Association of programmed death ligand‐1 (PD‐L1) expression with treatment outcomes in patients with BRAF mutation‐positive melanoma treated with vemurafenib or cobimetinib combined with vemurafenib

The prognostic significance of programmed death ligand‐1 (PD ‐L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD ‐L1 expression with progression‐free survival (PFS ) and overall survival (OS ) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD ‐L1⁺ melanoma, with hazard ratios (HR s; PD ‐L1⁺ vs. PD ‐L1^?) of 0.70 (95% CI , 0.46–1.07) and 0.69 (95% CI , 0.42–1.13) for PFS and OS , respectively. However, in patients treated with cobimetinib plus vemurafenib, a similar trend was not observed with HR s (PD ‐L1⁺ versus PD ‐L1^?) of 1.04 (95% CI , 0.66–1.68) and 0.94 (95% CI , 0.57–1.57) for PFS and OS , respectively. The combination cobimetinib plus vemurafenib appears to overcome the poor prognosis associated with low PD ‐L1 expression.     

Quantitative assessment of adverse events in clinical trials: Comparison of methods at an interim and the final analysis

In clinical study reports (CSRs), adverse events (AEs) are commonly summarized using the incidence proportion (IP). IPs can be calculated for all types of AEs and are often interpreted as the probability that a treated patient experiences specific AEs. Exposure time can be taken into account with time-to-event methods. Using one minus Kaplan–Meier (1-KM) is known to overestimate the AE probability in the presence of competing events (CEs). The use of a nonparametric estimator of the cumulative incidence function (CIF) has therefore been advocated as more appropriate. In this paper, we compare different methods to estimate the probability of one selected AE. In particular, we investigate whether the proposed methods provide a reasonable estimate of the AE probability at an interim analysis (IA). The characteristics of the methods in the presence of a CE are illustrated using data from a breast cancer study and we quantify the potential bias in a simulation study. At the final analysis performed for the CSR, 1-KM systematically overestimates and in most cases IP slightly underestimates the given AE probability. CIF has the lowest bias in most simulation scenarios. All methods might lead to biased estimates at the IA except for AEs with early onset. The magnitude of the bias varies with the time-to-AE and/or CE occurrence, the selection of event-specific hazards and the amount of censoring. In general, reporting AE probabilities for prespecified fixed time points is recommended.     

Efficacy and adverse events of five targeted agents in the treatment of advanced or metastatic non-small-cell lung cancer: A network meta-analysis of nine eligible randomized controlled trials involving 5,059 patients

Recently, targeted agents were reported to improve overall survival, progression-free survival (PFS), response rate, and quality of life compared with cytotoxic chemotherapies, which provides hope for the treatment of non-small-cell lung cancer (NSCLC). The network meta-analysis is applied to compare the efficacies and adverse events of five targeted agents (erlotinib, gefitinib, vandetanib, dacomitinib, and icotinib) for advanced or metastatic NSCLC. Nine eligible randomized controlled trials from PubMed and Cochrane Library database were included. Weighted mean difference, odds ratio, and surface under the cumulative ranking curve (SUCRA) values were evaluated for the efficacy and adverse events of the five targeted agents in the treatment of NSCLC. With regard to efficacy, the overall response rate (ORR) of advanced or metastatic NSCLC patients treated with gefitinib was relatively higher than those treated with placebo. Compared with patients treated with placebo, the disease control rate (DCR) of patients treated with erlotinib and with gefitinib was relatively higher. Furthermore, in terms of PFS and DCR, the SUCRA value of icotinib was the highest among the five targeted drugs. With regard to ORR, the SUCRA value of gefitinib was the highest among the five targeted drugs. In terms of fatigue, rash, and cough, erlotinib had the lowest SUCRA value, whereas vandetanib exhibited the lowest SUCRA value in terms of diarrhea. Our study suggests that the efficacies of gefitinib and icotinib for advanced or metastatic NSCLC were comparatively better, whereas the toxicities of erlotinib and vandetanib were relatively greater.     

Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0–1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3–50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.     

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C

Summary On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m², i.v. on day 1 and recombinant interleukin-2 700 U/m² (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.     

Impact of neoadjuvant chemoradiation on pathologic response and survival of patients with locally advanced rectal cancer

Background

The impact of neoadjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) has been controversial. Some studies have pointed to an improvement in OS and disease-free survival (DFS) in patients with pathologic complete response (pCR).

Aim

To evaluate the therapeutic response and impact on survival of preoperative RT, alone or combined with CT, in patients with locally advanced rectal cancer (LARC).

Materials and methods

A set of 132 patients with LARC were treated preoperatively. GROUP 1: RT alone, 19 patients. GROUP 2: RT and concomitant oral CT (Capecitabine or UFT + leucovorin), 68 patients. GROUP 3: RT and concomitant CT with 5-FU in continuous infusion, 45 patients. 58.2% of patients were submitted to adjuvant CT.

Results

GROUP 1: no pCR, tumoral downstaging was 26.7%. GROUP 2: pCR in 16.9%; tumoral downstaging was 47.7%. GROUP 3: pCR in 11.9%; tumor downstaging was 52.4%. The loco-regional control (LRC) was 95%. The 5-year OS (p = 0.038) and DFS (p = 0.05) were significantly superior in patients treated with CT + RT. Patients with pCR had a significant increase on DFS (p = 0.019). Patients cT3–4 that had a tumoral downstaging to ypT0–2, showed an increase on DFS, OS and LRC.

Conclusions

CT combined with RT has increased tumoral response and survival rate. Nodal downstaging and pCR were higher in the GROUP 2. The 5-year OS and DFS were significantly superior in CT + RT arms. Patients with pathologic response showed a better DFS. Adjuvant CT had no impact on LRC, DFS nor on OS.     

Quality‐of‐life outcomes in patients with advanced melanoma: A review of the literature

For patients with metastatic melanoma, the emergence of immune checkpoint inhibitors and targeted BRAF and MEK inhibitors has markedly enhanced clinical outcomes compared with chemotherapy. However, these novel agents are also associated with unique sets of adverse events, and increased overall survival can lead to prolonged exposure to some novel agents. Therefore, clinical evaluation of these therapies has now included the analysis of health‐related quality of life (HRQoL) in addition to more traditional efficacy and safety outcomes as a measure of patient perception of benefit. The current review focuses on HRQoL outcomes in clinical trials of immune checkpoint inhibitors and targeted therapies in patients with advanced and metastatic melanoma to inform healthcare providers about patient perception of HRQoL as a new perspective in treatment decision making.     

Association of ERCC1-C118T and -C8092A polymorphisms with lung cancer risk and survival of advanced-stage non-small cell lung cancer patients receiving platinum-based chemotherapy: A pooled analysis based on 39 reports

The published data on the predictive role of ERCC1 polymorphisms in lung cancer risk and survival of patients with advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy remains inconsistent. The aim of this meta-analysis was to determine the role of ERCC1 gene polymorphisms (C118T and C8092A) in this clinical situation. Eligible studies were included and assessed for quality using multiple search strategies. Thirty-nine published papers involving 9615 cases (4606 with Stage III/IV disease) and 5542 controls were included in the analysis. Pooled odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate risk. ERCC1-C118T was associated with lung cancer risk. The OR was 0.90 (95% CI: 0.81–0.99, p = 0.043) in an additive genetic model (C allele vs. T allele) and 0.77 (95% CI: 0.63–0.95, p = 0.013) in a recessive genetic model (CC/CT vs. TT). The corresponding risk was 0.74 (95% CI: 0.58–0.94, p = 0.013) based on a homozygous comparison (CC vs. TT). No significant correlation was found for ERCC1 C8092A and there was no obvious relationship between ERCC1 C118T/C8092A polymorphisms and objective response to platinum-based chemotherapy. Overall survival (OS) of patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy was significantly related to ERCC1 C118T (HR: 1.29, 95% CI: 1.07–1.56, p = 0.007, CT/TT vs. CC). There was no relationship between ERCC1 C8092A and survival (HR: 1.32, 95% CI: 0.84–2.10, p = 0.23, CA/AA vs. CC). These findings suggest that ERCC1 C118T polymorphisms may serve as a biomarker for lung cancer risk and have prognostic value in patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based treatment. Further studies with larger numbers of subjects from a worldwide arena are needed to validate the associations.     

Paracoccidioidomycosis: A comparative study of the evolutionary serologic,clinical and radiologic results for patients treated with ketoconazole or amphotericin B plus sulfonamides

A comparative study of two groups of patients with paracoccidioidomycosis was carried out with the objective of comparing the evolutionary serologic, clinical and radiologic results after 6, 12, 15 and 18 months of treatment with ketoconazole (22 patients) or amphotericin B plus sulfonamides (32 patients). The serologic data analyzed as a whole showed a tendency to sharper drops in antibody titers in the patients treated with ketoconazole. Clinically patients treated with ketoconazole fared better but the differences were not statistically significant. No statistical difference was detected between groups in terms of the results of radiologic evolution.     

Incidence of skeletal-related events in patients with breast or prostate cancer-induced bone metastasis or multiple myeloma: A 12-year longitudinal nationwide healthcare database study

BackgroundThis study examined the incidence of skeletal-related events (SRE) among patients with breast cancer (BC)- or prostate cancer (PC)-induced bone metastasis or multiple myeloma (MM) based on a population-based, 12-year healthcare database.MethodsPatients aged ≥18 years with bone metastasis from BC or PC or with MM between 2004 and 2015 were included. SRE was defined as pathologic fracture, spinal cord compression, radiation, or surgery to bone. Patients were followed-up from the initial diagnosis of bone metastasis (for those with BC or PC) or MM until SRE occurrence. To estimate multiple SREs, we applied a 21-day time window to ensure that subsequent SREs occurred independently from the previous event. We calculated the incidence and 95% confidence intervals (CIs), stratified according to the previous SRE history.ResultsOur cohort included 53,231 patients, including 23,811 with BC, 19,170 with PC, and 10,250 with MM. The incidence of multiple SREs in the 21-day time window was 1.03 (95% CI = 1.01–1.05) in patients with previous SRE history and 0.19 (95% CI = 0.19–0.20) in those without. The cumulative SRE incidences were 47%, 31.4%, and 38.0% in BC, PC, and MM patients.ConclusionThe incidences of multiple SREs in BC- or PC-induced bone metastasis or MM in this 12-year South Korean cohort were slightly higher than those in European countries. Our study provided real-world evidence that patients with BC- or PC-induced bone metastasis or MM are at high risk of SRE.     

A pilot study on the association between SLCO1B1 RS4363657 polymorphism and muscle adverse events in adults with newly diagnosed dyslipidaemia who were prescribed a statin: the Malaysian primary health care cohort

Abstract

Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited.

Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants.

Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient’s complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism.

Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49?±?12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p?=?0.0327); no significant association noted between CK and SAMAE (p?=?0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p?<?0.0001).

Conclusions: In this first pilot study of a multiethnic Malaysian population, the incidence of SAMAE was 18.6%. SAMAE were significantly higher in subjects on lovastatin compared to simvastatin. SLCO1B1 rs4363657 polymorphism was a significant risk factor for SAMAE.     

Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been targeted including malignant melanoma which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which are frequently claimed to have a possible influence on clinical response. These parameters include performance status, type of antigen, DC maturation status, route of vaccine administration, use of adjuvant, and vaccine induced immune response. In total, 38 articles found through Medline search, have been included for analysis covering a total of 626 patients with malignant melanoma treated with DC based therapy. Clinical response (CR, PR and SD) were found to be significantly correlated with the use of peptide antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and induction of antigen specific T cells (p = 0.0004). No significant correlations between objective response (CR and PR) and the tested parameters were found. However, a few non-significant trends were demonstrated; these included an association between objective response and use of immature DCs (p = 0.08), use of adjuvant (p = 0.09), and use of autologous antigen preparation (p = 0.12). The categorisation of SD in the response group is debatable. Nevertheless, when the SD group were analysed separately we found that SD was significantly associated with use of peptide antigens (p = 0.0004), use of adjuvant (p = 0.01), and induction of antigen specific T cells (p = 0.0003). No specific route of vaccine administration showed superiority. Important lessons can be learned from previous studies, interpretation of these findings should, however, be done with reservation for the many minor deviations in the different treatment schedules among the published studies, which were not considered in order to be able to process and group the data.     

Effect of the plastic pollutant bisphenol A on the biology of aquatic organisms: A meta‐analysis

Plastic pollution is a global environmental concern. In particular, the endocrine‐disrupting chemical bisphenol A (BPA) is nearly ubiquitous in aquatic environments globally, and it continues to be produced and released into the environment in large quantities. BPA disrupts hormone signalling and can thereby have far‐reaching physiological and ecological consequences. However, it is not clear whether BPA has consistent effects across biological traits and phylogenetic groups. Hence, the aim of this study was to establish the current state of knowledge of the effect of BPA in aquatic organisms. We show that overall BPA exposure affected aquatic organisms negatively. It increased abnormalities, altered behaviour and had negative effects on the cardiovascular system, development, growth and survival. Early life stages were the most sensitive to BPA exposure in invertebrates and vertebrates, and invertebrates and amphibians seem to be particularly affected. These data provide a context for management efforts in the face of increasing plastic pollution. However, data availability is highly biased with respect to taxonomic groups and traits studies, and in the geographical distribution of sample collection. The latter is the case for both measurements of the biological responses and assessing pollution levels in water ways. Future research effort should be directed towards biological systems, such as studying endocrine disruption directly, and geographical areas (particularly in Africa and Asia) which we identify to be currently undersampled.     

Detrimental effects of melanocortin‐1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors

Melanocortin‐1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF‐mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four ^V600BRAF melanoma cell lines with/without MC1R variants. We found a significant correlation between the presence of MC1R variants and worse outcomes in terms of both overall response rate (ORR; 59% versus 95%, P = 0.011 univariate, P = 0.028 multivariate analysis) and progression‐free survival (PFS) shorter than 6 months (72% versus 33%, P = 0.012 univariate, P = 0.027 multivariate analysis). No difference in overall survival (OS) was reported, probably due to subsequent treatments. Data in vitro showed a significant different phosphorylation of Erk1/2 and p38 MAPK during treatment, associated with a greater increase in vemurafenib IC50 in MC1R variant cell lines.     

Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study

BackgroundThe prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL.MethodsWe included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees.Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation.ResultsA total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01–1.07]), being a craftsman (EHR_{craftsmen/higher.employment}: 4.15 [0.86–20.15]), being a worker or an employee (EHR_{workers.employees/higher.employment}: 3.57 [1.19–10.7]), having a Binet staging of B or C (EHR: 3.43 [1.84–6.42]) and having a lymphocyte count > 15 G/L (EHR: 3.80 [2.17–6.65]) were statistically associated with a higher risk of excess mortality. EDI was not associated with excess mortality (EHR: 0.97 [0.90–1.04]).ConclusionSocioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.     

A comparison of clinical outcomes following atrial fibrillation ablation for heart failure patients with preserved or reduced left ventricular function: A systematic review and meta-analysis

BackgroundThis review aims to determine if patients who undergo atrial fibrillation (AF) ablation with heart failure with preserved ejection fraction (HFpEF) do better, or worse or the same compared to patients with heart failure with reduced ejection fraction (HFrEF).MethodsA search of MEDLINE and EMBASE was performed using the search terms: “atrial fibrillation”, “ablation” and terms related to HFpEF and HFrEF in order to identify studies that evaluated one or more of i) AF recurrence, ii) periprocedural complications and iii) adverse outcomes at follow up for patients with HFpEF and HFrEF who underwent AF ablation. Data was extracted from included studies and statistically pooled to evaluate adverse events and AF recurrence.Results5 studies were included in this review and the sample size of the studies ranged from 91 to 521 patients with heart failure. There was no significant difference in the pooled rate for no AF or symptom recurrence after AF ablation comparing patients with HFpEF vs HFrEF (RR 1.07 95%CI 0.86–1.33, p = 0.15). The most common complications were access site complications/haematoma/bleeding which occurred in similar proportion in each group; HFpEF (3.1%) and HFrEF (3.1%). In terms of repeat ablations, two studies were pooled to yield a rate of 78/455 (17.1%) for HFpEF vs 24/279 (8.6%) for HFrEF (p = 0.001.ConclusionsHeart failure patients with preserved or reduced ejection fraction have similar risk of AF or symptom recurrence after AF ablation but two studies suggest that patients with HFpEF are more likely to have repeat ablations.     

Effect of prior vaccination with a seasonal trivalent influenza vaccine on the antibody response to the influenza pandemic H1N1 2009 vaccine: a randomized controlled trial

Vaccination with the non-adjuvanted split-virion A/California/7/2009 influenza vaccine (pandemic H1N1 2009 vaccine) began in October 2009 in Japan. The present study was designed to assess the effect of prior vaccination with a seasonal trivalent influenza vaccine on the antibody response to the pandemic H1N1 2009 vaccine in healthy adult volunteers. One hundred and seventeen participants aged 22 to 62 were randomly assigned to two study groups. In Group 1 (the priming group), participants were first vaccinated with the seasonal trivalent influenza vaccine followed by two separate one-dose vaccinations of the pandemic H1N1 2009 vaccine, whereas in Group 2 (the non-priming group), the participants were first vaccinated with one dose of the pandemic H1N1 2009 vaccine, followed by simultaneous vaccination of the seasonal trivalent vaccine and the second dose of the pandemic H1N1 2009 vaccine. The participants in Group 2 had a seroprotection rate (SPR) of 79.7% and a seroconversion rate (SCR) of 79.7% in the hemagglutination-inhibition test after the first dose of the pandemic H1N1 2009 vaccine, indicating that the pandemic H1N1 2009 vaccine is sufficiently immunogenic. On the other hand, the participants of Group 1 had a significantly weaker antibody response, with a SPR of 60.8% and a SCR of 58.5%. These results indicate that prior vaccination with the seasonal trivalent influenza vaccine inhibits the antibody response to the pandemic H1N1 2009 vaccine. Therefore, the pandemic H1N1 2009 vaccine should be administered prior to vaccination with the seasonal trivalent influenza vaccine.     

Effect of laterality discrimination on joint position sense and cervical range of motion in patients with chronic neck pain: a randomized single-blind clinical trial

Purpose: The main objective of the present study was to evaluate the effects of laterality discrimination training on neck joint position sense and cervical range of motion (ROM) in patients with chronic non-specific neck pain (NSCNP).

Materials and methods: Forty-eight patients with NSCNP were randomly assigned to the neck group (NG) that observed neck images or the foot group (FG) that observed foot images. Response time, response accuracy, cervical ROM, and joint position error (JPE) were the main variables. The secondary outcome measures included psychosocial variables.

Results: Differences between groups in the cervical ROM for flexion (p?=?.043) were obtained, being NG group the one which obtained greater values. NG showed an improvement in right rotation (p?=?.018) and a decrease in flexion was found in the FG (p?=?.039). In JPE, differences between groups were obtained in the left rotation (p?=?.021) and significant changes were found in the NG for flexion, extension, and left rotation movements (p?<?.05). Moderate associations were found between left and right accuracy regarding to post-intervention flexion and right rotation (r?=?0.46, r?=?0.41; p?<?.05) in NG.

Conclusion: Improvements in cervical range of motion and joint position sense are obtained after the performance of the laterality discrimination task of images of the neck but not the feet. Visualization of images of the painful region presents moderate correlations with the accuracy and response time in the movements of flexion and right rotation.     

Switch to checkpoint inhibition after targeted therapy at time of progression or during ongoing response: A retrospective single‐centre experience in patients with BRAF‐mutated melanoma

BRAF + MEK inhibition is preferentially applied as first‐line therapy in BRAF V600‐mutated melanoma patients with unfavourable prognostic features, due to the ability of targeted therapy (TT) to induce rapid symptom control, decrease tumour burden and normalize lactate dehydrogenase (LDH) levels. In addition, short‐term TT transiently increases tumour antigen presentation and tumour influx of T cells. Therefore, it might be favourable to switch TT to checkpoint inhibition (CPI) before progression (PD). We retrospectively analysed melanoma patients treated first line with TT (TT1) and who subsequently switched to CPI during response to TT (sDR group) or at progression upon TT (sPD group). We identified 74 patients (n = 37 sDR group and n = 37 sPD group). ORR to CPI was 27.0% in the sDR group versus 24.3% in the sPD group (p = .790). Median was PFS 2.5 months versus 1.2 months (p = .145), and median OS was 30.6 versus 14.1 months (p = .007). After adjusting for baseline differences and known prognostic factors, hazard ratios (HRs) favouring sDR were 0.89 for PFS upon CPI (p = .956) and 0.48 for OS (p = .055). Thus, patients switching to CPI during ongoing clinical benefit from TT do not have an inferior outcome. Due to baseline imbalances and small patient population, a favourable trend for the sDR group can be hypothesized only.