Precision association of lymphatic disease spread with radiation-associated toxicity in oropharyngeal squamous carcinomas

doi:10.1016/j.radonc.2021.06.016

Radiotherapy and Oncology

Volume 161, August 2021, Pages 152-158

https://doi.org/10.1016/j.radonc.2021.06.016 Get rights and content

Highlights

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582 oropharyngeal cancer patients under radiation treatment were analyzed.
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We aim to predict post-treatment aspiration or gastronomy tube dependence.
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Tumor spread patterns to head and neck lymph nodes were identified.
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Patients were clustered based on their unique lymph node spread patterns.
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Patient clustered were significantly correlated with dysphagia 6 months post treatment.
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Lymph node spread patterns are an effective prognostic indicator of late toxicity.

Abstract

Purpose

To determine whether patient similarity in terms of head and neck cancer spread through lymph nodes correlates significantly with radiation-associated toxicity.

Materials and methods

582 head and neck cancer patients received radiotherapy for oropharyngeal cancer (OPC) and had non-metastatic affected lymph nodes in the head and neck. Affected lymph nodes were segmented from pretreatment contrast-enhanced tomography scans and categorized according to consensus guidelines. Similar patients were clustered into 4 groups according to a graph-based representation of disease spread through affected lymph nodes. Correlation between dysphagia-associated symptoms and patient groups was calculated.

Results

Out of 582 patients, 26% (152) experienced toxicity during a follow up evaluation 6 months after completion of radiotherapy treatment. Patient groups identified by our approach were significantly correlated with dysphagia, feeding tube, and aspiration toxicity (p < .0005).

Discussion

Our results suggest that structural geometry-aware characterization of affected lymph nodes can be used to better predict radiation-associated dysphagia at time of diagnosis, and better inform treatment guidelines.

Conclusion

Our work successfully stratified a patient cohort into similar groups using a structural geometry, graph-encoding of affected lymph nodes in oropharyngeal cancer patients, that were predictive of late radiation-associated dysphagia and toxicity.

Section snippets

Patient cohort

An IRB-approved, retrospective review of patients diagnosed with oropharyngeal cancer (OPC) and treated at MD Anderson Cancer Center from 2005 to 2013 was performed. Patients with lymph node positive, biopsy-proven, OPC who were treated with radiotherapy (RT) with or without chemotherapy with curative intent and had at least 6 months post-treatment follow-up assessment were eligible for inclusion. Patients’ demographic, clinical, treatment, and outcome measures are summarized in (Table 1).

Results

Out of 644 OPC patients available for the study, 582 patients had affected lymph nodes and were included in the final cohort. Ignoring laterality, 63 distinct patterns of affected LNs were present in the 582 patient cohort, with 6 patterns comprising 78% of the cases (Table 2). Of the patterns with over 10 cases, patients with bilaterally affected 2A-2B-3 levels showed the highest incidence of RAD (53%), while the group with unilaterally affected 2A-2B-3 regions had the lowest incidence (18%).

Discussion

Head and neck cancers account for nearly 3% of all malignancies in the U.S. with approximately 62,000 HNC cases diagnosed per year [3]. More than two-thirds of those diagnosed with HNC will survive 5 years or more if treated with locoregional curative therapy. However, almost all radiotherapy survivors will suffer from at least mild-to-moderate symptoms from head and neck radiation [26], [16]. Recent phase III studies [27], [28] suggest that concurrent chemoradiation will remain the standard

Conclusion

In conclusion, this study demonstrates that clustering based on lymph nodes spread is associated with radiation-associated dysphagia, both aspiration toxicity and feeding tube dependency. Our anatomical representation of lymph node spread showed superior association to RAD compared to the current N-category classification. Our method relies only on discrete information on nodal spread at time of diagnosis, and thus does not require complex dose-planning or organ segmentation to determine RAD

Co-author specific contributions

All listed co-authors performed the following:

1.
Substantial contributions to the conception or design of the work;
or the acquisition, analysis, or interpretation of data for the work;
2.
Drafting the work or revising it critically for important intellectual content;
3.
Final approval of the version to be published;
4.
Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Prior presentation

Preliminary analyses and portions of this data were accepted for a poster presentation at the 2019 American Society of Radiation Oncology (ASTRO) Annual Meeting, September 25–28, 2019, Chicago, IL, USA.

A detailed description of the spatial neighborhood similarity method used in this work has been published in the Journal of Biomedical Informatics in 2020.

A brief description of a subpart of Fig. 2 was accepted as a short conference presentation at the 2020 IEEE VIS conference, October 2020, Salt

Data sharing statement

Research data is not available at this time.

Conflict of interest statement

The authors have nothing to disclose.

Acknowledgements/funding disclosures

Dr. van Dijk receives funding from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek/Netherlands Research Organization Rubicon Award (452182317).

Dr. Mohamed receives funding support from an MD Anderson Institutional Research Grant (IRG).

Dr.s Canahuate, Fuller, Mohamed, Vock and Marai received/receive funding and salary support related to this project during the period of study execution from: the National Institutes of Health (NIH) Big Data to Knowledge (BD2K) Program of the National

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¹: Questions about statistical analyses can be directed to Andrew Wentzel.

View full text

Precision association of lymphatic disease spread with radiation-associated toxicity in oropharyngeal squamous carcinomas

Highlights

Abstract

Purpose

Materials and methods

Results

Discussion

Conclusion

Section snippets

Patient cohort

Results

Discussion

Conclusion

Co-author specific contributions

Prior presentation

Data sharing statement

Conflict of interest statement

Acknowledgements/funding disclosures

Oral Oncol

Oral Oncol

Cancer Treatment Rev

Int J Radiat Oncol Biol Phys

Radiother Oncol

J Biomed Inf: X

Radiother Oncol

Lancet (London, England)

Lancet (London, England)

Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma

Sci Rep

Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, DC

Head Neck

New strategies in human papillomavirus–related oropharynx cancer: effecting advances in treatment for a growing epidemic

Clin Cancer Res

Human papillomavirus–associated oropharyngeal cancer: review of current evidence and management

Curr Oncol

Precision risk analysis of cancer therapy with interactive nomograms and survival plots

IEEE Trans Visual Comput Graphics