Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain: OSIREX-Spanish Lung Cancer Group.

BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .

Prognostic factors that modify outcomes of vestibular rehabilitation in elderly patients with falls.

BACKGROUND: Our previous study has shown that vestibular rehabilitation (VR) is an effective technique to reduce falls in elderly patients. It would be interesting to establish patients' clinical characteristics in which vestibular rehabilitation is expected to be more effective. AIMS: Evaluate factors that could modify rehabilitation outcomes in elderly patients with previous falls. METHODS: Fifty-seven patients randomized to one of the intervention group (computerized dynamic posturography-CDP-training, optokinetic stimulus or exercise at home) and with previous falls were analyzed. Patients were assessed with objective outcome measures (sensorial organization test and limits of stability-LOS-of CDP, modified timed up and go test-TUG-and number of falls) and with subjective outcome measures (dizziness handicap inventory and Short falls efficacy scale-international-Short FES-I) during a 12-month follow-up period. RESULTS: In the logistic regression model, a worse score in the maximum excursion (MXM), and a shorter time in the TUG significantly associated with a reduction > 50% of falls. Also, association with a higher score in the Short FES-I was close to a statistical significance. There was no statistical significance association with other covariables. DISCUSSION: In patients with reduced limits of stability, VR seems to be more effective and they should be encouraged to perform it. But on the other hand, patients with longer time in the TUG show worse outcomes and may benefit more with gait training. CONCLUSIONS: VR in elderly people with previous falls is effective regardless of their age and gender.

Optimising costs in reducing rate of falls in older people with the improvement of balance by means of vestibular rehabilitation (ReFOVeRe study): a randomized controlled trial comparing computerised dynamic posturography vs mobile vibrotactile posturography system.

BACKGROUND: Accidental falls, especially for the elderly, are a major health issue. Balance disorders are one of their main causes. Vestibular rehabilitation (VR) has proven to be useful in improving balance of elderly patients with instability. Its major handicap is probably its cost, which has prevented its generalisation. So, we have designed a clinical trial with posturographic VR, to assess the optimum number of sessions necessary for a substantial improvement and to compare computerised dynamic posturography (CDP) (visual feedback) and mobile posturography (vibrotactile feedback). METHODS: Design: randomized controlled trial. It is an experimental study, single-center, open, randomized (balanced blocks of patients) in four branches in parallel, in 220 elderly patients with high risk of falls; follow-up period: twelve months. SETTING: Department of Otorhinolaryngology of a tertiary referral hospital. PARTICIPANTS: people over 65 years, fulfilling two or more of the following requirements: a) at least one fall in the last twelve months. b) take at least 16 s or require some support in perform the "timed up and go" test. c) a percentage of average balance in the sensory organization test (SOT) of the CDP < 68%. d) at least one fall in any of the conditions in SOT-CDP. e) a score in Vertiguard's gSBDT > 60%. INTERVENTION: Four differents protocols of vestibular rehabilitation (randomization of the patients). MAIN OUTCOME MEASURE: The percentage of average balance in the SOT-CDP. Secondary measures: time and supports in the "timed up and go" test, scores of the CDP and Vertiguard, and rate of falls. DISCUSSION: Posturographic VR has been proven to be useful for improving balance and reducing the number of falls among the aged. However, its elevated cost has limited its use. It is possible to implement two strategies that improve the cost-benefit of posturography. The first involves optimising the number of rehabilitation sessions; the second is based on the use of cheaper posturography systems. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03034655. Registered on 25 January 2017.

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

BACKGROUND: Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. METHODS: All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. RESULTS: Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare mutations. CONCLUSION: EGFR TKIs (gefitinib and erlotinib) are used as the preferred first-line treatment while chemotherapy is more frequently administered as a second- and third-line option in routine clinical practice in Spain. In addition, efficacy data obtained in the real-life setting seem to concur with data from EGFR TKI phase III pivotal studies in NSCLC.

Vestibular rehabilitation in elderly patients with postural instability: reducing the number of falls-a randomized clinical trial.

