Audiological Outcomes of Weekly vs. Triweekly Cisplatin in Head and Neck Cancer with Cochlear-Sparing Intensity-Modulated Radiation Therapy.

Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m2) for up to seven doses or in high doses triweekly (100 mg/m2) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8-27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.

A Phase 2 Trial of Primary Tumor Stereotactic Body Radiation Therapy Boost Before Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor before the start of CRT to improve PTC. METHODS AND MATERIALS: Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1 year, and the hypothesis was that the 1-year PTC rate would be ≥90%. Secondary objectives included objective response rate, regional and distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional magnetic resonance imaging and blood-based miRNA analysis. RESULTS: The study enrolled 21 patients (10 men and 11 women); the median age was 62 years (range, 52-78). The median pretreatment primary tumor size was 5.0 cm (range, 1.0-8.3). The most common nonhematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 nonhematologic toxicity occurred (respiratory failure/radiation pneumonitis), and no grade 5 toxicities occurred. The objective response rate at 3 and 6 months was 72.7% and 80.0%, respectively, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control rates were 81.6% and 70.3%, respectively. Disease-free survival and overall survival at 2 years were 46.1% and 50.3%, respectively, and median survival was 37.8 months. Functional magnetic resonance imaging detected a mean relative decrease in blood oxygenation level-dependent signal of -87.1% (P = .05), and miR.142.3p was correlated with increased risk of grade ≥3 pulmonary toxicity (P = .01). CONCLUSIONS: Dose escalation to the primary tumor using upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. Functional magnetic resonance imaging suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p was correlated with pulmonary toxicity.

Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

Using the PODCI to Measure Motor Function and Parent Expectations in Children With Cerebral Palsy.

OBJECTIVE: Involving parents in the evaluation of their child with cerebral palsy (CP) is associated with enhanced neurodevelopmental outcomes. The pediatric outcomes data collection instrument (PODCI) is a patient-reported outcome measure primarily used to assess motor function following orthopedic surgical intervention or for older children with more independent motor function. The PODCI expectations scale has infrequently been reported in previous studies. This study aims to determine the relationship between parent-reported motor performance using the PODCI and motor capacity assessed by pediatric therapists for young children with CP across all ability levels and to explore the use of the PODCI expectations scale for quantifying therapy-related parent expectations. METHODS: This prospective cohort study included 108 participants with CP, 2 to 8 years of age, gross motor function classification systems (GMFCS) levels I to V. Measures included the PODCI, gross motor function measure (GMFM), and GMFCS. RESULTS: There were moderate (r = 0.513) to large (r = 0.885) relationships between PODCI and GMFM scores. PODCI scores were significantly different across GMFCS levels. Weak, significant relationships (r = -0.28) were found between function expectations scores and measures of function. CONCLUSION: The PODCI, GMFM, and GMFCS provide different, but strongly related, information about the abilities of young children. The GMFM measures motor capacity. Parents report daily function and health-related quality of life for their child using the PODCI. Parent expectations for intervention outcomes may relate to a child's motor function. IMPACT: These study results are consistent with those for older children with greater independent mobility, indicating an opportunity for expanded use of the PODCI for measuring motor performance for younger children with CP across all ability levels. A strategy is provided for using the PODCI expectations scale to quantify parent therapy-related expectations in future research and clinical settings. Therapy-related expectations may relate to child outcomes.

Knowledge Driven Phenotyping.

Extracting patient phenotypes from routinely collected health data (such as Electronic Health Records) requires translating clinically-sound phenotype definitions into queries/computations executable on the underlying data sources by clinical researchers. This requires significant knowledge and skills to deal with heterogeneous and often imperfect data. Translations are time-consuming, error-prone and, most importantly, hard to share and reproduce across different settings. This paper proposes a knowledge driven framework that (1) decouples the specification of phenotype semantics from underlying data sources; (2) can automatically populate and conduct phenotype computations on heterogeneous data spaces. We report preliminary results of deploying this framework on five Scottish health datasets.

Clinical Outcomes and Multidisciplinary Patterns of Failure for Olfactory Neuroblastoma: The Ohio State Experience.

Purpose Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Methods and Materials Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan-Meier log-rank. Results Median follow-up time was 59 months (range: 5.2-236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% ( p = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients ( p = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5-235 months). Conclusion In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes.

Erratum: Clinical Outcomes and Multidisciplinary Patterns of Failure for Olfactory Neuroblastoma: The Ohio State Experience.

[This corrects the article DOI: 10.1055/s-0039-1692479.].

Daily and Weekly Rehabilitation Delivery for Young Children With Gross Motor Delay: A Randomized Clinical Trial Protocol (the DRIVE Study).

PURPOSE: The proposed project tests the principle that frequency of rehabilitation is an important regulator of therapeutic response in infants. METHODS: We will randomize 75 infants with cerebral palsy, 6 to 24 months of age and/or Gross Motor Function Classification System levels III to V (higher severity), to determine the short-term and long-term effects of 3 dosing protocols consisting of an identical number of 2-hour sessions of the same motor learning-based therapy applied over a different total number of calendar weeks. RESULTS AND CONCLUSIONS: The results will inform clinicians, families, and scientists about dosing and will provide needed recommendations for frequency of rehabilitation to optimize motor function and development of young children with cerebral palsy.

