Pretreatment Clinical Variables Research Articles

Utilizing machine learning to predict post-treatment outcomes in chronic non-specific neck pain patients undergoing cervical extension traction

This study explored the application of machine learning in predicting post-treatment outcomes for chronic neck pain patients undergoing a multimodal program featuring cervical extension traction (CET). Pre-treatment demographic and clinical variables were used to develop predictive models capable of anticipating modifications in cervical lordotic angle (CLA), pain and disability of 570 patients treated between 2014 and 2020. Linear regression models used pre-treatment variables of age, body mass index, CLA, anterior head translation, disability index, pain score, treatment frequency, duration and compliance. These models used the sci-kit-learn machine learning library within Python for implementing linear regression algorithms. The linear regression models demonstrated high precision and accuracy, and effectively explained 30–55% of the variability in post-treatment outcomes, the highest for the CLA. This pioneering study integrates machine learning into spinal rehabilitation. The developed models offer valuable information to customize interventions, set realistic expectations, and optimize treatment strategies based on individual patient characteristics as treated conservatively with rehabilitation programs using CET as part of multimodal care.

Gamma Knife radiosurgery for the management of glomus jugulare tumors: A systematic review and report of the experience of a radioneurosurgery unit in Latin America.

Glomus jugulare tumors (GJTs) are rare and mainly affect women between the 5th and 6th decades of life. Its localization and anatomic relationships make conventional surgical treatment difficult and with a considerable risk of complications. This manuscript aims to describe the results of Gamma Knife radiosurgery (GKR) in patients with GJT treated in a single center in Latin America, as well as to systematically review the literature to determine the clinical and radiological effectiveness of this technique. A search of information from January 1995 to June 2023 was performed. Twenty-two articles reporting 721 GJT patients treated with GKR were included in the study. Variables such as symptomatic control, control of tumor size, and complications were evaluated. These variables were described using measures of central tendency and proportions. For the institutional experience, 77 patients with GJT tumors were included in the study. Pre-treatment clinical variables and follow-up data were collected from medical charts and phone interviews. The Short Form-36 scale was applied to assess the quality of life. The data were analyzed using the statistical program STATA17.0. A total of 721 patients were considered. The median of patients included in these studies was 18.5. The mean age was 58.4 years. The median of symptom control was 89%, and the median of imaging control was 95.7%. In our institution, 77 patients were included in the study. The mean age was 53.2 years. The median hospital stay was 4.92 hours. For the clinical follow-up, information on 47 patients was obtained. An improvement in pre-treatment symptoms was described in 58%, with general symptomatic control of 97%. The tumor-control rate was 95%, and there were statistically significant differences in six of the nine Short Form-36 scale domains. GKR is an effective, safe, and cost-effective technique that offers a high degree of symptomatic and tumor size control in patients with GJT.

Clinical Predictors of Survival in Patients With BRAFV600-Mutated Metastatic Melanoma Treated With Combined BRAF and MEK Inhibitors After Immune Checkpoint Inhibitors.

Prospective and between trial comparisons indicate that first-line treatment with immune checkpoint inhibitors improves survival outcomes compared to first-line therapy with combined BRAF and MEK inhibitors in metastatic melanoma containing BRAFV600E/K mutations. Long-term outcomes for BRAF/MEK inhibition after progression on immunotherapy have not been reported. Moreover, clinical variables associated with outcome from treatment with combined BRAF/MEK inhibition were previously identified in the first-line setting but have not been investigated when targeted therapies are administered after progression on immune therapy. We performed a retrospective single institution analysis of 40 metastatic melanoma patients receiving combined BRAF/MEK inhibitors after progression on an anti-PD-1 or ipilimumab plus nivolumab to assess response rate by RECIST 1.1, progression-free and overall survival (PFS and OS). Pretreatment clinical variables were analyzed for association with OS. Ipilimumab/nivolumab was the first-line immunotherapy regimen in 39 patients (97.5%), and BRAFV600E/K mutations were present in 33 (83%) and 7 (17%) patients, respectively. The median OS from start of BRAF/MEK inhibitors was 20.3 months (1.73-106.4+, 95% CI of median 13.3-30.7). Clinical characteristics associated with worse survival prior to starting BRAF/MEK inhibitors included age > 60 years (median OS 14 vs. 28 months; HR 2.5; 95% CI 0.91-6.87, P = .023), ECOG-PS > 2 (median OS 7 vs. 33 months; HR 2.89; 95% CI 0.78-10.76, P = .018), and presence of bone metastases (median OS 9 vs. 52 months; HR 3.17; 95% CI 1.33-7.54, P = .002). These associations with shorter survival maintained their significance on multivariate analysis. If confirmed in larger cohorts, the identified prognostic variables can be used for stratification of patients in future randomized trials.

