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1.
Cephalalgia ; 43(6): 3331024231182126, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37317535

RESUMEN

BACKGROUND: Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. OBJECTIVE: This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. METHODS: Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4-12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3-11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3-12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6-12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. RESULTS: Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6-25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). CONCLUSION: Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11-30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Trastornos de Cefalalgia , Trastornos Migrañosos , Cefalea Postraumática , Cefalea de Tipo Tensional , Femenino , Embarazo , Humanos , Calidad de Vida , Trastornos Migrañosos/tratamiento farmacológico , Fenotipo , Cefalea
2.
J Headache Pain ; 24(1): 5, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36647006

RESUMEN

BACKGROUND: Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide monoclonal antibodies are a relatively novel molecular treatment for episodic and chronic migraine that have been shown to be effective in short duration clinical trials in approximately 40-50% of all chronic migraine patients. Patient Related Outcome Measures (PROM) or Quality of Life (QoL) questionnaires are used to help measure response to treatment in migraine. Although some open label extension studies have become available for erenumab, there is a lack of real-world data pertaining to quality of life in the medium to long-term for chronic and treatment resistant migraine patients. METHODS: A total of 177 treatment resistant CM patients were started on erenumab (70 mg or 140 mg subcutaneous injection every 4 weeks) in our three specialist Headache Clinics. Of these, 174 had their first injection between December 2018 and October 2019. All patients were evaluated with the following PROM: the Headache Impact Test- 6, Migraine Associated Disability Assessment test and Migraine-Specific QoL Questionnaire, before starting treatment with erenumab and at intervals of 3-12 months after starting treatment. The decision to continue treatment was based on subjective clinical improvement of at least 30% (as reported by the patient), supported with diaries and QoL questionnaires. We present here the QoL measurements for this group of 177 patients. Prior preventive migraine treatments included conventional oral prophylactic medications (such as topiramate, candesartan, propranolol, or amitriptyline), at least two cycles of PREEMPT protocol onabotulinumtoxin A or (in a small number of cases) neuromodulation with single pulse Transcranial Magnetic Stimulation. RESULTS: Of the 177 patients who started treatment with erenumab, 68/177 (38.4%) stopped during the first year, either due to lack of efficacy (no significant benefit or only minimal improvement) and/or possible side effects. 109/177 (61.6%) patients reported clinically significant improvement after 6-12 months and wished to stay on treatment. Twelve of these 109 patients subsequently stopped treatment in the period between 1 year and up to June 2021 (mainly due to a worsening of their migraine). Therefore, a total of 97/177 patients (54.8%) remained on treatment as of June 2021 (duration of treatment 17-30 months, median of 25 months). CONCLUSION: Approximately 55% of treatment resistant or difficult to treat CM patients who trialled erenumab in our clinics reported a subjective benefit and were still on treatment after 17-30 months.


Asunto(s)
Trastornos Migrañosos , Calidad de Vida , Humanos , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/farmacología , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/uso terapéutico , Método Doble Ciego , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Medición de Resultados Informados por el Paciente , Cefalea/tratamiento farmacológico , Resultado del Tratamiento
3.
Skeletal Radiol ; 50(10): 2107-2115, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33723633

RESUMEN

Desmoid tumor is considered a benign neoplasm, yet substantial morbidity can result from local invasion of structures adjacent to the tumor or from complications related to its treatment. We report two patients with extremity desmoid tumor who were each found at MRI to have an unsuspected pseudoaneurysm within their tumor after prior treatments (surgery and systemic therapy in one, surgery alone in the other). Such a pseudoaneurysm probably results from weakening of an arterial wall by adjacent desmoid tumor, as well as from local trauma. Due to the potential risk for life-threatening rupture of a pseudoaneurysm, one patient underwent surgical repair and the other, coil embolization. To our knowledge the presence of pseudoaneurysm has been reported within a few cases of abdominal desmoid tumor but not within an extremity desmoid tumor. This diagnosis has not been reported to have been made at MRI, either.


Asunto(s)
Aneurisma Falso , Fibromatosis Agresiva , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Extremidades , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/cirugía , Humanos , Imagen por Resonancia Magnética
4.
Ann Surg ; 271(4): 748-755, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-30418203

RESUMEN

OBJECTIVE: The aim of this study was to identify predictors of desmoid progression during observation. SUMMARY OF BACKGROUND DATA: Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified. METHODS: Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics. RESULTS: Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the "test" radiologist; hazard ratio = 11.3, P = 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75). CONCLUSION: The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.


Asunto(s)
Fibromatosis Agresiva/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Fibromatosis Agresiva/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga Tumoral
5.
J Comput Assist Tomogr ; 41(3): 437-441, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27768620

RESUMEN

OBJECTIVE: The aims of this study were to describe the computed tomographic features of organizing pneumonia (OP) in an oncologic patient population and to also identify features associated with lung cancer and patients undergoing hematopoietic stem cell transplant (HSCT). METHODS: In retrospective computed tomographies from 151 patients with pathologically confirmed OP between January 2009 and September 2014, number of lesions, location, size, margin type, and consistency, as well as volume of lymphadenopathy and the presence and size of pleural effusions, were recorded. Associated malignancy was noted. RESULTS: Organizing pneumonia most commonly presented as a diffuse process (n = 62, 41%), frequently occupied both a central and peripheral location (n = 79, 53%), and commonly presented with a solid appearance (n = 67, 44%) or with ground glass opacity (n = 80, 53%). Pleural effusions were seen in 68 patients (45%). Organizing pneumonia less frequently contained air bronchograms, cavitation, necrosis, surrounding ground glass opacity, or adjacent bronchiectasis. In patients with lung cancer (n = 25, 17%), OP more likely presented as discrete lesions and occupied a peripheral location as compared with patients with other malignancies (Ps = 0.025 and 0.002). In HSCT patients (n = 29, 19%), a diffuse process was more commonly seen than in non-HSCT patients (P = 0.038). CONCLUSIONS: Organizing pneumonia more commonly presents as discrete lesions with a peripheral location in patients with lung cancer and as a diffuse process in patients who had undergone HSCT.


Asunto(s)
Neumonía en Organización Criptogénica/complicaciones , Neumonía en Organización Criptogénica/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
6.
Ir J Med Sci ; 193(5): 2515-2523, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38743200

RESUMEN

BACKGROUND: MR arthrography (MRA) has previously been the radiological gold standard for investigating labral and chondral lesions of the hip joint. In recent years, 3T MRI has demonstrated comparable accuracy, being adopted as the first-line imaging investigation in many institutions. AIMS: We compare the associated increased cost and radiation dose of the fluoroscopic component of the MRA compared to MRI. METHODS: In this retrospective review over 2 years, 120 patients (mean age 27.3 years ± 13.2, range 8-67) underwent 3T MRA or non-contrast 3T MRI. Three musculoskeletal radiologists reported the data independently. Primary objectives included cost-comparison between each and radiation dose of the fluoroscopic component of the MRA. Secondary objectives included comparing detection of pathology involving the acetabular labrum, femoral cartilage, and acetabular cartilage. RESULTS: Then, 58 (48%) underwent 3T MRA and 62 (52%) patients underwent 3T MRI. The added cost of the fluoroscopic injection prior to MRA was €116.31/patient, equating to €7211.22 savings/year. MRA was associated with a small radiation dose of 0.003 mSv. CONCLUSIONS: Transitioning from 3T MRA to 3T MRI in the investigation of intra-articular hip pathology increases cost savings and reduces radiation dose.


Asunto(s)
Artrografía , Articulación de la Cadera , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/economía , Imagen por Resonancia Magnética/métodos , Adulto , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Adolescente , Anciano , Artrografía/economía , Artrografía/métodos , Adulto Joven , Fluoroscopía/economía , Fluoroscopía/métodos , Niño , Costos y Análisis de Costo , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Dosis de Radiación
7.
Ir J Med Sci ; 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37947993

RESUMEN

OBJECTIVES: To assess the most common lower limb acute muscle injuries on MRI imaging in a national specialist centre for orthopaedics and sports medicine and to explore potential gender differences. METHODS: Over a 3-year time period, all MRI lower limb studies with acute muscle injury (AMI) were reviewed. A British Athletics muscle injury classification (BAMIC) was given and a statistical analysis was performed. RESULTS: A total of 195 AMIs were diagnosed: 177 (91%) male and 18 (9%) female injuries (M to F = 9.8:1). The most common lower limb AMIs were BAMIC grade 1a injuries (n = 48, 25%). The most commonly injured muscle was biceps femoris (n = 87, 45%), specifically grade 1b and grade 2b injuries. There was no significant difference in age between men and women with acute lower limb muscle injuries (p = 0.19). Females were 1.5 times more likely to have a lower grade AMI than males, although this did not reach statistical significance (p = 0.7) owing to a striking lower number of female patients. There was no significant difference between genders in the likelihood of sustaining a hamstring or quadricep AMI (hamstrings OR = 2.47, p = 0.14 and quadriceps OR = 0.926, p 0.99). CONCLUSIONS: Grade 1a is the most common lower limb AMI grade in our institution, accounting for 25%. Biceps femoris is the most commonly injured muscle (45%) with grade 1b and grade 2b being the most frequently encountered grades of biceps femoris injuries. Lower-grade injuries are more common in females compared to males, although not significantly so. Further studies are required to explore possible reasons for this gender gap.

8.
AJR Am J Roentgenol ; 199(5): W613-7, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23096206

RESUMEN

OBJECTIVE: We present nondisplaced talar head fractures in two patient groups. CONCLUSION: Talar head insufficiency fractures should be considered in older patients, particularly perimenopausal women. Nondisplaced talar head fractures may occur in younger patients after trauma.


Asunto(s)
Traumatismos del Tobillo/diagnóstico , Fracturas Óseas/diagnóstico , Fracturas por Estrés/diagnóstico , Imagen por Resonancia Magnética/métodos , Astrágalo/lesiones , Absorciometría de Fotón , Adolescente , Traumatismos en Atletas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Posmenopausia , Estudios Retrospectivos , Factores de Riesgo
9.
Abdom Radiol (NY) ; 47(9): 2972-2985, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34825946

RESUMEN

The number of publications on texture analysis (TA), radiomics, and radiogenomics has been growing exponentially, with abdominal radiologists aiming to build new prognostic or predictive biomarkers for a wide range of clinical applications including the use of oncological imaging to advance the field of precision medicine. TA is specifically concerned with the study of the variation of pixel intensity values in radiological images. Radiologists aim to capture pixel variation in radiological images to deliver new insights into tumor biology that cannot be derived from visual inspection alone. TA remains an active area of investigation and requires further standardization prior to its clinical acceptance and applicability. This review is for radiologists interested in this rapidly evolving field, who are thinking of performing research or want to better interpret results in this arena. We will review the main concepts in TA, workflow processes, and existing challenges and steps to overcome them, as well as look at publications in body imaging with external validation.


Asunto(s)
Radiografía Abdominal , Radiología , Humanos , Oncología Médica , Medicina de Precisión , Radiografía
10.
Abdom Radiol (NY) ; 43(1): 169-178, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28765978

RESUMEN

PURPOSE: To evaluate the prevalence of major and ancillary imaging features from liver imaging reporting and data systems (LI-RADS) version 2014 and their interreader agreement when comparing hepatocellular carcinoma (HCC) to intrahepatic cholangiocarcinoma (ICC) and combined tumor (cHCC-CC). METHODS: The Institutional Review Board approved this HIPAA-compliant retrospective study and waived the requirement for patients' informed consent. Patients with resected HCC (n = 51), ICC (n = 40), and cHCC-CC (n = 11) and available pre-operative contrast-enhanced MRI were included from 2000 to 2015. Imaging features and final LI-RADS category were evaluated by four radiologists. Imaging features were compared by Fisher's exact test and interreader agreements were assessed by κ statistics. RESULTS: None of the features were unique to either HCC or non-HCC. Imaging features that were significantly more common among HCC compared to ICC and cHCC-CC included washout (76%-78% vs. 10%-35%, p < 0.001), capsule (55%-71% vs. 16%-49%, p < 0.05), and intralesional fat (27%-52% vs. 2%-12%, p < 0.002). Features that were more common among ICC and cHCC-CC included peripheral arterial phase hyperenhancement (40%-64% vs. 10%-14%, p < 0.001) and progressive central enhancement (65%-82% vs. 14%-25%, p < 0.001). The interreader agreement was moderate for each of these imaging features (κ = 0.41-0.55). Moderate agreement was also achieved in the assignment of LR-M (κ = 0.53), with an overall sensitivity and specificity for non-HCC malignancy of 86.3% and 78.4%, respectively. CONCLUSION: HCC and non-HCC show significant differences in the prevalence of imaging features defined by LI-RADS, and are identified by radiologists with moderate interreader agreement. Using LI-RADS, radiologists also achieved moderate interreader agreement in the assignment of the LR-M category.


Asunto(s)
Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Anciano , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos
11.
Cancer Immunol Res ; 6(9): 1093-1099, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29991499

RESUMEN

Considering retreatment following recovery from an immune-related adverse event (irAE) is a common clinical scenario, but the safety and benefit of retreatment is unknown. We identified patients with advanced non-small cell lung cancer (NSCLC) treated with anti-PD-(L)1 who had treatment held due to irAEs and divided them into two groups: those retreated with anti-PD-(L)1 (retreatment cohort) or those who had treatment stopped (discontinuation cohort). Out of 482 NSCLC patients treated with anti-PD-(L)1, 68 (14%) developed a serious irAE requiring treatment interruption. Of these, 38 (56%) were retreated and 30 (44%) had treatment discontinued. In the retreatment cohort, 18 (48%) patients had no subsequent irAEs, 10 (26%) had recurrence of the initial irAE, and 10 (26%) had a new irAE. Most recurrent/new irAEs were mild (58% grade 1-2) and manageable (84% resolved or improved to grade 1). Two treatment-related deaths occurred. Recurrent/new irAEs were more likely if the initial irAE required hospitalization, but the initial grade and time to retreatment did not influence risk. Among those with no observed partial responses prior to the irAE, progression-free survival (PFS) and overall survival (OS) were longer in the retreatment cohort. Conversely, for those with objective responses prior to the irAE, PFS and OS were similar in the retreatment and discontinuation cohorts. Among patients with early objective responses prior to a serious irAE, outcomes were similar, whether or not they were retreated. Together, data suggest that benefit may occur with retreatment in patients with irAEs who had no treatment response prior to irAE onset. Cancer Immunol Res; 6(9); 1093-9. ©2018 AACR.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia/efectos adversos , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos , Femenino , Humanos , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/inmunología , Retratamiento , Estudios Retrospectivos
12.
J Clin Oncol ; 36(28): 2872-2878, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-30125216

RESUMEN

PURPOSE: Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation. METHODS: We identified patients who were PD-(L)1-naïve with advanced non-small-cell lung cancer from two institutions-Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center-who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression. RESULTS: Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P < .001). CONCLUSION: Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non-small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended.


Asunto(s)
Corticoesteroides/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Interacciones Farmacológicas , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resultado del Tratamiento
13.
J Clin Oncol ; 36(7): 633-641, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29337640

RESUMEN

Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as partial response/stable disease that lasted > 6 months. Tumor mutation burden (TMB), fraction of copy number-altered genome, and gene alterations were compared among patients with DCB and no durable benefit (NDB). Whole-exome sequencing (WES) was performed for 49 patients to compare quantification of TMB by targeted NGS versus WES. Results Estimates of TMB by targeted NGS correlated well with WES (ρ = 0.86; P < .001). TMB was greater in patients with DCB than with NDB ( P = .006). DCB was more common, and progression-free survival was longer in patients at increasing thresholds above versus below the 50th percentile of TMB (38.6% v 25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number-altered genome was highest in those with NDB. Variants in EGFR and STK11 associated with a lack of benefit. TMB and PD-L1 expression were independent variables, and a composite of TMB plus PD-L1 further enriched for benefit to ICIs. Conclusion Targeted NGS accurately estimates TMB and elevated TMB further improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1 expression; both variables had similar predictive capacity. The incorporation of both TMB and PD-L1 expression into multivariable predictive models should result in greater predictive power.


Asunto(s)
Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Humanos , Mutación , Carga Tumoral , Secuenciación del Exoma
14.
Cancer Discov ; 8(7): 822-835, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29773717

RESUMEN

KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P < 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P < 0.001) and overall (P = 0.0015) survival compared with KRASMUT;STK11/LKB1WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1-positive non-small cell lung cancer. In Kras-mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS-mutant LUAC.Significance: This work identifies STK11/LKB1 alterations as the most prevalent genomic driver of primary resistance to PD-1 axis inhibitors in KRAS-mutant lung adenocarcinoma. Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets. Cancer Discov; 8(7); 822-35. ©2018 AACR.See related commentary by Etxeberria et al., p. 794This article is highlighted in the In This Issue feature, p. 781.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Nivolumab/uso terapéutico , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Inmunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Ratones , Persona de Mediana Edad , Nivolumab/farmacología , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión
15.
Abdom Radiol (NY) ; 42(1): 271-277, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27480976

RESUMEN

PURPOSE: Bone lesions on prostate MRI often raise concern about metastases. This study aimed to evaluate the prevalence of bone metastases on staging prostate MRI and evaluate associations between their MRI features and clinical/pathologic characteristics. METHODS: Retrospective, IRB-approved study of 3765 patients undergoing prostate MRI for newly diagnosed PCa between 2000 and 2014. The reference standard to calculate the prevalence of bone metastases was bone biopsy and/or ≥1-year follow-up after MRI. In a subsample of 228 patients, the MRI characteristics of bone lesions were recorded by two radiologists independently. Associations between MRI and clinical/pathologic findings, including National Comprehensive Cancer Network (NCCN) risk categories, were calculated. RESULTS: 57/3765 patients (1.5%, 95% CI 1.2-2.0%) had bone metastases. No patient with NCCN low-risk PCa (Gleason < 7, PSA < 10 ng/mL, cT1-2a) had bone metastases. In the subsample, ≥1 bone lesion was present on MRI in 74% (95% CI 0.67-0.79) and 72% (95% CI 0.66-0.78) of patients (R1 and R2). Larger lesion diameter (OR 1.33/1.19; p < 0.001 for both readers) and the absence of intralesional fat (OR 0.07/0.11; p = 0.004/0.002 for R1/R2) were significantly associated with bone metastases. CONCLUSION: Bone lesions are common in prostate MRI, but only rarely represent metastases. MRI should be interpreted in the context of clinical features that influence the likelihood of metastatic disease.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Neoplasias Óseas/epidemiología , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Prevalencia , Estudios Retrospectivos
16.
J Thorac Oncol ; 11(9): 1447-52, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27223458

RESUMEN

INTRODUCTION: The aim of this study was to describe the clinical characteristics and radiologic findings in patients with a previous history of malignancy who underwent computed tomography (CT) screening for lung cancer. METHODS: Patients with a previous history of malignancy and a life expectancy of at least 5 years who were referred for lung cancer screening between May 2, 2011, and September 24, 2014, were included. CT scan features assessed included nodule size, morphologic features, and number. The Lung-CT Reporting and Data System scoring system was retrospectively applied to all studies. RESULTS: A total of 139 patients were studied (mean age of 66 years and median smoking history of 50 pack-years). All had a previous history of cancer, most often breast cancer (60 patients [43%]), head or neck cancer (26 patients [19%]), and lung cancer (16 patients [12%]). Of these patients, 42 (30%) had a positive screening study result. Lung cancer was diagnosed in seven patients (5%), and a radiation-induced chest wall sarcoma was diagnosed in one patient (1%); 42 patients (30%) had a positive chest CT scan per the National Comprehensive Cancer Network lung cancer screening nodule follow-up algorithm. CONCLUSION: The rate of diagnosis of lung cancer in our patient population is higher than in several previously published studies. Smokers with a history of malignancy may be a group at particularly high risk for the development of subsequent lung cancer.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
17.
Insights Imaging ; 2(6): 679-698, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22347986

RESUMEN

BACKGROUND: 18F-FDG is a glucose analogue that is taken up by a wide range of malignancies. 18F-FDG PET-CT is now firmly established as an accurate method for the staging and restaging of various cancers. However, 18F-FDG also accumulates in normal tissue and other non-malignant conditions, and some malignancies do not take up F18-FDG or have a low affinity for the tracer, leading to false-positive and false-negative interpretations. METHODS: PET-CT allows for the correlation of two separate imaging modalities, combining both morphological and metabolic information. We should use the CT to help interpret the PET findings. In this article we will highlight specific false-negative and false-positive findings that one should be aware of when interpreting oncology scans. RESULTS: We aim to highlight post-treatment conditions that are encountered routinely on restaging scans that can lead to false-positive interpretations. We will emphasise the importance of using the CT component to help recognise these entities to allow improved diagnostic accuracy. CONCLUSION: In light of the increased use of PET-CT, it is important that nuclear medicine physicians and radiologists be aware of these conditions and correlate the PET and CT components to avoid misdiagnosis, over staging of disease and unnecessary biopsies.

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