PSMA PET as a predictive tool for sub-regional importance estimates in the parotid gland

Objective: Xerostomia (subjective dry mouth) and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the intra-parotid dose response. Here, we aim to compare several models of parotid gland regional importance with prostate specific membrane antigen (PSMA) positron emission tomography (PET), which has high concentrations of uptake in salivary glands and has been previously suggested to relate to gland functionality. Furthermore, we develop a predictive model of Clark et al.'s relative importance using radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population. Approach: Intra-parotid uptake was compared with four regional importance models using [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping sub-regions were defined, while a paired t-test was used when binary regions were defined. Radiomic PSMA PET/CT features within Clark et al.'s sub-regions were used to develop a predictive model of population importance. Main Results: Clark et al.'s relative importance regions were significantly (p < 0.02) anti-correlated with PSMA PET uptake. Van Luijk et al.'s critical regions had significantly lower (p < 0.01) uptake than in non-critical regions. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance. Significance: This study suggests that regions of relatively low PSMA PET concentration in parotid glands may exhibit relatively high dose-sensitivity. We've demonstrated the ability of PSMA PET radiomic features for predicting relative importance within the parotid glands.Comment: 9 Figures, 7 Table

Neural blind deconvolution for simultaneous partial volume correction and super-sampling of PSMA PET images

Objective: We aimed to simultaneously mitigate partial volume effects (PVEs) in prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images while performing super-sampling. Approach: Blind deconvolution is a method of estimating the hypothetical "deblurred" image along with the blur kernel (related to the point spread function) simultaneously. Traditional maximum a posteriori blind deconvolution methods require stringent assumptions and suffer from convergence to a trivial solution. A promising method of modelling the deblurred image and kernel with independent neural networks, called "neural blind deconvolution" was demonstrated on 2D natural images in 2020. In this work, we adapt neural blind deconvolution for PVE correction of PSMA PET images, along with simultaneous super-sampling. We compare this methodology with several interpolation methods, using blind image quality metrics, and test the model's ability to predict kernels by re-running the model after applying artificial "pseudo-kernels" to deblurred images. Main Results: Our results demonstrate improvements in image quality over other interpolation methods in terms of blind image quality metrics and visual assessment. Predicted kernels were similar between patients, and the model accurately predicted several artificially-applied pseudo-kernels, Significance: The intrinsically low spatial resolution of PSMA PET leads to PVEs which negatively impact uptake quantification in small regions. The proposed method can be used to mitigate this issue, and can be straightforwardly adapted for other medical imaging modalities.Comment: 10 Figures, 4 Tables, 19 page

Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies:ISOO/MASCC/ASCO Guideline

PURPOSE: To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS: A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS: For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy.Additional information can be found at www.asco.org/supportive-care-guidelines

Population-based analysis of curative therapies in stage II non-small cell lung cancer: the role of radiotherapy in medically inoperable patients

Objectives: Curative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome. Materials and methods: A retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention. Results: A total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes. Conclusions: Among patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.Other UBCNon UBCReviewedFacult

Combined chemoradiotherapy showed improved outcome with early-stage HPV-positive oropharyngeal cancers

Abstract: Background. The revised 8th Edition American Joint Committee on Cancer (AJCC) Head and Neck Staging Manual distinguishes HPV-mediated from non-HPV-mediated oropharyngeal cancer (OpSCC). The objective was to analyze OpSCC treatment modalities and outcomes. Methods A retrospective study of OpSCC patients treated with radiotherapy or chemoradiotherapy between January 1st, 2000, and December 31st, 2008, as identified from the BC Cancer Registry. All patients received treatment at cancer clinics and had at least 5 years follow-up post-treatment. A total of 1259 OpSCC patients were identified. After initial chart reviews, 288 patients were excluded from further analysis and the majority (n = 198) was due to not receiving curative treatment. Based on the availability of formalin-fixed, paraffin-embedded (FFPE) tissue, patients were divided into two cohorts: Study Cohort (FFPE available, n = 244) and General Cohort (FFPE unavailable, n = 727). The Study Cohort was restaged according to AJCC 8th Edition based on p16 immunohistochemistry status. Kaplan-Meier analysis was used to estimate the 5-year overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival (LFS). Results Among 971 patients, OpSCC age-adjusted incidence rate was observed to have increased from 2.1 to 3.5 per 100,000 between 2000 and 2008. The General Cohort was relatively older than the Study Cohort (60.1 ± 10.5 vs. 57.3 ± 9.4), but both cohorts were predominantly males (78.3% vs. 76.2%). Amongst the Study Cohort, 77.5% were p16-positive, of whom 98.4% were down staged in the 8th Edition. These early-stage patients showed OS improvement for those treated with chemoradiation, compared to radiation alone (85.8% vs. 73.1%, p = 0.05). Conclusions OpSCC incidence is increasing in BC. The addition of chemotherapy to radiotherapy may portend a benefit in OS even for early-stage p16-positive OpSCC. Additional research is necessary to assess the safety of treatment de-escalation even among early-stage disease.Dentistry, Faculty ofMedicine, Faculty ofNon UBCOral Biological and Medical Sciences (OBMS), Department ofPathology and Laboratory Medicine, Department ofReviewedFacultyOthe