BACKGROUND: Our previous study had shown the effectiveness of vestibular rehabilitation (VR) in improving balance in elderly patients, assessed immediately afterwards. AIMS: The main goal of the present study is to consider whether this improvement in balance assessment turns out in a reduction of the number of falls. METHODS: 139 elderly patients with high risk of falls were included and randomized to one of the following study arms: computerized dynamic posturography (CDP) training, optokinetic stimulus, exercises at home or control group. Patients were assessed with objective outcome measures (sensorial organization test and limits of stability of CDP, number of falls and number of hospital admissions due to falls) and subjective outcome measures (dizziness handicap inventory and short falls efficacy scale-international) during a 12-month follow-up period. RESULTS: Average number of falls significantly declined from 10.96 (before VR) to 3.03 (12-month follow-up) in the intervention group (p < 0.001); meanwhile, in the control group, the average number of falls changed from 3.36 to 2.61 during a 12-month follow-up period (p = 0.166). DISCUSSION: The present study provides evidence that VR can decisively improve balance in elderly patients with instability, which can lead in turn to a significant reduction of falls. CONCLUSION: We recommend performing VR in any older person with high risk of falls.

Short-term effectiveness of vestibular rehabilitation in elderly patients with postural instability: a randomized clinical trial.

Balance becomes more precarious with age, and even without pathological disorders, the physiological decline in balance that occurs with age is a factor that also favors falls. So the aim of the present study is to assess the short-term effectiveness of three different methods of vestibular rehabilitation, compared to a control group, in improving balance in elderly patients with postural instability. 139 elderly patients with high risk of falls were included and randomized to one of the following study arms: computer dynamic posturography (CDP) training, optokinetic stimulus, exercises at home, or control group. Patients were assessed with objective and subjective outcome measures. The individuals that trained using CDP improved significantly more than the control group on the average balance score (p < 0.001) and reducing the number of falls in the sensorial organization test (p < 0.001). In addition, the analysis showed a statistically significant effect in the limits of stability only with the CDP training in comparison with the control group (p < 0.001). In our present study, supervised and customized exercises with CDP were more effective than the control group in the posturographic short-term assessment. An increased age did not affect the potential for improvement after training. So we conclude that elderly patients with high risk of falling should begin vestibular rehabilitation as soon as possible in order to avoid the potential harm of falls, mainly injuries and psychological consequences due to fear of falling again.

Impact of obesity in elderly patients with postural instability.

OBJECTIVE: The aim of the study is to assess whether obesity affects balance in elderly patients with postural instability. STUDY DESIGN: It is a case-control study, with cases defined by BMI ≥30 kg/m(2), and developed in a third level university hospital. METHODS: We included 135 patients aged 65 years old or more who presented postural instability. Balance assessment was through the sensory organisation test (SOT), limits of stability (LOS) and rhythmic weight shift (RWS) of computerised dynamic posturography (CDP) and the modified timed up-and-go (TUG) test. The patients also completed the Dizziness Handicap Inventory and short Falls Efficacy Scale-International questionnaire. RESULTS: Patients with obesity took longer to perform the modified TUG and required more steps. Also these patients had poorer scores in the subjective tests. In the CDP there were no significant differences in the SOT nor the LOS, and only there was a statistical significant difference in the anterior-posterior directional control of the RWS. Obese patients have a higher risk of fallings compared to non-obese patients. CONCLUSION: In essence, our results indicate that obesity interferes in the balance of elderly patients with postural instability, putting them at a greater risk of fallings, performing worse dynamic tasks and feeling more disabled. Although continued education on training balance may be useful in older population, since the obese group shows more rate of fallers, rehabilitation programmes focus on dynamic tasks in these patients could be useful to reduce their fall risk and improve their quality of life.

Disability perception in Menière's disease: when, how much and why?

The purpose of the study was to evaluate self-perceived handicap in patients with definite Menière's disease (MD). A cross-sectional study was conducted. To examine the self-perception of disability, participants completed a DHI (Dizziness Handicap Inventory). Parameters compared with DHI scores: sex, age, unilateral/bilateral affectation, time elapsed since the onset of symptoms, pure-tone average (PTA), stages of MD, audiometric change (last 6 months), PTA in low frequencies (PTAl) and audiometric change in PTAl, subjective perception of fluctuating hearing threshold, tinnitus between attacks, number of vertiginous episodes (last 6 months), time elapsed since last attack, subjective perception of instability intercrises and Tumarkin attacks. 90 patients were included; they completed a total of 104 questionnaires. DHI scores ranged from 2 to 100 (average: 47.08, SD 24.45). In 29 cases (27.9 %) the disability perception was mild, in 43 (41.3 %) moderate, and in 32 (30.8 %) severe. Correlation between disability perception and some vestibular symptoms was found: number of typical attacks (last 6 months), time elapsed since last attack, instability intercrises and Tumarkin attacks. No relationship was found with the rest of variables. Disability perception in patients with MD depends primarily on vestibular symptoms (particularly, instability and frequency of attacks). So, we suggest to design a new staging system of MD taking into account both auditory criteria and also vestibular symptoms.

Factors affecting peri-implant bone loss: a post-five-year retrospective study.

INTRODUCTION: Although peri-implant bone loss is one of the parameters included in the criteria for determining implant success, its prevention is of vital importance. The goal of this article is to assess the factors that affect peri-implant bone loss. MATERIAL AND METHODS: An observational, longitudinal, retrospective study was conducted in 148 partially edentulous patients rehabilitated with implants and with a follow-up period of 5 years or more. A total of 585 implants were included in the study. Radiographic peri-implant bone loss was compared with radiographic periodontal bone loss, and other characteristics such as prosthesis design, hygiene, and implant size were studied as potential peri-implant bone loss modification factors. RESULTS: In the univariate analysis, a statistically significant relationship between peri-implant bone loss and gender (P < 0.05), implant system (P < 0.01), reason for extraction (P < 0.05), splinting (P < 0.0001), and distance between the implant platform and the horizontal component of the prosthesis (P < 0.0001) were observed. In multivariate analysis, the relationship between this peri-implant loss and gender (P < 0.05), implant system (P < 0.05), splinting (P < 0.001), and the aforementioned distance (P < 0.01) remains. CONCLUSIONS: The distance implant platform-horizontal component of the prosthesis has the greatest effect on peri-implant bone loss This distance must be >3.3 mm and <6 mm, above this range, it no longer influences in peri-implant bone loss and favors the appearance of embrasures and the buildup of bacterial plaque.

Reduction of falls in older people by improving balance with vestibular rehabilitation (ReFOVeRe study): design and methods.

MAIN OBJECTIVE: Evaluate the effectiveness of vestibular rehabilitation (VR) to improve the balance in older people, assessed immediately afterwards. SECONDARY OBJECTIVES: (a) To verify the maintenance of improvement of the balance achieved in the medium term (6-12 months). (b) To consider whether this improvement results in a reduction in the number of falls. (c) To compare among themselves the effectiveness of three different methods of VR in improving balance and to explore whether there are differences to achieve a reduction in the number of falls. DESIGN: Experimental study, single-centre, open, randomised (balanced blocks of patients) in four branches in parallel, in 220 elderly patients (over 64 years) with high risk of falls and a follow-up period of 12 months. SETTING: Department of Otolaryngology of the University Hospital of Santiago. PARTICIPANTS: People over 64 years, fulfilling one of the following requirements: (a) At least one fall in the last year. (b) Take at least 16 s or require some support in perform the test "timed up and go". (c) A percentage of average balance in the sensory organisation test (SOT) in the dynamic posturography (CDP) <68%. (d) At least one fall in any of the conditions in the SOT of CDP. INTERVENTION: Three different protocols of VR. MAIN OUTCOME MEASURE: The percentage of average balance in the SOT in CDP. Secondary measures: time and supports in the test of "timed up and go", scores of the dynamic posturography and SwayStar system, and rate of falls.

Is there a relationship between objective and subjective assessment of balance in elderly patients with instability?

To assess whether a subjective questionnaire that measures the disability caused by balance disorders in daily life activities is correlated to objective assessment of balance in elderly patients with age-related instability. We included 37 subjects aged 65 years or more who presented balance disorders induced solely by age. Balance assessment was through the sensory organisation test and limits of stability of computerised dynamic posturography, the SwayStar system and the modified timed up and go test. The patients also completed the dizziness handicap inventory (DHI) questionnaire. The SwayStar balance control index (BCI) was most significantly correlated to the DHI score and the score of its different scales. When we divided the patients into subgroups according to DHI score, we only found statistically significant differences in the BCI and number of falls. In our population of elderly patients with instability, there is practically no correlation between the DHI and the static balance assessment. However, there is greater correlation with the BCI, which could show that dynamic balance is perceived as more disabling for these patients. In this case, when designing a rehabilitation protocol we should focus more on dynamic activities such as gait.

Impact of subject's position and acoustic stimulus type on vestibular evoked myogenic potentials (VEMPs) in normal subjects.

Vestibular evoked myogenic potentials (VEMPs) are currently considered a diagnostic tool for studying the vestibular system, specifically the saccule and inferior vestibular nerve. This prospective study aimed at evaluating the impact of patient position and type of acoustic stimulus on VEMPs results using 60 healthy subjects who underwent otoscopy, pure tone audiometry and VEMPs in different conditions affecting their position and the type of acoustic stimulus. Corrected amplitude is significantly greater when the patient is seated and latency difference and amplitude asymmetry do not change with either patient position or type of stimulus. The results obtained in different test conditions are not comparable. Being seated is the most appropriate position for the test.

[Validation of the short FES-I scale in Spanish population over 70 years]. / Validación de la escala Short FES-I en población española mayor de 70 años.

INTRODUCTION: Falls deteriorate the quality of life of the elderly and the fear of falling has been shown to be an independent risk factor for frailty, so having tools for its evaluation is a priority. The short FES-I scale, short version (7 items) of the FES-I scale (16 items), assesses fear of falling. The objective of this study is to validate the short FES-I scale in the Spanish population over 70 years and to analyze the relationship between fear of falling, risk of falls and frailty. MATERIAL AND METHODS: Cross-sectional observational study. SAMPLE: 227 subjects (50.7% male; mean age 75.8 years). SETTING: northern Spain. VARIABLES: sociodemographic, clinical, short physical performance battery (SPPB) and timed up and go test (TUG) execution tests, FES-I and short FES-I. Analysis of psychometric properties: validity and reliability. RESULTS: The short FES-I scale shows excellent internal consistency (Cronbach's alpha = 0.90, intraclass correlation coefficient = 0.89) and test-retest reliability (rho Spearman = 0.76). It has a high concomitant criterion validity analyzed by its correlation with FES-I (rho Spearman = 0.90). The discriminant construct validity has been confirmed for both SPPB and TUG. Short FES-I presents good capacity for frailty classification (defined by SPPB) with AUC = 0.715. As a cut-off point, a short FES-I value > 8 is proposed for moderate/high fear of falling. CONCLUSIONS: The short FES-I scale is a good instrument to study fear of falling in the Spanish population over 70 years and is valid for clinical and research use.

Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study.

BACKGROUND: Insulin resistance has been associated with metabolic and hemodynamic alterations and higher cardio metabolic risk. There is great variability in the threshold homeostasis model assessment of insulin resistance (HOMA-IR) levels to define insulin resistance. The purpose of this study was to describe the influence of age and gender in the estimation of HOMA-IR optimal cut-off values to identify subjects with higher cardio metabolic risk in a general adult population. METHODS: It included 2459 adults (range 20-92 years, 58.4% women) in a random Spanish population sample. As an accurate indicator of cardio metabolic risk, Metabolic Syndrome (MetS), both by International Diabetes Federation criteria and by Adult Treatment Panel III criteria, were used. The effect of age was analyzed in individuals with and without diabetes mellitus separately. ROC regression methodology was used to evaluate the effect of age on HOMA-IR performance in classifying cardio metabolic risk. RESULTS: In Spanish population the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to 2.05 taking into account of MetS components. In non-diabetic women, but no in men, we found a significant non-linear effect of age on the accuracy of HOMA-IR. In non-diabetic men, the cut-off values were 1.85. All values are between 70th-75th percentiles of HOMA-IR levels in adult Spanish population. CONCLUSIONS: The consideration of the cardio metabolic risk to establish the cut-off points of HOMA-IR, to define insulin resistance instead of using a percentile of the population distribution, would increase its clinical utility in identifying those patients in whom the presence of multiple metabolic risk factors imparts an increased metabolic and cardiovascular risk. The threshold levels must be modified by age in non-diabetic women.

Correlation between bithermal caloric test results and vestibular evoked myogenic potentials (VEMPs) in normal subjects.

UNLABELLED: Bithermal caloric testing and vestibular evoked myogenic potentials (VEMPs) are both diagnostic tools for the study of the vestibular system. The first tests the horizontal semicircular canal and the second evaluates the saccule and lower vestibular nerve. The results of these two tests can therefore be expected to be correlated. The aim of this study was to compare bithermal caloric test results with VEMP records in normal subjects to verify whether they are correlated. MATERIAL AND METHOD: A prospective study was conducted in 60 healthy subjects (30 men and 30 women) who underwent otoscopy, pure tone audiometry, bithermal caloric testing and VEMPs. From the caloric test, we assessed the presence of possible vestibular hypofunction, whether there was directional preponderance and reflectivity of each ear (all based on both slow phase velocity and nystagmus frequency). The analysed VEMPs variables were: p1 and n1 latency, corrected amplitude, interaural p1 latency difference and p1 interaural amplitude asymmetry. We compared the reflectivity, hypofunction and directional preponderance of the caloric tests with the corrected amplitudes and amplitude asymmetries of the VEMPs. No correlations were found in the different comparisons between bithermal caloric testing results and VEMPs except for a weak correlation (p = 0.039) when comparing preponderance based on the number of nystagmus in the caloric test and amplitude asymmetry with 99 dB tone burst in the VEMPs test. The results indicate that the two diagnostic tests are not comparable, so one of them cannot replace the other, but the use of both increases diagnostic success in some conditions.

Method to calculate the protamine dose necessary for reversal of heparin as a function of activated clotting time in patients undergoing cardiac surgery.

Activated clotting time (ACT) has been used to monitor coagulation and guide management of anticoagulation control in patients undergoing cardiac surgery for decades. However, reversal of heparin with protamine is typically empirically based on total heparin administered. Dose-related adverse effects of protamine are well described. The aim of this study was to evaluate a heparin reversal strategy based on calculation of the protamine dose based on ACT measurements. We present a method using a mathematical formula based on the dose-response line (1). To check the formula, we performed a retrospective observational cohort study of 177 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The study group of 80 patients was administered the dose of protamine obtained using our formula, and the control group of 97 patients was administered the empirically calculated dose. The ACT returned to normal values in patients who were given doses of protamine that were calculated using our formula; all but two had a final ACT of 141. The application of the formula resulted in a significant reduction in the dose of protamine (p < .023). The formula we present is a valid method for calculating the dose of protamine necessary to neutralize heparin. This same method can be used working with a target ACT to adjust the dose of heparin. As a result of its functionality, it allows application on a daily basis standardizing the process. We believe that the formula we developed can be applied in all those procedures in which it is necessary to anticoagulate patients with heparin and later neutralization (cardiac surgery with or without CPB, vascular surgery, procedures of interventional cardiology, and extracorporeal depuration procedures).

The role of p21Waf1/CIP1 as a Cip/Kip type cell-cycle regulator in oral squamous cell carcinoma (Review).

Oral Squamous Cell Carcinoma (OSCC) is biologically characterized by the accumulation of multiple genetic and molecular alterations that end up clinically characterized as a malignant neoplasm through a phenomenon known as multistep. The members of the Cip/Kip family, specifically p21Waf1/CIP1, are responsible for cell cycle control, blocking the transition from phase G1 to phase S. We made a search of articles of peer-reviewed Journals in PubMed/ Medline, crossing the keywords. The goal of this paper is to determine the relationship between p21Waf1/CIP1 expression and several clinical and pathological aspects of OSCC, their relationship with p53 and HPV, as well as genetic alterations in their expression pattern, their use as a prognosis market in the evolution of precancerous lesions and their roles in anticancer treatments. The results of p21WAF1/CIP1 expression in OSCC showed mixed results in terms of positivity/negativity throughout different studies. It seems that, although p21Waf1/CIP1 expression is controlled in a p53-dependent manner, coexpression of both in OSCC is not intrinsically related. Although the presence of HPV viral oncoproteins increases p21Waf1/CIP1 levels, the small number of studies, have forced us to disregard the hypothesis that HPV infected lesions that present better prognosis are due to a p21Waf1/CIP1-dependent control. The role of p21WAF1/CIP1 as cell-cycle regulator has been well described; however, its relationship to OSCC, the clinical and pathological variables of tumors, HPV and different treatments are not entirely clear. Thus, it would be very interesting to pursue further study of this protein, which may have a significant value for the diagnosis, prognosis and therapy of this type of tumors.

Immunogenicity of COVID-19 vaccines in lung cancer patients.

OBJECTIVE: Patients with lung cancer are at increased risk of SARS-CoV-2 infection and severe complications from COVID-19, but information on the efficacy of anti-SARS-CoV-2 vaccine in these patients is scarce. We aimed at evaluating the safety and immunogenicity of COVID-19 vaccines in this population. PATIENTS AND METHODS: The prospective, nationwide SOLID substudy, enrolled adults with lung cancer who were fully vaccinated against COVID-19. Serum anti-SARS-CoV-2 IgG antibody levels were quantitatively assessed two weeks and six months after receipt of the last dose using a chemiluminescent microparticle immunoassay. Multivariate odds ratios for the association between demographic and clinical factors and seronegativity after vaccination were estimated. RESULTS: 1973 lung cancer patients were enrolled. Most patients had stage IV disease (66%) and were receiving active cancer treatment (82.7%). No significant differences were found in the probability of being seronegative for anti-SARS-CoV-2 IgG antibodies after full vaccination between patients who were receiving active cancer treatment and those who were not (p = 0.396). The administration of immunotherapy or oral targeted therapy and immunization with mRNA-1273 COVID-19 vaccine were factors independently associated with increased odds of being seropositive after vaccination. From all patients, 1405 received the second dose of vaccine and high levels of antibody titers were observed in 93.6% of patients two weeks after second dose. At six months, multivariate logistic regression analysis showed that performance status ≥ 2 was independently associated with a higher probability of being seronegative after full vaccination with an OR 4.15. On the other hand, received chemotherapy or oral target therapy and vaccination with mRNA-1273 were a factor independently associated with lower odds of being seronegative after full vaccination with an OR 0.52, 0.37 and 0.34, respectively. CONCLUSIONS: Lung cancer patients can safely achieve a strong immune response against SARS-CoV-2 after full vaccination, regardless of the cancer treatment received. TRIAL REGISTRATION: NCT04407143.

Alectinib after failure to crizotinib in patients with ALK-positive non-small cell lung cancer: results from the Spanish early access program.

This retrospective observational study analyzed the clinical characteristics, treatment patterns and outcomes of 120 patients with advanced ALK-positive non-small-cell lung cancer (ALK+ NSCLC) according to data collected between November 2019 and October 2020 in 38 Spanish hospitals. Patients had progressed after 1-5 prior treatment lines (which included crizotinib in any prior line) and received subsequent therapy with alectinib in a local expanded access program. Median age was 58.7 years, 50% of patients were female, 64.1% had ECOG PS of 0-1, 85% presented stage IV, 95% had adenocarcinoma histology and 20.8% had brain metastases. After a median 9.6 months of alectinib treatment, objective response rate (ORR) was 54.5%, disease control rate (DCR) was 80%, median progression-free survival (PFS) was 9.4 months and median overall survival (OS) was 24.1 months. Patients with brain metastases achieved an intracranial DCR of 71.4%. Adverse events (AEs) were reported in 35.8% of patients (14.2% of AEs were grade ≥3). Over 40% of patients received some treatment after alectinib, most frequently lorlatinib (65.2%) and brigatinib (32.6%). This study provides information on real-world treatment patterns and confirms the tolerability and prolonged PFS and OS observed with alectinib in clinical trials, in unselected pretreated patients with advanced ALK+ NSCLC.