Oropharyngeal Squamous Carcinoma Research Articles

Multi-Specialty Physician Performance in Predicting Radiographic Extranodal Extension in Nodal Metastases of Oropharyngeal Squamous Carcinoma

The presence of extranodal extension (ENE) in oropharyngeal (OPC) cancer patients is an important prognostic factor and can be used to determine the optimal course of treatment; however, currently, the gold standard method for ENE assessment is performed pathologically, which can only be done in a post-hoc fashion after surgical treatment has already been performed. Anatomic imaging features are being explored as a possible method for the pre-therapeutic determination of ENE, but there is currently no objective standard for the assessment of ENE from radiographic images. In this study we recruited expert clinicians, including surgeons, radiation oncologists, and radiologists, across multiple institutions to individually evaluate the presence of ENE from CT scans in order to assess the performance of radiographic ENE evaluation in human experts across different specialties. Pre-therapy contrast-enhanced CT scans were collected from 25 OPC patients with lymph node metastasis that were pathologically evaluated for ENE after surgical resection. 5 scans were randomly chosen to be duplicated and left/right inverted, resulting in a total of 30 scans of which 21 had pathologically-confirmed ENE. To hide the inversion, all images were cropped to only show the oropharynx region. 34 expert head and neck cancer physicians, comprised of 12 surgeons, 11 radiation oncologists, and 11 radiologists, then separately evaluated the 30 CT scans using 3D Slicer for ENE presence or absence with their prediction confidence. For each physician, discriminative performance metrics were measured by calculating the accuracy, sensitivity, specificity, area under the receiver-operating characteristic curve (AUC), and Brier score, a measure of the probabilistic prediction accuracy calculated from their confidence where a lower Brier score is better. Statistical tests were performed using the Mann Whitney U test. The median (interquartile) study results are shown in Table 1. There was no statistically significant difference among groups for accuracy or AUC, but significant differences among groups for Brier score, sensitivity, and specificity. In this study we provide evidence that expert physicians, regardless of specialty, show poor performance in assessing the presence of ENE from CT scans in OPC patients. These results agree with conclusions from previous literature, and suggest the need for further research in the automated analysis of radiographic ENE.

Definitive chemoradiation for oropharyngeal squamous carcinomas: Outcomes with intensity-modulated radiation therapy using simultaneous integrated boost, in a majorly p16 negative cohort.

The literature on modern-era outcomes of oropharyngeal squamous carcinoma (OPSCC) in India is limited. We analyzed records of consecutive patients with OPSCC treated using a curative SIB IMRT regimen of 66 Gy/30#/6 weeks. One hundred fifteen patients from July 2011 to December 2018 were analyzed. Twenty of 69 patients tested positive for p16. In p16 positive patients, the K-M probability of being disease free and alive at 2 years, with at least one follow-up 3months after treatment, was 83% (median not reached) compared with 48% if p16 was unknown/negative. Patients staged as IVB p16 negative had a 2-year DFS of 25%. Patients unfit for cisplatin and consequently received other agents had 2-year DFS estimated at 20%. Intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy was feasible, with toxicity and disease control comparable to available literature. AJCC Stage IVB p16 negative disease had notably poor outcome.

Systematic review and meta-analysis of occult contralateral nodal metastases in patients with oropharyngeal squamous carcinoma undergoing elective neck dissection.

A systematic review and meta-analysis was conducted to evaluate the occult contralateral nodal metastases (OCM) in patients undergoing bilateral neck dissection for surgically treated oropharyngeal squamous cell carcinoma (OPSCC). Following PRISMA guidelines, MEDLINE, Embase and Cochrane Controlled Register of Trials databases were searched for observational and experimental studies until March 2021. Search yielded 175 articles, of which 13 were included. Overall, OCM were seen in 9.8% of patients (95% CI: [5.7, 16.4], 839 patients, 12 studies, I2 65%). For ipsilateral cN0 necks, the OCM rate was 1.7% (95% CI: [0.1, 22.4], 150 patients, 8 studies, I2 0%) and for cN+necks the OCM rate was 9.8% (95% CI: [4.4, 20.3], 429 patients, 8 studies, I2 72%). Occult contralateral nodal metastases are uncommon in OPSCC patients with clinico-radiologically negative ipsilateral necks. Occult rates are higher in the contralateral neck when the ipsilateral neck is clinico-radiologically node positive.

