Validation of daily 0.35 T diffusion-weighted MRI for MRI-guided glioblastoma radiotherapy.

BACKGROUND: MRI-Linac systems enable daily diffusion-weighed imaging (DWI) MRI scans for assessing glioblastoma tumor changes with radiotherapy treatment. PURPOSE: Our study assessed the image quality of echoplanar imaging (EPI)-DWI scans compared with turbo spin echo (TSE)-DWI scans at 0.35 Tesla (T) and compared the apparent diffusion coefficient (ADC) values and distortion of EPI-DWI on 0.35 T MRI-Linac compared to high-field diagnostic MRI scanners. METHODS: The calibrated National Institute of Standards and Technology (NIST)/Quantitative Imaging Biomarkers Alliance (QIBA) Diffusion Phantom was scanned on a 0.35 T MRI-Linac, and 1.5 T and 3 T MRI with EPI-DWI. Five patients were scanned on a 0.35 T MRI-Linac with a TSE-DWI sequence, and five other patients were scanned with EPI-DWI on a 0.35 T MRI-Linac and a 3 T MRI. The quality of images was compared between the TSE-DWI and EPI-DWI on the 0.35 T MRI-Linac assessing signal-to-noise ratios and presence of artifacts. EPI-DWI ADC values and distortion magnitude were measured and compared between 0.35 T MRI-Linac and high-field MRI for both phantom and patient studies. RESULTS: The average ADC differences between EPI-DWI acquired on the 0.35 T MRI-Linac, 1.5 T and 3 T MRI scanners and published references in the phantom study were 1.7%, 0.4% and 1.0%, respectively. Comparing the ADC values based on EPI-DWI in glioblastoma tumors, there was a 3.36% difference between 0.35 and 3 T measurements. Susceptibility-induced distortions in the EPI-DWI phantoms were 0.46 ± 1.51 mm for 0.35 MRI-Linac, 0.98 ± 0.51 mm for 1.5 T MRI and 1.14 ± 1.88 mm for 3 T MRI; for patients -0.47 ± 0.78 mm for 0.35 T and 1.73 ± 2.11 mm for 3 T MRIs. The mean deformable registration distortion for a phantom was 1.1 ± 0.22 mm, 3.5 ± 0.39 mm and 4.7 ± 0.37 mm for the 0.35 T MRI-Linac, 1.5 T MRI, and 3 T MRI scanners, respectively; for patients this distortion was -0.46 ± 0.57 mm for 0.35 T and 4.2 ± 0.41 mm for 3 T. EPI-DWI 0.35 T MRI-Linac images showed higher SNR and lack of artifacts compared with TSE-DWI, especially at higher b-values up to 1000 s/mm2. CONCLUSION: EPI-DWI on a 0.35 T MRI-Linac showed superior image quality compared with TSE-DWI, minor and less distortions than high-field diagnostic scanners, and comparable ADC values in phantoms and glioblastoma tumors. EPI-DWI should be investigated on the 0.35 T MRI-Linac for prediction of early response in patients with glioblastoma.

Socioeconomic Influence on Speech Rehabilitation After Total Laryngectomy.

OBJECTIVE: Speech rehabilitation following a total laryngectomy significantly impacts the quality of life. Indwelling prosthetic voice restoration provides optimal outcomes; however, the long-term maintenance of these devices carries considerable financial costs, which are not universally covered by insurance. This investigation aimed to analyze associations between socioeconomic factors and outcomes in postlaryngectomy speech rehabilitation. STUDY DESIGN: Retrospective cohort analysis. SETTING: Academic tertiary-care center from May 2014 to September 2021. METHODS: In patients undergoing total laryngectomy, the incidence of tracheoesophageal puncture with indwelling vocal prostheses (TEP-VP) placement within the first postoperative year was compared among household income, demographic factors, and disease characteristics. Functional and maintenance outcomes served as secondary endpoints. RESULTS: Seventy-seven patients were included. Forty-five (58%) underwent indwelling TEP-VP (41 primaries). Eighty-nine percent of patients with annual incomes greater than $50k underwent TEP-VP compared to only 35% with incomes less than $50k/year. TEP-VP was performed in 85% of patients with commercial insurance, 70% with Medicare, 42% with Medicaid, and 0% with no insurance. On multivariate analysis, annual household incomes greater than $50k were predicted for TEP-VP placement (odds ratio: 12.7 [2.45-65.8], p = .002). The utilization of postoperative speech therapy and functional communication outcomes were similar among socioeconomic groups. Twelve patients were unable to afford supplies within the first year, with differences noted among insurance (p = .015) and income status (p = .003). CONCLUSION: Disparities in vocal and speech rehabilitation following laryngectomy may disproportionally affect underserved patients.

