3D Variation in delineation of head and neck organs at risk

<p>Abstract</p> <p>Background</p> <p>Consistent delineation of patient anatomy becomes increasingly important with the growing use of highly conformal and adaptive radiotherapy techniques. This study investigates the magnitude and 3D localization of interobserver variability of organs at risk (OARs) in the head and neck area with application of delineation guidelines, to establish measures to reduce current redundant variability in delineation practice.</p> <p>Methods</p> <p>Interobserver variability among five experienced radiation oncologists was studied in a set of 12 head and neck patient CT scans for the spinal cord, parotid and submandibular glands, thyroid cartilage, and glottic larynx. For all OARs, three endpoints were calculated: the Intraclass Correlation Coefficient (ICC), the Concordance Index (CI) and a 3D measure of variation (3D SD).</p> <p>Results</p> <p>All endpoints showed largest interobserver variability for the glottic larynx (ICC = 0.27, mean CI = 0.37 and 3D SD = 3.9 mm). Better agreement in delineations was observed for the other OARs (range, ICC = 0.32-0.83, mean CI = 0.64-0.71 and 3D SD = 0.9-2.6 mm). Cranial, caudal, and medial regions of the OARs showed largest variations. All endpoints provided support for improvement of delineation practice.</p> <p>Conclusions</p> <p>Variation in delineation is traced to several regional causes. Measures to reduce this variation can be: (1) guideline development, (2) joint delineation review sessions and (3) application of multimodality imaging. Improvement of delineation practice is needed to standardize patient treatments.</p

Cost-Effectiveness of Surgery Versus Organ Preservation in Advanced Laryngeal Cancer

Objective: Treatment decision-making for patients with laryngeal cancer consists of a complex trade-off between survival and quality of life. For decision makers on coverage and guidelines, costs come in addition to this equation. Our aim was to perform a cost-effectiveness analysis of surgery (laryngectomy with or without radiotherapy) versus organ preservation (OP: radiotherapy, chemo- and/or bioradiation) in advanced laryngeal cancer patients from a healthcare perspective. Methods: A cost-effectiveness analysis was conducted using a Markov model. For each modality, data on survival and quality-adjusted life years (QALYs) were sourced from relevant articles in agreement with experts, and national benchmark cost prices were included regarding treatment, follow-up, adverse events, and rehabilitation. Results: Total QALYs of the surgical approach (6.59) were substantially higher compared to the OP approach (5.44). Total lifetime costs were higher for the surgical approach compared to the OP approach, namely €95,881 versus €47,233. The surgical approach was therefore more effective and more costly compared to OP, resulting in an incremental cost-effectiveness ratio of €42,383/QALY. Conclusion: Based on current literature, surgical treatment was cost-effective compared to OP in advanced laryngeal cancer within most willingness-to-pay thresholds. The study provides information on the survival adjusted for quality of life in combination with costs of two different approaches for advanced laryngeal cancer, relevant for patients, physicians, and policy makers. As financial toxicity is a relevant aspect in this population, collection of real-world data on country-specific costs and utilities is strongly recommended to enable further generalization. Level of Evidence: N/A. Laryngoscope, 2020

Baseline peripheral blood leukocytosis: Biological marker predicts outcome in oropharyngeal cancer, regardless of HPV-status

To study the prognostic value of abnormalities in baseline complete blood count in patients with oropharyngeal cancer (OPC) treated with (chemo) radiation. The prognostic value of baseline complete blood count on outcome in 234 patients with OPC treated between 2010 and 2015 was examined in multivariate analysis together with other conventional prognostic variables including HPV-status, tumor stage, tumor and nodal size. The 3-year overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant control (DC) of the whole group were 74%, 64%, 79%, and 88%, respectively. Leukocytosis and HPV-status were the only significant prognosticators for OS and DFS at the multivariate analysis. Patients without leukocytosis had a significantly better DC compared to those with leukocytosis (92% and 70%, respectively, p  < 0.001). Patients with HPV-negative OPC had significantly worse LRC compared to HPV-positive patients (67% and 90%, respectively, p  < 0.001). The 3-year OS in HPV-positive group with leukocytosis compared to those without leukocytosis were 69% and 95%, respectively (p  < 0.001). The figures for HPV-negative patients were 41% vs. 61%, respectively (p = 0.010). This is the first study to date reporting the independent impact of leukocytosis and HPV-status on outcome of patients with OPC. The poor outcome of patients with leukocytosis is mainly caused by the worse DC. The significant impact of leukocytosis on outcome was even more pronounced in HPV-positive patients. These biomarkers could help identifying patients with poor prognosis at baseline requiring intensification of local and/or systemic treatment while treatment de-intensification might be offered to the low-risk grou

