Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance.

BACKGROUND: Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC. PATIENTS AND METHODS: The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis. RESULTS: High intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs. CONCLUSION: Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.

Surgery for maxillary oral squamous cell carcinoma: the effect of surgical resection margins and elective neck dissection on oncological outcomes.

Maxillary oral squamous cell carcinoma (OSCC) is uncommon. Surgical resection is challenging due to the anatomy, and the role of elective neck dissection (END) is not well-defined. A retrospective cohort study of patients with maxillary OSCC treated with primary surgery between 2007 and 2019 was conducted. Primary tumours of sinonasal origin with extension into the oral cavity were excluded. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards models. Sixty-seven patients were included; mean follow-up was 55 months. On univariate analysis, clear (≥5 mm) margins were associated with higher disease-free (68% vs 36%, P = 0.019) and overall survival (75% vs 36%, P = 0.004) than close/involved (<5 mm) margins. In clinically node-negative patients, the risk of occult cervical metastasis in tumours with depth of invasion (DOI) ≥ 3 mm and T2-4 tumours was 22% and 25%, respectively. END in these groups was associated with a lower rate of loco-regional recurrence (DOI ≥3 mm subgroup: 5% vs 38%, P = 0.029; T2-4 subgroup: 6% vs 50%, P = 0.028) and longer time to recurrence (DOI ≥3 mm subgroup: 119 months vs 96 months, P = 0.042; T2-4 subgroup: 117 months vs 56 months, P = 0.031) than observation of the neck. On multivariate analysis, close/involved margins were associated with an increased risk of overall mortality (hazard ratio 3.4, 95% confidence interval 1.0-11.3, P = 0.043) and disease recurrence (hazard ratio 2.8, 95% confidence interval 1.1-7.1, P = 0.031). In maxillary OSCC, a ≥ 5 mm histological margin should remain the goal of ablative surgery. END should be considered in tumours with DOI ≥ 3 mm.

Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis.

This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran's Q-test (p<0.001) and Higgins I2=98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran's Q-test (p<0.001) and Higgins I2=80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.

Facial artery musculomucosal flaps in oropharyngeal reconstruction following salvage transoral robotic surgery: a review of outcomes.

OBJECTIVE: There has been little reported on the transoral reconstructive options following salvage transoral robotic surgery. This paper describes the facial artery musculomucosal flap as a method to introduce vascularised tissue to a previously irradiated resection bed. METHODS: A facial artery musculomucosal flap was used to reconstruct the lateral pharyngeal wall in 13 patients undergoing salvage transoral robotic surgery for oropharyngeal squamous cell carcinoma. Outcomes recorded include flap and donor site complications, length of stay, and swallowing and speech outcomes. RESULTS: There were no immediate or late flap complications, or cases of delayed wound healing in this series. There were two facial artery musculomucosal related complications requiring surgical management: one bleed from the facial artery musculomucosal donor site and one minor surgical revision. Healing of the flap onto the resection bed was successful in all cases. CONCLUSION: The facial artery musculomucosal flap provides a suitable transoral local flap option for selected patients undergoing salvage transoral robotic surgery for oropharyngeal malignancies.

Complexity and accuracy of image registration methods in SPECT-guided radiation therapy.

The use of functional imaging in radiotherapy treatment (RT) planning requires accurate co-registration of functional imaging scans to CT scans. We evaluated six methods of image registration for use in SPECT-guided radiotherapy treatment planning. Methods varied in complexity from 3D affine transform based on control points to diffeomorphic demons and level set non-rigid registration. Ten lung cancer patients underwent perfusion SPECT-scans prior to their radiotherapy. CT images from a hybrid SPECT/CT scanner were registered to a planning CT, and then the same transformation was applied to the SPECT images. According to registration evaluation measures computed based on the intensity difference between the registered CT images or based on target registration error, non-rigid registrations provided a higher degree of accuracy than rigid methods. However, due to the irregularities in some of the obtained deformation fields, warping the SPECT using these fields may result in unacceptable changes to the SPECT intensity distribution that would preclude use in RT planning. Moreover, the differences between intensity histograms in the original and registered SPECT image sets were the largest for diffeomorphic demons and level set methods. In conclusion, the use of intensity-based validation measures alone is not sufficient for SPECT/CT registration for RTTP. It was also found that the proper evaluation of image registration requires the use of several accuracy metrics.