Radiotherapy For Oropharyngeal Cancer Research Articles

Detection of alteration in carotid artery volumetry using standard-of-care computed tomography surveillance scans following unilateral radiation therapy for early-stage tonsillar squamous cell carcinoma survivors: a cross-sectional internally-matched carotid isodose analysis.

This study leveraged standard-of-care CT scans of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer to detect volumetric changes in the carotid arteries, and determine whether there is a dose-response relationship. Disease-free cancer survivors (>3 months since therapy and age>18years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5Gy increments (i.e. received 50-55Gy, 55-60Gy, etc.). The percent-change in sub-volumes across each dose range was examined. Among 46 patients, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (-7.0±9.0 vs.+3.5±7.2, respectively, p<0.0001). Chemotherapy use, in addition to RT, was associated with a significant mean %-decrease in carotid artery volume compared to RT alone. No significant dose-response trend was observed in the carotid artery volume change within 5Gy ranges. Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50Gy.

“Why am I still suffering?”: Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy

BackgroundLate effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck–specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. MethodsThis work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. ConclusionsFatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT

PurposeThis study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer. MethodsThe treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. ResultsXerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. ConclusionsBased on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.

Multi-organ spatial stratification of 3-D dose distributions improves risk prediction of long-term self-reported severe symptoms in oropharyngeal cancer patients receiving radiotherapy: development of a pre-treatment decision support tool.

Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering. All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients' treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient's dose histograms for relevant organs. The clusters with the highest total mean doses were translated into dose thresholds using rule mining. Patient stratifications were compared against Tumor staging information using multivariate likelihood ratio tests. Model performance for prediction of moderate/severe symptoms at 6 months was compared against normal tissue complication probability (NTCP) models using cross-validation. A total of 349 patients were included for long-term symptom prediction. High-risk clusters were significantly correlated with outcomes for severe late drymouth (p <.0001, OR = 2.94), swallow (p = .002, OR = 5.13), mucus (p = .001, OR = 3.18), and voice (p = .009, OR = 8.99). Simplified clusters were also correlated with late severe symptoms for drymouth (p <.001, OR = 2.77), swallow (p = .01, OR = 3.63), mucus (p = .01, OR = 2.37), and voice (p <.001, OR = 19.75). Proposed cluster stratifications show better performance than NTCP models for severe drymouth (AUC.598 vs.559, MCC.143 vs.062), swallow (AUC.631 vs.561, MCC.20 vs -.030), mucus (AUC.596 vs.492, MCC.164 vs -.041), and voice (AUC.681 vs.555, MCC.181 vs -.019). Simplified dose thresholds also show better performance than baseline models for predicting late severe ratings for all symptoms. Our results show that leveraging the 3-D dose histograms from radiation therapy plan improves stratification of patients according to their risk of experiencing long-term severe radiation associated symptoms, beyond existing NTPC models. Our rule-based method can approximate our stratifications with minimal loss of accuracy and can proactively identify risk factors for radiation-associated toxicity.

Serial Changes in Parotid Gland Volume and Symptoms After Radiation Therapy in Oropharyngeal Cancer.

Objective: To evaluate the serial changes in the volume of the parotid gland and clinical symptoms after a course of radiation therapy (RT) in patients with oropharyngeal cancer. Methods: A total of 33 patients who were diagnosed with oropharyngeal cancer and had been treated with RT or concurrent chemoradiation therapy were evaluated. Parotid gland volumes were measured serially by head and neck computed tomography with contrast-enhanced images before RT, and 6 months, 1 year, and 2 years after RT. Patients also filled out EORTC (European Organization for the Research and Treatment of Cancer) QLQ-C30 questionnaires on the quality of life (QOL) at the same time. This questionnaire included questions about salivary gland function: dry mouth, sticky saliva, and taste disorder. Higher scores on EORTC questionnaire translates to worse QOL. Results: All patients received more than 60 Gy irradiation in total. The mean volume of parotid gland decreased from 23.30 mL before RT to 15.80 mL, 15.93 mL, and 16.67 mL after 6 months, 1 year, and 2 years, respectively (P < 0.001 between pre-RT and all other 3 periods). The scores on the QOL questionnaire were higher (worsened QOL) at all 3 times after radiation than in the pre-RT period. The mean score of QOL increased from pre-RT to 2 years post-RT: "dry mouth" from 1.65 to 2.70, "sticky saliva" from 1.19 to 2.00, and "taste disorder" from 1.12 to 1.94. All 3 of these parameters were correlated with the volume of the parotid gland (P < 0.005 each). Conclusions: The volume of the parotid gland decreases significantly after RT for oropharyngeal cancer and does not recover significantly for at least 2 years. There was a significant correlation between decreased parotid volume and a lower QOL involving salivation.

