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

Wentzel, Andrew; Luciani, Timothy; Dijk, Lisanne V. van; Taku, Nicolette; Elgohari, Baher; Mohamed, A.S.R.; Canahuate, Guadalupe; Fuller, Clifton D.; Vock, David M.; Marai, G. Elisabeta; Smart, Toxicity Team

doi:10.1016/j.radonc.2021.06.016

Cited by 9 publications

(7 citation statements)

References 28 publications

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“…This is an observation that has not been widely investigated. To our knowledge there is only one recent publication verifying this hypothesis, which found that the toxicity profile in HNC patients is associated with the topography and extent of the disease in the neck stations (22). Our finding could promote further investigation to identify patients at higher risk of adverse reactions based on the pattern of disease spread in the lymph node stations.…”

Section: Discussionsupporting

confidence: 59%

Investigating factors associated to dysphagia and need for percutaneous endoscopic gastrostomy in patients with head and neck cancer receiving radiation therapy

Alexidis¹,

Bangeas²,

Efthymiadis³

et al. 2022

J. Cancer

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Purpose:In this study we sought to investigate factors associated to dysphagia and subsequent need for percutaneous gastrostomy (PEG) usage, in patients with head and neck cancer receiving radiation therapy. Methods: The records of 123 patients with non-metastatic, stage I-IV head and neck cancer who were submitted to radiation therapy were retrospectively reviewed. Logistic regression models were used to investigate for associations between the outcomes of interest (grade ≥2 dysphagia and need for [PEG] usage) and potential predictive factors. Results: Mean dose to pharyngeal constrictor muscles (OR=1.08, p=.002), concurrent chemotherapy (OR=3.78, p=0.015) and upper aerodigestive tract malignancies (OR=3.27, p=0.044) were associated with dysphagia grade≥2. A threshold of constrictors mean dose for dysphagia manifestation was also identified at 43 Gy (OR=4.51, p=0.002). Need for PEG use was correlated with definitive treatment (OR=7.03, p=.022), nasopharyngeal (OR=12.62, p=0.003), upper aerodigestive tract (OR=9.12, p=0.007) or occult primary malignancies (OR=10.78, p=0.016). Conclusion: Patients suffering from upper aerodigestive tract malignancies, those with calculated constrictors mean dose >43 Gy, or planned to receive concurrent chemotherapy-radiotherapy should be closely monitored during treatment for dysphagia manifestation. Prophylactic PEG could be considered for patients receiving definitive therapy of the nasopharynx, upper aerodigestive tract or occult primary malignancies.

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Section: Discussionsupporting

confidence: 59%

Investigating factors associated to dysphagia and need for percutaneous endoscopic gastrostomy in patients with head and neck cancer receiving radiation therapy

Alexidis¹,

Bangeas²,

Efthymiadis³

et al. 2022

J. Cancer

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“…In summary, this was an extremely unusual, unique case where additional unannotated local information made the difference between the DQL and the prescriber’s sequence. Future work that includes nodal involvement methodology [ 3 , 4 ] not currently reflected in the AJCC 8th Edition could address this type of borderline case.…”

Section: Resultsmentioning

confidence: 99%

“…Head and neck cancer, which includes cancers of the larynx, throat, lips, mouth, nose, and salivary glands, is now an epidemic, with 65,000 new cases in the United States annually [ 1 ], whose treatment is, as in many other types of cancers, a dynamic and complex process. This therapy process involves making multiple, patient-specific treatment decisions to maximize efficacy—for example, reduction in tumor size, time of local region control, and survival time—while minimizing side effects [ 2 - 4 ]. For example, a specific patient may undergo radiotherapy (RT) alone, RT with concurrent chemotherapy (CC), or induction chemotherapy (IC) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Optimal Treatment Selection in Sequential Systemic and Locoregional Therapy of Oropharyngeal Squamous Carcinomas: Deep Q-Learning With a Patient-Physician Digital Twin Dyad

Tardini¹,

Zhang²,

Canahuate³

et al. 2022

J Med Internet Res

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Background Currently, selection of patients for sequential versus concurrent chemotherapy and radiation regimens lacks evidentiary support and it is based on locally optimal decisions for each step. Objective We aim to optimize the multistep treatment of patients with head and neck cancer and predict multiple patient survival and toxicity outcomes, and we develop, apply, and evaluate a first application of deep Q-learning (DQL) and simulation to this problem. Methods The treatment decision DQL digital twin and the patient’s digital twin were created, trained, and evaluated on a data set of 536 patients with oropharyngeal squamous cell carcinoma with the goal of, respectively, determining the optimal treatment decisions with respect to survival and toxicity metrics and predicting the outcomes of the optimal treatment on the patient. Of the data set of 536 patients, the models were trained on a subset of 402 (75%) patients (split randomly) and evaluated on a separate set of 134 (25%) patients. Training and evaluation of the digital twin dyad was completed in August 2020. The data set includes 3-step sequential treatment decisions and complete relevant history of the patient cohort treated at MD Anderson Cancer Center between 2005 and 2013, with radiomics analysis performed for the segmented primary tumor volumes. Results On the test set, we found mean 87.35% (SD 11.15%) and median 90.85% (IQR 13.56%) accuracies in treatment outcome prediction, matching the clinicians’ outcomes and improving the (predicted) survival rate by +3.73% (95% CI –0.75% to 8.96%) and the dysphagia rate by +0.75% (95% CI –4.48% to 6.72%) when following DQL treatment decisions. Conclusions Given the prediction accuracy and predicted improvement regarding the medically relevant outcomes yielded by this approach, this digital twin dyad of the patient-physician dynamic treatment problem has the potential of aiding physicians in determining the optimal course of treatment and in assessing its outcomes.

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“…When higher RT dose is delivered to lymph nodes that are in close proximity to critical anatomical structures involved in swallowing (e.g., constrictors muscles or oral cavity), the impact on the toxicity profile might be greater compared to the anatomical volume that receives the corresponding dose. A study by Wentzel et al [41], which investigated the potential correlation of toxicity manifestation and lymph node spread pattern of the disease, verified that the topography of the disease in the neck plays a role in the toxicity profile. More specifically, they found that patients with disease in bilateral lymph node stations 2A,B and 3 were more likely to develop adverse events compared with bilateral 2A,B and unilateral 3 or unilateral 2A,B, 3, and 4.…”

Section: Discussionmentioning

confidence: 97%

Investigating Predictive Factors of Dysphagia and Treatment Prolongation in Patients with Oral Cavity or Oropharyngeal Cancer Receiving Radiation Therapy Concurrently with Chemotherapy

et al. 2023

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Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51–20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84–27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021–1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53–10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

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

Cited by 9 publications

References 28 publications

Investigating factors associated to dysphagia and need for percutaneous endoscopic gastrostomy in patients with head and neck cancer receiving radiation therapy

Investigating factors associated to dysphagia and need for percutaneous endoscopic gastrostomy in patients with head and neck cancer receiving radiation therapy

Optimal Treatment Selection in Sequential Systemic and Locoregional Therapy of Oropharyngeal Squamous Carcinomas: Deep Q-Learning With a Patient-Physician Digital Twin Dyad

Investigating Predictive Factors of Dysphagia and Treatment Prolongation in Patients with Oral Cavity or Oropharyngeal Cancer Receiving Radiation Therapy Concurrently with Chemotherapy

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