Forecasting smog-related health hazard based on social media and physical sensor.

Smog disasters are becoming more and more frequent and may cause severe consequences on the environment and public health, especially in urban areas. Social media as a real-time urban data source has become an increasingly effective channel to observe people׳s reactions on smog-related health hazard. It can be used to capture possible smog-related public health disasters in its early stage. We then propose a predictive analytic approach that utilizes both social media and physical sensor data to forecast the next day smog-related health hazard. First, we model smog-related health hazards and smog severity through mining raw microblogging text and network information diffusion data. Second, we developed an artificial neural network (ANN)-based model to forecast smog-related health hazard with the current health hazard and smog severity observations. We evaluate the performance of the approach with other alternative machine learning methods. To the best of our knowledge, we are the first to integrate social media and physical sensor data for smog-related health hazard forecasting. The empirical findings can help researchers to better understand the non-linear relationships between the current smog observations and the next day health hazard. In addition, this forecasting approach can provide decision support for smog-related health hazard management through functions like early warning.

The safety and efficacy of anterior cervical discectomy and fusion with polyetheretherketone spacer and recombinant human bone morphogenetic protein-2: a review of 200 patients.

OBJECT: The goal in this study was to demonstrate the safety and efficacy of anterior cervical discectomy and fusion ([ACDF]; single- or multilevel procedure) performed using titanium plates and polyetheretherketone (PEEK) spacers filled with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated in a type I collagen sponge to achieve fusion. METHODS: The authors retrospectively reviewed 200 patients who underwent a single- or multilevel ACDF with titanium plate fixation and PEEK spacer filled with a collagen sponge impregnated with low-dose rhBMP-2. Clinical outcomes were assessed using pre- and postoperative Nurick grades and the Odom criteria. Radiographic outcomes were assessed using dynamic radiographs and computed tomography (CT) scans. RESULTS: The follow-up period ranged from 8 to 36 months (mean 16.7 months). A single-level ACDF was performed in 96 patients, 2-level ACDF in 62 patients, 3-level ACDF in 36 patients, and 4-level ACDF in 6 patients. Long-term follow-up was available for 193 patients. The Odom outcomes were rated as good to excellent in 165 patients (85%), fair in 24 (12.4%), and poor in 4 (2%). Among patients with myelopathy, Nurick grades improved from a preoperative mean of 1.42 to a postoperative mean of 0.26. All patients (100%) achieved solid radiographic fusion on dynamic radiographs and CT scans. Fourteen patients (7%) in this series experienced clinically significant dysphagia, and 4 (2%) required repeated operation for hematoma or seroma. CONCLUSIONS: An ACDF performed using a PEEK spacer filled with rhBMP-2 leads to good to excellent clinical outcomes and solid fusion, even in multilevel cases and in patients who are smokers. The incidence of symptomatic dysphagia may be decreased with a lower dose of rhBMP-2 that is placed only within the PEEK spacer.

Contribution of recombinant human bone morphogenetic protein-2 to the rapid creation of interbody fusion when used in transforaminal lumbar interbody fusion: a preliminary report. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

OBJECT: The authors compared fusion rates in transforaminal lumbar interbody fusion (TLIFs) when using either autograft or bone morphogenetic protein (BMP) placed in the interbody space. METHODS: Between September 2002 and December 2003, the authors performed 44 TLIF operations. Follow-up data were available for 40 patients. Of the 40 procedures, 19 involved cages filled with iliac crest autograft (Group 1) and 21 involved cages filled with a medium kit of recombinant human (rh) BMP-2 (Group 2). In all Group 2 patients, one BMP sponge was placed anterior to the cage and another was placed within the cage. In 12 of the Group 2 patients, iliac crest autograft was placed posterior to the BMP-filled cage (Group 2A). In the remaining nine Group 2 patients, only local autograft was placed posterior to the BMP-filled cage (Group 2B). Assessment of fusion was performed using dynamic radiography at 3-month intervals. Outcomes were assessed using the Prolo Scale, and iliac crest donor site pain was measured using a Visual Analog Scale (VAS). The mean follow-up period was 9 months (range 3-18 months). In Group 1 patients, one pseudarthrosis was detected. In Group 2 patients, dynamic radiography demonstrated solid fusion in all patients except one in Group 2B. Fifty-eight percent of patients in whom iliac crest autograft was used complained of donor site pain 6 months after surgery (5 of 10 points on the VAS). Symptomatic foraminal bone formation was not observed in any Group 2 patient. CONCLUSIONS: The use of rhBMP-2 is safe in TLIFs when the sponges are placed away from the dura mater, and BMP promotes a more rapid fusion than iliac crest autograft alone. The use of rhBMP-2 in combination with local autograft is an excellent option for promoting solid fusion with TLIF, and it eliminates the possibility of iliac donor site pain.