Development and Testing of a Machine Learning Model Using18F-Fluorodeoxyglucose PET/CT-Derived Metabolic Parameters to Classify Human Papillomavirus Status in Oropharyngeal Squamous Carcinoma

To develop and test a machine learning model for classifying human papillomavirus (HPV) status of patients with oropharyngeal squamous cell carcinoma (OPSCC) using 18F-fluorodeoxyglucose (18F-FDG) PET-derived parameters in derived parameters and an appropriate combination of machine learning methods in patients with OPSCC. This retrospective study enrolled 126 patients (118 male; mean age, 60 years) with newly diagnosed, pathologically confirmed OPSCC, that underwent 18F-FDG PET-computed tomography (CT) between January 2012 and February 2020. Patients were randomly assigned to training and internal validation sets in a 7:3 ratio. An external test set of 19 patients (16 male; mean age, 65.3 years) was recruited sequentially from two other tertiary hospitals. Model 1 used only PET parameters, Model 2 used only clinical features, and Model 3 used both PET and clinical parameters. Multiple feature transforms, feature selection, oversampling, and training models are all investigated. The external test set was used to test the three models that performed best in the internal validation set. The values for area under the receiver operating characteristic curve (AUC) were compared between models. In the external test set, ExtraTrees-based Model 3, which uses two PET-derived parameters and three clinical features, with a combination of MinMaxScaler, mutual information selection, and adaptive synthetic sampling approach, showed the best performance (AUC = 0.78; 95% confidence interval, 0.46-1). Model 3 outperformed Model 1 using PET parameters alone (AUC = 0.48, p = 0.047) and Model 2 using clinical parameters alone (AUC = 0.52, p = 0.142) in predicting HPV status. Using oversampling and mutual information selection, an ExtraTree-based HPV status classifier was developed by combining metabolic parameters derived from 18F-FDG PET/CT and clinical parameters in OPSCC, which exhibited higher performance than the models using either PET or clinical parameters alone.

Extratumoral invasion: A unique phenomenon of aggressive recurrent oropharyngeal squamous cell carcinoma

BackgroundOropharyngeal squamous carcinomas cause significant morbidity and mortality. Poor prognosticators include lymphovascular and perineural invasion. Extratumoral phenotypes of these histologic findings confer worse prognoses. MethodsWe report eight cases of recurrent oropharyngeal cancer with diffuse extratumoral lymphovascular invasion (ELVI) or extratumoral perineural invasion (EPNI) and review the existing literature. ResultsOn salvage resection for recurrence following primary radiation or chemoradiation, six patients manifested ELVI and two showed EPNI. These patterns conferred difficulty with complete surgical clearance; final pathologic analysis demonstrated positive margins for all eight patients. The six patients with ELVI were p16+ and the two with EPNI were p16-. Currently, two patients are deceased and six patients are alive at an average follow-up of 17.4 months. Of the six living patients, 2 have a new recurrence and are in hospice while 4 have no evidence of disease. ConclusionsELVI and EPNI have received little consideration in the literature as unique histopathologic features of oropharyngeal squamous carcinoma. We present the first series on these adverse extratumoral features in recurrent disease. We call attention to these unique histologic features in the setting of recurrent oropharyngeal cancer to encourage others to track the results of therapeutic intervention and to identify successful strategies for treatment.

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

BackgroundCurrently, 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.ObjectiveWe 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.MethodsThe 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.ResultsOn 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.ConclusionsGiven 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.

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

PurposeTo determine whether patient similarity in terms of head and neck cancer spread through lymph nodes correlates significantly with radiation-associated toxicity. Materials and methods582 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. ResultsOut 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). DiscussionOur 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. ConclusionOur 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.

Disparities and guideline adherence for HPV testing among patients with oropharyngeal squamous cell carcinoma, NCDB, and SEER.

Human papilloma virus testing for oropharyngeal squamous-cell carcinoma has been recommended by the National Comprehensive Cancer Network since 2012. We examine disparities, reported rates of human papillomavirus (HPV) testing, and the impact on these findings of limitations with the variable in database registries. The HPV variable was queried for patients with oropharyngeal squamous carcinoma (OPSCC) from 2013 to 2016 in National Cancer Data Base (NCDB) and Surveillance, Epidemiology, and End Results (SEER). Multivariable regression was used to identify disparities based on sociodemographic variables. Sensitivity analyses were used to investigate limitations of the variable. Despite limitations in the HPV variable in the databases, there was less than 100% adherence to recommended testing, and there were significant disparities in multiple sociodemographic variables. For example, in NCDB 70% of white versus 60.4% of black patients were tested (odds ratio [OR] 0.75, confidence interval [CI] 0.66-0.85, p ≤ 0.0001); in SEER 59.8% of white and 47.6% of black patients were tested (OR 0.73, CI 0.67-0.81; p ≤ 0.0001). Disparities exist among patients undergoing testing for HPV-associated OPSCC and adherence to guideline recommended HPV testing has been suboptimal. In addition, the HPV variable definition, especially as it relates to p16 positivity, and use in these two registries should be improved.