Morphological, Functional and Texture Analysis Magnetic Resonance Imaging Features in the Assessment of Radiotherapy-Induced Xerostomia in Oropharyngeal Cancer

The aim of this single-center, observational, retrospective study was to investigate magnetic resonance imaging (MRI) biomarkers for the assessment of radiotherapy (RT)-induced xerostomia. Twenty-seven patients who underwent radiation therapy for oropharyngeal cancer were divided into three groups according to the severity of their xerostomia—mild, moderate, and severe—clinically confirmed with the Common Terminology Criteria for Adverse Events (CTCAE). No severe xerostomia was found. Conventional and functional MRI (perfusion- and diffusion- weighted imaging) performed both pre- and post-RT were studied for signal intensity, mean apparent diffusion coefficient (ADC) values, k-trans, and area under the perfusion curves. Contrast-enhanced T1 images and ADC maps were imported into 3D slicer software, and salivary gland volumes were segmented. A total of 107 texture features were derived. T-Student and Wilcoxon signed-rank tests were performed on functional MRI parameters and texture analysis features to identify the differences between pre- and post-RT populations. A p-value &lt; 0.01 was defined as acceptable. Receiver operating characteristic (ROC) curves were plotted for significant parameters to discriminate the severity of xerostomia in the pre-RT population. Conventional and functional MRI did not yield statistically significant results; on the contrary, five texture features showed significant variation between pre- and post-RT on the ADC maps, of which only informational measure of correlation 1 (IMC 1) was able to discriminate the severity of RT-induced xerostomia in the pre-RT population (area under the curve (AUC) &gt; 0.7). Values lower than the cut-off of −1.473 × 10−11 were associated with moderate xerostomia, enabling the differentiation of mild xerostomia from moderate xerostomia with a 73% sensitivity, 75% specificity, and 75% diagnostic accuracy. Therefore, the texture feature IMC 1 on the ADC maps allowed the distinction between different degrees of severity of RT-induced xerostomia in the pre-RT population. Accordingly, texture analysis on ADC maps should be considered a useful tool to evaluate salivary gland radiosensitivity and help identify patients at risk of developing more serious xerostomia before radiation therapy is administered.

Tooth extraction prior to radiotherapy for oropharyngeal cancer increases the risk of osteoradionecrosis

Osteoradionecrosis of the jaw is a therapy-resistant condition that may occur after treatment for head and neck cancer. The aim of this study was to investigate the incidence of osteoradionecrosis in patients with oropharyngeal cancer in relation to tooth extraction prior to radiation therapy. Patients who had undergone radiation therapy for oropharyngeal cancer 5-10 years earlier were included and evaluated for the development of osteoradionecrosis (n = 75). Among the 75 patients, 62 had molar teeth present in the >50 Gy radiation field and 36 of those patients had teeth extracted prior to radiation therapy. Extraction of molars before radiotherapy significantly increased the risk of developing osteoradionecrosis (P < 0.05). There were no identifiable statistically significant correlations between the time from tooth extraction and the start of radiation therapy, the number of teeth in the radiation field, smoking habits, human papillomavirus-status, gender, age or tumor location and the development of osteoradionecrosis. Tooth extraction prior to radiation therapy increases the risk of developing osteoradionecrosis. For patients with good oral hygiene and absence of dental disease, avoidance of tooth extraction in the radiation field could therefore reduce the risk of complications.