Developing a Machine Learning Algorithm for Improved Management of Congestive Heart Failure Patients in the Emergency Department

Background and aim: Congestive heart failure is a prevalent and serious condition that poses significant challenges in the emergency department setting. Prompt and accurate management of congestive heart failure patients is crucial for improving outcomes and optimizing resource utilization. This study aims to address these challenges by developing a machine learning algorithm and comparing it to a traditional logistic regression model that can assist in the triage, resource allocation, and long-term prognostication of congestive heart failure patients. Methods: In this investigation, we used the MIMIC-III database, a publicly accessible resource containing patient data from ICU settings. Traditional logistic regression, along with the robust XGBoost and random forest algorithms, was harnessed to construct predictive models. These models were built using a range of pretreatment clinical variables. To pinpoint the most pertinent features, we carried out a univariate analysis. Ensuring robust performance and broad applicability, we adopted a nested cross-validation approach. This method enhances the precision and validation of our models by implementing multiple cross-validation iterations. Results: The performance of machine learning algorithms was assessed using the area under the receiver operating characteristic curve (AUC). Notably, the random forest algorithm, despite having lower performance among the machine learning models still demonstrated significantly higher AUC than traditional logistic regression. The AUC for the XGBoost was 0.99, random forest 0.98, while traditional logistic regression was 0.57. The most important pretreatment variables associated with congestive heart failure include total bilirubin, creatine kinase, international normalized ratio (INR), sodium, age, creatinine, potassium, gender, alkaline phosphatase, and platelets. Conclusion: Machine learning techniques utilizing multiple pretreatment clinical variables outperform traditional logistic regression in aiding the triage, resource allocation, and long-term prognostication of congestive heart failure patients in the intensive care unit setting using MIMIC III data.

Prostate-specific antigen doubling time predicts the efficacy of site-directed therapy for oligoprogressive castration-resistant prostate cancer

BackgroundIn recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. MethodsWe reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). ResultsA PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). ConclusionPSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.

Explainable machine learning via intra-tumoral radiomics feature mapping for patient stratification in adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

This study aimed to discover intra-tumor heterogeneity signature and validate its predictive value for adjuvant chemotherapy (ACT) following concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). 397 LA-NPC patients were retrospectively enrolled. Pre-treatment contrast-enhanced T1-weighted (CET1-w) MR images, clinical variables, and follow-up were retrospectively collected. We identified single predictive radiomic feature from primary gross tumor volume (GTVnp) and defined predicted subvolume by calculating voxel-wised feature mapping and within GTVnp. We independently validate predictive value of identified feature and associated predicted subvolume. Only one radiomic feature, gldm_DependenceVariance in 3mm-sigma LoG-filtered image, was discovered as a signature. In the high-risk group determined by the signature, patients received CCRT + ACT achieved 3-year disease free survival (DFS) rate of 90% versus 57% (HR, 0.20; 95%CI, 0.05-0.94; P = 0.007) for CCRT alone. The multivariate analysis showed patients receiving CCRT + ACT had a HR of 0.21 (95%CI: 0.06-0.68, P = 0.009) for DFS compared to those receiving CCRT alone. The predictive value can also be generalized to the subvolume with multivariate HR of 0.27 (P = 0.017) for DFS. The signature with its heterogeneity mapping could be a reliable and explainable ACT decision-making tool in clinical practice.

Staging LaParoscopy to Assess Lymph NOde InvoLvement in Advanced GAstric Cancer (POLA)-Study protocol for a single-arm prospective observational multicenter study.

In the era of neoadjuvant chemotherapy in advanced gastric cancer (GC), the role of staging laparoscopy (SL) will become more established. However, despite guidelines recommendations, SL for optimal preoperative staging remains underutilized. Diagnostic value of near-infrared (NIR) / indocyanine green (ICG) guided sentinel node (SN) mapping in GC confirmed its technical feasibility, however no data exist regarding its potential role in pathological nodal staging. To the best of our knowledge, current study is the first to evaluate the role of ICG in nodal staging of advanced GC patients undergoing SL. This single-arm prospective observational multicenter study was approved by the Bioethical Committee of Medical University of Lublin (Ethic Code: KE-0254/331/2018). The protocol is registered at clinicaltrial.gov (NCT05720598), and the study results will be reported according to the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) statement. The primary endpoint of this study is the identification rate of ICG-guided SN in advanced GC patients. The secondary endpoints include pathological and molecular assessment of retrieved SNs and other pretreatment clinical variables potentially associated with SL: pattern of perigastric ICG distribution according to patients' pathological and clinical characteristics, neoadjuvant chemotherapy compliance, 30-day morbidity, and mortality. POLA study is the first to investigate the clinical value of ICG-enhanced sentinel node biopsy during staging laparoscopy in advanced GC patients in a Western cohort. Identifying pN status before multimodal treatment will improve GC staging process.

Long-Term Outcome of Adrenocorticotropic Hormone Therapy in Children With New-Onset Infantile Spasms

BackgroundTo investigate for pretreatment clinical variables to predict the outcome of new-onset epileptic spasms after adrenocorticotropic hormone (ACTH) therapy and to identify risk factors for poor long-term outcome. MethodsWe retrospectively studied 129 consecutive patients with infantile spasms syndrome (ISS). These patients received ACTH with antiseizure medication therapy for the first time and were regularly followed up for more than six months at our hospital. The response to treatment was assessed after two weeks of ACTH injection. Kaplan-Meier survival analysis and the multivariate Cox proportional hazard regression model were used. ResultsAmong the 129 patients, 61 (47.3%) had a good response after two weeks of ACTH treatment. At the time of the latest follow-up, 71 (55%) patients were seizure-free (International League Against Epilepsy class1). The univariate analysis revealed that normal neurodevelopment (P = 0.018), time lag of less than one month (P = 0.026), no hypsarrhythmia on EEG (P = 0.004), and serum calcium level ≥2.50 mmol/L (P = 0.035) were significantly associated with a good response. Only a good response to ACTH therapy was significantly associated with a positive long-term outcome. The Kaplan-Meier survival analysis showed that serum calcium level ≧2.50 mmol/L was significantly associated with a positive long-term outcome (P = 0.030). Multivariate analysis confirmed that no response to ACTH therapy was an independent variable that predicted long-term seizure recurrence (P < 0.001, hazard ratio = 4.602, confidence interval = 2.252 to 9.406). ConclusionsA good response to ACTH therapy had a significant predictive value for long-term seizure outcomes. Calcium may play an important role in the treatment of ISS with ACTH.

Identifying predictors of on-table adaptation for pancreas stereotactic body radiotherapy (SBRT).

702 Background: There is growing interest in the use of stereotactic body radiotherapy (SBRT) to treat pancreatic cancer. The purpose of this study was to identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas SBRT with MRI-guided radiotherapy. Methods: This was a single center retrospective study of patients undergoing MRI-guided SBRT to the pancreas from 2016 to 2022. An online daily adaptive workflow was in place for all fractions according to pre-specified criteria. Pre-treatment clinical variables and dosimetric parameters on the patient’s simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted. Results: Seventy-three SBRT courses consisting of 365 fractions were included in this study. Median prescription dose was 40 Gy in five fractions (range, 33-50 Gy); 56% and 44% of courses were prescribed ≤ 40 Gy and &gt; 40 Gy, respectively. Median gross and planning target volume (GTV and PTV) coverage were 94.7% and 84.3%, respectively. Median number of fractions adapted per course was three, with overall 58% (211 out of 365) total fractions adapted. On univariable analysis, the prescription dose ( &gt; 40 Gy vs ≤ 40 Gy), GTV size, stomach V20 and V25, duodenum V20 and Dmax, large bowel V33 and V35, heterogeneity index, and gradient index were significant determinants of the use of on-table adaptation (all p &lt; 0.05). On multivariable analysis, only prescription dose remained significant (adjusted odds ratio 7.66, p = 0.003). Conclusions: Prescription dose in MRI-guided pancreas SBRT is the only reliable predictor of on-table adaptation. Providers should strongly consider utilization of adaptive technology when delivering ablative doses to the pancreas.[Table: see text]

Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma

Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel. To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC. This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis was performed from April to May 2022. Patients were randomly assigned to receive gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) administered intravenously on days 1, 8, and 15 of every 4-week cycle, with or without intravenous NPC-1C 1.5 mg/kg every 2 weeks. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety. Pretreatment clinical variables were explored with Cox proportional hazards analysis. A total of 78 patients (median [range] age, 62 [36-78] years; 32 [41%] women; 9 [12%] Black; 66 [85%] White) received second-line treatment with gemcitabine plus nab-paclitaxel (n = 40) or gemcitabine plus nab-paclitaxel and NPC-1C (n = 38). Median OS was 6.6 months (95% CI, 4.7-8.4 months) with gemcitabine plus nab-paclitaxel vs 5.0 months (95% CI, 3.3-6.5 months; P = .22) with gemcitabine plus nab-paclitaxel and NPC-1C. Median PFS was 2.7 months (95% CI, 1.9-4.1 months) with gemcitabine plus nab-paclitaxel vs 3.4 months (95% CI, 1.9-5.3 months; P = .80) with gemcitabine plus nab-paclitaxel and NPC-1C. The ORR was 3.1% (95% CI, 0.4%-19.7%) in the gemcitabine plus nab-paclitaxel and NPC-1C group and 2.9% (95% CI, 0.4%-18.7%) in the gemcitabine plus nab-paclitaxel group. No differences in toxicity were observed between groups, except that grade 3 or greater anemia occurred more frequently in patients treated with gemcitabine plus nab-paclitaxel and NPC-1C than gemcitabine plus nab-paclitaxel (39% [15 of 38] vs 10% [4 of 40]; P = .003). The frequency of chemotherapy dose reductions was similar in both groups (65% vs 74%; P = .47). Lower performance status, hypoalbuminemia, PDAC diagnosis less than or equal to 18 months before trial enrollment, lymphocyte-to-monocyte ratio less than 2.8, and CA19-9 greater than 2000 IU/mL were independently associated with poorer survival. In this randomized clinical trial of advanced PDAC, NPC-1C did not enhance the efficacy of gemcitabine/nab-paclitaxel. These data provide a benchmark for future trials investigating second-line treatment of PDAC. ClinicalTrials.gov Identifier: NCT01834235.

Robustness Evaluation of a Deep Learning Model on Sagittal and Axial Breast DCE-MRIs to Predict Pathological Complete Response to Neoadjuvant Chemotherapy.

To date, some artificial intelligence (AI) methods have exploited Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to identify finer tumor properties as potential earlier indicators of pathological Complete Response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, they work either for sagittal or axial MRI protocols. More flexible AI tools, to be used easily in clinical practice across various institutions in accordance with its own imaging acquisition protocol, are required. Here, we addressed this topic by developing an AI method based on deep learning in giving an early prediction of pCR at various DCE-MRI protocols (axial and sagittal). Sagittal DCE-MRIs refer to 151 patients (42 pCR; 109 non-pCR) from the public I-SPY1 TRIAL database (DB); axial DCE-MRIs are related to 74 patients (22 pCR; 52 non-pCR) from a private DB provided by Istituto Tumori “Giovanni Paolo II” in Bari (Italy). By merging the features extracted from baseline MRIs with some pre-treatment clinical variables, accuracies of 84.4% and 77.3% and AUC values of 80.3% and 78.0% were achieved on the independent tests related to the public DB and the private DB, respectively. Overall, the presented method has shown to be robust regardless of the specific MRI protocol.

