Stereotactic body radiotherapy for distant metastases to the head and neck.

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.

Metastasis to gastrostomy sites from upper aerodigestive tract malignancies: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Metastasis to the gastrostomy site in patients with upper aerodigestive tract (UADT) malignancies is a rare but devastating adverse event that has been poorly described. Our aim was to determine the overall incidence and clinicopathologic characteristics observed with development of gastrostomy site metastasis in patients with UADT cancers. METHODS: This was a systematic review and meta-analysis of 6138 studies retrieved from Medline, EMBASE, CINAHL, and the Cochrane Register after being queried for studies including gastrostomy site metastasis in patients with UADT malignancies. RESULTS: The final analysis included 121 studies. Pooled analysis showed an overall event rate gastrostomy site metastasis of .5% (95% confidence interval [CI], .4%-.7%). Subgroup analysis showed an event rate of .56% (95% CI, .40%-.79%) with the pull technique and .29% (95% CI, .15%-.55%) with the push technique. Clinicopathologic characteristics observed with gastrostomy site metastasis were late-stage disease (T3/T4) (57.8%), positive lymph node status (51.2%), and no evidence of systemic disease (M0) (62.8%) at initial presentation. The average time from gastrostomy placement to diagnosis of metastasis was 7.78 ± 4.9 months, average tumor size on detection was 4.65 cm (standard deviation, 2.02), and average length of survival was 7.26 months (standard deviation, 6.23). CONCLUSIONS: Gastrostomy site metastasis is a rare but serious adverse event that occurs at an overall rate of .5%, particularly in patients with advanced-stage disease, and is observed with a very poor prognosis. These findings emphasize a need for clinical practice guidelines to include a regular assessment of the PEG site and highlight the importance of detection and management of gastrostomy site metastasis by the multidisciplinary care oncology team.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

AIM: Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. MATERIALS & METHODS: Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. RESULTS & CONCLUSION: We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers.

AIM: To provide a multi-institutional description of current practices of stereotactic body radiotherapy (SBRT) for head and neck cancer. MATERIALS & METHODS: 15 international institutions with significant experience in head and neck SBRT were asked to complete a questionnaire covering clinical and technical factors. RESULTS: SBRT is used 10-100% of the time for recurrent primary head and neck cancer, and 0-10% of the time in newly diagnosed disease. Five centers use a constraint for primary disease of 3-5 cm and 25-30 cc. Nine institutions apply a clinical target volume expansion of 1-10 mm and 14 use a planning target volume margin of 1-5 mm. Fractionation regimens vary between 15 and 22 Gy in 1 fraction to 30-50 Gy in 5 or 6 fractions. The risk of carotid blowout quoted in the re-irradiation setting ranges from 3 to 20%. CONCLUSION: There is considerable heterogeneity in patient selection and techniques in head and neck SBRT practice among experienced centers.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up.

Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns. Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3), or no agreement. Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2-5) and three within a single organ (range 2-5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up. Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.

"I didn't actually know there was such a thing as rehab": survivor, family, and clinician perceptions of rehabilitation following treatment for head and neck cancer.

PURPOSE: The purpose of this study was to obtain first-hand contributions from survivors, family members, and front-line health care professionals regarding the rehabilitation needs for head and neck cancer (HNC) patients, to inform development of a rehabilitation intervention. METHODS: The researchers conducted a series of focus groups with the three key stakeholder groups. RESULTS: A total of seven focus groups with 40 participants were conducted, two with survivors, one with family members, and four with health care professionals. All three participant groups reported that motivation based on a strong desire to return to meaningful roles and activities, and rehabilitation resources embedded within the cancer system were important facilitators of functional recovery. Lack of access to rehabilitation services was a concern expressed repeatedly. CONCLUSION: While generalization is limited by the small sample size, findings include a comprehensive list of rehabilitation needs following treatment for HNC, factors that facilitate and hinder recovery of functional health, and specific suggestions for the development of rehabilitation consult intervention for survivors of HNC.

