Descriptive Subgroup Analysis Research Articles

Quality of life in people with multiple sclerosis vs general population: differences increase by age

Abstract Background To enhance health care for chronically ill people, it is crucial to understand the impact of their disease on health-related quality of life (HRQoL). More than 240,000 people in Germany live with multiple sclerosis (PwMS), the most common immune-mediated neurodegenerative disease of the central nervous system. Little is known about HRQoL in PwMS in comparison to the general population and by subgroups. Methods In 2021, 6,928 statutorily-insured PwMS aged ≥18 years and living in the federal state of Lower Saxony, Germany, were invited to take part in an online survey. The German EQ-5D-5L value set was used to analyse HRQoL by index values. Descriptive subgroup analyses were conducted (age, sex) and compared to a general German reference population (Grochtdreis et al. 2019, DOI: 10.1007/s10198-019-01054-1). Mann-Whitney-U- or Kruskal-Wallis-tests were performed as appropriate. Results Of 1,935 respondents (response rate 27.9%), 1,916 PwMS were included in the current preliminary complete case analysis. HRQoL is reduced in PwMS compared to the general population: Mean (M) 0.67 vs. M 0.88, respectively. While no significant differences by sex were found in PwMS (male: M 0.66 vs. female: M 0.68, p = 0.1), HRQoL decreased with increasing age (p < 0.001). The reduction in HRQoL is more pronounced in PwMS than in the general population (difference between means 0.53 in 18-24 years old to ≥ 75 years old PwMS vs. 0.14 in the reference population, respectively). Conclusions PwMS report an overall lower level of HRQoL compared to the general population. Increasing age correlates with a substantial decrease of HRQoL in PwMS. Targeted research is needed to improve HRQoL of this vulnerable population. Key messages • The decline in HRQoL with increasing age is more pronounced in PwMS than in the general population in Germany. • Further research should focus particularly on the extent to which MS-related factors are solely attributable for the considerable decline of HRQoL in PwMS.

Clinical Effectiveness and Safety of Momelotinib Compared with Continued Ruxolitinib or Best Available Therapy in Patients with Myelofibrosis Who Required RBC Transfusions: Subgroup Analysis of the Phase 3 Simplify-2 Study