Stereotactic Radiosurgery for Brain Metastases in Patients With Small Cell Lung Cancer.

Purpose: Treatment of small cell lung cancer (SCLC) with brain metastatic disease has traditionally involved whole brain radiation therapy (WBRT). The role of stereotactic radiosurgery (SRS) is unclear. Methods and Materials: Our study was a retrospective review of an SRS database evaluating patients with SCLC who received SRS. A total of 70 patients and 337 treated brain metastases (BM) were analyzed. Forty-five patients had previous WBRT. The median number of treated BM was 4 (range, 1-29). Results: Median survival was 4.9 months (range, 0.70-23.9). The number of treated BM was correlated with survival; patients with fewer BM had improved overall survival (P < .021). The number of treated BM was associated with different brain failure rates; 1-year central nervous system control rates were 39.2% for 1 to 2 BM, 27.6% for 3 to 5 BM, and 0% for >5 treated BM. Patients with previous WBRT had worse brain failure rates (P < .040). For patients without previous WBRT, the 1-year distant brain failure rate was 48%, and median time to distant failure was 15.3 months. Conclusions: SRS for SCLC in patients with <5 BM appears to offer acceptable control rates. Patients with >5 BM have high rates of subsequent brain failure and are not ideal candidates for SRS.

Preoperative Stereotactic Body Radiation Therapy for Soft-Tissue Sarcoma: Results of Phase 2 Study.

Purpose: Preoperative radiation followed by surgical resection is a standard treatment for soft-tissue sarcomas (STS). We report on 2 consecutive, phase 2, single-arm studies evaluating 5 fraction stereotactic body radiation therapy (SBRT) treatments followed by surgical resection for STS (clinical trails.gov NCT02706171). Methods and Materials: A total of 16 patients were treated with preoperative SBRT. Tumor size in the greatest dimension was a median 6.7 cm (maximum: 14 cm) and the majority of STS were in the extremities. SBRT consisted of 35 to 40 Gy in 5 fractions every other day. Results: Median follow-up time was 1719 days (4.7 years). Grade ≥3 acute toxicity occurred in 1 patient (grade 3 skin changes). Fifteen patients proceeded with surgical resection. Three patients had a wound complication after surgery, 1 patient had grade ≥3 late toxicity (grade 4 requiring surgical intervention). There was 1 local recurrence and 5 distant recurrences. Conclusions: Long-term follow-up on SBRT for STS found acceptable control and toxicity rates, and warrants further evaluation.

Implementing and evaluating a high-resolution diode array for patient-specific quality assurance of robotic brain stereotactic radiosurgery/radiotherapy.

The purpose of the study was to introduce and evaluate a high-resolution diode array for patient-specific quality assurance (PSQA) of CyberKnife brain stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Thirty-three intracranial plans were retrospectively delivered on the SRS MapCHECK using fixed cone, Iris, and multileaf collimator (MLC). The plans were selected to cover a range of sites from large tumor bed, single/multiple small brain metastases (METs) to trigeminal neuralgia. Fiducial tracking using the four fiducials embedded around the detector plane was used as image guidance. Results were analyzed before and after registration based on absolute dose gamma criterion of 1 mm distance-to-agreement and 0.5%-3% dose-difference. Overall, the gamma passing rates (1 mm and 3% criterion) before registration for all the patients were above 90% for all three treatment modalities (96.8 ± 3.5%, the lowest passing rate of 90.4%), and were improved after registration (99.3 ± 1.5%). When tighter criteria (1 mm and 2%) were applied, the gamma passing rates after registration for all the cases dropped to 97.3 ± 3.2%. For trigeminal neuralgia cases, we applied 1 mm and 0.5% criterion and the passing rates dropped from 100 ± 0.0% to 98.5 ± 2.0%. The mean delivery time was 33.4 ± 11.7 min, 24.0 ± 4.9 min, and 17.1 ± 2.6 min for the fixed cone, Iris, and MLC, respectively. With superior gamma passing rates and reasonable quality assurance (QA) time, we believe the SRS MapCHECK could be a good option for routine PSQA for CyberKnife SRS/SRT.