Radiologic Differences between Human Papillomavirus-Related and Human Papillomavirus-Unrelated Oropharyngeal Carcinoma on Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: Human papilloma virus-related oropharyngeal carcinoma (HPV+ OPC) is a unique entity compared to HPV-unrelated (HPV-) OPC. Previous studies were inconclusive regarding the differences between HPV+ and HPV- OPCs on diffusion-weighted imaging (DWI). This study sought to determine if there is an association between HPV status and apparent diffusion coefficient (ADC) values as an imaging biomarker in OPCs. MATERIALS AND METHODS: OPC patients with pretreatment MRI including DWI were retrospectively reviewed and analyzed as a blinded, controlled cohort. HPV status was biopsy-ascertained with p16 staining. ADC values were determined by placing the largest possible circular region of interest in solid portions of primary tumors and/or metastatic lymph nodes. Necrotic and cystic portions were excluded. RESULTS: Twenty-eight HPV+ and 12 HPV- patients were included. Adjusted for age and sex, ADC values were significantly lower in HPV+ OPC primary tumors (p = 0.013) and lymph node metastases (p = 0.013). The area under the curve (AUC) was 0.85 and 0.90, respectively. A model with a linear combination of the 2 variables yielded an AUC of 0.92. CONCLUSION: ADC values were significantly lower in both the primary tumors and lymph node metastases in HPV+ OPCs compared to HPV- OPCs. These results confirm the results of prior studies.

Stereotactic body radiotherapy for head and neck cancer: an addition to the armamentarium against head and neck cancer.

In the recent years, stereotactic body radiation therapy (SBRT) has emerged as a potential therapy for head and neck malignancies. Although early results appear to be promising, serious acute and late effects have been observed, mainly in patients who have had prior external beam radiotherapy. This review will discuss the radiobiology of SBRT, clinical rationale and outcomes for SBRT in head and neck cancers and focus on the benefits and potential limitations in both de novo and re-irradiation settings.

Role of stereotactic body radiotherapy for symptom control in head and neck cancer patients.

PURPOSE: Our aim was to determine the efficacy and quality of life outcomes of head and neck (HN) stereotactic body radiotherapy (SBRT) in a palliative population with significant proportions of de novo HN tumors not amenable to surgery or protracted course of curative radiotherapy (RT). METHODS: A retrospective review of a prospective database identified 21 patients with 24 sites that were treated. Patients were treated with intensity modulated RT (IMRT), usually 7-9 static fields with a 2-3-mm margin from gross tumor volume to planning target volume only with no microscopic margin added. Electronic patient records and treatment plans were reviewed. Basic demographic information was collected. The EORTC QLQ-H&N35 questionnaire was the tool used to collect QOL data both pre- and on-treatment fraction 5. Univariate analysis was performed for predictors of local control (LC) and prognostic factors for overall survival (OS). RESULTS: A total of 21 patients had 24 sites that were treated. The median age was 87 (range 25-103) and median KPS was 70. The most common histology was squamous cell carcinoma (SCC) 19/24 (79 %), basal cell carcinoma (BCC) 3/24 (16 %), and melanoma (4 %). The median maximal diameter was 3.7 cm (range 1-10 cm). The most commonly treated site was lymph nodes in the neck 13/24 (54 %), skin 8/24 (33 %), 4/24 (16 %) other HN mucosal primary sites. Of the 24 lesions, 17 (71 %) were de novo, without prior treatment and 7/24 (29 %) were recurrent. The most commonly used dose/fraction (fx) was 40 Gy/5 (fx) (range 35/5fx-48/6fx). Of the 24 lesions, 6 (25 %) had complete response, 16/24 (67 %) had partial response, and 2/24 (8 %) had no response. Control was defined as no further progression after treatment. For the entire cohort, LC at 3, 6, and 9 months were 66, 50, and 33 %, respectively. In the de novo group, 2/16 (12.5 %) had local failures with the LC rate of 94, 94, and 87 % at 3 months, 6 months, and 1 year, respectively. In the recurrent group, 4/8 (50 %) had failure with LC rates of 87. 5, 62.5, and 50 % at 3 months, 6 months, and 1 year, respectively. Of the 21 patients, 10 died during follow up, with the OS rate at 3 months, 6 months, and 1 year of 90, 70, and 60 %, respectively. Being defined "de novo" showed a trend toward statistical significance p = 0.046 for local failure. Overall survival did not show significant difference between de novo and recurrent with a p value of 0.267. No significant prognostic variables for OS were found. Pre-treatment QOL scores for the entire cohort were 53/130 versus 38/130 (lower scores indicating better QOL) scores with a trend toward statistical significance p = 0.05. CONCLUSIONS: SBRT is efficacious with improved quality of life within this elderly frail population in the treatment of de novo and recurrent tumors of the head and neck with promising quality of life scores.

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review.

PURPOSE: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. METHODS AND MATERIALS: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. RESULTS: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. CONCLUSIONS: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Oropharyngeal Cancer Staging Health Record Extraction Using Artificial Intelligence.

Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for head and neck cancer: A phase 1 clinical trial.

BACKGROUND AND PURPOSE: Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN). MATERIALS AND METHODS: This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria. RESULTS: Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %). CONCLUSIONS: MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.

Lymph node yield: Impact on oncologic outcomes in oral cavity cancer.

BACKGROUND: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery. METHODS: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome. RESULTS: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93). CONCLUSIONS: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.

Quantitative US Delta Radiomics to Predict Radiation Response in Individuals with Head and Neck Squamous Cell Carcinoma.

Purpose To investigate the role of quantitative US (QUS) radiomics data obtained after the 1st week of radiation therapy (RT) in predicting treatment response in individuals with head and neck squamous cell carcinoma (HNSCC). Materials and Methods This prospective study included 55 participants (21 with complete response [median age, 65 years {IQR: 47-80 years}, 20 male, one female; and 34 with incomplete response [median age, 59 years {IQR: 39-79 years}, 33 male, one female) with bulky node-positive HNSCC treated with curative-intent RT from January 2015 to October 2019. All participants received 70 Gy of radiation in 33-35 fractions over 6-7 weeks. US radiofrequency data from metastatic lymph nodes were acquired prior to and after 1 week of RT. QUS analysis resulted in five spectral maps from which mean values were extracted. We applied a gray-level co-occurrence matrix technique for textural analysis, leading to 20 QUS texture and 80 texture-derivative parameters. The response 3 months after RT was used as the end point. Model building and evaluation utilized nested leave-one-out cross-validation. Results Five delta (Δ) parameters had statistically significant differences (P < .05). The support vector machines classifier achieved a sensitivity of 71% (15 of 21), a specificity of 76% (26 of 34), a balanced accuracy of 74%, and an area under the receiver operating characteristic curve of 0.77 on the test set. For all the classifiers, the performance improved after the 1st week of treatment. Conclusion A QUS Δ-radiomics model using data obtained after the 1st week of RT from individuals with HNSCC predicted response 3 months after treatment completion with reasonable accuracy. Keywords: Computer-Aided Diagnosis (CAD), Ultrasound, Radiation Therapy/Oncology, Head/Neck, Radiomics, Quantitative US, Radiotherapy, Head and Neck Squamous Cell Carcinoma, Machine Learning Clinicaltrials.gov registration no. NCT03908684 Supplemental material is available for this article. © RSNA, 2024.

Unanticipated Radiation Replanning for Stage III Non-small Cell Lung Cancer.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Detection of solid and subsolid pulmonary nodules with lung MRI: performance of UTE, T1 gradient-echo, and single-shot T2 fast spin echo.

BACKGROUND: Although MRI is a radiation-free imaging modality, it has historically been limited in lung imaging due to inherent technical restrictions. The aim of this study is to explore the performance of lung MRI in detecting solid and subsolid pulmonary nodules using T1 gradient-echo (GRE) (VIBE, Volumetric interpolated breath-hold examination), ultrashort time echo (UTE) and T2 Fast Spin Echo (HASTE, Half fourier Single-shot Turbo spin-Echo). METHODS: Patients underwent a lung MRI in a 3 T scanner as part of a prospective research project. A baseline Chest CT was obtained as part of their standard of care. Nodules were identified and measured on the baseline CT and categorized according to their density (solid and subsolid) and size (> 4 mm/ ≤ 4 mm). Nodules seen on the baseline CT were classified as present or absent on the different MRI sequences by two thoracic radiologists independently. Interobserver agreement was determined using the simple Kappa coefficient. Paired differences were compared using nonparametric Mann-Whitney U tests. The McNemar test was used to evaluate paired differences in nodule detection between MRI sequences. RESULTS: Thirty-six patients were prospectively enrolled. One hundred forty-nine nodules (100 solid/49 subsolid) with mean size 10.8 mm (SD = 9.4) were included in the analysis. There was substantial interobserver agreement (k = 0.7, p = 0.05). Detection for all nodules, solid and subsolid nodules was respectively; UTE: 71.8%/71.0%/73.5%; VIBE: 61.6%/65%/55.1%; HASTE 72.4%/72.2%/72.7%. Detection rate was higher for nodules > 4 mm in all groups: UTE 90.2%/93.4%/85.4%, VIBE 78.4%/88.5%/63.4%, HASTE 89.4%/93.8%/83.8%. Detection of lesions ≤4 mm was low for all sequences. UTE and HASTE performed significantly better than VIBE for detection of all nodules and subsolid nodules (diff = 18.4 and 17.6%, p = < 0.01 and p = 0.03, respectively). There was no significant difference between UTE and HASTE. There were no significant differences amongst MRI sequences for solid nodules. CONCLUSIONS: Lung MRI shows adequate performance for the detection of solid and subsolid pulmonary nodules larger than 4 mm and can serve as a promising radiation-free alternative to CT.

Toxicity and Efficacy of Multitarget Thoracic Stereotactic Body Radiation Therapy.

PURPOSE: With the increasing use of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multitarget thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data, we report the experience of this strategy from a large academic center. METHODS AND MATERIALS: Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets separated by ≤1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival, and overall survival. Competing risk analysis was used to evaluate the cumulative incidence of CSRP, LF, and ICST. Univariate and multivariable analyses were performed to look for clinical and dosimetric predictive factors of CSRP and LF. RESULTS: One hundred ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Indications for SBRT were oligometastases (n = 70; 36.8%), oligoprogression (n = 62; 32.6%), curative intent in patients with primary lung cancer (n = 37; 19.5%), and control of dominant areas of metastatic progression (n = 21; 11.0%). The number of irradiated tumors ranged from 2 to 7 and the majority of SBRT courses were delivered simultaneously (88.2%). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The cumulative incidence of CSRP at 6 and 12 months was 5.3% and 7.6%, respectively. The cumulative incidence of LF at 2 years was 10.5%. The cumulative incidence of ICST at 2 years was 41.1%. Median progression-free survival was 11.8 months and median overall survival was 51.3 months. On multivariable analysis, a higher lung V35Gy (hazard ratio, 2.59; P = .02) was a statistically significant predictor of CSRP and colorectal histology predicted for higher LF (hazard ratio, 2.12; P = .02). CONCLUSIONS: In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Optimizing plans to lower the lung V35Gy may decrease the risk of CSRP.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases.

PURPOSE: Stereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. METHODS: Patients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. RESULTS: A total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. CONCLUSION: SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

Cine MRI-based analysis of intrafractional motion in radiation treatment planning of head and neck cancer patients.

PURPOSE/OBJECTIVE(S): To investigate intrafraction motion of (HN) target volumes and to determine patient-specific planning target volume (PTV) margins. MATERIALS/METHODS: MR-cine imaging was performed for radiation treatment planning in HN cancer patients treated with definitive EBRT (n = 62) or SBRT (n = 4) on a 1.5 T MRI between 2017-2019. Dynamic MRI scans (sagittal orientation, 2 × 82 × 7 mm3 resolution), ranging from 3-5 min and 900-1500 images, were acquired. The position of the maximum tumor displacement along each direction in the anterior/posterior (A/P) and superior/inferior (S/I) position was recorded and analyzed to determine average PTV margins. RESULTS: Primary tumor sites (n = 66) were oropharynx (n = 39), larynx (n = 24) and hypopharynx (n = 3). PTV margins for A/P/S/I positions were 4.1/4.4/5.0/6.2 mm and 4.9/4.3/6.7/7.7 mm for oropharyngeal and laryngeal/hypopharyngeal cancers when accounting for all motion. V100 for PTV was calculated and compared to the original plans. The mean drop in PTV coverage was in most cases under 5%. For a subset of patients with 3 mm plans available, V100 for PTV had more substantial decreases in coverage averaging 8.2% - and 14.3% for oropharyngeal and laryngeal/hypopharynx plans, respectively. CONCLUSION: The use of MR-cine in treatment planning allows for quantification of tumor motion during swallow and resting periods and should be accounted for during treatment planning. With motion considered, the derived margins may exceed the commonly used 3-5 mm PTV margins. Quantification and analysis of tumor and patient-specific PTV margins is a step towards real-time MRI guidance adaptive radiotherapy.