P189 A longitudinal study of psychological predictors of response to adalimumab in patients with rheumatoid arthritis

Abstract Background/Aims The treatment of rheumatoid arthritis (RA) has improved since the introduction of targeted biological disease-modifying antirheumatic drugs (bDMARDs), such as adalimumab. However, no treatment options for RA are universally effective. Psychological factors may have an important role in treatment response. Published data reported that pre-treatment psychological variables such as an increased treatment necessity belief correlated with better adherence to adalimumab in RA patients. This current study aimed to investigate whether psychological factors correlate with change in 4V-DAS28-CRP as well as subcomponents of the score in adalimumab-treated RA patients. Methods Psychological, clinical and demographic data and DAS28 scores were collected pre-treatment, and at 3,6, and 12-months post-treatment, as part of a prospective national study, BRAGGSS. Sixteen pre-treatment clinical and psychological variables were tested for association with treatment response at 3 and 12 months. Multiple linear regression models were analysed and a Bonferroni corrected p-value of &amp;lt; 0.003 was applied at each interval to assess significance. Results Data was available for 501 patients at 3 months follow up. Pre-treatment Beliefs about Medicine Questionnaire (BMQ) scores with regards to treatment necessity (P = 0.001), and two domains of the Illness Perception Questionnaire (IPQ), which were treatment belief and treatment control (P = 0.0001), correlated with the change in DAS28 by 3 months (Table 1). At 12 months, data were available for 362 patients. The treatment belief domain of the pre-treatment Illness Perception Questionnaire correlated with the change in tender joint count (P = 0.001) (Table 1). At 12 months no other sub-components correlated with the psychological variables. Conclusion Pre-treatment scores with regards to Illness Perception and Beliefs about Medicine correlated with 4V-DAS28-CRP response at 3 months. Of the subcomponents of DAS28, the psychological variables showed the highest correlation with tender joint count; as the tender joint count receives the highest weighting in the 4 variable DAS28 score, this may confound the assessment of treatment response. It will be necessary to undertake further analyses to assess the predictive value of these potentially modifiable psychological variables identified, but to also understand factors contributing to these psychological scores, such as the role of severe disease itself on psychological beliefs. Disclosure N. Raza: None. N. Nair: None. D. Plant: None. K. Hyrich: None. A.W. Morgan: None. J. Isaacs: None. A.G. Wilson: None. A. Barton: None.

Racial and Ethnic Disparities in Prostate Cancer Outcomes in the Veterans Affairs Health Care System

Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans. To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital. This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated. Self-identified African American (or Black) and White race and ethnicity. Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis. Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who received nondefinitive treatment classified as “other” were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000). This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.

Exposure Quality in Cognitive Behavioral Treatment for Youth Anxiety Disorders\u2014Predictors and Associations with Outcomes

To optimize cognitive behavioral therapy (CBT) outcomes for anxiety disorders in youth, more knowledge is needed about how specific CBT components work. Exposure to feared situations is an effective CBT component. However, there is little observation-based empirical research on how exposure relates to outcomes and other clinical variables. In a randomized controlled community clinic trial for youth with anxiety disorders, observers reliably rated exposure quality for 68 youths aged 8 to 15 years based on 118 videotaped sessions. The treatment program was the manual-based FRIENDS program. Three exposure quality elements (preparation, post-processing, and parent contribution to exposure) were examined in relation to pre-treatment demographic and clinical variables, outcomes, and youth- and therapist-rated alliance using multilevel hierarchical regression models. The outcomes were diagnostic recovery, clinical severity and anxiety symptoms change from pre- to post-treatment and one-year follow-up, and treatment dropout. The results showed that parent contribution to exposure was higher for boys and younger children. Parent contribution to exposure, but no other exposure element, was associated with a larger likelihood of diagnostic recovery and larger clinical severity reduction at one-year follow-up. Exposure quality was unrelated to outcomes at post-treatment, dropout, or alliance. We conclude that enhancing parent contribution to exposure during treatment could improve long-term outcomes after CBT for youth anxiety disorders. Exposure elements should be observed in larger samples to further examine their potential role for CBT outcomes.

