Inadequate Treatment Response Research Articles

Montelukast deprescribing in outpatient specialty clinics: A single center cross-sectional study

ObjectiveTo identify and evaluate montelukast deprescribing in outpatient specialty clinics. MethodsThis was a single-center, retrospective, cross-sectional study conducted at an academic health system in the southern US including 21 specialty clinics. Subjects included adults ≥18 years with an active prescription for montelukast who attended at least one appointment in pulmonology, otolaryngology, or neurology outpatient specialty clinics between January 1, 2021 to December 31, 2022. Patients <18 years and those with diagnoses of uncontrolled asthma or allergic rhinitis were excluded. Outcomes assessed included the frequency and period prevalence of montelukast deprescribing, defined by a documented montelukast discontinuation within the medical record, and evaluation of reasoning for discontinuation mentioned in visit notes. ResultsThere were 1152 patients who met inclusion criteria. Of these, 43 (3.7 %) experienced a montelukast deprescribing event: 18 (41.9 %) in neurology, 13 (30.2 %) in otolaryngology, and 12 (27.9 %) in pulmonology. Documented reasons for deprescribing were only available for 11 patients (25.6 %); reasons for deprescribing included patient-provider shared decision-making regarding the Black Box Warning [n = 5 (11.6 %)], inadequate treatment response [n = 3 (7.0 %)], suicidal thought development [n = 1 (2.3 %)], adverse drug event [n = 1 (2.3 %)], and pregnancy planning [n = 1 (2.3 %)]. ConclusionMontelukast deprescribing rates were less than 5 % in outpatient specialty clinics. Factors associated with montelukast deprescribing beget further investigation.

Dual metabolic modification of tumor-targeted bacteria for synergistic chemo-photodynamic therapy and immunotherapy

Conventional anti-tumor methods face challenges such as limited targetability and severe side effects, even when using carrier-assisted delivery of corresponding agents. Additionally, relying on a single modality often leads to an inadequate treatment response. Leveraging the facultative bacteria’s migration tendency to hypoxic tumor tissue and the effectiveness of physicochemical approaches in bacterial engineering, non-pathogenic Escherichia coli MG1655 was metabolically modified for tumor-targeted and synergistic therapy. By taking advantage of the essential D-alanine (D-Ala) component in bacterial peptidoglycan, chemotherapeutic D-Ala-OXA and photosensitizing D-Ala-PPa were firstly prepared and simultaneously labeled on MG1655, creating the multimodal platform (O/P@MG1655). When exposed to red light irradiation, O/P@MG1655 effectively eliminated tumor cells through chemo-photodynamic therapy and induced immunogenic cell death to trigger immunotherapy. Notably, significant inhibition of tumor growth and excellent biosafety were observed in a subcutaneous CT26 mouse tumor model. This dual metabolic modification strategy represents a remarkable advancement in the development of functionalized targeted bacteria for precise tumor treatment.

The immune landscape of the inflamed joint defined by spectral flow cytometry.

Cellular phenotype and function are altered in different microenvironments. For targeted therapies it is important to understand site-specific cellular adaptations. Juvenile Idiopathic Arthritis (JIA) is characterised by autoimmune joint inflammation, with frequent inadequate treatment responses. To comprehensively assess the inflammatory immune landscape, we designed a 37-parameter spectral flow cytometry panel delineating mononuclear cells from JIA synovial fluid (SF) of autoimmune inflamed joints, compared to JIA and healthy control blood. Synovial monocytes and NK cells (CD56bright) lack Fc-receptor CD16, suggesting antibody-mediated targeting may be ineffective. B cells and DCs, both in small frequencies in SF, undergo maturation with high 4-1BB, CD71, CD39 expression, supporting T cell activation. SF effector and regulatory T cells were highly active with newly described co-receptor combinations that may alter function, and suggestion of metabolic reprogramming via CD71, TNFR2 and PD-1. Most SF effector phenotypes, as well as an identified CD4-Foxp3+ T cell population, were restricted to the inflamed joint, yet specific SF-predominant CD4+Foxp3+ Treg subpopulations were increased in blood of active but not inactive JIA, suggesting possible recirculation and loss of immunoregulation at distal sites. This first comprehensive dataset of the site-specific inflammatory landscape at protein level will inform functional studies and the development of targeted therapeutics to restore immunoregulatory balance and achieve remission in JIA.

The trace amine-associated receptor 1 agonists - non-dopaminergic antipsychotics or covert modulators of D2 receptors?

A major effort of the pharmaceutical industry has been to identify and market drug treatments that are effective in ameliorating the symptoms of psychotic illness but without the limitations of the current treatments acting at dopamine D2 receptors. These limitations include the induction of a range of adverse effects, the inadequate treatment response of a substantial proportion of people with schizophrenia, and the generally poor response to negative and cognitive features of the disease. Recently introduced drug treatments have gone some way to avoiding the first of these, with a reduced propensity for weight gain, cardiovascular risk and extrapyramidal motor effects. Despite claims of some small improvements in negative symptoms, these drugs have not demonstrated substantial increases in efficacy. Of the drugs currently in development as antipsychotic agents, several are misleadingly described as having novel 'non-dopaminergic' mechanisms that may offer improvements in addressing the limitations of adverse effects and efficacy. It will be argued, using the trace amine-associated receptor 1 agonist as an example, that several of these new drugs still act primarily through modulation of dopaminergic neurotransmission and, in not addressing the primary pathology of schizophrenia, are therefore unlikely to have the much-needed improvements in efficacy required to address the unmet need associated with resistance to current treatments.

Discontinuation of Fumaric Acid Esters is Affected by Depressive Symptomatology: A Retrospective Analysis.

Fumaric acid esters (FAEs) remain a widespread therapy option for moderate-to-severe psoriasis. However, drug survival of FAEs is limited by adverse events (AEs) or inadequate treatment response. Depressive disturbances are highly prevalent in psoriasis patients and are hypothesized to be associated with the reporting of AEs and therapy discontinuation. This study's aim was to analyze whether psoriasis patients with comorbid depressive symptomatology are more likely to discontinue treatment with FAEs due to AEs and/or inadequate treatment response. Data were retrospectively extracted from the records of patients starting therapy with FAEs in the Department of Dermatology, University Hospital Essen, Germany between 2017 and 2022, covering the first 52 weeks of treatment. Psoriasis severity and depressive symptomatology, as well as AEs and therapy discontinuation, were analyzed. Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression. The results support the hypothesis that among psoriasis patients with depressive symptoms, the associated introspection and somatization may result in increased sensitivity for AEs and thus in quicker therapy discontinuation. In these patients, the occurrence of nocebo effects should be minimized, e.g. by special communication techniques.

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.

Melanoma biology and treatment: a review of novel regulated cell death-based approaches

AbstractThe incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.

Drug- or Vaccine-Induced/Aggravated Psoriatic Arthritis: A Systematic Review.

Drugs and vaccines have been less studied as inducing or aggravating factors for psoriatic arthritis (PsA) compared with psoriasis. Thus, the present study collected and summarized the publications to date about this issue. We conducted a systematic literature search through the PubMed, Embase, and Cochrane databases to identify all reports on potential drug- and vaccine-related PsA events until 28 February 2023. In total, 179 cases from 79 studies were eligible for study. Drugs commonly reported include coronavirus disease 2019 (COVID-19) mRNA vaccines (6 cases), bacillus Calmette-Guerin (BCG) vaccine (3 cases), interferon (18 cases), immune-checkpoint inhibitors (ICI) (19 cases), and biologic disease-modifying antirheumatic drugs (bDMARDs) (127 cases). Drugs causing psoriasis may also induce or aggravate PsA (6 cases). BDMARD-related PsA mostly occurred in a "paradoxical" setting, in which the bDMARDs approved for the treatment of psoriasis induce or aggravate PsA. The reported latency may be delayed up to 2years. Peripheral arthritis (82.3%) was the most common manifestation of drug- and vaccine-related PsA, followed by dactylitis (29.1%), enthesitis (23.4%), and spondyloarthritis (17.7%). Drugs and vaccines may be implicated in the aggravation of PsA. Possible mechanisms include cytokine imbalance, immune dysregulation, or inadequate PsA treatment response compared with psoriasis. Most reports are case based without controls, so more studies are needed to further prove the causality. However, early recognition of factors causing or aggravating PsA is important to prevent the irreversible joint damage.

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry

Objective To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. Methods We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. Results Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. Conclusion Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Understanding Sociodemographic Factors among Hispanics Through a Population-Based Study on Testicular Cancer in Mexico

AbstractTesticular cancer (TCa) is a rare malignancy affecting young men worldwide. Sociodemographic factors, especially socioeconomic level (SEL) and healthcare access, seem to impact TCa incidence and outcomes, particularly among Hispanic populations. However, limited research has explored these variables in Hispanic groups. This study aimed to investigate sociodemographic and clinical factors in Mexico and their role in health disparities among Hispanic TCa patients. We retrospectively analyzed 244 Mexican TCa cases between 2007 and 2020 of a representative cohort with diverse social backgrounds from a national reference cancer center. Logistic regression identified risk factors for fatality: non-seminoma histology, advanced stage, and lower education levels. Age showed a significant trend as a risk factor. Patient delay and healthcare distance lacked significant associations. Inadequate treatment response and chemotherapy resistance were more likely in advanced stages, while higher education positively impacted treatment response. Cox regression highlighted non-seminoma histology, below-median SEL, higher education, and advanced-stage survival rates. Survival disparities emerged based on tumor histology and patient SEL. This research underscores the importance of comprehensive approaches that integrate sociodemographic, biological, and environmental factors to address health disparities improving outcomes through personalized interventions in Hispanic individuals with TCa.

Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice.

Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives. The clinical details, thyroid ultrasound, cytology and thyroid scan findings were reviewed. Allele-specific PCR for BRAF p.V600E, KRAS, NRAS, and HRAS mutations, and FISH assays for ETV6::NTRK3 fusion and RET fusions were performed. There were four cases of IEFVPTC-MF diagnosed between 2021 and 2022, involving two males and two females. The median age at presentation was 27years, and the duration of the disease was 1-10years. Thyroid ultrasound was TR1 (benign; n = 1), TR2 (not suspicious; n = 2), or TR4 (moderately suspicious; n = 1). Cytology was categorized as nondiagnostic (n = 1), benign (n = 1), andatypia of undetermined significance (n = 1). The three nodules with available cytology smears showed abundant colloid. Cells were arranged as sheets/microfollicles/clusters. Nuclei were predominantly round with minimal/focal elongation, membrane irregularity, and cellular crowding. On gross examination, cut surfaces of the tumors showed variable amounts of colloid. The tumors were solid-cystic. Histopathology revealed partially encapsulated multinodular tumors. There were prominent pseudopapillae projecting into the lumina of macrofollicles. Nuclei were predominantly round with variable nuclear atypia, including chromatin clearing and multifocal presence of nuclear grooves. Pseudoinclusions were identified in two. Molecular analysis revealed NRAS codon 61 mutation and ETV6::NTRK3 fusion in one case each. Two patients had cervical lymph node and hematogenous metastases. Post-radio-active iodine, the response was structurally incomplete (n = 2), indeterminate (n = 1) and excellent (n = 1). Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.

Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.

The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

The significance of metabolic response to neoadjuvant androgen deprivation therapy detected with [68Ga]Ga-PSMA-11-PET/CT in high-risk prostate cancer patients treated with definitive radiotherapy.

We examined the prognostic significance of early changes in primary tumor SUV measured with Gallium-68-labeled prostate-specific membrane antigen positron emission tomography ([68Ga]Ga-PSMA-11-PET/CT) and serum PSA values after neoadjuvant androgen deprivation treatment (nADT) in high-risk prostate cancer (PCa) patients treated with definitive radiotherapy (RT). The clinical data and SUV parameters of 71 PCa patients were reviewed retrospectively. The serum PSA and primary tumor SUV values were calculated before and after the start of ADT. Using univariable and multivariable analyses, the prognostic factors predicting biochemical disease free survival (bDFS) and prostate cancer specific survival (PCSS) were investigated. In addition, logistic regression analysis was used to identify predictors of biochemical failure (BF). All but one patient responded with a 98.8% reduction in serum PSA (21.8ng/mL vs. 0.3ng/mL; p < 0.001), and 64 patients (91.1%) had a median 66.6% decrease in primary tumor SUV after ADT (13.2 vs. 4.8, p < 0.001). The primary tumor SUV response rate was significantly higher in patients with Gleason score (GS) of 7 than in patients with GS > 7 (59.5% vs. 40.5%; p = 0.04), and it was significantly lower in patients with inadequate treatment response than in those with complete (CR) or partial response (PR) (1.1% vs. 66.1%; p < 0.001). There was a strong and significant correlation (Spearman = 0.41, p < 0.001) and a high concordance (91.5%) between PSA response and SUV response after ADT. With a median follow-up time of 76.1months, the 5-year bDFS and PCSS rates were 77.2% and 92.2%, respectively. Nineteen patients (26.7%) patients had recurrence at a median of 44.6months after the completion of RT. In multivariate analysis, lymph node metastasis, GS greater than 7, and SD/PD after nADT were independent predictors of worse bDFS. However, no significant factor for PCSS was identified. In the multivariable logistic regression analysis, advanced age, GS of > 7 disease, lymph node metastasis, and SD or PD after nADT were independent predictors of BF. These results imply that the metabolic response measured with [68Ga]Ga-PSMA-11-PET/CT after nADT could be used to predict progression in high-risk PCa patients treated with definitive RT.

Expert Recommendations for the Diagnosis, Treatment, and Management of Adult B-Cell Acute Lymphoblastic Leukemia in Latin America.

Despite strong induction chemotherapy response rates, only 30%-40% of patients with adult B-cell acute lymphoblastic leukemia (ALL) attain long-term remission. This study analyzes ALL in Latin America (LA) and recommends diagnosis, treatment, and management protocols. The Americas Health Foundation organized a panel of hematologists from Argentina, Brazil, Chile, Colombia, and Mexico to examine ALL diagnosis and therapy and produce recommendations. Lack of regional data, unequal access to diagnosis and therapy, inadequate treatment response, and uneven health care distribution complicate adult ALL management. The panel recommended diagnosis, first-line and refractory treatment, and post-transplantation maintenance. Targeted treatments, including rituximab, blinatumomab, and inotuzumab ozogamicin, are becoming available in LA and must be equitably accessed. This review adapts global information on treating ALL to LA. Governments, the medical community, society, academia, industry, and patient advocates must work together to improve policies.

Efficacy of AXS-07 (MOSEIC™ Meloxicam and Rizatriptan) in Patients with Risk Factors for Inadequate Response to Acute Migraine Medications (P13-12.001)

Efficacy of AXS-07 (MOSEIC™ Meloxicam and Rizatriptan) in Patients with Risk Factors for Inadequate Response to Acute Migraine Medications (P13-12.001)

P023 National care of patients with Polymyalgia Rheumatica: Audit of steroid usage from UK GP data - a cause for concern?

Abstract Background/Aims Polymyalgia rheumatica (PMR) is the most common autoimmune musculoskeletal condition in the developed world. Current BSR guidelines recommend glucocorticoid treatment for one to two years and give suggested taper regimens. The project examines national primary care data to assess the level of adherence to current guidelines, and the proportion of patients at risk from the deleterious effects of prolonged steroid exposure. Methods The ECLIPSE databased covers over 25m patients across 2400 general practices in England and provides insights for enhanced clinical pathway management and to support patient safety in primary care. Routinely recorded diagnoses from primary care data are updated daily, along with administrative prescribing data. Using standardised nationally agreed disease coding frameworks, all diagnoses of PMR were retrieved from the live patient population of 25.4m individuals registered with general practices across England. Primary care diagnosis data for patients with a new diagnosis of PMR recorded in primary care on or after 01/01/2016 were linked with prescribing data from the same time period and followed to 10/10/2022. From the current BSR guidelines the following thresholds were taken to represent above recommended cumulative glucocorticoid exposure: 0-6 months &amp;gt;2100mg, 7 to 12 months &amp;gt;1400mg, 13 to 18 months &amp;gt;910mg and 19 to 24 months &amp;gt;910mg. Finally total numbers of those still prescribed glucocorticoids past 60 months was taken as to represent those who had become steroid-dependent. Results Over the observation period of 6.8 years there were 95,862 people diagnosed with PMR from the UK national data, of whom 22,677 were diagnosed in the East of England and 5,315 from the Norfolk and Waveney Integrated Care System. The prevalence was 0.99%, 1.00% and 1.5% for those aged older than 50 years across the three areas respectively consistent with published disease estimates. There was considerable number of individuals with PMR prescribed glucocorticoids above the recommend levels (see Table 1). Conclusion There is significant departure from the suggested PMR tapering regimens which may be due to frequency of relapse, inadequate treatment response or inadequate guideline implementation. Strategies to reduce glucocorticoid exposure in this older co-morbid population are required urgently. Disclosure P. Saha: None. J. Brown: None. A. MacGregor: None. C. Aldus: None. M. Yates: None.

Reliability and validity of the difficult to treat depression questionnaire (DTDQ)

It has recently been recommended that treatment resistant depression be reconceptualized and renamed as difficult to treat depression (DTD). A consensus statement by an expert panel identified multiple variables associated with DTD and emphasized the importance of conducting a comprehensive evaluation of patients to identify predictors of inadequate treatment response. For practical reasons, it would be desirable to develop a self-report scale that can be incorporated into clinical practice that identifies patient, clinical, and treatment risk factors for DTD. Nine hundred twenty depressed patients completed the Difficult to Treat Depression Questionnaire (DTDQ). A subset of patients completed the scale a second time and completed the Remission from Depression Questionnaire at admission and discharge from a partial hospital program.The DTDQ demonstrated excellent internal consistency and test-retest reliability. Both the total DTDQ and the number of prior failed medication trials, the metric primarily relied upon to classify treatment resistant depression, predicted outcome. However, the DTDQ continued to be significantly associated with outcome after controlling for the number of failed trials, whereas the number of failed trials did not predict outcome after controlling for DTDQ scores. The DTDQ is a reliable and valid measure of the recently discussed concept of DTD.

Characteristics of Cancer-Related Fatigue and an Efficient Model to Identify Patients with Gynecological Cancer Seeking Fatigue-Related Management.

Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients' quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF.

Long-Term Survival of Patients with Mantle Cell Lymphoma after Total Body Irradiation, High-Dose Chemotherapy and Stem Cell Transplantation: A Monocenter Study.

In patients with mantle cell lymphoma (MCL), long-term remissions can be achieved by stem cell transplantation (SCT). Different conditioning treatment protocols exist with or without total body irradiation (TBI). There are few data published on the role of TBI before autologous stem cell transplantation (autoSCT) or allogenic stem cell transplantation (alloSCT). We report on the long-term survival data of patients treated by TBI prior to autologous or allogenic SCT at our center. In a retrospective analysis, the data of patients treated at the University Hospital of Muenster from May 2004 to February 2015 were collected and evaluated. For the analysis, all data of patients who were histopathologically diagnosed with MCL and underwent TBI prior to stem cell transplantation (SCT) were evaluated. A total of 22 patients (19 men and 3 women) were treated with a TBI-based conditioning prior to SCT. The median age at initial diagnosis was 57.5 years (38-65 years). Seventeen patients had Ann Arbor stage IV, two patients had Ann Arbor stage III, and three patients Ann Arbor stage II disease. AutoSCT was performed in 19 patients and alloSCT was performed in 3 patients. In 18 patients, autoSCT was applied as part of first-line therapy, and in one patient after relapse. Two patients received alloSCT after relapse of MCL, and one patient received alloSCT during first-line therapy after an inadequate treatment response. TBI was performed in 12 patients with 10 Gy and in 6 patients with 12 Gy, these patients subsequently received autoSCT. In the group of four patients who received TBI with four Gy, four patients subsequently received alloSCT and one patient received autoSCT. Median overall survival after autoSCT and previous TBI was 11.4 years (142 months). In total, 11 out of 19 patients treated with autoSCT lived longer than 6.8 years (82-202 months). After alloSCT and previous TBI, the median overall survival was 3.25 years (14-59 months). A large proportion of patients with advanced MCL survived remarkably longer than 11.4 years after high-dose chemotherapy, TBI, and SCT. The present results of multimodal treatment support the published reports that TBI-based high-dose therapy followed by autoSCT is highly effective in this prognostically unfavorable disease situation.

P854 Race and ethnicity in ulcerative colitis clinical trial enrolment: a post hoc analysis of patient demographics and clinical characteristics from GEMINI 1, VARSITY, and VISIBLE 1

Abstract Background The incidence of inflammatory bowel disease (IBD) has risen among Black individuals and Hispanic or Latino individuals in the USA in recent decades; however, these patients are underrepresented in clinical trials of IBD therapies. We aimed to perform a post hoc analysis of the baseline demographics and clinical characteristics in three phase 3 clinical trials of vedolizumab for ulcerative colitis (UC) to identify differences between racial and ethnic groups. Methods The baseline demographics and clinical characteristics of patients with UC who were enrolled in GEMINI 1, VARSITY, and VISIBLE 1 were pooled and stratified by race and ethnicity, which were self-reported. The inclusion criteria for these trials included adult patients with moderately to severely active UC who had a prior inadequate treatment response, loss of response, or intolerance to conventional therapies or anti-tumour necrosis factor α treatment. Data were analysed using descriptive statistics, with mean or median values calculated for continuous variables, and the number and proportion of patients reported for categorical variables. T-tests and exact tests were used to compare continuous and categorical variables, respectively, between Black and White patients and between Hispanic or Latino patients and those who were not Hispanic or Latino. Results We included 1,358 patients, of whom 1,171 (86.2%) were White, 148 (10.9%) were Asian, 14 (1.0%) were Black, and 25 (1.8%) were of multiple or unspecified racial groups (Table 1). Black patients had significantly higher mean weight (87.9 kg vs 74.8 kg, p &amp;lt; 0.01) and body mass index (30.5 kg/m2 vs 25.2 kg/m2, p &amp;lt; 0.01), but lower albumin (38.5 g/L vs 41.2 g/L, p &amp;lt; 0.05) and haemoglobin levels (115.5 g/L vs 126.1 g/L, p &amp;lt; 0.05) than White patients (Table 1). Ethnicity data were recorded for 465 patients (34.2%). Hispanic or Latino patients were shorter in height (166.6 cm vs 171.0 cm, p &amp;lt; 0.01) and had shorter mean disease duration (4.6 years vs 7.6 years, p &amp;lt; 0.01) than those who were not Hispanic or Latino (Table 2). A non-significant, but numerically greater proportion of Hispanic or Latino patients had pancolitis than those who were not Hispanic or Latino (50.0% vs 35.8%). Conclusion In this post hoc analysis of vedolizumab clinical trials, Black patients and Hispanic or Latino patients with UC had differences in certain demographic and disease characteristics versus White patients and patients who were not Hispanic or Latino, respectively. These differences may have implications for therapy. Thus, inclusion of a more diverse patient population that reflects the demographics of the general population is warranted to adequately ascertain drug efficacy across racial and ethnic groups.