significantly related to the overall survival. Taken together, we revealed the differential RNA expression profiling and the differential ceRNA network in the p16-positive and p16-negative group of HNSCC. Our findings provided a novel insight into this HPV-related cancer and potential biomarkers and therapeutic targets for HNSCC based on p16 status.

Project description:BackgroundStandard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation.MethodsThe ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start.DiscussionThe primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1.Trial registrationClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.

Dataset Information

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study.

Introduction

Material and methods

Results

Conclusion

Publications

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study.

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