Online dosimetric evaluation of larynx SBRT: A pilot study to assess the necessity of adaptive replanning

PURPOSE: We have initiated a multi-institutional phase I trial of 5-fraction stereotactic body radiotherapy (SBRT) for Stage III-IVa laryngeal cancer. We conducted this pilot dosimetric study to confirm potential utility of online adaptive replanning to preserve treatment quality. METHODS: We evaluated ten cases: five patients enrolled onto the current trial and five patients enrolled onto a separate phase I SBRT trial for early-stage glottic larynx cancer. Baseline SBRT treatment plans were generated per protocol. Daily cone-beam CT (CBCT) or diagnostic CT images were acquired prior to each treatment fraction. Simulation CT images and target volumes were deformably registered to daily volumetric images, the original SBRT plan was copied to the deformed images and contours, delivered dose distributions were re-calculated on the deformed CT images. All of these were performed on a commercial treatment planning system. In-house software was developed to propagate the delivered dose distribution back to reference CT images using the deformation information exported from the treatment planning system. Dosimetric differences were evaluated via dose-volume histograms. RESULTS: We could evaluate dose within 10 minutes in all cases. Prescribed coverage to gross tumor volume (GTV) and clinical target volume (CTV) was uniformly preserved; however, intended prescription dose coverage of planning treatment volume (PTV) was lost in 53% of daily treatments (mean: 93.9%, range: 83.9-97.9%). Maximum bystander point dose limits to arytenoids, parotids, and spinal cord remained respected in all cases, although variances in carotid artery doses were observed in a minority of cases. CONCLUSIONS: Although GTV and CTV SBRT dose coverage is preserved with in-room three-dimensional image guidance, PTV coverage can vary significantly from intended plans and dose to critical structures may exceed tolerances. Online adaptive treatment re-planning is potentially necessary and clinically applicable to fully preserve treatment quality. Confirmatory trial accrual and analysis remains ongoing

Targeting NAD+ Metabolism to Enhance Radiation Therapy Responses

Nicotinamide adenine dinucleotide (NAD+) metabolism is integrally connected with the mechanisms of action of radiation therapy and is altered in many radiation-resistant tumors. This makes NAD+ metabolism an ideal target for therapies that increase radiation sensitivity and improve patient outcomes. This review provides an overview of NAD+ metabolism in the context of the cellular response to ionizing radiation, as well as current therapies that target NAD+ metabolism to enhance radiation therapy responses. Additionally, we summarize state-of-the-art methods for measuring, modeling, and manipulating NAD+ metabolism, which are being used to identify novel targets in the NAD+ metabolic network for therapeutic interventions in combination with radiation therapy

A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent

PURPOSE: Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have to rely on visual and tactile information. Fluorescence-guided surgery using tumor-specific imaging agents can assist in clinical decision-making. However, a standardized imaging methodology is lacking. In this study, we determined whether a standardized, specimen-driven, fluorescence imaging framework using ONM-100 could assist in clinical decision-making during surgery. PROCEDURES: Thirteen patients with histologically proven HNSCC were included in this clinical study and received ONM-100 24 ± 8 h before surgery. Fluorescence images of the excised surgical specimen and of the surgical cavity were analyzed. A fluorescent lesion with a tumor-to-background ratio (TBR) > 1.5 was considered fluorescence-positive and correlated to standard of care (SOC) histopathology. RESULTS: All six tumor-positive surgical margins were detected immediately after excision using fluorescence-guided intra-operative imaging. Postoperative analysis showed a median TBR (±IQR) of the fluorescent lesions on the resection margin of 3.36 ± 1.62. Three fluorescence-positive lesions in the surgical cavity were biopsied and showed occult carcinoma and severe dysplasia, and a false-positive fluorescence lesion. CONCLUSION: Our specimen-driven fluorescence framework using a novel, pH-activatable, fluorescent imaging agent could assist in reliable and real-time adequate clinical decision-making showing that a fluorescent lesion on the surgical specimen with a TBR of 1.5 is correlated to a tumor-positive resection margin. The binary mechanism of ONM-100 allows for a sharp tumor delineation in all patients, giving the surgeon a clinical tool for real-time margin assessment, with a high sensitivity

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Hyperspectral Imaging of Head and Neck Squamous Cell Carcinoma for Cancer Margin Detection in Surgical Specimens from 102 Patients Using Deep Learning

Surgical resection of head and neck (H and N) squamous cell carcinoma (SCC) may yield inadequate surgical cancer margins in 10 to 20% of cases. This study investigates the performance of label-free, reflectance-based hyperspectral imaging (HSI) and autofluorescence imaging for SCC detection at the cancer margin in excised tissue specimens from 102 patients and uses fluorescent dyes for comparison. Fresh surgical specimens (n = 293) were collected during H and N SCC resections (n = 102). The tissue specimens were imaged with reflectance-based HSI and autofluorescence imaging and afterwards with two fluorescent dyes for comparison. A histopathological ground truth was made. Deep learning tools were developed to detect SCC with new patient samples (inter-patient) and machine learning for intra-patient tissue samples. Area under the curve (AUC) of the receiver-operator characteristic was used as the main evaluation metric. Additionally, the performance was estimated in mm increments circumferentially from the tumor-normal margin. In intra-patient experiments, HSI classified conventional SCC with an AUC of 0.82 up to 3 mm from the cancer margin, which was more accurate than proflavin dye and autofluorescence (both p < 0.05). Intra-patient autofluorescence imaging detected human papilloma virus positive (HPV+) SCC with an AUC of 0.99 at 3 mm and greater accuracy than proflavin dye (p < 0.05). The inter-patient results showed that reflectance-based HSI and autofluorescence imaging outperformed proflavin dye and standard red, green, and blue (RGB) images (p < 0.05). In new patients, HSI detected conventional SCC in the larynx, oropharynx, and nasal cavity with 0.85–0.95 AUC score, and autofluorescence imaging detected HPV+ SCC in tonsillar tissue with 0.91 AUC score. This study demonstrates that label-free, reflectance-based HSI and autofluorescence imaging methods can accurately detect the cancer margin in ex-vivo specimens within minutes. This non-ionizing optical imaging modality could aid surgeons and reduce inadequate surgical margins during SCC resections

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial.

To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer.Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA).Median follow-up is 13.4 months (range: 5.6-24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up.We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity.ClinicalTrials.gov NCT01984502