OROPHARYNGEAL SQUAMOUS CELL CARCINOMA TREATED CONCURRENTLY WITH CETUXIMAB: A CASE REPORT OF INTOLERANCE TO CISPLATIN IN YOUNG AGE

Squamous cell carcinoma of the oropharynx is a common case of head and neck cancer related to human papillomavirus. We present a case of moderately (G2) differentiated squamous cell carcinoma, which responded well to concurrent radiotherapy with cetuximab after intolerance of cisplatin. A 37-year-old woman referred to our hospital for a locally advanced cancer of the base of tongue. Physical examination revealed an ulcerative tumor with spread to the supraglottic structures, and swelling of the right side cervical lymph node at group IIA. The histological diagnosis from a biopsy specimen was moderately differentiated p16 positive squamous cell carcinoma. The patient underwent cisplatin-based concurrent chemoradiotherapy. Two – three weeks after receiving an intravenous cisplatin dose 100 mg/m 2 for the first day of chemorradiation, the patient presented with profound bilateral sensorineural hearing loss. The cisplatin-based chemotherapy had changed to alternative agent. The patient continuously underwent concurrently radiation with cetuximab without the break of radical radiotherapy course. The patient experienced partial recovery of hearing after radical treatment of cancer. Complete clinical and radiological response of oropharyngeal squamous carcinoma was achieved. Conclusions. Toxicity with only one standard dose of cisplatin can be profound also in young age. This risk should be addressed when counseling patient prior to initiation of treatment. In case of platinum ineligibility, replacing cisplatin with less toxic agent cetuximab may be taken into consideration for p16 positive carcinoma of the oropharynx.

PD-L1 Expression and a High Tumor Infiltrate of CD8+ Lymphocytes Predict Outcome in Patients with Oropharyngeal Squamous Cells Carcinoma

Carcinogenesis of human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative (–) OPSCC. HPV-related immune-escape-mechanism could be responsible for the development and progression of HPV+ tumors and an immunophenotype different from HPV– OPSCC is expected. The purpose of this study was to analyze the expression of programmed cell death protein 1 ligand 1 (PD-L1) and its prognostic relevance in relation to CD8+ tumor infiltrating lymphocytes (TILs) and the major histocompatibility complex (MHC) I expression in OPSCC. We quantified PD-L1 expression on tumor cells (TC) and macrophages and MHC I expression in association to CD8+ TILs by immunohistochemistry on tissue microarray derived from 171 HPV+/-OPSCC. HPV-status was determined by p16INK4a immunohistochemistry/HPV-DNA detection. Presence of CD8+ TILs, PD-L1 expression on TC, and a more frequent loss of MHC I in HPV+ compared to HPV- OPSCC was detected. A high amount of CD8+ TILs in the whole cohort and in HPV+ OPSCC and PD-L1 expression on TC in HPV- OPSCC was associated with favorable overall survival. There was a trend for an improved outcome according to PD-L1 expression (macrophages) in HPV+ OPSCC without reaching statistical significance. CD8+ TILs and PD-L1-expression have prognostic impact in OPSCC and might present useful biomarkers for predicting clinical outcome and personalized therapy concepts.

Rethinking the 10-pack-year rule for favorable human papillomavirus-associated oropharynx carcinoma: A multi-institution analysis.

De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers,139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.

Distinguishing between HPV-Associated Metastatic Anal Squamous Cell Cancer and HPV-Associated Oropharyngeal Cancer

The histology and immunohistochemistry (IHC) of primary and metastatic diseases from a human papilloma virus- (HPV-) related anal squamous carcinoma (ASCC) would typically demonstrate the same histology as an HPV-related oropharyngeal squamous carcinoma (OPSCC). However, determining whether a site of squamous cell carcinoma represents distant metastatic ASCC versus a metastatic HPV-related metastasis from an OPSCC to a regional lymph node carries profound prognostic and therapeutic implications. A patient with a history of locally advanced ASCC treated with standard concurrent radiation therapy and chemotherapy in 2015 is described. In 2018, an enlarged supraclavicular lymph node was excised demonstrating squamous cell carcinoma and radiographic staging revealed no other areas suspicious for malignancy. Direct laryngoscopy with operating telescope and biopsies demonstrated squamous cell carcinoma at the tongue base. Described here are assays that might be considered in distinguishing between whether a focus distant from a previously identified ASCC represents metastatic disease or instead a separate primary HPV-related cancer.