Stereotactic Body Radiotherapy and Systemic Dose Chemotherapy for Locally Advanced Lung Cancer: Single Arm Phase 2 Study.

PURPOSE: This is a single arm phase 2 study (Clinical trials.gov NCT02568033) to examine the role of stereotactic body radiotherapy (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 nonsmall cell lung cancer. Primary endpoints are disease free survival and toxicity. MATERIALS: Patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40 to 50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy consisted of 4 cycles of pemetrexed and cisplatin or carboplatin and paclitaxel for nonsquamous histology and cisplatin and docetaxel or cisplatin and paclitaxel for squamous histology. SBRT was given in between the chemotherapy cycles. There was a 7 days break between chemotherapy and SBRT. Quality of life was measured using functional assessment of cancer therapy-lung. RESULTS: Twenty two patients were enrolled and analyzed. Seventeen (77%) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at 1 year was 82% and overall survival at 2 years was 53%. Median disease free survival is 16.0 months with a 2-year regional failure rate of 19% and 2-year distant failure rate of 47.2%. There were 6 grade 3 acute toxicities and 2 late grade 3 or higher toxicities including 1 grade 5 hemoptysis. Quality of life scores were unchanged compared with baseline. CONCLUSION: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation.

Cancer Stem Cells in Tumor Modeling: Challenges and Future Directions.

Microfluidic tumors-on-chips models have revolutionized anticancer therapeutic research by creating an ideal microenvironment for cancer cells. The tumor microenvironment (TME) includes various cell types and cancer stem cells (CSCs), which are postulated to regulate the growth, invasion, and migratory behavior of tumor cells. In this review, the biological niches of the TME and cancer cell behavior focusing on the behavior of CSCs are summarized. Conventional cancer models such as three-dimensional cultures and organoid models are reviewed. Opportunities for the incorporation of CSCs with tumors-on-chips are then discussed for creating tumor invasion models. Such models will represent a paradigm shift in the cancer community by allowing oncologists and clinicians to predict better which cancer patients will benefit from chemotherapy treatments.

Osteoradionecrosis of the hyoid presenting as acute airway compromise.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a well-known complication of radiation therapy for head and neck cancer. However, few reports have described hyoid bone ORN and its clinical implications. METHODS: We describe a retrospective case series of previously irradiated patients who were seen with sudden airway compromise, found to have underlying pathological hyoid fractures secondary to osteoradionecrosis. RESULTS: Six patients within postchemoradiation period (3-9 months) for oropharyngeal squamous cell carcinoma were seen with acute-onset dyspnea. Computed topography (CT) imaging was remarkable for severe airway luminal narrowing and pathological hyoid fractures. All six patients required urgent intervention with direct laryngoscopy and tracheostomy. Intraoperatively, five patients were seen with exposed necrotic hyoid bones. CONCLUSION: The hyoid and its associated musculature strongly influence upper airway patency. ORN may compromise its physiological function and leads to acute airway compromise. Hyoid ORN may hold significant and imperative clinical implications in head and neck cancer post-treatment surveillance.

A Statewide Multi-Institutional Study of Asymptomatic Pretreatment Testing of Radiation Therapy Patients for SARS-CoV-2 in a High-Incidence Region of the United States.

PURPOSE: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. METHODS AND MATERIALS: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. RESULTS: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. CONCLUSIONS: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Neuro-oncology Multidisciplinary Clinic and Improvements in Patient Outcome.

BACKGROUND: Neuro-oncology care is becoming increasingly complex and patients often see multiple specialists. Multidisciplinary clinic (MDC) is a patient-centric option to allow multiple specialists to be involved where patients see multiple providers on the same day. OBJECTIVE: The objective of this study was to evaluate the role of a neuro-oncology MDC on patient outcomes. MATERIALS AND METHODS: Retrospective study was performed on consecutive patients who received radiosurgery for central nervous system (CNS) disease. We evaluated patients 2 years before and 2 years after the implementation of a MDC. RESULTS: A total of 351 patients were analyzed, 163 patients before MDC and 188 after implementation of MDC. Before MDC the median follow-up was dependent on which department ordered follow-up radiographic imaging. This discrepancy decreased after the MDC. Overall survival for patients with CNS metastatic disease improved in the MDC cohort (median survival of 248 before MDC and 315 d after, P<0.027). CONCLUSION: We found that neuro-oncology MDC improved follow-up across disciplines and improved overall survival for patients with CNS metastatic disease.

