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In those undergoing treatment for head and neck cancer (HNC), sarcopenia is a strong prognostic factor for outcomes and mortality. This review identified working definitions and methods used to objectively assess sarcopenia in HNC. The scoping review was performed in accordance with Arksey and O'Malley's five-stage methodology and the Joanna Briggs Institute guidelines. Eligible studies were identified using MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases. Inclusion criteria represented studies of adult HNC patients in which sarcopenia was listed as an outcome, full-text articles written in English, and empirical research studies with a quantitative design. Eligible studies were assessed using a proprietary data extraction form. General information, article details and characteristics, and details related to the concept of the scoping review were extracted in an iterative process. Seventy-six studies published internationally from 2016 to 2021 on sarcopenia in HNC were included. The majority were retrospective (n = 56; 74%) and the prevalence of sarcopenia ranged from 3.8% to 78.7%. Approximately two-thirds of studies used computed tomography (CT) to assess sarcopenia. Skeletal muscle index (SMI) at the third lumbar vertebra (L3) (n = 53; 70%) was the most prevalent metric used to identify sarcopenia, followed by SMI at the third cervical vertebra (C3) (n = 4; 5%). Currently, the most effective strategy to assess sarcopenia in HNC depends on several factors, including access to resources, patient and treatment characteristics, and the prognostic significance of outcomes used to represent sarcopenia. Skeletal muscle mass (SMM) measured at C3 may represent a practical, precise, and cost-effective biomarker for the detection of sarcopenia. However, combining SMM measurements at C3 with other sarcopenic parameters-including muscle strength and physical performance-may provide a more accurate risk profile for sarcopenia assessment and allow for a greater understanding of this condition in HNC.

Patients with oligometastases who develop a small number of metastatic lesions might achieve long-term survival with the use of ablative surgery or stereotactic radiotherapy. More patients are receiving aggressive treatment for oligometastatic disease, yet long-term survival might not be due to the treatments themselves, but rather to the selection of patients with slow-growing indolent disease. The authors examine the key evidence supporting or refuting the existence of an oligometastatic state and its appropriate treatment. The oligometastatic paradigm implies that patients who develop a small number of metastatic lesions might achieve long-term survival if all these lesions are ablated with surgery or stereotactic radiotherapy. Clinical data indicate that the number of patients with oligometastatic disease receiving aggressive treatment is increasing rapidly. We examine the key evidence supporting or refuting the existence of an oligometastatic state. Numerous single-arm studies suggest that long-term survival is 'better-than-expected' after ablative treatment. However, the few studies with adequate controls raise the possibility that this long-term survival might not be due to the treatments themselves, but rather to the selection of patients based on favourable inclusion criteria. Furthermore, ablative treatments carry a risk of harming healthy tissue, yet the risk–benefit ratio cannot be quantified if the benefits are unmeasured. If the strategy of treating oligometastases is to gain widespread acceptance as routine clinical practice, there should be stronger evidence supporting its efficacy.

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for patients with early-stage lung cancer who are inoperable. However, SABR causes benign radiation-induced lung injury (RILI) which appears as lesion growth on follow-up CT scans. This triggers the standard definition of progressive disease, yet cancer recurrence is not usually present, and distinguishing RILI from recurrence when a lesion appears to grow in size is critical but challenging. In this study, we developed a tool to do this using scans with apparent lesion growth after SABR from 68 patients. We performed bootstrapped experiments using radiomics and explored the use of multiple regions of interest (ROIs). The best model had an area under the receiver operating characteristic curve of 0.66 and used a sphere with a diameter equal to the lesion’s longest axial measurement as the ROI. We also investigated the effect of using inter-feature and volume correlation filters and found that the former was detrimental to performance and that the latter had no effect. We also found that the radiomics features ranked as highly important by the model were significantly correlated with outcomes. These findings represent a key step in developing a tool that can help determine who would benefit from follow-up invasive interventions when a SABR-treated lesion increases in size, which could help provide better treatment for patients.

Background Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease. Methods Up to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes. Discussion This study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.

Background Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone. Methods After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy. Discussion This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study. Trial registration Clinicaltrials.gov identifier: NCT01446744

Background Palliative radiotherapy (PRT) is an effective treatment for managing symptoms of advanced cancer. At least half of all radiation treatments are delivered with palliative intent, aimed at relieving symptoms, such as pain or shortness of breath. Symptomatic patients must receive PRT quickly, therefore expeditious treatment planning is essential. Standard radiation planning requires a dedicated CT scan acquired at the cancer centre, called a ‘CT simulation’, which facilitates treatment planning (i.e. tumor delineation, placement of radiation beams and dose calculation). However, the CT simulation process creates a bottleneck and often leads to delays in starting treatment. Other researchers have indicated that CT simulation can be replaced by the use of standard diagnostic CT scans for target delineation and planning, which are normally acquired through the radiology department as part of standard patient workup. The goals of this feasibility study are to assess the efficacy, acceptability and scalability of diagnostic-CT-enabled planning, compared to conventional CT simulation planning, for patients receiving PRT to bone, soft tissue and lung disease. Methods This is a randomized, phase II study, with 33 PRT patients to be randomized in a 1:2 ratio between conventional CT simulation (Arm 1), and the diagnostic CT enabled planning workflow (Arm 2). Patients will be stratified by treatment target volume (bone and soft tissue metastasis vs. primary or metastatic intrathoracic disease targets). The primary endpoint is the amount of time the patient spends at the cancer centre. Secondary endpoints include efficacy (rate of plan deliverability and rate of plan acceptability on blinded dose distribution review), stakeholder acceptability (based on patient and clinician perception of acceptability questionnaires) and scalability. Discussion This study will investigate the efficacy, acceptability and scalability of a “sim-free” PRT pathway compared to conventional CT simulation. The workflow may provide opportunity for resource optimization by using pre-existing diagnostic imaging and requires minimal investment due to its similarity to current PRT models. It also offers potential benefit to patients by eliminating an imaging procedure, reducing the amount of time spent at the cancer centre, and expediting time to treatment. Trial registration Clinicaltrials.gov identifier: NCT05233904. Date of registration: February 10, 2022; current version: 1.4 on April 29, 2022.

Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC. Methods/Design The target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required. Discussion This study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes. Trial registration NCT01590355

Background Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. Methods This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. Discussion If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. Trial registration Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. Protocol version: 1.1 on December 9, 2021.

Background Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. As there is no consensus regarding the optimal radiotherapy treatment regimen for these tumors, we performed a modeling study to evaluate the trade-offs between predicted toxicity and local control for commonly used high-precision dose-fractionation regimens. Methods Ten patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for 3 different hypofractionated schemes: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each regimen, one plan was created that prioritized planning target volume (PTV) coverage, potentially at the expense of organ at risk (OAR) tolerance, and a second that compromised PTV coverage to respect OAR dose constraints. Published radiobiological models were employed to evaluate competing treatment plans based on estimates for local control and the likelihood for toxicity to OAR. Results The risk of esophageal or pulmonary toxicity was low (< 5%) in all scenarios. When PTV coverage was prioritized, tumor control probabilities were 92.9% for 50 Gy in 5 fractions, 92.4% for 60 Gy in 8 fractions, and 52.0% for 60 Gy in 15 fractions; however the estimated risk of grade ≥ 4 toxicity to the proximal bronchial tree was 68%, 44% and 2% respectively. When dose to OAR was prioritized, the risk of major pulmonary toxicity was reduced to < 1% in all schemes, but this compromise reduced tumor control probability to 60.3% for 50 Gy in 5 fractions, 65.7% for 60 Gy in 8 fractions and 47.8% for 60 Gy in 15 fractions. Conclusions The tradeoff between local control and central airway toxicity are considerable in the use of 3 commonly used hypofractionated radiotherapy regimens for ultra-central lung cancer. The results of this planning study predict that the best balance may be achieved with 60 Gy in 8 fractions compromising PTV coverage as required to maintain acceptable doses to OAR. A prospective phase I trial (SUNSET) is planned to further evaluate this challenging clinical scenario.

Background Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD. Methods ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1–2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy 10 or 217 Gy 3 ), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy 10 or 133 Gy 3 ) and 45 Gy in 15 fractions daily (58 Gy 10 or 90 Gy 3 ). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR. Discussion ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD. Trial registration Clinicaltrials.gov identifier: NCT03485378 . Date of registration: April 2, 2018.