Effectiveness of Platelet-Rich Fibrin in the Treatment of Intrabony Defects with or Without Bone Graft: A Clinical Comparative Study.

Background:Periodontal diseases are a group of inflammatory diseases causing alveolar bone loss and eventually leading to loss of teeth. The present study was evaluated the effectiveness of platelet-rich fibrin (PRF) in the treatment of intrabony defects with or without bone graft.Materials and Methods:Thirty subjects with the presence of intrabony defects were enrolled. All subjects were included irrespective of age and gender. A questionnaire was prepared for extracting demographic and personal details of all the patients. William probe and moth mirror-tweezers set was used for carrying out clinical examination of all subjects. Random and unbiased division of all the subjects was done with ten patients in each group as follows: Group I: Subjects in which treatment was carried out using PRF with demineralized bone matrix, Group II: Subjects in which treatment was carried out using PRF alone, and Group III: Subjects in which treatment was carried in the form of open flap debridement (OFD). Pretreatment and posttreatment clinical variables were assessed which included plaque index (PI), gingival index (GI), probing depth (PD), relative attachment level (RAL), and gingival recession (GR) were assessed at baseline and 9 months postoperatively were calculated.Results:Mean PI among Group 1, Group 2, and Group 3 at baseline was 0.78, 0.8, and 0.84, respectively. Mean PI among Group 1, Group 2, and Group 3 at 9 months follow-up was 0.56, 0.55, and 0.72, respectively. Significant results were obtained while comparing the PI among the three study groups at follow-up. Mean GI among Group 1, Group 2, and Group 3 at baseline was 0.78, 0.8, and 0.84, respectively. Mean GI among Group 1, Group 2, and Group 3 at 9 months follow-up was 0.56, 0.55, and 0.72, respectively. Significant results were obtained while comparing the GI among the three study groups at follow-up. Significant difference was seen in PD, RAL, and GR from baseline to 9 months in all groups (P < 0.05).Conclusion:PRF leads to significantly better improvement in the clinical parameters on follow-up in comparison to OFD alone in patients with the presence of intrabony defects.

Predictors of the timing of interval cytoreduction based on the number of cycles of neoadjuvant chemotherapy: a retrospective cohort

Objectives: To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. Methods: We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. Results: A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Conclusions: Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes. To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes.

A Mathematical Model to Estimate Chemotherapy Concentration at the Tumor-Site and Predict Therapy Response in Colorectal Cancer Patients with Liver Metastases.

Simple SummaryIt is known that drug transport barriers in the tumor determine drug concentration at the tumor site, causing disparity from the systemic (plasma) drug concentration. However, current clinical standard of care still bases dosage and treatment optimization on the systemic concentration of drugs. Here, we present a proof of concept observational cohort study to accurately estimate drug concentration at the tumor site from mathematical modeling using biologic, clinical, and imaging/perfusion data, and correlate it with outcome in colorectal cancer liver metastases. We demonstrate that drug concentration at the tumor site, not in systemic circulation, can be used as a credible biomarker for predicting chemotherapy outcome, and thus our mathematical modeling approach can be applied prospectively in the clinic to personalize treatment design to optimize outcome.Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (p < 0.001). The eTSCC was significantly lower than the observed plasma concentration and dropped by a factor of ~5 between patients with complete response (TRG = 1) and those with no response (TRG = 5), while the plasma concentration remained stable across TRG groups. TRG variations were driven and predicted by differences in tumor perfusion and eTSCC. If confirmed in carefully planned prospective studies, these findings will form the basis of a paradigm shift in the care of patients with potentially curable colorectal cancer and liver metastases.

Radiomic signatures to predict survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib +/- doxorubicin: Correlative science from CALGB 80802 (Alliance).