Erythema multiforme induced by acetaminophen requiring differentiation from mucositis caused by radiotherapy for oropharyngeal cancer: A case report

Erythema multiforme induced by acetaminophen requiring differentiation from mucositis caused by radiotherapy for oropharyngeal cancer: A case report

Impact of Mandated Online Prescription Drug Monitoring Programs on Opiate Analgesic Use and Patient-Reported Pain during Radiotherapy for Oropharyngeal Cancer

<h3>Purpose/Objective(s)</h3> Owing to the dramatic rise in opiate-related deaths, the use of online prescription drug monitoring programs (PDMPs) concurrent with new laws restricting opiate administration has become commonplace across the U.S. Some oncologists, however, have expressed concerns that they may unintentionally limit treatment access to at-risk oncology populations. As opiates are frequently used in the acute management strategies for those undergoing radiotherapy for squamous cell carcinoma of the oropharynx, we sought to evaluate changes in short-term opiate prescription use following the implementation of mandated use of an online PDMP in an outpatient radiation oncology practice. <h3>Materials/Methods</h3> Between July of 2017 and December of 2019, 64 patients with biopsy-confirmed oropharyngeal squamous cell carcinoma undergoing curative-intent radiotherapy were evaluated and divided into two cohorts: (1) 26 patients treated 1 year before and (2) 38 patients treated 1.5 years following mandated PDMP use and implementation of new opiate prescription laws. The primary endpoint was opiate prescriptions during therapy and within 3 months after therapy as well as patient-reported pain per the Defense and Veterans Pain Rating Scale. Opiate doses were treated as the response in a series of chi-square tests using a three-level format: no vs. 40 to 3000 vs. 3000+ MME. Cochran-Mantel-Haenszel chi-square analysis with the row mean score test statistic assessed any proportional shifts in dose rates between strata of selected prognostic factors. <h3>Results</h3> The median total opiate doses were 975 MME and 1025 MME in the pre- and postintervention groups with no significant differences in MMEs prescribed (p=0.8441). There was also no difference in patient-reported uncontrolled pain (p=0.38) between the treatment cohorts. Univariate analysis showed tonsillar/soft-palate subsite (p<0.01) and alcohol use (p=0.04) were associated with higher rates of prescribed opioids. While 75% of patients (n=48) received opiates during their acute care, 78% (n=50) were off all prescription narcotics by 3 months or sooner following treatment. <h3>Conclusion</h3> Although potential concerns that mandated PDMP use would affect opiate utilization, there was no associated change in total opiate use by MME for the management of acute pain during radiotherapy for patients with oropharyngeal squamous cell carcinoma nor differences in patient-reported uncontrolled pain. Furthermore, despite high utilization of opiates during radiotherapy, few patients continued use past 3 months after treatment.

Estimating the optimal linear combination of predictors using spherically constrained optimization

BackgroundIn the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing the area under the receiver operating characteristic curve. For ordinal responses, the optimal predictor combination can similarly be obtained by maximization of the hypervolume under the manifold (HUM). Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases.ResultsWe propose an efficient derivative-free black-box optimization technique based on pattern search to solve this problem, which we refer to as Spherically Constrained Optimization Routine (SCOR). Through extensive simulation studies, we demonstrate that the proposed method achieves better performance than existing methods including the step-down algorithm. Finally, we illustrate the proposed method to predict the severity of swallowing difficulty after radiation therapy for oropharyngeal cancer based on radiation dose to various structures in the head and neck.ConclusionsOur proposed method addresses an important challenge in combining multiple biomarkers to predict an ordinal outcome. This problem is particularly relevant to medical research, where it may be of interest to diagnose a disease with various stages of progression or a toxicity with multiple grades of severity. We provide the implementation of our proposed SCOR method as an R package, available online at https://CRAN.R-project.org/package=SCOR.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer.

PURPOSEThere is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.PATIENTS AND METHODSThis was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.RESULTSPretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018).CONCLUSIONFor OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer.

BackgroundRed cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT).Materials and methodsThis retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis.ResultsThe OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51–0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50–0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12–1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06–1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03–1.29, p = 0.012).ConclusionsIn the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.