Deterioration of intended target volume radiation dose due to anatomical changes in patients with head-and-neck cancer

Delivered radiation dose can differ from intended dose. This study quantifies dose deterioration in targets, identifies predictive factors, and compares dosimetric to clinical patient selection for adaptive radiotherapy in head-and-neck cancer patients. One hundred and eighty-eight consecutive head-and-neck cancer patients treated up to 70 Gy were analyzed. Daily delivered dose was calculated, accumulated, and compared to the planned dose. Cutoff values (1 Gy/2 Gy) were used to assess plan deterioration in the highest/lowest dose percentile (D1/D99). Differences in clinical factors between patients with/without dosimetric deterioration were statistically tested. Dosimetric deterioration was evaluated in clinically selected patients for adaptive radiotherapy with CBCT. Respectively, 16% and 4% of patients had deterioration over 1 Gy in D99 and D1 in any of the targets, this was 5% (D99) and 2% (D1) over 2 Gy. Factors associated with deterioration of D99 were higher baseline weight/BMI, weight gain early in treatment, and smaller PTV margins. The sensitivity of visual patient selection with CBCT was 22% for detection of dosimetric changes over 1 Gy. Large dose deteriorations in targets occur in a minority of patients. Clinical prediction based on patient characteristics or CBCT is challenging and dosimetric selection tools seem warranted to identify patients in need for ART, especially in treatment with small PTV margins

Disease course after the first recurrence of head and neck squamous cell carcinoma following (chemo)radiation

Purpose: Recurrent head and neck squamous cell carcinoma (HNSCC) after chemoradiation is a challenging clinical problem. Salvage surgery (SS) is often extensive and mutilating. Oncological outcomes of SS are relatively well known, but little is published about the course of disease after the first recurrence, especially in patients without salvage possibilities. The aim of this study was to analyze the course of disease in patients with recurrent HNSCC after chemoradiation. Methods: We retrospectively analyzed and descriptively reported the disease course in 198 patients with recurrent HNSCC after chemoradiation in the time period after the first recurrence. We scored any type of event, salvage treatment, systemic treatment and overall survival (OS). Results: Of the 198 patients with recurrent HNSCC, salvage surgery was attempted in 104 (53%). SS was more frequently given in patients with recurrent laryngeal cancer, isolated regional failure (p < 0.001) and HPV-positive disease (p = 0.09). The 2-year OS of the whole group was 31% and was significantly different by tumor site, type of failure and SS. HPV-positive disease and salvaged recurrences were significantly predictive for better survival. One third of that salvaged patients was still alive without second recurrence. Median survival in patients that received any palliative systemic treatment without surgery, compared to those were no treatment was given, was 6 and 3 months, respectively (p = 0.006). Conclusions: Main factors influencing the course of disease in recurrent HNSCC are the possibilities for SS and HPV-status. Therefore, SS should always be considered and discussed. In patients without possibilities for SS, overall survival is 3–6 months

The impact of hyperbaric oxygen therapy on late irradiation injury in oral microcirculation

Background: Late side effects of radiotherapy in patients with head and neck cancer (HNCPs) result in decreased tissue vascularity, a compromised healing capacity and spontaneous breakdown of tissue. The aim of this study was to examine the in vivo effect of hyperbaric oxygen therapy (HBOT) on the microcirculation in irradiated oral tissue. Methods: Using a handheld microscope, the effect of HBOT on oral mucosal microcirculation parameters was measured in 34 previously irradiated HNCPs prior to HBOT and at 4 weeks and 6 months posttreatment. Results: A significant increase in mean buccal vessel density and decrease in buccal vessel diameter was found 6 months after HBOT compared to baseline, 22 ± 11 versus 25 ± 7 cpll/mm2 (p < 0.05) and 20 ± 4 versus 16 ± 5 μm (p < 0.05), respectively. Conclusion: Our results indicate that oral microcirculation histopathology associated with irradiation is able to respond to HBOT by redirecting oral microcirculation parameters towards values consistent with healthy tissue

Adaptive FDG-PET/CT guided dose escalation in head and neck squamous cell carcinoma: Late toxicity and oncologic outcomes (The ADMIRE study)