Dosimetric comparison of inverse and forward planning for Gamma Knife stereotactic radiosurgery of brain metastases.

The Leksell GammaPlan (LGP) with an inverse planning (IP) tool has been upgraded to version 11.1 since its launch in 2010. We evaluated its IP planning performance by re-planning 16 targets that had been planned using forward planning (FP). The FP and IP plans were compared. A planning guideline for IP process was developed aiming for an unbiased comparison. Sixteen brain metastases (BMs) without nearby critical structures were included in the study (size > 1 cm for all targets). All prior FP were re-planned in the LGP using IP and maintaining the same beam-on time and coverage. The dose to all the targets was scaled to 20 Gy in a single fraction at 50% isodose line (IDL) for FP and IP comparison purpose. The coverage and beam-on time were nearly the same for both the FP and IP plans. For all the IP plans, the mean selectivity was 0.85 ± 0.04 (vs 0.83 ± 0.04 in FP plans, p = 0.02), the mean GI was 2.92 ± 0.21 (vs 3.18 ± 0.60 in FP plans, p = 0.047), the mean V12Gy was 8.18 ± 8.57 cc (vs 9.09 ± 9.08 cc in FP plans, p = 0.001), the mean V8Gy was 14.63 ± 15.14 cc (vs 16.34 ± 16.17 cc in FP plans, p = 0.001), and the mean V5Gy was 29.01 ± 28.77 cc (vs 32.77 ± 31.41 cc in FP plans, p = 0.001). The number of shots was higher in IP plans (means of 16.69 ± 8.11 vs 10.81 ± 6.87 in FP plans, p = 0.001). We retrospectively re-planned 16 FP plans using the IP tool while meeting the quality limiting factors for the FP plans. The dosimetry parameters from the IP plans outperformed the treated FP plans and the IP tool should be preferred for tumors with size > 1 cm.

Next-Generation Sequencing in 305 Consecutive Patients: Clinical Outcomes and Management Changes.

PURPOSE: Next-generation sequencing (NGS) is increasingly used to identify actionable mutations for oncology treatment. We examined the results and use of NGS assays at our institution. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 305 consecutive patients who had NGS testing of tumor samples from March 2014 to April 2017. NGS was performed by FoundationOne. RESULTS: Of the 305 tissue samples sent to FoundationOne, 189 reports were potentially usable. Of these reports, 76 (40.21%) demonstrated an aberration targetable by on-label therapies and 126 (66.67%) by off-label therapies, and 170 (89.94%) revealed actionable aberrations via all potential avenues, including clinical trials; 21 of these 189 potentially usable reports (11.1%) yielded a change in management, including use of on-label therapies (n = 7), use of off-label therapies (n = 6), enrollment in a clinical trial (n = 6), and discontinuation of a medication with a predicted poor response (n = 3; one report was used twice). For the six patients with off-label use, median duration of treatment was 46 days and discontinued after death (n = 3) or progression (n = 3). CONCLUSION: Only a minority of NGS assay results (6.9% percent of all tests ordered and 11.1% of useable tests) resulted in a management change. A small minority of patients started off-label therapy on the basis of NSG assay results and overall had poor responses to off-label treatment. Although in theory NGS assays may improve oncologic outcomes, the results of our initial 305 patients showed low clinical utility.

Stereotactic Body Radiotherapy Treatment for Recurrent, Previously Irradiated Head and Neck Cancer.

PURPOSE: Locally recurrent, previously irradiated primary head and neck tumors have historically been associated with poor outcomes. Stereotactic body radiation therapy has emerged as a feasible and promising treatment option for tumor recurrence, particularly in nonsurgical candidates. This study aimed to assess the associated outcomes of stereotactic body radiation therapy used in this setting. METHODS: Retrospective analysis of a prospectively collected database of 25 patients treated with CyberKnife for unresectable, recurrent head and neck cancer in a previously irradiated field. The primary end points evaluated were rates of survival, tumor control, and treatment-related toxicities. RESULTS: Median survival of the study population was 7.5 months (range, 1.5-47.0 months). Median survival of the 20 (80%) patients who were treated with curative purpose was 8.3 months. One-year overall survival rate for the entire population was 32%. The respective 1-year and 2-year survival rates for the curative subcohort were 40% and 20%, respectively. Local and locoregional failure occurred in 8 (32%) and 7 (28%) patients, respectively. Low severe acute (4%) and late (6%) treatment-related toxicity rates were observed. No grade 4 or 5 toxicities were observed. CONCLUSION: Stereotactic body radiation therapy is a viable treatment option for patients with unresectable, recurrent head and neck cancer. Significant tumor control rates are achievable with minimal severe toxicity. Although perhaps associated with patient selection and a heterogeneous sample, overall survival of stereotactic body radiation therapy outcomes appears unfavorable.