Artificial Intelligence-Guided Prediction of Dental Doses Before Planning of Radiation Therapy for Oropharyngeal Cancer: Technical Development and Initial Feasibility of Implementation

PurposeThe aim was to develop a novel artificial intelligence (AI)–guided clinical decision support system, to predict radiation doses to subsites of the mandible using diagnostic computed tomography scans acquired before any planning of head and neck radiation therapy (RT). Methods and MaterialsA dose classifier was trained using RT plans from 86 patients with oropharyngeal cancer; the test set consisted of an additional 20 plans. The classifier was trained to predict whether mandible subsites would receive a mean dose >50 Gy. The AI predictions were prospectively evaluated and compared with those of a specialist head and neck radiation oncologist for 9 patients. Positive predictive value (PPV), negative predictive value (NPV), Pearson correlation coefficient, and Lin concordance correlation coefficient were calculated to compare the AI predictions to those of the physician. ResultsIn the test data set, the AI predictions had a PPV of 0.95 and NPV of 0.88. For 9 patients evaluated prospectively, there was a strong correlation between the predictions of the AI algorithm and physician (P = .72, P < .001). Comparing the AI algorithm versus the physician, the PPVs were 0.82 versus 0.25, and the NPVs were 0.94 versus 1.0, respectively. Concordance between physician estimates and final planned doses was 0.62; this was 0.71 between AI-based estimates and final planned doses. ConclusionAI-guided decision support increased precision and accuracy of pre-RT dental dose estimates.

Association Between Objective Ratings of Swallowing and Dysphagia-Specific Quality of Life in Patients Receiving (Chemo)radiotherapy for Oropharyngeal Cancer.

The pervasive nature of dysphagia in the head/neck cancer (HNC) population necessitates a comprehensive evaluation approach, including both objective assessment of dysphagia, and subjective patient-reported functional measures. However, the congruence between clinician-rated and patient-perceived function is still not well understood. The current study investigated the association between objective clinician-rated swallow physiology (using the MBSImP) and patient-reported measures of swallowing-related quality of life (using the MDADI) in a secondary analysis of patients with oropharyngeal HNC treated with (chemo)radiotherapy. Seventy-nine patients with oropharyngeal HNC receiving (chemo)radiotherapy completed a standardised videofluoroscopic swallow study (VFSS) rated using the MBSImP, and the MDADI, at pre-treatment (baseline), 6weeks and 3months post-treatment as per a previous prospective RCT. Data on n = 67 participants were analysed as part of the secondary analysis. Association between MBSImP oral and pharyngeal composite scores versus MDADI Global and subscale scores was examined using ordinary least squares regression and mixed-effects general linear modelling (GLM). Univariable analyses demonstrated significant associations between MBSImP oral composite scores and each of the MDADI subscales, as well as the MBSImP pharyngeal composite scores and all MDADI subscales. GLM analysis revealed significant associations were maintained between MBSImP pharyngeal scores and the MDADI global and emotional subscale scores at the multivariable level, with the physical subscale trending towards significance. No significant association was observed between the MBSImP oral composite scores and any of the MDADI subscales at the multivariable level. This study found significant associations between objective measures of pharyngeal swallow physiology and patient-perceived swallowing-related quality of life. These findings suggest a higher degree of concordance between clinician-rated and patient-reported measures up to 3months post-(C)RT than previously reported.

Intrinsic radiomic expression patterns after 20 Gy demonstrate early metabolic response of oropharyngeal cancers.