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer.

For definitive chemoradiotherapy (chemoRT) of head and neck squamous cell carcinoma (HNSCC), cisplatin is the preferred concurrent agent, with superiority over cetuximab for HPV-associated oropharyngeal squamous carcinoma recently shown in 2 randomized trials (RTOG 1016 and De-ESCALaTE). Patients who are not candidates for cisplatin may be treated with carboplatin instead, but its comparative efficacy is unclear. We analyzed nationwide patterns of care and cancer-specific outcomes after cisplatin- versus carboplatin-based chemoRT. Patients with locoregionally advanced (stages III-IVB according to the 6th and 7th editions of the AJCC Cancer Staging Manual) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received definitive radiotherapy (RT) were identified in the linked SEER-Medicare database. The concurrent chemotherapy regimen was determined through corresponding Medicare claims. Death caused by HNSCC (cancer-specific mortality [CSM]) was analyzed with competing risks. Propensity score analysis and multivariable Fine-Gray regression were used to adjust for baseline differences, including age and comorbidity. We identified 807 patients who received cisplatin-based chemoRT and 342 who received carboplatin-based chemoRT. Most carboplatin recipients (68%) had combination chemotherapy, predominantly with paclitaxel. Carboplatin- and cisplatin-based chemoRT had similar incidences of death attributable to HNSCC (3-year CSM, 29% vs 26%; P=.19), which persisted in propensity score-matched analysis. In addition, no significant difference in overall survival was seen in the matched cohorts. ChemoRT with either cisplatin or carboplatin was superior to RT alone and RT with concurrent cetuximab. In the multivariable model, the adjusted hazard ratio of CSM for carboplatin relative to cisplatin was 1.01 (95% CI, 0.79-1.28; P=.94). Definitive carboplatin-based chemoRT was equivalent to cisplatin-based therapy and superior to RT alone and RT with concurrent cetuximab. In light of recent results of the RTOG 1016 and De-ESCALaTE trials, our findings suggest that carboplatin-based regimens warrant prospective investigation as an alternative to cisplatin for patients who are not cisplatin candidates.

Association of Estrogen Receptor Alpha Expression With Survival in Oropharyngeal Cancer Following Chemoradiation Therapy.

Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC. To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression. Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status. In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC.

Phosphohistone H3 as the standard of immunohistochemical study in the assessment of differentiation level of oropharyngeal zone squamous cell carcinomas

Сегодня верификация и градуировки опухолей орофарингеального участка, определение их потенциала злокачественности остаются актуальной проблемой как в диагностике, так и прогнозировании течения опухолей. Цель работы – определение пролиферативного индекса (Ki67) и действительного количества митозов (pHH3), сравнение с морфологической (гистологической) картиной. Материалы и методы. В работе исследован 121 случай плоскоклеточного рака с использованием моноклональных и поликлональных антител. Исследована зависимость между пролиферативным индексом (Ki67), количеством митозов (pHH3) и морфологическими критериями. В работе использовалась оценка уровня дифференцировки по методике Anneroth et al., 1987 і Bryne et al., 1992. Результаты и их обсуждение. После повторной оценки уровня дифференцировки получили распределение по трём основным группам. К группе 1, в которую входят G1 опухоли, относятся 22 пациента, к группе 2, G2 – 45 и к группе 3, G3–54 пациента. Все три группы морфологически нами описаны. В дальнейшем в группах проведена оценка результатов ИГХИ по маркерам Ki67 и рНН3. При сравнении показателей Ki67, pHH3 обнаружено статистически значимое различие между группами (p<0,001 по критерию Крускала-Уоллиса для всех показателей). Таким образом, с уменьшением Ме уровня дифференциация Кі67 существенно (р<0,05) увеличивается, а увеличение рНН3 свидетельствует о росте степени злокачественности опухолей. Выводы. Статистически в работе доказана взаимосвязь Кі67, рНН3 и уровня дифференцировки плоскоклеточных карцином орофарингеального участка. Установлена возможность использования рHH3 маркера как достоверного критерия оценки уровня дифференцировки опухолей, в том числе тяжёлых, для диагностики плоскоклеточных карцином.

HPV and oropharyngeal cancer mystery: a glimmer of hope!

Viral associated cancer brings to forth the intricate relationships between viruses and host innate immunity and genetic susceptibility1. This interplay is particularly germane to viral associated nasopharyngeal and oropharyngeal squamous carcinomas, where lymphoid rich submucosa characterizes these sites. The inability of the existing immune defenses to neutralize EBV and HPV (both are dsDNA viruses) is currently unknown. This is largely due to the lack of direct cause/effect, the ubiquitous presence of these viruses and the unique demographic and epidemiologic characteristics of the affected subjects2. Therefore, multiple interacting factors including genetic, environmental, viral/host susceptibility and innate immunity underlie viral induced tumors at these locations. This article is protected by copyright. All rights reserved.

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma

A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.

Cervista HPV 16/18 and HPV HR assays can be used in tissue specimens of oropharyngeal squamous carcinoma patients to determine high-risk HPV status

Cervista HPV 16/18 and HPV HR assays can be used in tissue specimens of oropharyngeal squamous carcinoma patients to determine high-risk HPV status

Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma.

Background:Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than those with HPV-negative tumours. There is interest in de-escalating their treatment but strategies are needed for risk stratification to identify subsets with a poor prognosis. This study investigated tumour-infiltrating lymphocytes (TILs) in relation to HPV tumour status and patient survival.Methods:Biopsies from 218 patients diagnosed with OPSCC between 2002 and 2011, who underwent chemo/radiotherapy were analysed for HPV by PCR, in-situ hybridisation and p16 immunohistochemistry (IHC). One hundred and thirty-nine samples with concordant HPV detection were analysed for CD3, CD4, CD8 and FoxP3 expression in tumour and stromal regions using multiplexIHC and multispectral image analysis. Labelling of smooth muscle actin (SMA) identified activated stroma.Results:Human papillomavirus-positive compared with HPV-negative OPSCC had higher infiltration in both tumour and stromal areas of CD4 and CD8 T cells but not FoxP3 T regulatory cells. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). There was significantly higher SMA expression in HPV-positive compared with -negative tumours, which did not correlate with survival.Conclusions:Studies of TILs for risk stratification in OPSCC should assess stromal infiltration.

Prospective functional outcomes in sequential population based cohorts of stage III/ IV oropharyngeal carcinoma patients treated with 3D conformal vs. intensity modulated radiotherapy.

Background and purposeTo compare early (3 and 6 month) and later (12 and 24 month) functional outcomes of stage III and IV (M0) oropharyngeal squamous cancer patients treated in sequential cohorts with 3D conformal (3DCRT) or intensity modulated radiotherapy (IMRT).Patients and methods200 patients in sequential population based cohorts of 83 and 117 patients treated at a single institution with 3DCRT and then IMRT respectively were prospectively assessed at pre-treatment and 3, 6, 12 and 24 months post treatment. A standard functional outcomes protocol including performance status (KPS, ECOG), 3 Performance Status scales for Head and Neck (PSS-HN), the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), Voice Handicap Index-10 (VHI-10) and self-rated xerostomia were applied.ResultsMean age at diagnosis was 59 years. The primary site was base of tongue in 77 and tonsil or soft palate in 123 patients. Median follow up was 2.5 years for the second cohort. Concomitant therapy was used in 159 (79.5%). Overall survival at 3 years was 75.6% and 71.5% for IMRT and 3DCRT cohorts respectively (not significant). A multiple imputation technique was used to estimate missing values in order to avoid a healthy patient bias. KPS and ECOG reached nadirs at 3 to 6 months but approached baseline values at 12 to 24 months and did not differ by treatment. The 3 PSS-HN scales, Eating in Public (p < 0.001), Understandability of Speech (p = 0.009) and Oral Diet Texture (p = 0.002) and all showed significantly better outcomes in favor of IMRT. The RBHOMS showed a difference in favor of IMRT which appeared during 3 to 6 months (p < 0.001). The VHI-10 also showed a difference in favor of IMRT (p = 0.015). Self-rated xerostomia did not differ at 3 and 6 months but was significantly better in favor of IMRT after 12 months p = 0.005ConclusionsA prospectively administered functional outcomes protocol showed meaningful differences in favor of IMRT over 3DCRT early (3–6 months) and later (12–24 months) in the treatment of oropharyngeal carcinoma with equivalent survival. These data support the adoption of IMRT as the standard radiation treatment method for patients with stage III and IV (M0) oropharyngeal squamous carcinoma. KPS and ECOG may not be sensitive to oropharyngeal cancer patients’ functional outcomes by treatment.