Preoperative Radiosurgery for Soft Tissue Sarcoma.

OBJECTIVES: Preoperative radiation followed by surgical resection is a standard treatment for soft tissue sarcomas (STSs). The conventional method of radiation is 5 weeks to approximately 50 Gy. We report on our initial experience and phase II single-arm study assessing 5 fractions of stereotactic body radiotherapy (SBRT), followed by surgical resection for STS. METHODS: Thirteen patients and 14 tumors were treated with preoperative SBRT; tumors were mostly poorly differentiated (5) or myxoid (5) and were located on the leg (10), arm (2) or groin (2). The median tumor size in greatest dimension was 7.6 cm (maximum 16 cm). Twelve patients received 35 Gy in 5 fractions; for 2 deeper tumors the dose was 40 Gy in 5 fractions. Ten patients were administered 0.5 cm bolus to improve the dose. Gross tumor volume was expanded 0.5 cm radially and 3 cm along the tissue plane. Treatment was to an isodose line (median 81%) and was delivered every other day. Maximum dose to the skin was 46 Gy (median 41 Gy). RESULTS: The median follow-up period was 279 days. Surgical resection occurred a median of 37 days after completion of SBRT. Four patients had acute toxicity consisting of 2 grade 2 and 2 grade 3 skin reactions; all cases of skin toxicity resolved by the time of surgery. Percent tumor necrosis ranged from 10% to 95% (median 60%). All patients had negative margins. Planned vacuum-assisted wound closure was used in 4 patients; there were no other major wound complications. There was 1 local recurrence and 7 distant recurrences. CONCLUSION: This is the initial experience of radiosurgery for preoperative treatment of STSs. We have found this to be well tolerated, convenient for the patients, and a much shorter treatment course, allowing patients to undergo surgery and subsequent chemotherapy quicker. Surgical complications and control rates are satisfactory. The initial results are encouraging for further investigation.

Stereotactic Body Radiotherapy for Large (> 5 cm) Non-Small-Cell Lung Cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a well-established treatment option for early stage non-small-cell lung cancer (NSCLC) tumors < 5 cm. There is limited information on tumors > 5 cm. PATIENTS AND METHODS: We performed retrospective data collection of patients enrolled onto a prospective SBRT registry study. Eligible patients for this study had node-negative NSCLC measuring > 5 cm in any dimension. Data from 41 patients were analyzed. Median patient age was 75 years, and median tumor size was 5.6 cm (range, 5.0-12.2 cm). Sixteen patients had squamous disease, 20 patients adenocarcinoma, and 1 mixed tumor; 4 patients had no biopsy. Median radiation dose per fraction was 50 Gy in 5 fractions. Radiation was prescribed to isodose line, median 66% (range, 50%-84%). RESULTS: Before SBRT, 6 patients had previous chemotherapy and 7 patients had previous radiation. Median follow-up for all patients was 15.2 months (range, 0.56-48.1 months). At last follow-up, 16 patients were still alive, with a median follow-up of 16.1 months for surviving patients. The median survival was 17.5 months with 1- and 2-year survivals of 65% and 34%. Two patients (4.8%) had local failure, and 13 patients (31%) had distant failure. Four patients (9.8%) had acute toxicity, and 7 patients (17.1%) had late toxicity, including 2 (4.8%) grade 3 late toxicities. CONCLUSION: SBRT for tumors > 5 cm is effective, with good local control rates and acceptable toxicity. The main pattern of failure is distant, suggesting a possible role for systemic chemotherapy in these patients.

Stereotactic Radiosurgery for Poor Performance Status Patients.

PURPOSE: Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients. METHODS AND MATERIALS: In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNS lesions treated was 3. RESULTS: Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%). CONCLUSIONS: Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers.