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PURPOSE: We assessed the 27-gene RT-qPCR-based DetermaIO assay and the same score calculated from RNA sequencing (RNA-seq) data as predictors of sensitivity to immune checkpoint therapy in the neoTRIPaPDL1 randomized trial that compared neoadjuvant carboplatin/nab-paclitaxel chemotherapy (CT) plus atezolizumab with CT alone in stage II/III triple-negative breast cancer. We also assessed the predictive function of the immuno-oncology (IO) score in expression data of patients treated with pembrolizumab plus paclitaxel (N = 29) or CT alone (N = 56) in the I-SPY2 trial. EXPERIMENTAL DESIGN: RNA-seq data were obtained from pretreatment core biopsies from 242 (93.8%) of the 258 patients in the per-protocol-population. The DetermaIO RT-qPCR test, performed in the CAP/CLIA-accredited laboratory of Oncocyte Corp., was available for 220 patients (85.3%). A previously established threshold was used to assign DetermaIO-positive versus DetermaIO-negative status. Publicly available microarray data were used from I-SPY2. RESULTS: IO scores calculated from RNA-seq and RT-qPCR data were highly concordant. In neoTRIPaPDL1, DetermaIO-positive cancers (N = 92, 41.8%) had pathologic complete response (pCR) rates of 69.8% and 46.9% in the CT + atezolizumab and CT arms, respectively. In DetermaIO-negative cases, pCR rates were similar in both arms (44.6% vs. 49.2%; interaction test P = 0.04). PDL1 protein expression and stromal tumor-infiltrating lymphocyte count were not predictive of differential benefit from atezolizumab. In I-SPY2, IO-positive cancers (45.9%) had pCR rates of 85.7% and 16%, with and without immunotherapy, respectively. In IO-negative cancers, pCR rates were 46.7% versus 16.1%. CONCLUSIONS: DetermaIO identified patients who benefited from neoadjuvant immunotherapy resulting in improved pCR rate, independently of PDL1.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Paclitaxel , Neoplasias de la Mama Triple Negativas , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Femenino , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Biomarcadores de Tumor/genética , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Transcriptoma , Anciano , Adulto , Pronóstico , Resultado del Tratamiento , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , AlbúminasRESUMEN
Electrodiagnostic evaluation is often requested for persons with peripheral nerve injuries and plays an important role in their diagnosis, prognosis, and management. Peripheral nerve injuries are common and can have devastating effects on patients' physical, psychological, and socioeconomic well-being; alongside surgeons, electrodiagnostic medicine specialists serve a central function in ensuring patients receive optimal treatment for these injuries. Surgical intervention-nerve grafting, nerve transfers, and tendon transfers-often plays a critical role in the management of these injuries and the restoration of patients' function. Increasingly, nerve transfers are becoming the standard of care for some types of peripheral nerve injury due to two significant advantages: first, they shorten the time to reinnervation of denervated muscles; and second, they confer greater specificity in directing motor and sensory axons toward their respective targets. As the indications for, and use of, nerve transfers expand, so too does the role of the electrodiagnostic medicine specialist in establishing or confirming the diagnosis, determining the injury's prognosis, recommending treatment, aiding in surgical planning, and supporting rehabilitation. Having a working knowledge of nerve and/or tendon transfer options allows the electrodiagnostic medicine specialist to not only arrive at the diagnosis and prognosticate, but also to clarify which nerves and/or muscles might be suitable donors, such as confirming whether the branch to supinator could be a nerve transfer donor to restore distal posterior interosseous nerve function. Moreover, post-operative testing can determine if nerve transfer reinnervation is occurring and progress patients' rehabilitation and/or direct surgeons to consider tendon transfers.
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The sciatic nerve is the body's largest peripheral nerve. Along with their two terminal divisions (tibial and fibular), their anatomic location makes them particularly vulnerable to trauma and iatrogenic injuries. A thorough understanding of the functional anatomy is required to adequately localize lesions in this lengthy neural pathway. Proximal disorders of the nerve can be challenging to precisely localize among a range of possibilities including lumbosacral pathology, radiculopathy, or piriformis syndrome. A correct diagnosis is based upon a thorough history and physical examination, which will then appropriately direct adjunctive investigations such as imaging and electrodiagnostic testing. Disorders of the sciatic nerve and its terminal branches are disabling for patients, and expert assessment by rehabilitation professionals is important in limiting their impact. Applying techniques established in the upper extremity, surgical reconstruction of lower extremity nerve dysfunction is rapidly improving and evolving. These new techniques, such as nerve transfers, require electrodiagnostic assessment of both the injured nerve(s) as well as healthy, potential donor nerves as part of a complete neurophysiological examination.
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Neuropatía Ciática , Humanos , Electrodiagnóstico/métodos , Neuropatía Ciática/diagnóstico , Neuropatía Ciática/fisiopatología , Neuropatía Tibial/diagnósticoAsunto(s)
Fiebre , Pulmón , Masculino , Humanos , Adulto , Fiebre/etiología , Pulmón/diagnóstico por imagenRESUMEN
BACKGROUND: A central tenet of competency-based medical education is the formative assessment of trainees. There are currently no assessments designed to examine resident competence on-call, despite the on-call period being a significant component of residency, characterized by less direct supervision compared to daytime. The purpose of this study was to design a formative on-call assessment tool and collect valid evidence on its application. METHODS: Nominal group technique was used to identify critical elements of surgical resident competence on-call to inform tool development. The tool was piloted over six months in the Division of Plastic & Reconstructive Surgery at our institution. Quantitative and qualitative evidence was collected to examine tool validity. RESULTS: A ten-item tool was developed based on the consensus group results. Sixty-three assessments were completed by seven staff members on ten residents during the pilot. The tool had a reliability coefficient of 0.67 based on a generalizability study and internal item consistency was 0.92. Scores were significantly associated with years of training. We found the tool improved the quantity and structure of feedback given and that the tool was considered feasible and acceptable by both residents and staff members. CONCLUSIONS: The Western University Call Assessment Tool (WUCAT) has multiple sources of evidence supporting its use in assessing resident competence on-call.
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Internado y Residencia , Humanos , Educación de Postgrado en Medicina/métodos , Reproducibilidad de los Resultados , Universidades , Competencia Clínica , Evaluación Educacional/métodosRESUMEN
Peripheral nerve injuries are common and can have a devastating effect on physical, psychological, and socioeconomic wellbeing. Peripheral nerve transfers have become the standard of care for many types of peripheral nerve injury due to their superior outcomes relative to conventional techniques. As the indications for, and use of, nerve transfers expand, the importance of pre-operative assessment and post-operative optimization increases. There are two principal advantages of nerve transfers: (1) their ability to shorten the time to reinnervation of muscles undergoing denervation because of peripheral nerve injury; and (2) their specificity in ensuring proximal motor and sensory axons are directed towards appropriate motor and sensory targets. Compared to conventional nerve grafting, nerve transfers offer opportunities to reinnervate muscles affected by cervical spinal cord injury and to augment natural reinnervation potential for very proximal injuries. This article provides a narrative review of the current scientific knowledge and clinical understanding of nerve transfers including peripheral nerve injury assessment and pre- and post-operative electrodiagnostic testing, adjuvant therapies, and post-operative rehabilitation for optimizing nerve transfer outcomes.
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BACKGROUND: Eagle's syndrome (ES) classically describes dysphagia, globus sensation, and otalgia from an elongated and calcified styloid process or stylohyoid ligament. Compression of the spinal accessory nerve (SAN) has not been reported as an associated feature of ES or related variants. OBSERVATIONS: The authors describe two cases of an atypical "winged" variant with SAN palsy resulting from compression by a posteriorly angulated or calcified styloid process. Both patients exhibited lateral scapular winging and atrophy of the trapezius and sternocleidomastoid muscles. Electrophysiological studies demonstrated motor unit preservation; therefore, surgical exploration, styloidectomy, and SAN decompression were performed through a transcervical approach. Postoperatively, both patients had improvements in pain and shoulder mobility, the return of muscle strength, and electrophysiological evidence of trapezius reinnervation. LESSONS: Compression of the SAN, which can be identified both clinically and on electrodiagnostic testing, is an atypical finding that can result from a posteriorly angulated or calcified styloid process. This winged variant of ES should be included in the differential for SAN palsy, and a multidisciplinary approach is recommended for assessment and management.
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BACKGROUND: With advances in the surgical management for severe ulnar neuropathy with the introduction of the super charged-end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfer, a simple and reliable outcome measure is required. There is currently not "one" standardized outcome measure used to represent and compare results. PURPOSE: To present the abduction hand diagram as a "novel", reproducible, and simple outcome measure for patients with severe ulnar neuropathy. STUDY DESIGN: Retrospective case series. METHODS: Nine patients with severe entrapment/compressive ulnar neuropathy at the elbow were reviewed. Clinical parameters included preoperative and postoperative abduction tracings, Medical Research Grade (MRC) muscle strength, key pinch strength, Disability of the Hand Arm and Shoulder (DASH) score, and crossed finger test. Electrodiagnostic data included change in compound muscle action potentials (CMAP) amplitude of the first dorsal interosseous (FDI), and abductor digiti minimi (ADM). Summary statistics were used for demographic and clinical data. RESULTS: Average follow-up was 22.8 ± 9.3 months. At 18-months of follow up, 44% had ADM MRC grade 3 strength or higher, mean key pinch strength improved to 72 ± 19.3%, and mean DASH was 33 ± 28.7. There was a mean increase of 16.7 ± 9.1 mm and 31.5 ± 12 mm in total and summed hand abduction tracing measurements respectively. CONCLUSIONS: Hand abduction tracings are a quantitative outcome measure to follow recovery over time for intrinsic hand function and can be used in patients with severe ulnar neuropathy following surgical intervention.
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Background: Before the development of antithyroid drugs in the 1940s, treatment of Graves' hyperthyroidism was primarily surgical. Surgical mortality was quite variable, but a significant minority of patients died during or after surgery. Summary: In 1936, Karl Compton, President of the Massachusetts Institute of Technology, in a lecture attended by Massachusetts General Hospital physicians, suggested that artificially radioactive isotopes might be useful for studying metabolism. By 1942, Hertz and Roberts reported on the successful use of radioactive iodine (RAI) to treat Graves' hyperthyroidism. RAI uptake was subsequently demonstrated in well-differentiated thyroid cancer metastases. In 1948, Seidlin demonstrated stimulation of uptake in thyroid cancer metastases by thyrotropin (TSH). By 1990, 69% of endocrinologists in North America recommended RAI for Graves' hyperthyroidism. Currently RAI is less frequently used for Graves' hyperthyroidism, related to concerns about exacerbation of thyroid eye disease, about radiation exposure, and about potential adverse consequences of permanent hypothyroidism. Similarly, RAI was administered to the majority of patients with thyroid cancer for decades, but its use is now more selective. Conclusions: RAI is a remarkable example of interinstitutional cooperation between physicians and scientists to transition from bench to bedside in only three years. It is the model for a theranostic approach to disease (the simultaneous use of a radioactive drug for diagnosis and therapy). The future of RAI is less certain; inhibition of TSH receptor stimulating antibodies in Graves' disease and more precise targeting of genes that drive thyroid oncogenesis may diminish the use of RAI. Alternatively, redifferentiation techniques may improve the efficacy of RAI in RAI-refractory thyroid cancer.
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Enfermedad de Graves , Hipertiroidismo , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo , RadiofármacosRESUMEN
BACKGROUND: The anterior interosseus nerve (AIN) to ulnar motor nerve transfer has been popularized as an adjunct to surgical decompression in patients with severe cubital tunnel syndrome (CuTS) and high ulnar nerve injuries. The factors influencing its implementation in Canada have yet to be described. METHODS: An electronic survey was distributed to all members of the Canadian Society of Plastic Surgery (CSPS) using REDCap software. The survey examined 4 themes: previous training/experience, practice volume of nerve pathologies, experience with nerve transfers, and approach to the treatment of CuTS and high ulnar nerve injuries. RESULTS: A total of 49 responses were collected (12% response rate). Of all, 62% of surgeons would use an AIN to ulnar motor supercharge end-to-side (SETS) transfer for a high ulnar nerve injury. For patients with CuTS and signs of intrinsic atrophy, 75% of surgeons would add an AIN-SETS transfer to a cubital tunnel decompression. Sixty-five percent would also release Guyon's canal, and the majority (56%) use a perineurial window for their end-to-side repair. Eighteen percent of surgeons did not believe the transfer would improve outcomes, 3% cited lack of training, and 3% would preferentially use tendon transfers. Surgeons with hand fellowship training and those less than 30 years in practice were more likely to use nerve transfers in the treatment of CuTS (P < .05). CONCLUSIONS: Most CSPS members would use an AIN-SETS transfer in the treatment of both a high ulnar nerve injury and severe CuTS with intrinsic atrophy.
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PURPOSE: AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC), with a modest benefit among proficient mismatch repair (pMMR). DetermaIO is an immune-related 27-gene expression signature able to predict benefit from immune checkpoint inhibition in triple-negative breast cancer. In this analysis of AtezoTRIBE, we investigated the predictive impact of DetermaIO in mCRC. EXPERIMENTAL DESIGN: Patients with mCRC unselected for MMR status were randomly assigned (1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizumab (atezolizumab arm). qRT-PCR by DetermaIO was performed on RNA purified from pretreatment tumors of 132 (61%) of 218 enrolled patients. A binary result (IOpos vs. IOneg) adopting the preestablished DetermaIO cut-off point (0.09) was obtained, and an exploratory optimized cut-off point (IOOPT) was computed in the overall population and in pMMR subgroup (IOOPTpos vs. IOOPTneg). RESULTS: DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumors were IOpos. IOpos tumors achieved higher PFS benefit from atezolizumab arm than IOneg (HR: 0.39 vs. 0.83; Pinteraction = 0.066). In pMMR tumors (N = 110), a similar trend was observed (HR: 0.47 vs. 0.93; Pinteraction = 0.139). In the overall population, with the computed IOOPT cut-off point (0.277), 16 (13%) tumors were IOOPTpos and they derived higher PFS benefit from atezolizumab than IOOPTneg (HR: 0.10 vs. 0.85, Pinteraction = 0.004). Similar results were found in the pMMR subgroup. CONCLUSIONS: DetermaIO may be useful to predict benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in mCRC. The exploratory IOOPT cut-off point should be validated in independent mCRC cohorts.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/genética , Transcriptoma , Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina/uso terapéutico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéuticoRESUMEN
Characterizing spatial distribution of HIV outcomes is vital for targeting interventions to areas most at risk. We performed spatial analysis to identify geographic clusters and factors associated with mortality in KwaZulu-Natal, South Africa. We utilized Sizanani trial (NCT01188941) data, which enrolled participants August 2010-January 2013 and obtained vital status at 5.8 (IQR 5.0-6.4) years of follow-up. We mapped geocoded addresses to 2011 Census-defined small area layer (SAL) centroids, used Kulldorff's spatial scan statistic to identify mortality clusters, and compared socio-demographic factors for SALs within and outside mortality clusters. We assigned 1,143 participants living with HIV (260 [23%] of whom died during follow-up) to 677 SALs. One lower mortality cluster (n = 90, RR = 0.23, p = 0.022) was identified near a hospital outside Durban. SALs in the cluster were younger (24y vs 25y, p < 0.001); had fewer bedrooms/household (3 vs 4, p < 0.001); had more females (52% vs 51%, p = 0.013) and residents with no schooling past age 20 (4% vs 3%, p < 0.001) or no education at all (4% vs 3%, p < 0.001); had fewer residents with income >3,200 ZAR/month (5% vs 9%, p < 0.001); and had reduced access to piped water (p < 0.001), refuse disposal (p < 0.001), and toilets (p < 0.001). Targeted interventions may improve outcomes in areas with similar characteristics.
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Infecciones por VIH , Femenino , Humanos , Adulto Joven , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Sudáfrica/epidemiología , Composición Familiar , Renta , EscolaridadRESUMEN
In this clinical trial, patients were randomized to receive a pedicled vascularized bone graft, based on the 1,2-intercompartmental supraretinacular artery, or a non-vascularized iliac crest graft. Fixation was done with K-wires. Union and time to union were assessed using CT scans at regular intervals. Twenty-three patients received a vascularized graft, and 22 received a non-vascularized graft. Thirty-eight patients were available for union assessment and 23 for clinical measurements. There were no significant differences in union incidence, time to union, incidence of complications, patient-reported outcome scores, or wrist mobility and grip strength at final follow-up between the treatment groups. Smokers were 60% less likely to achieve union, independent of graft type. When controlling for smoking, patients receiving a vascularized graft were 72% more likely to achieve union. Given our small sample size, results should be interpreted with caution.Level of evidence: I.
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Fracturas no Consolidadas , Hueso Escafoides , Humanos , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/cirugía , Trasplante Óseo/métodos , Curación de Fractura , Estudios Retrospectivos , Hueso Escafoides/cirugía , Necrosis , Fijación Interna de Fracturas/métodosRESUMEN
Multiple targeted therapeutics have been approved by the FDA for mUC, including immune checkpoint inhibitors (ICIs) and more recently targeted agents for both FGFR and Nectin-4. FGFR3-aberrant and Nectin-4 expressing cells have been associated with an immunosuppressed phenotype. Given that less than half of all patients respond to these agents as monotherapies and less than 20% are eligible to receive salvage therapy, effective personalized treatment plans are critical. Typical biomarkers for ICIs such as PD-L1 and TMB have not been definitive in mUC, yet a biomarker-driven optimization of first-line therapy and subsequent sequencing have the potential to achieve higher and more durable response rates. The IO score is a 27-gene tumor immune microenvironment (TIME) classifier that has been associated with the clinical benefits of ICIs in multiple cancer types, including mUC. This study demonstrates that the IO score was associated with both progression-free survival (PFS) and overall survival (OS) in a real-world cohort of mUC patients treated with ICIs. Furthermore, the IO score was independent of and provided information incremental to TMB. Interestingly, the IO score predicted benefit in patients with high FGFR expression, despite conflicting data regarding response rates among the FGFR aberrant population. Taken together, these results demonstrate that the IO score assessment of the TIME is associated with a clinical benefit from ICI therapy and that this novel biomarker may inform therapeutic sequencing decisions in mUC, potentially improving outcomes for this notoriously difficult-to-treat disease.
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Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Transicionales , Neoplasias Pulmonares , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/uso terapéutico , Nectinas , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1 , Microambiente TumoralRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICI) are standard of care in advanced non-small cell lung cancer (NSCLC). However, not all patients benefit, even among PD-L1 tumor proportional score (TPS) ≥50%, indicating an unmet need for additional biomarkers such as those assessing the tumor immune microenvironment (TIME). DetermaIO is a 27-gene assay that classifies TIME and has previously demonstrated association with ICI response. METHODS: FFPE samples were selected from BC Cancer and West Clinic Cancer Center patients with performance status (PS) ≤2 who received at least 2 cycles of ICI monotherapy in the first (1L) or second line (2L). IO scores were generated and analyzed for association with PFS and OS. RESULTS: In the entire cohort (N=147), IO score was significantly associated with OS (HR=0.68, 95%CI 0.47-0.99, P = .042) and PFS (HR=0.62, 95%CI 0.43-0.88, P = .0069). In 1L treated patients (PD-L1≥50%, N=78), IO score was significantly associated with PFS (HR=0.55, 95%CI 0.32-0.94, P = .028). In exploratory analyses, IO score was associated with benefit in 1L PS2 patients for OS (HR = 0.26, 95%CI 0.091-0.74, P = .012) and PFS (HR = 0.27, 95%CI 0.098-0.72, P = .0095) which was confirmed in PFS subgroup analysis in the independent West Cancer Center study (N=13 HR=0.14, 95%CI 0.027-0.76, P = .023). CONCLUSION: These data confirm the association of DetermaIO with ICI clinical benefit in NSCLC, and expand on previous studies by demonstrating that first line treated PD-L1≥50% patients can further be stratified by IO score to identify efficacy. Exploratory analysis suggested that the IO score identifies benefit in patients with poor PS.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Antígeno B7-H1 , Estudios Retrospectivos , Inmunoterapia , Microambiente TumoralRESUMEN
BACKGROUND: The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score's binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor210 clinical trial treated with the ICI, atezolizumab. METHODS: We identified a list of tumor immune microenvironment (TIME) related genes expressed across the TCGA breast, lung squamous and lung adenocarcinoma cohorts (TCGA-BRCA, TCGA-LUSQ, and TCGA-LUAD, 939 genes total) and then examined the expression of these 939 genes in TCGA-BLCA, to identify patients as having high inflammatory gene expression. Using this as a test of classification, we assessed the previously established threshold of IO Score. We then evaluated the IO Score with this threshold in the IMvigor210 cohort for its association with overall survival (OS). RESULTS: In TCGA-BLCA, IO Score positive patients had a strong concordance with high inflammatory gene expression (p < 0.0001). Given this concordance, we applied the IO Score to the ICI treated IMvigor210 patients. IO Score positive patients (40%) had a significant Cox proportional hazard ratio (HR) of 0.59 (95% CI 0.45-0.78 p < 0.001) for OS and improved median OS (15.6 versus 7.5 months) compared to IO Score negative patients. The IO Score remained significant in bivariate models combined with all other clinical factors and biomarkers, including PD-L1 protein expression and tumor mutational burden. CONCLUSION: The IMvigor210 results demonstrate the potential for the IO Score as a clinically useful biomarker in mUC. As this is the third tumor type assessed using the same algorithm and threshold, the IO Score may be a promising candidate as a tissue agnostic marker of ICI clinical benefit. The concordance between IO Score and inflammatory gene expression suggests that the classifier is capturing common features of the TIME across cancer types.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos como Asunto , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/patología , Microambiente TumoralRESUMEN
BACKGROUND: Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies. METHODS: In this retrospective cohort, we assessed a 27-gene RT-qPCR immuno-oncology (IO) gene expression assay of the tumor immune microenvironment and determined its association with the efficacy of ICI therapy in 67 advanced-stage NSCLC patients. The 27-gene IO test score (IO score), programmed cell death ligand 1 immunohistochemistry tumor proportion score (PD-L1 TPS), and tumor mutational burden (TMB) were analyzed as continuous variables for response and as binary variables for one-year progression free survival. The threshold for the IO score was prospectively set based upon a previously described training cohort. Prognostic implications of the IO score were evaluated in a separate cohort of 104 advanced-stage NSCLC patients from The Cancer Genome Atlas (TCGA) who received non-ICI therapy. RESULTS: The IO score was significantly different between responders or non-responders (p = 0.007) and associated with progression-free survival (p = 0.001). Bivariate analysis established that the IO score was independent of PD-L1 TPS and TMB in identifying patients benefiting from ICI therapy. In a separate cohort of late-stage NSCLC patients from TCGA, the IO score was not prognostic of outcome from non-ICI-treated patients. CONCLUSIONS: This study is the first application of this 27-gene IO RT-qPCR assay in a clinical cohort with outcome data. IO scores were significantly associated with response to ICI therapy and prolonged progression-free survival. Together, these data suggest the IO score should be further studied to define its role in informing clinical decision-making for ICI treatment in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Microambiente TumoralRESUMEN
BACKGROUND: Breast reconstructive services are medically necessary, time-sensitive procedures with meaningful health-related quality of life benefits for breast cancer survivors. The COVID-19 global pandemic has resulted in unprecedented restrictions in surgical access, including access to breast reconstructive services. A national approach is needed to guide the strategic use of resources during times of fluctuating restrictions on surgical access due to COVID-19 demands on hospital capacity. METHODS: A national team of experts were convened for critical review of healthcare needs and development of recommendations and strategies for patients seeking breast reconstruction during the pandemic. Following critical review of literature, expert discussion by teleconference meetings, and evidenced-based consensus, best practice recommendations were developed to guide national provision of breast reconstructive services. RESULTS: Recommendations include strategic use of multidisciplinary teams for patient selection and triage with centralized coordinated use of alternate treatment plans during times of resource restrictions. With shared decision-making, patient-centered shifting and consolidation of resources facilitate efficient allocation. Targeted application of perioperative management strategies and surgical treatment plans maximize the provision of breast reconstructive services. CONCLUSIONS: A unified national approach to strategically reorganize healthcare delivery is feasible to uphold standards of patient-centered care for patients interested in breast reconstruction.