Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Real-Time Tracking of Laryngeal Motion via the Surface Depth-Sensing Technique for Radiotherapy in Laryngeal Cancer Patients.

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left-right, cranio-caudal, and anterior-posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were -0.7 ± 1.0 mm (-18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left-right, cranio-caudal, and anterior-posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.

Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer.

INTRODUCTION: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. METHODS: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). RESULTS: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<-0.16) was associated with improved PFS (p < 0.05). CONCLUSIONS: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

Sarcopenia and Systemic Inflammation Synergistically Impact Survival in Oral Cavity Cancer.

OBJECTIVES: Sarcopenia and systemic inflammation can affect survival of advanced-stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. STUDY DESIGN: Retrospective review at a tertiary cancer center. METHODS: Patients with stage III-IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex-specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C-reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. RESULTS: A total of 174 patients were included in the study. The cut-off values for sarcopenia were set at SMI <52.4 cm2 /m2 (men) and < 36.2 cm2 /m2 (women) corresponding to the lowest sex-specific tertile. An mGPS 1-2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06-3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1-2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17-3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7-16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1-2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01-46.99; P < .001). CONCLUSIONS: Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced-stage OSCC patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1530-E1538, 2021.

Neoadjuvant Chemoradiotherapy and Larynx-Preserving Surgery for Cervical Esophageal Cancer.

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. This study evaluated the feasibility of neoadjuvant CCRT as a larynx preservation strategy for treating cervical esophageal squamous cell carcinoma (SCC) by a multidisciplinary team. Fifteen patients with cervical esophageal SCC who received neoadjuvant CCRT and radical surgery at our institution were reviewed. All patients received CCRT using the intensity-modulated radiation therapy with 48 Gy to gross tumor and 43.2 Gy to regional lymphatic basin in 24 fractions. Side effects, clinical tumor responses, pathological responses, and surgical margin status were analyzed. Pathological T down-staging was noted in seven patients (46.7%); pathological complete response was achieved in three patients (20%). Fourteen patients (93.3%) had larynx preservation; eight patients (53.3%) achieved negative surgical margins. The 2-year overall survival, local relapse-free survival, and regional relapse-free survival were 50.6%, 62.2%, and 47.5%, respectively. Neoadjuvant CCRT and larynx-sparing surgery are feasible and tolerable in patients with cervical esophageal SCC. Prospectively designed studies for large patient groups and long-term follow-up results are needed for validating this multimodality therapy.

Bio-physic constraint model using spatial registration of delta 18F-fluorodeoxyglucose positron emission tomography/computed tomography images for predicting radiation pneumonitis in esophageal squamous cell carcinoma patients receiving neoadjuvant chemoradiation.

PURPOSE: This study integrated clinical outcomes and radiomics of advanced thoracic esophageal squamous cell carcinoma patients receiving neoadjuvant concurrent chemoradiotherapy (NACCRT) to establish a novel constraint model for predicting radiation pneumonitis (RP). PATIENTS AND METHODS: We conducted a retrospective review for thoracic advanced esophageal cancer patients who received NACCRT. From 2013 to 2018, 89 patients were eligible for review. Staging workup and response evaluation included positron emission tomography/computed tomography (PET/CT) scans and endoscopic ultrasound. Patients received RT with 48 Gy to gross tumor and 43.2 Gy to elective nodal area in simultaneous integrated boost method divided in 24 fractions. Weekly platinum-based chemotherapy was administered concurrently. Side effects were evaluated using CTCAE v4. Images of 2-fluoro-2-deoxyglucose PET/CT before and after NACCRT were registered to planning CT images to create a region of interest for dosimetry parameters that spatially matched RP-related regions, including V10, V20, V50%, V27, and V30. Correlation between bio-physic parameters and toxicity was used to establish a constraint model for avoiding RP. RESULTS: Among the investigated cohort, clinical downstaging, complete pathological response, and 5-year overall survival rates were 59.6%, 40%, and 34.4%, respectively. Multivariate logistic regression analysis demonstrated that each individual set standardized uptake value ratios (SUVRs), neither pre- nor post-NACCRT, was not predictive. Interestingly, cutoff increments of 6.2% and 8.9% in SUVRs (delta-SUVR) in registered V20 and V27 regions were powerful predictors for acute and chronic RP, respectively. CONCLUSION: Spatial registration of metabolic and planning CT images with delta-radiomics analysis using fore-and-aft image sets can establish a unique bio-physic prediction model for avoiding RP in esophageal cancer patients receiving NACCRT.

Development of delineation for the left anterior descending coronary artery region in left breast cancer radiotherapy: An optimized organ at risk.

BACKGROUND AND PURPOSE: The left anterior descending coronary artery (LAD) and diagonal branches (DBs) are blurred on computed tomography (CT). We aimed to define the LAD region (LADR) with adequate inclusion of the LAD and DBs and contouring consistency. METHODS AND MATERIALS: The LADR was defined using coronary CT angiograms. The inclusion ratio was used to assess the LAD and DBs inclusion by the LADR. Four radiation oncologists delineated the LAD and LADR, using contrast-enhanced CT of 15 patients undergoing left breast radiotherapy. The Sørensen-Dice similarity index (DSI), Jaccard similarity index (JSI), and Hausdorff distance (HD) were calculated to assess similarity. The mean dose (Dmean) and maximum dose (Dmax) to the LAD and LADR were calculated to compare consistency. Correlations were evaluated using Pearson's correlation coefficient. RESULTS: The inclusion ratio of the LAD by the LADR was 96%. The mean DSI, JSI, and HD values were respectively 27.9%, 16.7%, and 0.42mm for the LAD, and 83.1%, 73.0%, and 0.18mm for the LADR. The Dmean between the LAD and LADR were strongly correlated (r=0.93). CONCLUSION: Delineation of the LADR significantly improved contouring similarity and consistency for dose reporting. This could optimize dose estimation for breast radiotherapy.