Pretreatment Patient Characteristics Research Articles

Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

AbstractEngineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day –28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.

Identifying trajectories of change in sleep disturbance during psychological treatment for depression

BackgroundSleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making. MethodThis analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services. ResultsSix distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, employment status, psychotropic medication use, long-term health condition status, severity of depressive symptoms, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well. LimitationSingle item on sleep disturbance used, no data on treatment adherence. ConclusionsThese findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance.

A Multicenter Study of CAR-T Cell Therapy for Relapse of B-ALL Post Allogeneic Stem Cell Transplantation

BACKGROUND: Patients with acute B-cell lymphoblastic leukemia (B-ALL) relapsed after allogeneic stem cell transplantation (allo-HSCT) have very poor prognosis. Chimeric antigen receptor T (CAR-T) cells targeting CD19 have been developed as one of the effective immunotherapies for relapsed/refractory B-ALL. The safety and efficacy of CAR-T cells in patients relapsed after allo-HSCT remain unclear. METHODS: This study analyzed 60 B-ALL patients relapsed after allo-HSCT treated with CAR-T cells between October 2015 and February 2022 from four Chinese centers. Their pre-treatment patient characteristics, treatment regimens, efficacy, adverse effects, and follow-up data were comprehensively analyzed. RESULTS: One patient refused efficacy evaluation. 7 patients died before day 28 after CAR-T infusion. A total of 52 were assessed for efficacy within 28 days after CAR-T infusion.76.92% (40/52) patients achieved complete remission (CR) at Day 28 after CAR-T infusion, including 38 patients who achieved MRD-negative CR. 4 of the 40 patients relapsed at a median follow-up date of 12.1 months. The 1-year OS and EFS of all patients were 52.8% ± 7.0% and 51.5% ± 7.0%, respectively, and the 2-year OS and EFS were 40.1% ± 8.6% and 45.1% ± 8.6%, respectively. Multifactorial analysis showed that patients with severe CRS had worse OS and EFS, and other factors including age, gender, site of CAR-T tumor involvement, type of previous transplantation, previous transplantation type, CAR-T product and CRS grade, etc., did not affect the long-term survival of patients. The incidence of CRS was 80.00%, the incidence of grade ≥3 CRS was 20.83%, and the median time of CRS was 2 days after CAR-T cell infusion (range: 0-34 days). 3 patients (5.00%) died due to multiorgan failure caused by severe CRS, and the rest of the patients' CRS was controlled, and the grade of CRS was related to the proportion of blast cells in the bone marrow prior to CAR-T cell infusion., independent of the type of transplantation and the source of CAR-T cells. The incidence of ICANS was 5.00%. The incidence of aGvHD was 30.00%, and patients who had received prior haploidentical allogeneic HSCT were significantly more likely to develop aGvHD after CAR-T cell infusion than those who had received prior matched allogeneic HSCT. The occurrence of aGvHD after CAR-T treatment was not associated with the occurrence of CRS (p = 1), the presence of aGvHD after prior transplantation (p = 0.3484), the presence of cGvHD after prior transplantation (p = 0.3167), the presence of cGvHD at the time of CAR-T infusion (p = 0.5136), and the presence of prior donor lymphocyte infusion (p = 0.7404), and whether CAR-T cells were from autologous or donor (p = 0.4819). CONCLUSIONS: CAR-T cells are safe and effective in treating B-ALL patients with post-transplant relapse, and donor-derived CAR-T cells do not exacerbate CRS with aGVHD, and there is a high incidence of aGVHD after CAR-T therapy in patients with HLA-haplotype-matched transplantation.

Sustained remissions in CLL after frontline FCR treatment with very-long-term follow-up

AbstractChemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up compared with the patients in our prior report in 2015. Only 4 of 45 patients (9%) with IGHV-M progressed beyond 10 years. Excluding Richter transformation, 96 of 300 patients (32%) developed 106 other malignancies, with 19 of 300 (6.3%) developing therapy-related myeloid neoplasms (tMNs), which were fatal in 16 of 19 (84%). No pretreatment patient characteristics predicted the risk of tMNs. In summary, FCR remains an option for patients with IGHV-M chronic lymphocytic leukemia (CLL), with a significant fraction achieving functional cure of CLL. A risk-benefit assessment is warranted when counseling patients, balancing potential functional cure with the risk of late relapses and serious secondary malignancies.

Predictive factors requiring high-dose evocalcet in hemodialysis patients with secondary hyperparathyroidism.

The dosage of evocalcet required to control serum parathyroid hormone (PTH) levels varies among secondary hyperparathyroidism (SHPT) patients. This post hoc analysis evaluated the dose-dependent efficacy of evocalcet on serum intact PTH (iPTH) levels, corrected calcium (Ca) and phosphate (P) levels, and safety, in an evaluation period (week 28 to week 30) by stratifying the previous phase 3 data with the final evocalcet dosages (low 1-2 mg [131 patients], medium 3-4 mg [90 patients], high 5-8 mg [92 patients]), and identified pre-treatment patient characteristics predicting the use of higher final evocalcet dosages via univariate and multivariate logistic regression models. At the end of the study at week 30, the median serum iPTH level was higher and the achievement ratio for the target range of Japanese Society for Dialysis Therapy (60-240 pg/mL) was lower in the final high-dose subgroup (216 pg/mL and 58%, respectively) than in the other subgroups (low: 149 pg/mL and 79%; medium: 149 pg/mL and 73%, respectively). Among the three subgroups, the mean serum corrected Ca and P levels demonstrated similar trends, and similar ratio of patients achieved the target range (corrected Ca, 8.4-10 mg/dL; P, 3.5-6.0 mg/dL) from week 28 to week 30. No dose-dependent safety concerns were identified. Younger age, prior cinacalcet use, higher serum levels of iPTH and corrected Ca, procollagen type 1 N-terminal propeptide, intact fibroblast growth factor-23, and larger maximum parathyroid gland volume were significantly associated with final high-dose evocalcet (p < 0.05 in all cases). Patients requiring final high-dose evocalcet had pre-treatment characteristics indicating severe SHPT, leading to a lower final achievement rate for the target PTH levels of Japanese Society for Dialysis Therapy. Therefore, the early initiation of evocalcet treatment for SHPT is critical. Trial registration: This trial was registered as follows: ClinicalTrials.gov: NCT02549391 and JAPIC: JapicCTI-153013.

Multiparametric MRI as a Predictor of PSA Response in Patients Undergoing Stereotactic Body Radiation (SBRT) Therapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> In order to maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially amongst those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiotherapy and/or brachytherapy. This is the first study to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing SBRT. <h3>Materials/Methods</h3> We identified all patients treated at our institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent SpaceOAR placement followed by pre-treatment MRI. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. A two-sample t-test was used to compare preoperative mpMRI features with clinical outcomes. <h3>Results</h3> 123 men were included in the study. The table below summarizes the pretreatment patient characteristics. Patients with higher pretreatment diameter of the largest intraprostatic lesion, number of prostate lesions, and maximal PI-RADS score were associated with higher PSA nadir and longer time to PSA nadir (p<0.0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT (p<0.001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir (p<0.01) but not with PSA nadir (p>0.30). <h3>Conclusion</h3> Our experience shows a significant association between mpMRI features and PSA outcome in patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and / or boost to dominant intraprostatic lesion.

The Predictive Value of Adipokines and Metabolic Risk Factors for Dropouts and Treatment Outcomes in Children With Obesity Treated in a Pediatric Rehabilitation Center.

BackgroundInpatient pediatric obesity treatments are highly effective, although dropouts and weight regain threaten long-term results. Preliminary data indicate that leptin, adiponectin, and cardiometabolic comorbidities might predict treatment outcomes. Previous studies have mainly focused on the individual role of adipokines and comorbidities, which is counterintuitive, as these risk factors tend to cluster. This study aimed to predict the dropouts and treatment outcomes by pre-treatment patient characteristics extended with cardiometabolic comorbidities (individually and in total), leptin, and adiponectin.MethodsChildren aged 8–18 years were assessed before, immediately after and 6 months after a 12-month inpatient obesity treatment. Anthropometric data were collected at each visit. Pre-treatment lipid profiles; glucose, insulin, leptin, and adiponectin levels; and blood pressure were measured. The treatment outcome was evaluated by the change in body mass index (BMI) standard deviation score (SDS) corrected for age and sex.ResultsWe recruited 144 children with a mean age of 14.3 ± 2.2 years and a mean BMI of 36.7 ± 6.2 kg/m2 corresponding to 2.7 ± 0.4 BMI SDS. The 57 patients who dropped out during treatment and the 44 patients who dropped out during aftercare had a higher pre-treatment BMI compared to the patients who completed the treatment (mean BMI, 38.3 ± 6.8 kg/m2 vs 35.7 ± 5.5 kg/m2) and those who completed aftercare (mean BMI, 34.6 ± 5.3 kg/m2 vs 37.7 ± 6.3 kg/m2) (all p<0.05). Additionally, aftercare attenders were younger than non-attenders (mean age, 13.4 ± 2.3 years vs 14.9 ± 2.0, p<0.05).Patients lost on average 1.0 ± 0.4 SDS during treatment and regained 0.4 ± 0.3 SDS post-treatment corresponding to regain of 43 ± 27% (calculated as the increase in BMI SDS post-treatment over the BMI SDS lost during treatment). A higher BMI and more comorbidities inversely predicted BMI SDS reduction in linear regression (all p<0.05).The absolute BMI SDS increase after returning home was predicted by pre-treatment leptin and systolic blood pressure, whereas the post-treatment BMI SDS regain was predicted by pre-treatment age, leptin, and adiponectin levels (all p<0.05) in multivariate linear regressions.ConclusionPatients who need treatment the most are at increased risk for dropouts and weight regain, emphasizing the urgent need for interventions to reduce dropout and support inpatients after discharge. Furthermore, this study is the first to report that pre-treatment leptin and adiponectin levels predict post-treatment BMI SDS regain, requiring further research.

Psychosocial and behavioral therapy in conjunction with medication for opioid use disorder: Patterns, predictors, and association with buprenorphine treatment outcomes

IntroductionCurrent evidence indicates that buprenorphine is a highly effective treatment for opioid use disorder (OUD), though premature medication discontinuation is common. Research on concurrent psychosocial and behavioral therapy services and related outcomes is limited.The goal of this study was to define patterns of OUD-related psychosocial and behavioral therapy services received in the first 6 months after buprenorphine initiation, identify patients' characteristics associated with service patterns, and examine the course of buprenorphine treatment, including the association of therapy with medication treatment duration. MethodsWe analyzed 2013–2018 MarketScan Multi-State Medicaid claims data. The sample included adults aged 18–64 years at buprenorphine initiation with treatment episodes of at least 7 days (n = 61,976). We used group-based trajectory models to define therapy service patterns and multinomial logistic regression to identify pre-treatment patient characteristics associated with therapy trajectories. Multinomial propensity-score weighted Cox proportional hazards regression estimated time to buprenorphine discontinuation and unweighted Cox proportional hazards models estimated risk of adverse health care events during buprenorphine treatment (all-cause and opioid-related inpatient and emergency department services, overdose treatment). ResultsWe identified three trajectories of psychosocial and behavioral therapy services: none (73.8%), low-intensity (17.2%), and high-intensity (9.0%). Compared to those without therapy, low-intensity and high-intensity service patterns were associated with behavioral health diagnoses and medical treatment for opioid overdose in the baseline period prior to buprenorphine initiation. The hazard of buprenorphine discontinuation was significantly lower for low-intensity (HR = 0.55; 95% CI, 0.54–0.57) and high-intensity (HR = 0.71; 95% CI, 0.67–0.74) therapy groups compared to those without therapy services. Yet patients in the high-intensity therapy group had increased risk of opioid-related health care events during buprenorphine treatment, including medical treatment for opioid overdose (HR = 1.29; 95% CI, 1.01–1.64). ConclusionMost patients received little or no OUD-related psychosocial and behavioral therapy after initiating buprenorphine treatment. Patients who received therapy had characteristics indicating greater treatment needs as well as more complex treatment courses. Concurrent therapy services may help to address premature buprenorphine discontinuation, particularly for patients with high-risk clinical profiles; however, future prospective research should determine whether therapy is effective for extending buprenorphine retention.

Impact of Tobacco, Marijuana and Alcohol Use on Overall Survival in Recurrent Metastatic Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors

<h3>Purpose/Objective(s)</h3> Tobacco, marijuana, and alcohol use have all been associated with immune suppressive effect. This study assess the impact of smoking status, marijuana use and alcohol consumption on overall survival (OS) in patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICI). <h3>Materials/Methods</h3> Between January 15^th 2016 and April 9^th 2020, 201 pts with R/M HNSCC were treated with ICI. Data on smoking status, marijuana use and alcohol consumption were collected through retrospective chart review. We had p16 status, hemoglobin, albumin, lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet count recorded initially at the time of starting ICI. OS was defined from the start of ICI to death. Progression Free Survival (PFS) was defined from the start of ICI to disease progression (PD) or death. <h3>Results</h3> 201 pts were analyzed, sex: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), ipilimumab+nivolumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), others 72 (36%). p16 status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Laboratory values: median neutrophil count: 4.58 (IQR: 3.43-6.47), median lymphocyte count: 0.69 (IQR: 0.47-1.08), median platelet count: 229 (IQR: 187-300), hemoglobin: normal/low 101/100 (50%/50%), albumin: normal/low 156/45 (78%/22%), LDH: normal/high 124/77 (62%/38%). Overall response rate: 36 (18%). Median OS: 12 months (CI: 9.4-14.8), median PFS: 4 months (CI: 3.5-5.7). Tobacco: former [HR 0.92 (0.62-1.36), <i>p=0.3</i>], current [HR 0.66 (0.39-1.14), <i>p=0.3</i>]. Marijuana: yes [HR 0.66 (0.43-1.01), <i>p=0.054</i>]. Alcohol: yes [HR 0.91 (0.65-1.28), <i>p=0.6</i>]. The variables associated with OS were high neutrophil count [HR 1.28 (1.08 – 1.51), <i>p=0.004</i>], high lymphocyte count [HR 0.75 (0.60 – 0.95), <i>p=0.015</i>], albumin (low) [HR 2.06 (1.37 – 3.10), <i>p<0.001</i>], hemoglobin (low) [HR 1.64 (1.14 – 2.35), <i>p=0.007</i>], LDH (high) [HR 1.78 (1.23 – 2.56), <i>p=0.002</i>] and p16 status (positive) [HR 0.58 (0.39-0.87), <i>p=0.009</i>]. <h3>Conclusion</h3> In our single institutional cohort, smoking status, marijuana use and alcohol consumption did not appear to have a significant impact on OS in patients with R/M HNSCC treated with ICI. As we previously reported, the pre-treatment patient characteristics associated with OS include neutrophil count, lymphocyte count, hemoglobin, albumin, LDH and p16 status.

Abstract PD5-04: Risk factors for long-term adjuvant chemotherapy toxicity using pre-treatment host factors and self-rated treatment bother (GP5) in a clinical trial population

Abstract Background: Chemotherapy-induced toxicities are prevalent in patients treated with adjuvant chemotherapy and often impact on activities of daily living and other aspects of function and well-being. Understanding which patients are more likely to experience long-term chemotherapy-induced peripheral neuropathy (CIPN) and hot flashes may help tailor treatment recommendations. Methods: Patients enrolled in the NRG Oncology/NSABP B-30 clinical trial were randomized to doxorubicin and docetaxel (AT), doxorubicin, docetaxel, and cyclophosphamide (ATC), or doxorubicin and cyclophosphamide followed by docetaxel (AC-T) (with increasing docetaxel doses across regimens). 1840 patients completed patient-reported outcomes (PRO) questionnaires including a symptom checklist asking about bother due to “numbness or tingling in hands or feet” and “hot flashes” as well as the FACT-General question 5 (GP5; “I am bothered by side effects of treatment”), assessed using a 5 category response scale. We examined the impact of pre-treatment host factors (demographic and clinical) on development and persistence of CIPN and hot flashes in NSABP B-30 patients. Analyses were performed using the Toxicity Index (TI), which summarizes the severity and frequency of toxicities over time. Univariate and multivariable probabilistic index models, a rank-based method that is a more general version of the Kruskal-Wallis test, for the cumulative TI of toxicity in the acute period (cycle 4 day 1 through 12 months post-randomization) and long-term follow-up (18 and 24 months post-randomization) were performed, and included baseline demographic, clinical, and PRO data. Results: Multivariable analysis revealed a higher probability of CIPN in the acute period for patients randomized to the AC-T treatment regimen and those with pre-existing numbness, higher GP5 at baseline, Black race, and obesity. In the long-term follow-up period, all the above factors except race were statistically significant. Older age at surgery and mastectomy were also associated with persistence of CIPN. GP5 at 12 months was significantly associated with the probability of CIPN in the longer-term period (0.577, p&amp;lt;.001). Multivariable analysis revealed a higher probability of hot flashes in the acute period for patients treated randomized to the ATC treatment regimen and those with pre-existing hot flashes, greater GP5 at baseline, younger age, and obesity. In the longer-term period, all the above factors except baseline GP5 and obesity remained statistically significant. Endocrine therapy was also significantly associated with long-term hot flashes. GP5 at 12 months was statistically significantly associated with the probability of hot flashes in the longer-term period (0.561, p&amp;lt;.001). Conclusions: Most pre-treatment patient characteristics that influence early development of CIPN and hot flashes are also associated with persistence of toxicity beyond 1 year. Persistent bother from side effects of treatment at 12 months (GP5) predicts continued toxicity during the subsequent year. Support: U10CA180868; U10CA180822. Multivariable probabilistic index models for cumulative TIsVariableComparison A&amp;lt;BProbability CIPN - AcuteP valueProbability CIPN - Long-termP valueProbability Hot Flashes - AcuteP valueProbability Hot Flashes - Long-termP valueTreatmentAT &amp;lt; ATC0.537&amp;lt;.0010.519.2450.567&amp;lt;.0010.577&amp;lt;.001AT &amp;lt; AC-T0.688&amp;lt;.0010.591&amp;lt;.0010.502.9050.542.058ATC &amp;lt; AC-T0.655&amp;lt;.0010.573&amp;lt;.0010.435&amp;lt;.0010.465.167Numbness at baselinePer 1-unit increment0.597&amp;lt;.0010.595&amp;lt;.001NANANANAHot flashes at baselinePer 1-unit incrementNANANANA0.601&amp;lt;.0010.592&amp;lt;.001GP5 at baselinePer 1-unit increment0.516.0330.523.0040.521.0040.509.289Age at surgeryPer 1-year increment0.501.0880.503.0010.492&amp;lt;.0010.498.016BMIObesity &amp;lt; Normal0.453.0010.411&amp;lt;.0010.516.3760.510.582Obesity &amp;lt; Overweight0.475.1470.470.0870.536.0420.532.087RaceWhite &amp;lt; Black0.587.0010.523.3630.499.9710.518.547Breast surgeryLumpectomy &amp;lt; Mastectomy0.515.2500.548&amp;lt;.0010.503.8290.507.629Endocrine therapyNo &amp;lt; YesNANA0.490.576NANA0.655&amp;lt;.001 Citation Format: N. Lynn Henry, Sungjin Kim, Ron D. Hays, Marcio A. Diniz, Michael Luu, Mourad Tighiouart, Reena S. Cecchini, Greg Yothers, Andre Rogatko, Patricia A. Ganz. Risk factors for long-term adjuvant chemotherapy toxicity using pre-treatment host factors and self-rated treatment bother (GP5) in a clinical trial population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-04.

Towards personalizing cognitive remediation therapy: Examining moderators of response for euthymic people with bipolar disorder

BackgroundRecent evidence suggests that cognitive remediation (CR) may reduce cognitive and functional difficulties in people with bipolar disorder (BD). However, there is a limited understanding of whether, and which, pre-treatment factors influence who will benefit from CR and this information could help to develop optimal therapy delivery. We aim to identify and examine baseline factors moderating post-treatment improvement. MethodsThis is a secondary analysis of data from a randomized controlled trial comparing CR (n = 40) to treatment-as-usual (TAU; n = 40) in euthymic people with BD. Elastic net regression was used to identify patient characteristics and baseline measures associated with post-treatment improvement in cognition, psychosocial functioning, and goal attainment. We then tested the moderating effect of retained variables on each outcome using multivariable linear regression. ResultsDespite lower baseline cognitive performance being associated with greater post-treatment changes in cognition and psychosocial functioning, there was no evidence of treatment response moderation. CR effect on goal attainment was larger for participants with better baseline cognitive performance, but this moderating effect did not reach significance (p = 0.09). Those with more severe baseline subjective cognitive complaints (p = 0.03) and more previously completed psychological therapies (p = 0.02) had also larger gains in goal attainment. ConclusionsTreatment benefits in cognition and psychosocial functioning might not be affected by pre-treatment factors and patient characteristics. However, baseline cognition and perceived deficits may influence the effect of CR on achieving recovery goals. Therapy adaptations may be required to exert greater benefits for less responsive patients.

Long term clinical outcomes and associated predictors of progression free survival in anal canal cancer.

Reports of long term clinical outcomes for patients with squamous cell carcinoma (SCC) of the anal canal treated with chemotherapy and intensity modulated radiation therapy (IMRT) are limited. Pre-treatment hematologic variables associated with outcomes remain understudied. We sought to report the long-term clinical outcomes of a cohort of patients treated with definitive chemoradiation (CRT) utilizing helical tomotherapy (HT) IMRT at a single tertiary referral center. We further sought to examine for any correlations between pre-treatment hematologic parameters and progression free survival (PFS). Data from patients with SCC of the anal canal treated with definitive CRT using HT IMRT from 2005 to 2017 were collected. Pre-treatment patient characteristics examined for correlations with PFS included: hemoglobin (Hgb) level, age, diabetes mellitus (DM) status, smoking status, neutropenia, thrombocytopenia, leukopenia, neutrophil/lymphocyte ratio, neutrophil/WBC ratio, lymphocyte/WBC ratio, sex, transplant status, HIV status, Karnofsky performance score, T-stage, and N-stage. Pre-treatment Hgb levels were recorded within two weeks prior to starting CRT. Clinical outcomes, including PFS, were described using the Kaplan-Meier estimator. A multivariable (MVA) Cox model of PFS evaluated the impact of pre-treatment Hgb and diabetes while adjusting for T-stage and age. The median patient age was 57 years old (range, 26-87) and there were 39 females (63.9%) with the remaining patients identifying as males. Median patient follow up was 5.8 years. The PFS was 83% at 5 years. The median pre-treatment Hgb was 13 g/dL. On multivariable analysis (MVA), Hgb ≤10 g/dL (HR: 11.891, 95% CI: 2.649-53.391, P=0.001) and a diagnosis of diabetes mellitus (HR: 4.524, 95% CI: 1.436-14.252, P=0.010) were both significantly associated with a worse PFS. These factors were independent of T-stage and age. Long-term clinical outcomes for patients with SCC of the anal canal treated with definitive CRT are presented. Pre-treatment hemoglobin of ≤10 g/dL and diabetes were both independently associated with worse PFS on MVA. This retrospective data supports further prospective study of the impact of hematologic markers and medical co-morbidities such as DM and their management on clinical outcomes for patients with SCC of the anal canal treated with curative-intent CRT.

What patient characteristics predict treatment success or failure in short- and long-term psychotherapies?

Background Patient factors make a strong contribution to psychotherapy outcome. Pre-treatment patient characteristics – demographic, pathology and personal – may either facilitate achievement of recovery and lasting benefits or constitute a risk for different kinds of treatment failure. Methods A narrative review focused on evaluating the role of pre-treatment patient characteristics on the success or failure of short- and long-term psychotherapy for mood and anxiety disorders. Success was conceptualized as significant improvement or recovery and failure as non-improvement, deterioration, or non-attendance/dropout. Results There is no consistent evidence of demographic variables as predictors of treatment failure, except for lower socioeconomic status, being male and ethnic minority status for therapy non-attendance. Patients’ pathology, i.e. severity of psychiatric symptoms, greater functional impairment, personality disorder and other comorbidities, have been shown to be mostly associated with lesser recovery across different types of disorders, especially in short-term therapies, but it does not consistently predict treatment failure. Some pre-treatment personal characteristics (e.g. secure attachment style) and capacities (e.g. motivation, self-observing capacity and good overall psychological suitability) mostly increase the likelihood of therapy success whereas some vulnerabilities and poor psychological suitability, or overall complexity (i.e. combination of demographic, clinical and personality factors), increase the risk of poor outcome mostly in short-term but not in long-term therapy, or moderate dropout. Likewise, the subsequent match between therapy type and patient’s pre-treatment expectations and preferences may account for different aspects of treatment failure. Conclusions The relative importance of pre-treatment patient characteristics on treatment failure is not known. Meta-analyses on this issue are needed.

Finding suitable candidates for vacuum bell therapy in pectus excavatum patients

Vacuum bell therapy has been acceptable substitute for pectus excavatum patients who want to improve their appearance but avoid surgical correction. The aim of this study was to assess the pre-treatment characteristics of patients with pectus excavatum and to establish characteristics that can potentially help identify ideal candidates for vacuum bell therapy. Expected improvements in thoracic indices were evaluated using pre-treatment chest computed tomography, which was performed before and after applying a vacuum bell device. Treatment results after 1-year of application were evaluated using changes in the Haller index before and after treatment. The patients were categorized into two groups according the post- treatment changes in Haller index calculated using chest radiographs: those with changes in Haller index less than 0.5 (Group 1) and those with greater than or equal to 0.5 (Group 2). Pre-treatment Haller index was significantly lower in Group 1 than in Group 2 (3.1 ± 0.46 vs. 4.2 ± 1.14, respectively, p < 0.001). The expected improvement in Haller index in Group 2 was significantly higher than that in Group 1 (3.3 ± 0.60 vs. 2.8 ± 0.54, respectively, p = 0.001). The cut-off value of the expected improvement in Haller index was 0.46 with a sensitivity of 75.8% and a specificity of 83.3%. Patients who demonstrated pliability with a vacuum bell were identified as suitable candidates.

Venetoclax Consolidation in Patients with High-Risk CLL Who Have Been on Ibrutinib More Than a Year Achieves a High Rate of Undetectable Minimal Residual Disease

Venetoclax Consolidation in Patients with High-Risk CLL Who Have Been on Ibrutinib More Than a Year Achieves a High Rate of Undetectable Minimal Residual Disease

Psychotherapy Dropout: Using the Adolescent Psychotherapy Q-Set to Explore the Early In-Session Process of Short-Term Psychodynamic Psychotherapy.

Research suggests that short-term psychodynamic psychotherapy (STPP) is an effective treatment for depression in adolescence, yet treatment dropout is a major concern and what leads to dropout is poorly understood. Whilst studies have begun to explore the role of patient and therapist variables, there is a dearth of research on the actual therapy process and investigation of the interaction between patient and therapist. This study aims to address this paucity through the utilisation of the Adolescent Psychotherapy Q-set (APQ) to examine the early treatment period. The sample includes 69 adolescents aged 16–18 years with major depressive disorder receiving STPP as part of the First Experimental Study of Transference Work–in Teenagers (FEST-IT) trial. Of these, 21 were identified as dropouts and were compared to completers on pre-treatment patient characteristics, symptomatology, functioning, and working alliance. APQ ratings available for an early session from 16 of these drop out cases were analysed to explore the patient-therapist interaction structure. Results from the Q-factor analysis revealed three distinct interaction structures that explained 54.3% of the total variance. The first described a process of mutual trust and collaboration, the second was characterised by patient resistance and emotional detachment, the third by a mismatch and incongruence between therapist and adolescent. Comparison between the three revealed interesting differences which taken together provide further evidence that the reasons why adolescents drop out of therapy vary and are multidimensional in nature.

Moderators of treatment response to exercise in participants with stimulant use disorder: Exploratory results from the Stimulant Reduction using Dosed Exercise (STRIDE)CTN-0037 study

Exercise is a promising treatment for stimulant use disorder. However, efficacy has not been clearly demonstrated in a general stimulant using population where response to exercise is expected to be heterogeneous. Thus, examination of response heterogeneity to identify subgroups for whom exercise is either clearly indicated or not indicated is of considerable interest as findings will support more effective tailoring of patient treatments in practice and guide future research in stimulant use disorder. A secondary analysis of the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) randomized controlled trial of 302 stimulant using or dependent participants was conducted to identify baseline clinical and demographic characteristics associated with differential response between participants in the exercise and health education control groups. Characteristics (i.e., moderators of treatment response) were identified using an established Best Approximating Modeling (BAM) method. Six moderators of treatment response were identified: Quick Inventory of Depressive Symptomatology-Clinician (QIDS-C) rated total score, exercise test maximum systolic blood pressure, number of lifetime drug treatments, Stimulant Craving Questionnaire (STCQ) total score, Addiction Severity Index (ASI) Family subscale score, and Cognitive and Physical Functioning Questionnaire (CPFQ) total score. For all moderators, the odds ratio of response to exercise vs. health education ranged from 0.32 to 2.52 or more depending on the level of the moderator. These results demonstrate that it is possible to identify pre-treatment patient characteristics that predict statistically and clinically meaningful differential treatment response to exercise.

Survival, CD4 T lymphocyte count recovery and immune reconstitution pattern during the first-line combination antiretroviral therapy in patients with HIV-1 infection in Mongolia.

Mongolia has a low incidence of human immunodeficiency virus (HIV) infection, with 281 cases reported at the end of 2019 and an estimated incidence rate of <0.01 cases per 1000 population.However, no study has analyzed the association between antiretroviral therapy (ART) outcomes and pretreatment characteristics of patients with HIV/acquired immunodeficiency syndrome (AIDS) in Mongolia. This retrospective study aimed to determine the survival, CD4 T cell recovery, and immune reconstitution pattern during ART in HIV patients and to determine baseline patient characteristics associated with ART outcomes. Based on three different World Health Organization (WHO) guidelines, we analyzed the 3-year observation data of 166 patients with HIV/AIDS who received treatment between 2010 and 2017. An increase of >50 cells/μL indicated CD4 T cell count recovery, and a cell count of ≥500 cells/μL in patients with a baseline cell count of <500 cells/μL indicated immune reconstitution. In this study, the 3- and 1-year mortality rates were 5.4% (survival rate: 94.6%) and 3.6%, respectively. A total of 83% of deaths that occurred in the observation time occurred within the first 3 months. The CD4 T cell count recovery rates at 3, 12, and 36 months were 62.7%, 80.7%, and 89.2%, respectively. The CD4 T cell count increased to >500 cells/μL in 95 of 145 (65.5%) patients with a baseline cell count of <500 cells/μL after 36 months of ART. The baseline CD4 T cell count was found to be a sensitive indicator for immune reconstitution. An advanced pretreatment clinical stage of HIV infection (as classified by the WHO classification), a low CD4 T cell count in the peripheral blood, and a high viral load before the initiation of the first-line ART accurately predicted survival, CD4 T cell count recovery, and immune reconstitution in Mongolian patients with HIV/AIDS.

Predictors of Mortality Among Very Low Birth Weight Infants With Gastrointestinal Perforation.

Gastrointestinal (GI) perforation is a risk factor for mortality in very low birth weight (VLBW) infants. Little data exist regarding pretreatment factors and patient characteristics known to independently correlate with risk of death. A retrospective review of all VLBW infants who sustained GI perforation between 2011 and 2018 was conducted. Birth, laboratory, and disease-related factors of infants who died were compared to those who survived. 42 VLBW infants who sustained GI perforations were identified. Eleven (26.19%) died. There were no significant differences in birth-related factors, hematological lab levels at diagnosis, presence of pneumatosis, or bacteremia. Portal venous gas (P = .03), severe metabolic acidosis (P < .01), and elevated lactate at diagnosis (P < .01) were statistically more likely to occur among infants who died. Portal venous gas, severe metabolic acidosis, and elevated lactate were associated with an increased risk of mortality among VLBW infants who develop a GI perforation. Further research is required to better identify risk factors.

Spinal Dural Arteriovenous Fistula: Diagnosis, Outcomes, and Prognostic Factors

Typically, the clinical presentation of a spinal dural arteriovenous fistula (SDAVF) will be insidious, with patients' symptoms regularly attributed to other conditions. Although previous studies have characterized the neurologic outcomes after treatment for SDAVFs, little is known about the pretreatment patient characteristics associated with poor and/or positive patient outcomes. We sought to characterize the pretreatment patient demographics, diagnostic history, and neurologic outcomes of patients treated for SDAVFs and to identify the patient factors predictive of these outcomes. The medical records of patients who had been treated for SDAVFs from 2006 to 2018 across 1 healthcare system were retrospectively analyzed. Neurologic status was assessed both before and after intervention using the Aminoff-Logue scales for gait and micturition disturbances. Of 46 total patients, 16 (35%) had a documented misdiagnosis. Patients with a history of misdiagnosis had had a significantly longer symptom duration before treatment compared with those without a misdiagnosis (median, 2.3 vs. 0.9 years; P= 0.018). A shorter symptom duration before intervention was significantly associated with both improved motor function (median, 0.8 vs. 3.1 years; P= 0.001) and improved urinary function (median, 0.8 vs. 2.2 years; P= 0.040) after intervention. Misdiagnosis has been relatively common in patients with SDAVFs and contributes to delays in treatment. Delays in diagnosis and treatment of SDAVFs appear to be associated with worse clinical outcomes for patients who, ultimately, receive treatment.