Pulmonary interstitial lymphography: A prospective trial with potential impact on stereotactic ablative radiotherapy planning for early-stage lung cancer.

This prospective feasibility trial investigated pulmonary interstitial lymphography to identify thoracic primary nodal drainage (PND). A post-hoc analysis of nodal recurrences was compared with PND for patients with early-stage lung cancer; larger studies are needed to establish correlation. Exploratory PND-inclusive stereotactic ablative radiotherapy plans were assessed for dosimetric feasibility.

Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas.

Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9-26.1 months), while median LPFS was 9 months (95% CI: 6.2-11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0-1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

Factors Influencing Repurchase Intention in Drive-Through Fast Food: A Structural Equation Modeling Approach.

The drive-through fast-food industry has been one of the fastest businesses growing over the past decades in developing countries, including the Philippines. The purpose of this study was to evaluate factors influencing costumers' repurchase intention in a drive-through fast food in the Philippines by utilizing the structural equation modeling (SEM) approach. A total of 305 Filipinos answered the online questionnaire, which contained 38 questions. The results of SEM indicated that subjective appetite (SA) was found to have a significant direct effect on menu options (MO). Consequently, MO was found to have significant direct effects on imagery elaboration (IE), vividness (VV), and convenience (CO), and an indirect effect on order accuracy (OA). Finally, SA, MO, IE, VV, OA, and CO were found to have significant effects on satisfaction (S), which subsequently led to loyalty (L) and repurchase intention (RI). Interestingly, MO was found to have the highest indirect effect on RI, indicating that MO is an important consideration for RI. This is the first comprehensive study evaluating drive-through fast food in the Philippines. The causal relationships of the present study can be applied and extended to evaluate the repurchase intention of drive-through fast food in other countries.

Factors affecting perceived effectiveness of COVID-19 prevention measures among Filipinos during Enhanced Community Quarantine in Luzon, Philippines: Integrating Protection Motivation Theory and extended Theory of Planned Behavior.

OBJECTIVE: The current study integrated Protection Motivation Theory (PMT) and extended Theory of Planned Behavior (TPB) to evaluate factors affecting the perceived effectiveness of COVID-19 prevention measures among Filipinos during Enhanced Community Quarantine (ECQ) in Luzon, Philippines. METHODS: A total of 649 Filipinos answered an online questionnaire, which contained 63 questions. Structural Equation Modeling (SEM) was utilized to derive the causal relationships of the latent variables construct. RESULTS: SEM showed that understanding of COVID-19 had significant direct effects on perceived vulnerability and perceived severity. Also, perceived vulnerability and perceived severity had significant indirect effects on intention to follow. Intention to follow had significant direct effects on actual behavior and adapted behavior, which subsequently led to perceived effectiveness. Of note, an understanding of COVID-19 was found to have a significant indirect effect on perceived effectiveness. CONCLUSIONS: The current study is one of the first studies to analyze factors affecting the perceived effectiveness of COVID-19 prevention measures during the global pandemic. It is proposed that the integrated PMT and extended TPB of this study can be applied and extended to evaluate the perceived effectiveness of COVID-19 measures in other countries that are currently dealing with COVID-19 pandemic.

Modeling the residential distribution of enrolled students to assess boundary-induced disparities in public school access.

Given school enrollments but in the absence of a student residence census, we present a gravity-like model to infer the residential distribution of enrolled students across various administrative units. Multi-scale analysis of the effects of aggregation across different administrative levels allows for the identification of administrative units with sub-optimally located schools and highlights the challenges in allocating resources. Using this method, we verify that the current scheme of free cross-enrollment across administrative boundaries is needed in achieving universal education in the Philippines.

Safety and efficacy of fulranumab in osteoarthritis of the hip and knee: results from four early terminated phase III randomized studies.

Objective: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis.Methods: Osteoarthritic patients (aged ≥18 years) from four phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week post-treatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic, and joint-related events of interest. Efficacy assessments included pain and physical function sub-scales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.Results: Of 245 patients from the ITT set (median age = 64 years; 62% women), 84 (34%) completed the DB phase; the majority of discontinuations (57%) were due to early study termination. In the DB phase, the incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC sub-scale scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims.Conclusions: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery.Clinical trial registration numbers: NCT02336685; NCT02336698; NCT02289716; NCT02301234KEY POINTSFulranumab as adjuvant or monotherapy was well tolerated with no new safety signalsFulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and kneeFulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis.

Evidence-Based Integration of Yttrium-90 Radioembolization in the Contemporary Management of Hepatic Metastases from Colorectal Cancer.