343 Background: Alliance/CALGB 80802, a randomized phase III trial, evaluated sorafenib plus doxorubicin vs. doxorubicin in pts with HCC and showed no improvement in median overall survival (OS) (HR[95CI] 1.05[0.83-1.31]) or PFS (HR[95CI] 0.93[0.75-1.16]). In HCC surrogacy of tumor response with OS remains controversial, in part due to varying criteria used for response evaluation (e.g., RECIST1.1 and mRECIST). We evaluated the performance of several models to predict OS using pretreatment clinical and radiomic variables. Methods: In CALBG 80802, we segmented all measurable tumor lesions on sequential CT scans. A lesion’s imaging phenotype was deciphered with 23 uncorrelated quantitative imaging features measured at baseline and week (wk) 10 (first follow-up). An OS landmark survival analysis was conducted at wk 10. Patients were randomly assigned (3:1) to training (n = 92) and validation (n = 37) sets. In a training set, 6 random forest predictive models (6 signatures) used features that best predicted OS using 3 sets of variables: radiomics only (n = 23), clinical only (n = 9), radiomics and clinical (n = 32). Two time points (baseline only or baseline + wk 10) were assessed. Each signature's output was an individualized prediction and a continuous value ranging from 0 to 1 (from most to least favorable predicted OS). The primary endpoint was to compare these models' performance to predict OS using error rate (Harrell's concordance-index) in the validation set. Results: Of the 6 training signatures evaluated, the one achieving the highest performance in the validation set was an 8-feature signature combining radiomics and clinical variables measured at two time points (baseline + wk 10) with an error rate of 35.6%. The variables [rank of importance] (table) selected by the signature included baseline clinical features (albumin[1], AFP[2], Child-Pugh[4]), baseline radiomics features (component 17[3], component 1[5], component 9[7], tumor volume[8]) and wk 10 radiomics features (delta tumor volume[6]). Variable delta tumor volume [6] used a more enhanced estimation of tumor burden at baseline and a delta tumor volumetric measurement; compared to RECIST1.1 measurement of percentage change in unidimensional measurement of a subset of target lesions. The four quartiles of the signature were significantly associated with OS (Log-Rank, P &lt; 0.0001). Conclusions: The selected combined radiomic and clinical composite signature provided the best prediction for OS in the 80802 study patients’ population. It is a suggested way forward to go beyond single anatomic measurement techniques such as RECIST or mRECIST. [Table: see text]

Prognostic impact of clinical, haematological, and histopathological variables in 102 canine cutaneous perivascular wall tumours.

Identification of prognostic factors for perivascular wall tumours (PWTs) is desirable to accurately predict prognosis and guide treatment. 100 and two dogs with surgically excised PWTs without distant metastasis were retrospectively enrolled in this multi-institutional study, and the impact of pre-treatment leukocyte parameters, clinical and histopathological variables on local recurrence (LR) and overall-survival time (OST) were evaluated. Increasing values of white blood cell count (WBCC), neutrophil count (NC) and neutrophil-to-lymphocyte ratio (NLR) were significantly correlated with the hazard of LR in univariate analysis. WBCC and NC remained prognostic when adjusted for margins, grade, tumour size, location and skin ulceration, but lost their significance when adjusted for mitotic index and necrosis, whilst NLR remained prognostic only when close margins where categorised as infiltrated. Castrated males had a higher hazard of LR than intact males in univariate analysis, but significance was lost in multivariate models. Ulcerated PWTs and those located on the distal extremities had a higher hazard of LR both in univariate and multivariate analysis. Histological grade, necrosis, mitotic count, and infiltrated margins were all associated with LR both in univariate and multivariate analysis. Boxer breed, older age, ulceration, grade III, necrosis >50% and higher mitotic count were correlated with shorter OST, although breed and age lost their significance in multivariate analysis. Prognostication of surgically excised PWTs should be based on both clinical and histopathological variables. If validated in further studies, leukocyte counts and NLR may aid the clinician in identifying dogs at higher risk of LR before treatment.

Early neurological deterioration following thrombolysis for minor stroke with isolated internal carotid artery occlusion

Better understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions. From a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24h. END and no-END patients were compared for (i) pre-treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow-up imaging. Seventy-four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre-treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio=4.0, 95% confidence interval: 1.3-12.2; P=0.015). On follow-up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no-END patients, respectively (P<0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P=0.07). As compared to no-END, END was strongly associated with a poor 3-month outcome. Early neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site-largely a function of underlying stroke etiology-may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting.