ABSTRACT
Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up.
Subject(s)
Alzheimer Disease , RNA, Long Noncoding , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Humans , RNA, Long Noncoding/genetics , Female , Male , Aged , Precision Medicine/methods , Biomarkers , Machine Learning , Aged, 80 and over , Case-Control Studies , Gene Expression Profiling/methods , Computational Biology/methodsABSTRACT
PURPOSE: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small-cell lung cancer (ES-SCLC). EXPERIMENTAL DESIGN: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was objective response rate (ORR). Prespecified exploratory biomarker analyses were conducted in arms A and C. RESULTS: In arm A (n=41), arm B (n=10), and arm C (n=21), confirmed ORR was 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells [TC] or immune cells [IC]) ≥1% appeared to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (TC and IC) <1%, and lower baseline circulating tumor DNA (ctDNA) and reduction in on-treatment ctDNA level were both associated with longer overall survival (OS). Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers. CONCLUSIONS: In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer OS suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.
ABSTRACT
The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.
ABSTRACT
PURPOSE: The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non-small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti-PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported. METHODS: Patients were randomly assigned 1:1 (stratified by histology, best response to last anti-PD-(L)1-containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m2 intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety. RESULTS: In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death. CONCLUSION: Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.
ABSTRACT
Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts.
Subject(s)
Adrenalectomy , Delphi Technique , Laparoscopy , Machine Learning , Humans , Adrenalectomy/education , Adrenalectomy/methods , Laparoscopy/education , Laparoscopy/methods , Pilot Projects , Video RecordingABSTRACT
PURPOSE: The use of outpatient surgery in inguinal hernia is heterogeneous despite clinical recommendations. This study aimed to analyze the utilization trend of outpatient surgery for bilateral inguinal hernia repair (BHIR) in Spain and identify the factors associated with outpatient surgery choice and unplanned overnight admission. METHODS: A retrospective observational study of patients undergoing BIHR from 2016 to 2021 was conducted. The clinical-administrative database of the Spanish Ministry of Health RAE-CMBD was used. Patient characteristics undergoing outpatient and inpatient surgery were compared. A multivariable logistic regression analysis was performed to identify factors associated with outpatient surgery choice and unplanned overnight admission. RESULTS: A total of 30,940 RHIBs were performed; 63% were inpatient surgery, and 37% were outpatient surgery. The rate of outpatient surgery increased from 30% in 2016 to 41% in 2021 (p < 0.001). Higher rates of outpatient surgery were observed across hospitals with a higher number of cases per year (p < 0.001). Factors associated with outpatient surgery choice were: age under 65 years (OR: 2.01, 95% CI: 1.92-2.11), hospital volume (OR: 1.59, 95% CI: 1.47-1.72), primary hernia (OR: 1.89, 95% CI: 1.71-2.08), and laparoscopic surgery (OR: 1.47, 95% CI: 1.39-1.56). Comorbidities were negatively associated with outpatient surgery. Open surgery was associated (OR: 1.26, 95% CI: 1.09-1.47) with unplanned overnight admission. CONCLUSIONS: Outpatient surgery for BHIR has increased in recent years but is still low. Older age and comorbidities were associated with lower rates of outpatient surgery. However, the laparoscopic repair was associated with increased outpatient surgery and lower unplanned overnight admission.
Subject(s)
Ambulatory Surgical Procedures , Hernia, Inguinal , Herniorrhaphy , Humans , Hernia, Inguinal/surgery , Ambulatory Surgical Procedures/statistics & numerical data , Male , Female , Middle Aged , Retrospective Studies , Herniorrhaphy/statistics & numerical data , Aged , Spain , Adult , Patient Admission/statistics & numerical dataABSTRACT
PURPOSE: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. EXPERIMENTAL DESIGN: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.
Subject(s)
Biomarkers, Tumor , Gene Expression Profiling , Immunotherapy , Lung Neoplasms , Small Cell Lung Carcinoma , Transcriptome , Humans , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/therapy , Biomarkers, Tumor/genetics , Male , Female , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Aged , Immunotherapy/methods , Middle Aged , Neoplasm Staging , Treatment Outcome , Gene Expression Regulation, Neoplastic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Basic Helix-Loop-Helix Transcription Factors/genetics , PrognosisABSTRACT
OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
Subject(s)
Antibodies, Monoclonal , Carcinoma, Non-Small-Cell Lung , Chemoradiotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Male , Female , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Retrospective Studies , Aged , Middle Aged , Spain , Antibodies, Monoclonal/therapeutic use , Adult , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Neoplasm Staging , Progression-Free Survival , Consolidation Chemotherapy , B7-H1 Antigen/antagonists & inhibitorsABSTRACT
Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Precision Medicine , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Precision Medicine/methods , Medical Oncology/methods , Europe , Societies, Medical , Neoplasm Metastasis , Oncogenes , Practice Guidelines as TopicABSTRACT
Desde sus inicios, la medicina nuclear se ha enfrentado a cambios tecnológicos que la han obligado a modificar sus modos operativos y a adecuar sus protocolos. En el campo de la cirugía radioguiada (CRG), la incorporación de la imagen gammagráfica preoperatoria y la detección intraoperatoria con la sonda gamma proporcionó un impulso definitivo a la biopsia del ganglio centinela (GC) para convertirse en el procedimiento estándar de aplicación en el melanoma y el cáncer de mama. Las diversas innovaciones tecnológicas y la adaptación consiguiente de protocolos confluyen en lo disruptivo y lo gradual. Como ejemplos evidentes tenemos la introducción de la tomografía por emisión de fotón único/tomografía computarizada (SPECT/TC) en el campo preoperatorio y las sondas Drop-in (Lightpoint Medical Ltd; Crystal photonics, Eurorad) en el intraoperatorio. Otros aspectos innovadores con posible aplicación en la CRG se basan en la utilización de la inteligencia artificial (IA), navegación y teleasistencia (AU)
Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare (AU)
Subject(s)
Humans , Sentinel Lymph Node Biopsy , Surgery, Computer-Assisted , Artificial Intelligence , In Situ Hybridization, FluorescenceABSTRACT
BACKGROUND: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy. METHODS: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, and objective response rate. Exploratory analyses included efficacy by tumor PD-L1 expression and histology and in patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events (TRAEs), and a treatment-switching adjustment analysis using inverse probability of censoring weighting. RESULTS: With a 47.9-month minimum follow-up for OS, nivolumab plus ipilimumab with chemotherapy continued to prolong OS over chemotherapy in all randomized patients (HR 0.74, 95% CI 0.63 to 0.87; 4-year OS rate: 21% versus 16%), regardless of tumor PD-L1 expression (HR (95% CI): PD-L1<1%, 0.66 (0.50 to 0.86) and ≥1%, 0.74 (0.60 to 0.92)) or histology (squamous, 0.64 (0.48 to 0.84) and non-squamous, 0.80 (0.66 to 0.97)). In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy due to TRAEs (n=61), the 4-year OS rate was 41%. With treatment-switching adjustment for the 36% of patients receiving subsequent immunotherapy in the chemotherapy arm, the estimated HR of nivolumab plus ipilimumab with chemotherapy versus chemotherapy was 0.66 (95% CI 0.55 to 0.80). No new safety signals were observed. CONCLUSIONS: In this 4-year update, patients treated with nivolumab plus ipilimumab with chemotherapy continued to have long-term, durable efficacy benefit over chemotherapy regardless of tumor PD-L1 expression and/or histology. A greater estimated relative OS benefit was observed after adjustment for subsequent immunotherapy use in the chemotherapy arm. These results further support nivolumab plus ipilimumab with chemotherapy as a first-line treatment for patients with metastatic/recurrent NSCLC, including those with tumor PD-L1<1% or squamous histology, populations with high unmet needs.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Adult , Humans , Nivolumab/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , B7-H1 Antigen/metabolism , Treatment Switching , Lung Neoplasms/pathology , Neoplasm Recurrence, LocalABSTRACT
INTRODUCTION AND IMPORTANCE: Lipomatous neoplasms of the parotid gland represent an exceptionally rare and often underdiagnosed category of tumors, accounting for an incidence ranging from 0.6 % to 4.4 % of all neoplasms detected within the parotid gland. Sialolipoma is defined as an uncommon variant of lipoma, characterized by a well-defined proliferation of mature adipocytes with secondary entrapment of salivary gland elements, including serous acini, ducts, and myoepithelial cells. CASE PRESENTATION: The current case pertains to a 17-year-old female who presented with a one-year history of enlargement in the left preauricular region. CLINICAL DISCUSSION: The case we present poses a complex diagnostic challenge due to two distinct characteristics. The diagnostic challenge lies in its remarkably low incidence and the propensity for confusion with pleomorphic adenoma, which is the most common tumor of the parotid gland. It is a benign disease entity characterized by the absence of dysplasia, in marked contrast to pleomorphic adenoma. CONCLUSIONS: The infrequency in the manifestation of these tumor types, coupled with their prolonged asymptomatic course, can pose a diagnostic challenge. Enhancing our knowledge to comprehensively delineate these entities is imperative to effectively address the diagnostic complexities from both clinical and histopathological standpoints.
ABSTRACT
Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare.
Subject(s)
Melanoma , Surgery, Computer-Assisted , Humans , Artificial Intelligence , Sentinel Lymph Node Biopsy/methods , Single Photon Emission Computed Tomography Computed Tomography , Surgery, Computer-Assisted/methodsABSTRACT
BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer. METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events. CONCLUSIONS: Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.).
Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cytokines , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Administration, Intravenous , Cytokine Release Syndrome/chemically induced , Cytokine Release Syndrome/etiologyABSTRACT
Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13-2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97-2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence.
ABSTRACT
BACKGROUND: The guidelines recommend laparoscopic repair for bilateral inguinal hernia. However, few studies compare the totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) techniques in bilateral inguinal hernias. This study aimed to compare the outcomes of TEP and TAPP in bilateral inguinal hernia. METHODS: We conducted a retrospective cohort study of patients operated on for bilateral inguinal hernia by TEP and TAPP repair from 2016 to 2020. Intraoperative complications, operative time, acute postoperative pain, hospital stay, postoperative complications, chronic inguinal pain, and recurrence were compared. RESULTS: A total of 155 patients were included in the study. TEP was performed in 71 patients (46%) and TAPP in 84 patients (54%). The mean operative time was longer in the TAPP group than in the TEP group (107 min vs. 82 min, p < 0.001). The conversion rate to open surgery was higher in the TEP group than in the TAPP group (8.5% vs. 0%, p = 0.008). The mean hospital stay was longer in the TAPP group than in the TEP group (p < 0.001). We did not observe significant differences in the proportion of postoperative complications (p = 0.672), postoperative pain at 24 h (p = 0.851), chronic groin pain (p = 0.593), and recurrence (p = 0.471). We did not observe an association between the choice of surgical technique (TEP vs. TAPP) with conversion rate, operative time, hospital stay, postoperative complications, chronic inguinal pain, or hernia recurrence when performing a multivariable analysis adjusted for the male sex, age, BMI, ASA, recurrent hernia repair, surgeon, and hernia size > 3cm. CONCLUSIONS: Bilateral inguinal hernia repair by TEP and TAP presented similar outcomes in our study.
Subject(s)
Hernia, Inguinal , Laparoscopy , Humans , Male , Hernia, Inguinal/surgery , Pain, Postoperative , Laparoscopy/methods , Postoperative Complications/epidemiology , Chronic Pain , Retrospective Studies , Pneumoperitoneum , Operative TimeABSTRACT
SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022) (AU)