Hepatic metastases are common in patients with metastatic colorectal cancer and are frequently the most life-threatening source of morbidity and mortality. The contemporary management of patients with liver-dominant or liver-only metastatic colorectal cancer is characterized by resection of metastases when feasible and successive lines of systemic treatment regimens consisting of chemotherapy drugs and/or targeted biological agents. Yttrium-90 radioembolization has emerged as a promising liver-directed therapy for patients with unresectable colorectal cancer liver metastases (CLM). The integration of radioembolization into the current treatment algorithm for unresectable CLM is dependent on the line of therapy it is being considered and whether it is to be used alone or in combination with systemic treatment options. This article provides background information on the current management of CLM and uses this framework to discuss the existing data that define when and how radioembolization can benefit patients with CLM.

Fulranumab as Adjunctive Therapy for Cancer-Related Pain: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.

This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks. The study failed to demonstrated efficacy at the end of the DB phase (primary endpoint, mean [SD] change in average cancer-related pain intensity was -.8 (1.26) for fulranumab and -.7 (1.56) for placebo; P = .592). However, potential benefit is suggested based on secondary endpoints (30% responder rate [P = .020], Brief Pain Inventory-Short Form [BPI-SF] pain intensity subscale [P = .003], and pain interference subscale [P = .006]). The most commonly reported treatment-emergent adverse events were (fulranumab vs placebo): asthenia (16% vs 10%), decreased appetite (12% vs 6%), fatigue (10% vs 0%), and malignant neoplasm progression (10% vs 0%). Although no differences were seen between fulranumab and placebo groups on the primary endpoint, improvements in BPI-SF pain subscale scores and responder rates support further research of anti-nerve growth factor therapy in cancer-related pain. PERSPECTIVE: Efficacy and safety of fulranumab as adjunctive pain therapy in terminally ill cancer patients were assessed. Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics.

Quantification of Activity Lost to Delivery-System Residual and Decay in Yttrium-90 Radioembolization.

PURPOSE: To measure the decay activity loss and delivery system residual activity loss of yttrium-90 (Y90) radioembolization treatments across resin and glass microsphere activities. MATERIALS AND METHODS: For Y90 administrations between December 2009 and June 2017 at the study institution, the prescribed activity, prepared activity, and delivered activity were recorded. Six hundred sixty-two administrations were reviewed-345 glass (0.21-8.52 GBq) and 317 resin (0.18-3.28 GBq). Twenty-five patients (all resin) were excluded for arterial stasis or catheter clogging. The percentage and actual losses of activity lost to decay and to delivery system residual were calculated for glass and resin microspheres. RESULTS: The median time between activity premeasurement and administration was 2.20 hours, resulting in a median activity lost to decay of 0.030 GBq or 2.35%, with no significant difference observed between glass and resin despite differences in preparation (P = .0697). Resin showed significantly higher activity lost to delivery system residual than glass (0.039 GBq vs 0.010 GBq, 3.01% vs 0.61%, P < .001). The percent activity lost to residual varied with activity prepared, with a maximum of 20.1% and 16.2% for the smallest activities of resin and glass, respectively. CONCLUSIONS: Residual activity loss differs between glass and resin microspheres. For resin microspheres in particular, percent residual activity loss increases with lower prepared activities. Protocols for activity calculation and preparation, patient dosimetry, and regulatory compliance must take these losses into consideration prospectively.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

PURPOSE: The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. METHODS: The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. RESULTS: Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. CONCLUSION: Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Noninvasive radiomics signature based on quantitative analysis of computed tomography images as a surrogate for microvascular invasion in hepatocellular carcinoma: a pilot study.

We explore noninvasive biomarkers of microvascular invasion (mVI) in patients with hepatocellular carcinoma (HCC) using quantitative and semantic image features extracted from contrast-enhanced, triphasic computed tomography (CT). Under institutional review board approval, we selected 28 treatment-naive HCC patients who underwent surgical resection. Four radiologists independently selected and delineated tumor margins on three axial CT images and extracted computational features capturing tumor shape, image intensities, and texture. We also computed two types of "delta features," defined as the absolute difference and the ratio computed from all pairs of imaging phases for each feature. 717 arterial, portal-venous, delayed single-phase, and delta-phase features were robust against interreader variability ([Formula: see text]). An enhanced cross-validation analysis showed that combining robust single-phase and delta features in the arterial and venous phases identified mVI (AUC [Formula: see text]). Compared to a previously reported semantic feature signature (AUC 0.47 to 0.58), these features in our cohort showed only slight to moderate agreement (Cohen's kappa range: 0.03 to 0.59). Though preliminary, quantitative analysis of image features in arterial and venous phases may be potential surrogate biomarkers for mVI in HCC. Further study in a larger cohort is warranted.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma.

PURPOSE: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed cell type primary liver cancer with limited data to guide management. Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This study explored the safety and efficacy of RE for unresectable cHCC-CC. METHODS: Patients with histopathologically confirmed cHCC-CC treated with RE were retrospectively evaluated. Clinical and biochemical toxicities were assessed using the Common Toxicity Criteria for Adverse Events v4.03. Radiological response was analyzed using the Response Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated and prognostic variables identified. RESULTS: Ten patients (median age 59 years; six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal pain. No significant biochemical toxicities were observed. Median overall survivals from the first RE treatment and from initial diagnosis were 10.2 and 17.7 months, respectively. Six of seven patients with elevated tumor biomarker levels before RE showed decreased levels after treatment (median decrease of 72%, range 13-80%). Best hepatic radiological response was 60% partial response and 40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1. Poor performance status and the presence of macrovascular invasion were identified as predictors of reduced survival after RE. CONCLUSION: RE appears to be a safe and promising treatment option for patients with unresectable cHCC-CC. LEVEL OF EVIDENCE: Level 4.

The Role of Dual-Phase Cone-Beam CT in Predicting Short-Term Response after Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To identify computational and qualitative features derived from dual-phase cone-beam CT that predict short-term response in patients undergoing transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 43 patients with 59 HCCs. Six features were extracted, including intensity of tumor enhancement on both phases and characteristics of the corona on the washout phase. Short-term response was evaluated by modified Response Evaluation Criteria in Solid Tumors on follow-up imaging, and extracted features were correlated to response using univariate and multivariate analyses. RESULTS: Univariate and multivariate analyses did not reveal a correlation between absolute and relative tumor enhancement characteristics on either phase with response (arterial P = .21; washout P = .40; ∆ P = .90). On multivariate analysis of qualitative characteristics, the presence of a diffuse corona was an independent predictor of incomplete response (P = .038) and decreased the odds ratio of objective response by half regardless of tumor size. CONCLUSIONS: Computational features extracted from contrast-enhanced dual-phase cone-beam CT are not prognostic of response to transarterial chemoembolization in patients with HCC. HCCs that demonstrate a diffuse, patchy corona have reduced odds of achieving complete response after transarterial chemoembolization and should be considered for additional treatment with an alternative modality.

Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery.

PURPOSE: To evaluate safety of resin microsphere radioembolization (RE) without prophylactic embolization of the gastroduodenal artery (GDA). MATERIALS AND METHODS: Between July 2013 and April 2015, all patients undergoing RE with resin microspheres for liver-dominant metastatic disease were treated without routine embolization of the GDA. Selective embolization of distal hepaticoenteric vessels was performed if identified by digital subtraction angiography, cone-beam computed tomography, or technetium-99m macroaggregated albumin scintigraphy. Resin microspheres were administered using 5% dextrose flush distal to the origin of the GDA in lobar or segmental fashion, with judicious use of an antireflux microcatheter in recognized high-risk situations. Gastrointestinal toxicity was evaluated by the performing physician for at least 3 months. RESULTS: RE with resin microspheres was performed in 62 patients undergoing 69 treatments. During planning angiography, embolization of 0 or 1 vessel (median, 1; range, 0-4) was performed in 86% of patients, most commonly the right gastric and supraduodenal arteries. Prophylactic embolization of the GDA was performed in only 2 patients (3%). In 6 treatments (9%), adjunctive embolization was required immediately before RE, and an antireflux microcatheter was used in 14% of treatments. Clinical follow-up was available in 60 of 62 patients (median, 134 d; range, 15-582 d). No signs or symptoms of gastric or duodenal ulceration were observed. CONCLUSIONS: RE using resin microspheres without embolization of the GDA can be performed safely.

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.

PURPOSE: To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. MATERIALS AND METHODS: From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. RESULTS: Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. CONCLUSION: Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.

Core samples for radiomics features that are insensitive to tumor segmentation: method and pilot study using CT images of hepatocellular carcinoma.

The purpose of this study is to investigate the utility of obtaining "core samples" of regions in CT volume scans for extraction of radiomic features. We asked four readers to outline tumors in three representative slices from each phase of multiphasic liver CT images taken from 29 patients (1128 segmentations) with hepatocellular carcinoma. Core samples were obtained by automatically tracing the maximal circle inscribed in the outlines. Image features describing the intensity, texture, shape, and margin were used to describe the segmented lesion. We calculated the intraclass correlation between the features extracted from the readers' segmentations and their core samples to characterize robustness to segmentation between readers, and between human-based segmentation and core sampling. We conclude that despite the high interreader variability in manually delineating the tumor (average overlap of 43% across all readers), certain features such as intensity and texture features are robust to segmentation. More importantly, this same subset of features can be obtained from the core samples, providing as much information as detailed segmentation while being simpler and faster to obtain.