This study investigated the prognostic potential of intra-treatment PET radiomics data in patients undergoing definitive (chemo) radiation therapy for oropharyngeal cancer (OPC) on a prospective clinical trial. We hypothesized that the radiomic expression of OPC tumors after 20Gy is associated with recurrence-free survival (RFS). Sixty-four patients undergoing definitive (chemo)radiation for OPC were prospectively enrolled on an IRB-approved study. Investigational 18 F-FDG-PET/CT images were acquired prior to treatment and 2weeks (20Gy) into a seven-week course of therapy. Fifty-five quantitative radiomic features were extracted from the primary tumor as potential biomarkers of early metabolic response. An unsupervised data clustering algorithm was used to partition patients into clusters based only on their radiomic expression. Clustering results were naïvely compared to residual disease and/or subsequent recurrence and used to derive Kaplan-Meier estimators of RFS. To test whether radiomic expression provides prognostic value beyond conventional clinical features associated with head and neck cancer, multivariable Cox proportional hazards modeling was used to adjust radiomic clusters for T and N stage, HPV status, and change in tumor volume. While pre-treatment radiomics were not prognostic, intra-treatment radiomic expression was intrinsically associated with both residual/recurrent disease (P=0.0256, test) and RFS (HR=7.53, 95% CI=2.54-22.3; P=0.0201). On univariate Cox analysis, radiomic cluster was associated with RFS (unadjusted HR=2.70; 95% CI=1.26-5.76; P=0.0104) and maintained significance after adjustment for T, N staging, HPV status, and change in tumor volume after 20Gy (adjusted HR=2.69; 95% CI=1.03-7.04; P=0.0442). The particular radiomic characteristics associated with outcomes suggest that metabolic spatial heterogeneity after 20Gy portends complete and durable therapeutic response. This finding is independent of baseline metabolic imaging characteristics and clinical features of head and neck cancer, thus providing prognostic advantages over existing approaches. Our data illustrate the prognostic value of intra-treatment metabolic image interrogation, which may potentially guide adaptive therapy strategies for OPC patients and serve as a blueprint for other disease sites. The quality of our study was strengthened by its prospective image acquisition protocol, homogenous patient cohort, relatively long patient follow-up times, and unsupervised clustering formalism that is less prone to hyper-parameter tuning and over-fitting compared to supervised learning.

PV-0535 Pilot study on immunomodulation role of radiotherapy in oropharyngeal cancer: preliminary results

PV-0535 Pilot study on immunomodulation role of radiotherapy in oropharyngeal cancer: preliminary results

PO-183 Pilot study on immunomodulation role of radiotherapy in oropharyngeal cancer: preliminary results

PO-183 Pilot study on immunomodulation role of radiotherapy in oropharyngeal cancer: preliminary results

Prognostic Impact of HPV-Associated p16 Expression and Smoking Status on Outcomes Following Radiation Therapy for Oropharyngeal Cancer: the MARCH-HPV Project

To evaluate the prognostic and predictive impact of HPV-associated p16-expression and to assess the combined prognostic impact of p16 and smoking on altered fractionated radiation therapy (RT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Patients with OPC, known tumor p16 status, and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). HPV status was determined according to p16 immunohistochemistry. Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T stage, N stage, type of radiation therapy fractionation, p16 status, and smoking. Primary endpoint was progression-free survival (PFS). In total, 465 patients (57%) of the patients had p16-positive tumors and 350 (43%) p16-negative. Patients with p16-positive tumors were significantly younger (mean: 56 vs 59 years, P = .0002), in better performance (PS = 0: 74% vs 50%, P < .0001), had smaller tumors (T1-2: 46% vs 33%, P < .0001) and more advanced N stage (N+: 87% vs 76%, P <. 0001) compared with the p16-negative subgroup. p16-positive patients had significantly better PFS (HR = 0.42 [95% CI 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years) than patients with p16-negative tumors. No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). The strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT.

Prognostic Impact of Leukocyte Counts Before and During Radiation Therapy for Oropharyngeal Cancer

Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010 to 2012 and 50 treated with IMPT in 2011 to 2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiation therapy. We retained 137 patients with recorded pretreatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. The radiation therapy type (IMRT vs IMPT) was not associated with lymphopenia (grade 3, P>.99; grade 4, P = .55). In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99-15.7, P = .001), pretreatment leukocytosis (HR 4.85, 95% CI 1.73-13.6, P = .003), grade 4 lymphopenia during radiation therapy (HR 3.28, 95% CI 1.14-9.44, P = .03), and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01-8.18, P = .05), but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99-7.00, P = .05). Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis. Treatment modality did not affect blood counts during radiation therapy. Pretreatment neutrophilia, pretreatment leukocytosis, and grade 4 lymphopenia during radiation therapy were associated with worse outcomes after, but establishing causality will require additional work with increased statistical power.