Purpose: To report on the late toxicity and local control (LC) of head and neck cancer patients treated with adaptive FDG-PET/CT response-guided radiotherapy (ADMIRE) with dose escalation (NCT03376386). Materials and methods: Between December 2017 and April 2019, 20 patients with stage II-IV squamous cell carcinoma of the larynx, hypopharynx or oropharynx were treated within the ADMIRE study where FDG-PET/CT response-guided (Week 2&4) dose escalation was applied (total dose 70–78 Gy). Cisplatin or cetuximab was added to radiotherapy in case of T3-4 and/or N2c disease. To compare the LC and late toxicity of the study population, we used an external control group (n = 67) consisting of all eligible patients for the study (but not participated). These patients were treated in our institution during the same period with the current standard of 70 Gy radiotherapy. To reduce the effect of confounding, logistic regression analyses was done using stabilized inverse probability of treatment weighting (SIPTW). Results: After median follow-up of 40 and 43 months for the ADMIRE and control groups, the 3-year LC-rates were 74% and 78%, respectively (adjusted HR after SIPTW 0.80, 95 %CI 0.25–2.52, p = 0.70). The incidences of any late G3 toxicity were 35% and 18%, respectively. The adjusted OR for any late G3 toxicity was 5.09 (95 %CI 1.64–15.8, p = 0.005), for any late G ≥ 2 toxicity was 3.67 (95 %CI 1.2–11.7, p = 0.02), for persistent laryngeal edema was 10.95 (95% CI 2.71–44.29, p = 0.001), for persistent mucosal ulcers was 4.67 (95% CI 1.23–17.7, p = 0.023), and for late G3 radionecrosis was 15.69 (95 %CI 2.43–101.39, p = 0.004). Conclusion: Given the comparable LC rates with increased late toxicity in the ADMIRE group, selection criteria for future adaptive dose escalation trials (preferably randomized) need to be refined to include only patients at higher risk of local failure and/or lower risk of severe late toxicity

Local control in sinonasal malignant melanoma:Comparing conventional to hypofractionated radiotherapy

BackgroundThe purpose of this study was to analyze the effect of fractionation schedule on local control in postoperative radiotherapy (RT) for sinonasal malignant melanoma. MethodsSixty-three patients who were treated with surgery and postoperative RT in 4 accredited head and neck cancer centers in the Netherlands between 1998 and 2013 were retrospectively studied. Outcomes with conventional fractionation (2-2.4 Gy per fraction; n=27) were compared to hypofractionation (4-6 Gy per fraction; n=36). The primary endpoint was local control and the secondary endpoint was toxicity. ResultsComparable local control rates were found after 2 and 5 years (63% vs 64% and 47% vs 53%; P=.73 for, respectively, conventional fractionation vs hypofractionation). Local recurrences were predominantly present ipsilateral (92%) and within the irradiated volume (88%). Late toxicity grade3 was observed in 2 of 63 patients, 1 patient in both groups. ConclusionRadiotherapy fractionation schedule did not influence the local control rate or the incidence of late toxicity in patients treated with surgery and RT for sinonasal malignant melanoma in this retrospective analysis. Due to this retrospective nature and the limited number of patients, strong recommendations cannot be made. Expected toxicity, patient convenience, and workload may be taken into account for the choice of fractionation schedule until conclusive evidence becomes available

Cost‐Effectiveness of Surgery Versus Organ Preservation in Advanced Laryngeal Cancer

Objective: Treatment decision-making for patients with laryngeal cancer consists of a complex trade-off between survival and quality of life. For decision makers on coverage and guidelines, costs come in addition to this equation. Our aim was to perform a cost-effectiveness analysis of surgery (laryngectomy with or without radiotherapy) versus organ preservation (OP: radiotherapy, chemo- and/or bioradiation) in advanced laryngeal cancer patients from a healthcare perspective. Methods: A cost-effectiveness analysis was conducted using a Markov model. For each modality, data on survival and quality-adjusted life years (QALYs) were sourced from relevant articles in agreement with experts, and national benchmark cost prices were included regarding treatment, follow-up, adverse events, and rehabilitation. Results: Total QALYs of the surgical approach (6.59) were substantially higher compared to the OP approach (5.44). Total lifetime costs were higher for the surgical approach compared to the OP approach, namely €95,881 versus €47,233. The surgical approach was therefore more effective and more costly compared to OP, resulting in an incremental cost-effectiveness ratio of €42,383/QALY. Conclusion: Based on current literature, surgical treatment was cost-effective compared to OP in advanced laryngeal cancer within most willingness-to-pay thresholds. The study provides information on the survival adjusted for quality of life in combination with costs of two different approaches for advanced laryngeal cancer, relevant for patients, physicians, and policy makers. As financial toxicity is a relevant aspect in this population, collection of real-world data on country-specific costs and utilities is strongly recommended to enable further generalization. Level of Evidence: N/A. Laryngoscope, 131:E509–E517, 2021