Introduction: Splenomegaly, constitutional symptoms, and anemia are key clinical features of myelofibrosis (MF); approximately one-third of patients (pts) are anemic at diagnosis, and most develop anemia over time. While Janus kinase (JAK) inhibitors such as ruxolitinib (RUX) and fedratinib (FED) may address symptoms and splenomegaly, they do not manage and may exacerbate anemia. Treatments for anemia include erythropoiesis-stimulating agents (ESAs), often in combination with RUX or FED, and androgens such as danazol; however, these have shown limited efficacy. Red blood cell (RBC) transfusions are the mainstay of anemia management in MF, but transfusion dependency is associated with diminished quality of life and is a negative prognostic factor for survival. Treatments that address anemia as well as spleen volume and symptoms are needed. Momelotinib (MMB), a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated clinically meaningful and durable improvements in anemia, splenomegaly, and symptoms in pts with MF across 3 phase 3 trials. To evaluate outcomes in pts who switched to MMB vs continuing RUX or best available therapy (BAT) despite transfusion requirement, we present a descriptive subgroup analysis of pts enrolled in SIMPLIFY-2 (NCT02101268) who were considered transfusion dependent (TD; ≥4 units of RBC transfusions in the previous 8 wk or hemoglobin [Hb] level <8 g/dL) or transfusion requiring (TR; receiving transfusions but not meeting TD criteria) at baseline (BL). Methods: SIMPLIFY-2 was an international, multicenter, open-label, phase 3 clinical trial investigating the efficacy and safety of MMB vs BAT in pts with MF who had suboptimal responses or hematologic toxicities while receiving RUX. Pts (N=156) were randomized 2:1 to receive open-label MMB or BAT, which was RUX in 88.5% of pts. Treatment washout from prior RUX was not permitted before study enrollment. The primary endpoint was spleen volume reduction ≥35% (SVR35). Total Symptom Score (TSS) response rate (≥50% reduction; TSS50) and transfusion independence response (TI-R; no RBC transfusions for ≥12 wk immediately before the end of wk 24, with all Hb levels ≥8 g/dL) were key secondary endpoints. This post hoc, descriptive analysis focused on pts treated with either MMB or BAT, who were considered non-transfusion-independent (non-TI), defined as either TD or TR, at BL. Results: In SIMPLIFY-2, 72 of 104 pts (69%) in the MMB arm and 33 of 52 pts (63%) in the BAT arm were non-TI at BL, and BL characteristics were balanced between both patient groups. Mean duration of prior treatment with RUX was 64.6 and 59.5 wk in non-TI pts in the MMB and RUX arms, respectively. Average BL TSS for this subpopulation was 18.6. All pts randomized to the MMB arm received a starting dose of 200 mg daily. In the BAT arm, 29 of 33 pts (88%) were treated with RUX, with 59% receiving a BL dose of ≤20 mg daily. ESAs were administered to 5 pts in the BAT arm. At wk 24, SVR35 was observed in 7 of 72 pts (10%) treated with MMB and 1 of 33 pts (3%) treated with BAT. TSS50 was achieved in 21 of 72 pts (29%) treated with MMB, but there were no responses in the BAT arm. Additionally, TI-R was achieved in 25 of 72 pts (35%) treated with MMB compared with only 1 of 33 (3%) treated in the BAT arm on RUX. Many responders with MMB achieved 2 or all 3 endpoints (16 of 36 responders [44%]) (Figure); there were no dual or triple responses in the BAT arm. Of the 5 pts in the BAT arm who received ESAs, only 1 pt each (different pts per response) achieved SVR35, TSS50, or TI. Safety outcomes were consistent with those previously reported for the intent-to-treat (ITT) population. Conclusions: In RUX/BAT-treated pts with MF who required RBC transfusions, continued treatment with RUX/BAT in most pts resulted in poor treatment outcomes compared with MMB. Specifically, treatment with MMB demonstrated an ability to deliver higher SVR, TI, and TSS response rates. The lower SVR35 rate in both arms, similar to the overall ITT population, was likely a result of lack of washout from prior JAK inhibitor treatment. While pt numbers were limited, similar findings were observed compared with pts who received ESAs. Overall, these data support MMB as a potential alternative treatment option for pts with MF who require RBC transfusions. Figure. Responses at Week 24 for Non-TI Patients at Baseline

Otolaryngologic Symptom Severity Post SARS-CoV-2 Infection

To assess laryngologic symptomatology following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and determine whether symptom severity correlates with disease severity. Single-institution survey study in participants with documented SARS-CoV-2 infection between March 2020 and February 2021. Data acquired included demographic, infection severity characteristics, comorbidities, and current upper aerodigestive symptoms via validated patient reported outcome measures. Primary outcomes of interest were scores of symptom severity questionnaires. Coronavirus disease of 2019 (COVID-19) severity was defined by hospitalization status. Descriptive subgroup analyses were performed to investigate differences in demographics, comorbidities, and symptom severity in hospitalized participants stratified by ICU status. Multivariate logistical regression was used to evaluate significant differences in symptom severity scores by hospitalization status. Surveys were distributed to 5300 individuals with upper respiratory infections. Ultimately, 470 participants with COVID-19 were included where 352 were hospitalized and 118 were not hospitalized. Those not hospitalized were younger (45.87 vs. 56.28 years), more likely female (74.17 vs. 58.92%), and less likely white (44.17 vs. 52.41%).Severity of dysphonia, dyspnea, cough, and dysphagia was significantly worse in hospitalized patients overall and remained worse at all time points. Cough severity paradoxically worsened in hospitalized respondents over time. Dyspnea scores remained abnormally elevated in respondents even 12 months after resolution of infection. Results indicate that laryngologic symptoms are expected to be worse in patients hospitalized with COVID-19. Dyspnea and cough symptoms can be expected to persist or even worsen by 1-year post infection in those who were hospitalized.Dysphagia and dysphonia symptoms were mild. Nonhospitalized participants tended to have minimal residual symptoms by 1 year after infection.

Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study.

Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n=13; bosutinib, n=3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.

69. Relugolix combination therapy in European women with symptomatic uterine fibroids in the liberty long-term extension (lte) study

Introduction and aims: In LIBERTY 1&2, once-daily relugolix combination therapy (Relugolix-CT; 40mg relugolix, estradiol 1mg, norethindrone acetate 0.5mg) improved uterine fibroid (UF)-associated heavy menstrual bleeding (HMB) versus placebo, was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. In LIBERTY LTE, MBL reduction was sustained with no new safety signals and BMD maintenance through 52 weeks. A descriptive subgroup analysis of European vs overall population is reported.

Efficacy of Tisagenlecleucel in Adult Patients (Pts) with High-Risk Relapsed/Refractory Follicular Lymphoma (r/r FL): Subgroup Analysis of the Phase II Elara Study

Efficacy of Tisagenlecleucel in Adult Patients (Pts) with High-Risk Relapsed/Refractory Follicular Lymphoma (r/r FL): Subgroup Analysis of the Phase II Elara Study

The German Version of the Satisfaction with Prosthesis Questionnaire: Translation, Adaptation, Reliability, and Validity in Adults with Major Lower-Limb Amputation

ABSTRACT Introduction The aim of this study was to translate and cross-culturally adapt the Satisfaction with Prosthesis Questionnaire (SAT-PRO) into German and to evaluate its validity and reliability. Materials and Methods The 2-fold forward and backward translations were carried out according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Subsequently, the German version of the SAT-PRO was administered to 68 patients with major lower-limb amputation (LLA) fitted with a prosthesis. The internal consistency, floor and ceiling effects, item-to-total correlation, and test-retest reliability were determined. In addition, the standard error of the mean (SEM) and minimal detectable change (MDC) were calculated. Convergent construct validity was assessed by correlation to a Numerical Rating Scale for Satisfaction Level (NRS-SAT), the 36-Item Short-Form Health Survey (SF-36), the Rivermead Mobility Index (RMI), and the Medicare Functional Classification Level (K-Levels). Descriptive subgroup analysis included levels of amputation (transtibial vs. transfemoral persons with amputations) and user type (long-term vs. subacute users). Results The mean SAT-PRO total score was 32.27 ± 6.89 (77.6%). Internal consistency was high (Cronbach α = 0.88), and reproducibility demonstrated excellent findings with an intraclass correlation coefficient (ICC2,1) of 0.90 (95% confidence interval [CI], 0.84–0.94). Floor or ceiling effects were not detected. Convergent construct validity indicated a strong correlation to the NRS-SAT (r = 0.89), K-Levels (r = 0.66), and RMI (r = 0.52, all with P < 0.001). Moderate to high correlations were shown to all eight domains of the SF-36 (in a range of r = 0.55 [physical function] to r = 0.39 [mental health], all with P < 0.001). MDC was 2.32 (MDC% = 3.4%). Conclusions The translation according to ISPOR guidelines and cross-cultural adaptation of the SAT-PRO into German were successfully conducted in the pilot study. The psychometric testing showed high reliability and validity of the German version of the SAT-PRO. Hence, it can be used as an outcome measure to assess a patient's satisfaction with prosthesis in a German-speaking population. Clinical Relevance Statement The SAT-PRO can make an important contribution to the treatment of patients with major LLA. The use of objective measurement parameters and guideline-based translation should be applied to increase the validity and comparability of the data.

Efficacy of ruxolitinib cream in vitiligo by patient characteristics and affected body areas: Descriptive subgroup analyses from a phase 2, randomized, double-blind trial

To the Editor: Vitiligo is a chronic autoimmune disease resulting in patches of depigmented skin1 and reduced quality of life.2 In a randomized, dose-ranging phase 2 study (NCT03099304) in 157 adult patients, the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib cream produced substantial repigmentation of facial and total body vitiligo lesions after 24 weeks, with continued improvement through week 52, and was well tolerated.3 Here, we present treatment response subanalyses from the phase 2 trial.

Clinical outcomes following polymer-free sirolimus-eluting stent implantations in unselected patients: A descriptive subgroup analysis in patients with renal impairment.

Patients with chronic kidney disease (CKD are frequently excluded from coronary artery disease trials. The aim of this assessment was to study the clinical outcomes of polymer-free sirolimus-eluting stent implantations in patients with impaired renal function.Large-scale, international, single-armed, multicenter, ‘all comers’ observational studies (ClinicalTrials.gov Identifier: NCT02629575 and NCT02905214) were used for this post-hoc subgroup analysis to compare the clinical outcomes in patients with normal renal function (NRF) to those with renal insufficiency (CKD, dialysis dependence). The accumulated target lesion revascularization rate was the primary endpoint at 9 to 12 months whereas the accumulated major adverse cardiac event, stent thrombosis (ST) and procedural success rates were part of the secondary endpoints.There were 6791 patients with NRF, whereas 369 patients had CKD and 83 patients were dialysis dependent. The target lesion revascularization rate at 9 to 12 months was significantly higher in dialysis patients (2.1% vs 3.3% vs 6.7%, P = .011). The accumulated major adverse cardiac events rates in the dialysis and in the CKD group were significantly higher as compared to patients with NRF (13.3% vs 4.0%, P < .001; 6.5% vs 4.0%, P = .024). Finally, ST rates (NRF: 0.7%, CKD: 0.6%, dialysis: 1.3%) were not statistically different between subgroups (P = .768). All-cause cumulative mortality rates were 3.3% (CKD) and 4.0% (dialysis) respectively.Percutaneous coronary interventions with polymer-free, ultra-thin strut sirolimus-eluting stents have comparable revascularization rates in CKD and dialysis dependent patients as compared to percutaneous coronary interventions with other 2nd generation drug-eluting stents. ST and all-cause mortality rates were low as compared to available literature references.

Profiling trial burden and patients\u2019 attitudes to improve clinical research in epidermolysis bullosa

BackgroundEpidermolysis bullosa (EB) comprises inherited mechanobullous dermatoses with considerable morbidity and mortality. While current treatments are symptomatic, a growing number of innovative therapeutic compounds are evaluated in clinical trials. Clinical research in rare diseases like EB, however, faces many challenges, including sample size requirements and recruitment failures. The objective of this study was to determine attitudes of EB patients towards clinical research and trial participation as well as the assessment of contextual motivating and discouraging factors in an effort to support patient-centered RD trial designing.MethodsA 53-items questionnaire was handed over to EB patients (of all types and ages) in contact with the EB House Austria, a designated national center of expertise for EB care. Main categories included level of interest in and personal knowledge about clinical studies, pros/cons for participation and extent of individual expenses considered acceptable for participation in a clinical study. Descriptive subgroup analysis was calculated with SPSS 20.0 and Microsoft Excel.ResultsThirty-six individuals (mean age 25.7 years), diagnosed for recessive dystrophic EB (36.1%), EB simplex (33.4%), junctional EB (8.3%), dominant dystrophic EB (2.8%) and acral peeling syndrome (2.8%) participated. Motivation for participation in and the desire to increase personal knowledge about clinical trials were (outmost) high in 57.2 and 66.7%, respectively. Altruism was the major motivating factor, followed by hope that alleviation of the own symptoms can be achieved. The greatest hurdle was travel distance, followed by concerns about possible adverse reactions. Patients diagnosed for severe subgroups (RDEB, JEB) were more impaired by the extent of scheduled invasive investigations and possible adverse reactions of the study medication. Patients with generally milder EB forms and older patients were accepting more frequent outpatient study visits, blood takes, skin biopsies and inpatient admissions in association with trial participation.ConclusionsThis study provides additional indications to better determine and address attitudes towards clinical research among EB patients as well as guidance to improve clinical trial protocols for patient centricity.

CheckMate 067: Long-term outcomes in patients with mucosal melanoma.

10019 Background: Mucosal melanoma is a rare but aggressive malignancy with a poor prognosis. Here we report 5-y outcomes in a subgroup of patients with mucosal melanoma treated in CheckMate 067 with nivolumab plus ipilimumab (NIVO+IPI), NIVO alone, or IPI alone. Methods: Patients with previously untreated stage III or IV melanoma were randomized 1:1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo until progression or unacceptable toxicity. Mucosal histology was not a stratification factor, and patients with mucosal melanoma were identified by local investigators in the study. Descriptive subgroup analyses were performed to evaluate efficacy (objective response rate [ORR], progression-free survival [PFS], overall survival [OS]), and safety. Results: A total of 79 patients with mucosal melanoma were treated. With a minimum follow-up of 60 mo, NIVO+IPI treatment was associated with the highest 5-y ORR (43% [vs 30% with NIVO and 7% with IPI]), PFS (29% [vs 14% and 0%, respectively]), and OS (36% [vs 17% and 7%, respectively]; Table), consistent with trends in the intent-to-treat (ITT) population; however, efficacy outcomes were generally less favorable overall relative to the ITT population. Complete response rates were higher with NIVO+IPI (14%) relative to monotherapy (NIVO, 4%; IPI, 0%) in patients with mucosal melanoma. Safety outcomes, including the grade 3/4 treatment-related adverse event rates of 54%, 26%, and 25%, respectively, were similar to the ITT population. Conclusions: This 5-y analysis showed that patients with mucosal melanoma in CheckMate 067 had similar safety outcomes but poorer long-term efficacy vs the ITT population. Patients with mucosal melanoma treated with NIVO+IPI appeared to have more favorable survival outcomes than those treated with NIVO or IPI alone. Novel therapies are needed to further improve long-term benefit in patients with mucosal melanoma. Clinical trial information: NCT01844505. [Table: see text]

Which procedures are performed by general internists practicing primary care in Germany? - a cross-sectional study

BackgroundDue to differences of residency training programs’ emphases – inpatient vs office-based – internal medicine and family medicine residents consistently reported differences in preparedness to care for common adult conditions. Study’s aim was to add knowledge about procedures that a) are performed by general internists working in primary care and b) should be learned during residency in general internists’ appraisal.MethodsA cross-sectional postal survey was carried out by using a questionnaire that comprised 90 procedures relevant in primary care. Each procedure implied the two questions “Do you perform this procedure in your own practice?” and “How important do you think it is to learn this procedure during residency?” The final questionnaire was sent to 1002 general internists working in primary care in Germany in May 2015. Data analysis was performed using SPSS Version 24.0 (SPSS inc., IBM). Next to descriptive statistics subgroup analyses were performed using cross tabulation and Chi-square tests for evaluation of differences in the performance of most frequently performed procedures in urban or rural areas as well as by male or female physicians.ResultsTwenty-eight percent of sent questionnaires (276/1002) could be included in analysis. Mean age of participants was 52 years with 13 years of practice experience; 40% were female.Twenty-nine (32%) of 90 given procedures were performed by at least half of the participants, foremost technical diagnostics, punctures, procedures of the integument and resuscitation. After Bonferroni correction, five of those procedures were performed by more male than female physicians and two procedures by more physicians working in a rural practice than physicians practicing in an urban location. Moreover, 46 (51%) procedures were assessed as important to learn during residency by at least 50% of participants.ConclusionsGeneral internists working in German primary care perform a narrow scope of procedures offered by primary care physicians. In order to provide best ambulatory care for patients, residency training programs must ensure training in procedures that are necessary for providing high quality care. Therefore, a consensus aligned with patients’ and health-systems’ needs on procedures required for working as a general internist in primary care is necessary.

Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial

BackgroundElderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.Methods/designThis prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or “frail” (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1).Patients are stratified according to modified Cancer and Age Research Group (CARG) score: “fit” patients are allocated to combination CT (carboplatin/nab-paclitaxel) and “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks.The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.DiscussionThe DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.Trial registrationClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017.Eudra-CT, 2016–003963-20; initially registered on 3 January 2017.

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial

BackgroundHypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.Methods/designIn the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities.The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria.DiscussionThe FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses.Trial registrationClinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017).Eudra-CT Number: 2015–005741-31 (Date of initial registration: 18 December 2015).

Metabolic and Endocrine Disorders in Pseudarthrosis.

Retrospective Cohort. Establish 1-year patient-reported outcomes after spine surgery for symptomatic pseudarthrosis compared with other indications. In the subgroup of pseudarthrosis patients, describe preexisting metabolic and endocrine-related disorders, and identify any new diagnoses or treatments initiated by an endocrine specialist. Despite surgical advances in recent decades, pseudarthrosis remains among the most common complications and indications for revision after fusion spine surgery. A better understanding of the outcomes after revision surgery for pseudarthrosis and risk factors for pseudarthrosis are needed. Using data from our institutional spine registry, we retrospectively reviewed patients undergoing elective spine surgery between October 2010 and November 2016. Patients were stratified by surgical indication (pseudarthrosis vs. not pseudarthrosis), and 1-year outcomes for satisfaction, disability, quality of life, and pain were compared. In a descriptive subgroup analysis of pseudarthrosis patients, we identified preexisting endocrine-related disorders, frequency of endocrinology referral, and any new diagnoses and treatments initiated through the referral. Of 2721 patients included, 169 patients underwent surgery for pseudarthrosis. No significant difference was found in 1-year satisfaction between pseudarthrosis and nonpseudarthrosis groups (77.5% vs. 83.6%, respectively). A preexisting endocrine-related disorder was identified in 82% of pseudarthrosis patients. Endocrinology referral resulted in a new diagnosis or treatment modification in 58 of 59 patients referred. The most common diagnoses identified included osteoporosis, vitamin D deficiency, diabetes, hyperlipidemia, sex-hormone deficiency, and hypothyroidism. The most common treatments initiated through endocrinology were anabolic agents (teriparatide and abaloparatide), calcium, and vitamin D supplementation. Patients undergoing revision spine surgery for pseudarthrosis had similar 1-year satisfaction rates to other surgical indications. In conjunction with a bone metabolic specialist, our descriptive analysis of endocrine-related disorders among patients with a pseudarthrosis can guide protocols for workup, indications for endocrine referral, and guide prospective studies in this field.

CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

4513 Background: Patients (pts) with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognosis and suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus ipilimumab (N+I) demonstrated superior objective response rate (ORR) and overall survival (OS) vs sunitinib (S) in previously untreated pts with International Metastatic RCC Database Consortium (IMDC) intermediate/poor (I/P)-risk, clear-cell, advanced RCC in the phase 3 CheckMate 214 trial. Methods: We performed a post-hoc exploratory analysis of N+I vs S in CheckMate 214 sRCC pts. The presence of sarcomatoid features was assessed by keyword search for “sarcomatoid” in pts with available local pathology reports accompanying pretreatment tumor samples. Results: 842 (77%) of 1096 intention-to-treat pts had local pathology reports available, including 112 randomized pts with I/P-risk sRCC (N+I, n = 60; S, n = 52). Baseline characteristics of sRCC pts were balanced between arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S arms had tumor PD-L1 expression ≥1% at baseline, which was higher than in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed at a minimum follow-up of 30 months, confirmed ORR and complete response rate per investigator (RECIST v1.1), OS, and progression-free survival (PFS) per investigator were improved with N+I vs S in I/P-risk pts with sRCC (Table). No new safety signals were seen in sRCC pts. Conclusions: In this post-hoc descriptive subgroup analysis of CheckMate 214, N+I demonstrated promising efficacy and prolonged survival vs S, with consistent safety, in previously untreated, I/P-risk, advanced clear-cell RCC with sarcomatoid features. Prospective studies of N+I that include pts with sRCC are ongoing. Clinical trial information: NCT02231749. [Table: see text]

A descriptive subgroup analysis of individual tumor cells from 4 patients with ovarian cancer

A descriptive subgroup analysis of individual tumor cells from 4 patients with ovarian cancer

Single cell sequencing: A descriptive subgroup analysis of individual tumor cells from 4 patients with ovarian cancer

Single cell sequencing: A descriptive subgroup analysis of individual tumor cells from 4 patients with ovarian cancer

Age and preoperative pain are major confounders for sex differences in postoperative pain outcome: A prospective database analysis.

ObjectivesCurrent literature is in disagreement regarding female sex as a risk factor for pain after surgery. We hypothesized, that sex differences exist but that they are influenced by certain factors. Here, we investigated the influence of sex for different clinically relevant postoperative pain (POP) outcome parameters and evaluated the role of assumed confounders for sex differences.MethodsFrom 1372 screened patients undergoing orthopedic surgery at the university hospital of Muenster between March 2010 and June 2011, 890 patients were included. The validated International Pain Outcomes questionnaire was used to assess the role of sex for several aspects of POP including pain severity, physical and emotional functional interference as well as the patient’s perceptions of the care they received on the first day after surgery. Assessed confounders were age, preoperative chronic pain, anesthetic technique employed and surgical procedure. All statistical analyses were performed with SPSS Statistics Software 22.ResultsLinear regression analysis demonstrated that sex was a statistically significant risk factor for “worst pain since surgery”. Additionally, significant sex differences in “time spent in severe pain”, “feeling anxious due to pain”, “feeling helpless due to pain” and “opioid consumption since surgery” could be identified. An univariate general linear model showed that “age” and “preoperative pain” were significant confounders for sex differences. Further descriptive subgroup analysis revealed consistent sex differences for several POP outcome variables especially in patients older than 50 years or patients with preoperative chronic pain. However, sex differences disappeared in younger patients and in patients without preoperative pain.DiscussionOur data confirmed that sex differences exist in pain intensity and frequency, pain interference with feelings and opioid consumption during the first 24 hours postoperatively. However, sex differences were significantly influenced by the factors “age” and “preoperative pain”. These findings may in part explain why clinical studies get different results related to sex differences and renders specific awareness in older women and female patients with preoperative chronic pain.

A descriptive subgroup analysis of within hospital glaucoma referral in a tertiary center in Portugal

PurposeGlaucoma is a progressive and irreversible optic neuropathy carrying tremendous burden in healthcare systems. The aim of our study was to characterize the population referred to a glaucoma subspecialty department (GSD) in a university hospital.MethodsWe analyzed retrospectively the within‐hospital referral to the GSD. Electronic medical records and referral letters between Jan and Dec 2014 were screened. Data was screened for ancillary exams, type of tonometry, number of IOP‐lowering medications and extent of the disease (HODAPP classification). Statistics were performed with STATA v13.0.ResultsA total of 151 patients (78 males) were referred. Mean age was 68.2 (range 18–91). Thirty‐six patients (23.8%) were referred with visual field, pachimetry and OCT. Of those with a visual field, 38 (55.1%) had a mean defect &gt;6 db (of which 17 had &gt;12 dB), with 34 patients having at least two exams. In contrast, 16 (10.6%) were referred with no ancillary exam performed and 67 (50%) had all IOP measurements performed with pneumotonometry. Sixteen patients (10.6%) had a description of a gonioscopy. All patients were under IOP‐lowering treatment, of which 83 (55%) were under 2 or more IOP‐lowering medications. The number of patients referred with more than 80 years old was 29 (19.2%), 5 (18.52)% of which had a complete documentation of the disease. In this subset of patients, 6 (42.8%) had an advanced form of the disease.ConclusionsBetter understanding of our population characteristics will lead to a more accurate referral system. In a significant part of GDS referrals there was insufficient or poor quality clinical data. Our study raises awareness on the importance of an efficient within hospital subspecialist referral, leading to economic and health gain in Ophthalmology departments.