RESUMEN
Advanced endometrial cancer is associated with poor outcomes and few treatment options exist. Recently, the US Federal Drug Administration approved pembrolizumab for the treatment of endometrial cancers that are deficient in mismatch repair and have high microsatellite instability (MSI). Lynch syndrome is an autosomal dominant disease that causes MSI-high endometrial cancer. We report a case of a 46-year-old woman with Lynch syndrome and advanced endometrial cancer who experienced progressive disease after treatment with chemotherapy with carboplatin and paclitaxel. She was then treated with single-agent pembrolizumab and had an exceptional response. She was noted to have a significant decrease in the size of a large uterine mass extending into the vagina and vulva, as well as decrease in the size of lymphadenopathy. Data are limited at this time for patients with Lynch syndrome treated with single-agent pembrolizumab. Our case report seeks to add to the body of literature that suggests that this patient population may particularly benefit from this novel therapy.
Asunto(s)
Neoplasias Endometriales , Neoplasias Primarias Múltiples , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Endometrio , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/terapia , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/terapiaRESUMEN
We report a collision tumor in the ovary of a 60-yr-old woman composed of high-grade serous carcinoma and Sertoli-Leydig cell tumor. Collision tumors in the ovary are rare and to the best of our knowledge, combination of ovarian high-grade serous carcinoma and Sertoli-Leydig cell tumor has not been described before.
Asunto(s)
Carcinoma , Neoplasias Ováricas , Tumor de Células de Sertoli-Leydig , Masculino , Femenino , Humanos , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/patología , Neoplasias Ováricas/patologíaRESUMEN
Uterine carcinosarcomas (UCS) are aggressive tumors characterized by their biphasic nature, consisting of high-grade epithelial and mesenchymal elements. One component may predominate over the other. We present the case of a 59-year-old female who initially received a diagnosis of endometrial serous carcinoma and presented one year later with a malignant neoplasm in the lung featuring osteosarcomatous differentiation. Notably, the bone scan did not reveal any evidence of a primary bone tumor. However, additional sampling from the endometrium demonstrated a UCS with an osteosarcomatous component.Upon reviewing existing literature, it has been observed that metastases in carcinosarcoma cases generally arise from the carcinomatous component. Conversely, the sarcomatous component typically spreads locally to areas such as the vagina, cervix, or fallopian tubes. The presented case stands out as a unique instance of an undiagnosed UCS manifesting as metastatic osteosarcoma in the lung. This case underscores the complexity and diverse presentations of UCS and emphasizes the importance of comprehensive evaluation in understanding its clinical manifestations.
Asunto(s)
Neoplasias Óseas , Carcinosarcoma , Neoplasias Endometriales , Osteosarcoma , Femenino , Humanos , Persona de Mediana Edad , Osteosarcoma/diagnóstico , Carcinosarcoma/diagnóstico , Neoplasias Óseas/diagnóstico por imagen , PulmónRESUMEN
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1)-deficient undifferentiated uterine sarcoma (SDUS) is a recently described uterine sarcoma. It is characterized by predominantly rhabdoid or large epithelioid cells with abundant cytoplasm and varying components of small and spindle cells, resembling the 'large cell variant' of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). In addition, SMARCA4-inactivating mutations have been described as the driver mutations in SDUS. However, undifferentiated endometrial carcinoma (UDEC) and dedifferentiated endometrial carcinoma (DDEC) may show some clinical and morphological overlaps with SDUS, and about 20% of reported UDEC/DDEC cases also have loss expression of SMARCA4. SDUS is a very aggressive disease and universally lethal in all reported cases. Differentiating SDUS from UDEC/DDEC is relevant for the prognosis, pathogenesis, and possible targeted therapies for the disease. In this study, we compared the clinical, morphological, immunohistochemical, and molecular characteristics of 10 tumors including 2 SDUS, 2 SCCOHT, 1 uterine carcinoma with neuroendocrine differentiation (UDEC?), and 5 UDEC/DDEC. All 5 UDEC/DDEC cases showed strong and diffuse nuclear positivity for SOX2, while all SCCOHT and SDUS cases were completely negative. We concluded that SOX2 could be a useful marker for the differential diagnosis between SDUS and UDEC/DDEC.
Asunto(s)
Carcinoma Endometrioide , Carcinoma de Células Pequeñas , Neoplasias Endometriales , Neoplasias Pulmonares , Neoplasias Ováricas , Sarcoma , Neoplasias Uterinas , Biomarcadores de Tumor/genética , Carcinoma Endometrioide/diagnóstico , Carcinoma Epitelial de Ovario , Carcinoma de Células Pequeñas/diagnóstico , ADN Helicasas/genética , Diagnóstico Diferencial , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Proteínas Nucleares/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Factores de Transcripción SOXB1 , Sarcoma/patología , Factores de Transcripción/genética , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologíaRESUMEN
Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor of fibroblastic origin, which shows a prominent hemangiopericytoma-like branching pattern. It may be found at any location and can rarely involve the female genital tract with the vulva being the most common site of involvement. This is a case report of vulvar SFT in a 47-yr-old female who presented with a slow growing vulvar mass for 3 yr. Histologic examination showed a neoplasm composed of ovoid to spindle shaped cells with hypocellular and hypercellular areas in a collagenous background. Prominent hemangiopericytoma-like vessels were identified. Immunohistochemistry showed positive staining of the tumor cells for CD34, STAT6, ER, PR, and vimentin. Immunoshistochemical staining for desmin, SMA, and S100 was negative. The majority of SFTs have a NAB2-STAT6 gene fusion on chromosome 12, resulting in nuclear STAT6 overexpression, which is a sensitive and specific immunohistochemical marker for its diagnosis. Only 25 cases of vulvar SFT have been reported in the English literature and it should be considered in the differential diagnosis of spindle cell lesions at this site.
Asunto(s)
Biomarcadores de Tumor/genética , Hemangiopericitoma/diagnóstico , Proteínas Represoras/genética , Factor de Transcripción STAT6/genética , Tumores Fibrosos Solitarios/diagnóstico , Neoplasias de la Vulva/diagnóstico , Núcleo Celular/metabolismo , Diagnóstico Diferencial , Femenino , Hemangiopericitoma/genética , Hemangiopericitoma/patología , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Factor de Transcripción STAT6/metabolismo , Tumores Fibrosos Solitarios/genética , Tumores Fibrosos Solitarios/patología , Vulva/patología , Neoplasias de la Vulva/genética , Neoplasias de la Vulva/patologíaRESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) in patients with legacy cardiovascular implantable electronic devices (CIEDs) in situ is likely underutilized. We hypothesized the clinical benefit of MRI would outweigh the risks in legacy CIED patients. METHODS: This is a single-center retrospective study that evaluated and classified the utility of MRI using a prospectively maintained database. The outcomes were classified as aiding in diagnosis, treatment, or both for the patients attributable to the MRI. We then assessed the incidence of adverse effects (AE) when the MRI was performed. RESULTS: In 668, MRIs performed on 479 patients, only 13 (1.9%) MRIs did not aid in the diagnosis or treatment of the patient. Power-on reset events without clinical sequelae in three scans (0.45%) were the only AE. The probability of an adverse event happening without any benefit from the MRI scan was 1.1 × 10-4 . A maximum benefit in diagnosis using MRI was obtained in ruling out space-occupying lesions (121/185 scans, 65.4%). Scans performed in patients for elucidating answers to queries in treatment were most frequently done for disease staging at long term follow-up (167/470 scans, 35.5%). Conservative treatment (184/470 scans, 39%) followed by medication changes (153/470 scans, 28.7%) were the most common treatment decisions made. CONCLUSIONS: The utility of MRI in patients with non-MRI-conditional CIEDs far outweighs the risk of adverse events when imaging is done in the context of a multidisciplinary program that oversees patient safety.
Asunto(s)
Desfibriladores Implantables , Marcapaso Artificial , Desfibriladores Implantables/efectos adversos , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0-3 for HR (0-CR, 1-VGPR, 2-PR, 3-no response) and 0-2 for OR (0-AOR, 1-MOR, 2-NOR). Patients could be divided into two distinct CHOR groups (scores 0-3 and 4-5), with median OS in group 1 and group 2: Not reached vs. 34 months, p < 0.001 [Mayo] and 87 vs. 23 months, p < 0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies.
Asunto(s)
Antineoplásicos/uso terapéutico , Pruebas Hematológicas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Puntuaciones en la Disfunción de Órganos , Anciano , Estudios de Cohortes , Terapia Combinada , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Immunohistochemistry for mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 is an effective screen to detect individuals at risk for Lynch syndrome. College of American Pathologists guidelines stipulate that protein expression should be reported as present versus absent, as most patients with germline mutations in a mismatch repair gene have complete loss of protein expression in tumor cells. A similar approach is employed to screen for cancer patients eligible for immune checkpoint blockade. This "all or none" interpretive approach ignores substantial evidence that mismatch repair may be more finely regulated by other mechanisms. We have observed clinically that MSH6 expression is variable, even in carcinomas that are overall considered positive for MSH6 expression. A proof-of-principle study was therefore designed to more rigorously quantify the protein expression of MSH6 and its binding partner, MSH2, using image analysis applied to age-matched endometrioid grade 2 subsets that were either mismatch repair intact or MLH1-deficient due to MLH1 gene methylation. In both endometrioid groups, MSH6 expression was significantly lower than MSH2 expression. MSH6 expression increased in higher grade, mismatch repair intact serous carcinomas, but it was still significantly lower than that for MSH2. MSH2 expression was consistently high across the 3 different tumor groups. These results suggest that MSH6 expression is subject to wide fluctuations in expression, even when overall its expression is considered intact. While such fluctuations are likely not relevant for Lynch syndrome screening, they may be more impactful when considering patients eligible for immune checkpoint blockade.
Asunto(s)
Metilación de ADN/genética , Reparación de la Incompatibilidad de ADN/genética , Proteínas de Unión al ADN/genética , Neoplasias Endometriales/genética , Homólogo 1 de la Proteína MutL/genética , Anciano , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas de Unión al ADN/análisis , Neoplasias Endometriales/química , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/análisis , Proteína 2 Homóloga a MutS/química , Proteína 2 Homóloga a MutS/genéticaRESUMEN
This study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n = 229, 21%), both cardiac and renal involvement (n = 443, 41%) and cardiac involvement (n = 405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349 mg/l, P < 0.001). The proportion of patients with ≥ 10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P < 0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P < 0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16 months (P < 0.001) in patients not undergoing transplant and 5-year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P = 0.007), respectively. In conclusion, renal involvement alone or renal + cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.
Asunto(s)
Cardiomiopatías/terapia , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Enfermedades Renales/terapia , Anciano , Bortezomib/uso terapéutico , Cardiomiopatías/mortalidad , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Factores Inmunológicos/uso terapéutico , Enfermedades Renales/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre/métodos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and Asunto(s)
Mieloma Múltiple/terapia
, Tiempo de Tratamiento
, Resultado del Tratamiento
, Adulto
, Anciano
, Anciano de 80 o más Años
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Mieloma Múltiple/diagnóstico
, Mieloma Múltiple/mortalidad
, Análisis Multivariante
, Inducción de Remisión
, Factores de Riesgo
, Análisis de Supervivencia
RESUMEN
OBJECTIVE: To evaluate the prognostic impact of Holter findings in patients with light chain amyloidosis. PATIENTS AND METHODS: We evaluated 239 patients in whom light chain amyloidosis was diagnosed from January 1, 2010, through December 31, 2015, who underwent 24-hour Holter monitoring. RESULTS: Holter testing was done before stem cell transplant evaluation in 183 of the 239 patients (76.6%) and at diagnosis in 50 (20.9%). Holter findings were nonsustained ventricular tachycardia (NSVT) in 60 patients (25.1%), ventricular couplets in 103 (43.1)%, accelerated idioventricular rhythm in 32 (13.4%), and atrial fibrillation (AF) in 18 (7.5%). Overall survival (OS) at 3 and 6 months after Holter monitoring in patients with AF vs without AF was 78% (95% CI, 54%-91%) vs 96% (95% CI, 92%-98%) (P=.002) and 61% (95% CI, 38%-80%) vs 92% (95% CI, 87%-95%), (P<.001), respectively. In patients with and without NSVT, 3- and 6-month OS after Holter testing was 90% (95% CI, 80%-94%) vs 96% (95% CI, 91%-98%) (P=.12) and 77% (95% CI, 64%-85%) vs 94% (95% CI, 89%-97%) (P<.001), respectively. For patients with and without ventricular couplets, 3- and 6-month OS was 94% (95% CI, 88%-97%) vs 94% (95% CI, 89%-97%) (P=.98) and 84% (95% CI, 75%-89%) vs 94% (95% CI, 89%-97%) (P=.01), respectively. Atrial fibrillation (hazard ratio, 2.5; 95% CI, 1.2-5.0; P=.02) and NSVT (hazard ratio, 2.0; 95% CI, 1.1-3.5; P=.02) were independent predictors for OS after accounting for age and Mayo stage. For patients undergoing routine testing before stem cell transplant, AF (P=.002) and NSVT (P=.02) were associated with inferior OS at 6 months but did not retain statistical significance after adjusting for Mayo stage (P=.10 and P=.54, respectively). CONCLUSION: Atrial fibrillation and NSVT on 24-hour Holter monitoring are associated with inferior short-term OS outcomes but do not impact peritransplant mortality.
Asunto(s)
Fibrilación Atrial/fisiopatología , Electrocardiografía Ambulatoria/métodos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/fisiopatología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Anciano , Fibrilación Atrial/mortalidad , Electrocardiografía , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Achieving a complete response (CR) is associated with improved overall survival (OS) in multiple myeloma (MM), but data on duration of CR (DurCR) are limited. We evaluated 351 patients (2004-2016), achieving CR with first-line therapy. Patients with sustained DurCR ≥ 24 months (n = 177) had better OS; 150 vs. 81 months, p < 0.001. DurCR ≥ 24 months remained a significant predictor for OS (HR: 0.3, 95% CI: 0.2-0.5, p < 0.001) after adjusting for age, revised ISS stage, transplant and maintenance therapy. Landmark analysis at 24 months demonstrated similar results, OS: 150 vs. 83 months, p < 0.001. Survival benefit persisted even after loss of CR, with median OS being 89 vs. 56 months (p = 0.005), respectively. Patterns of loss of CR were heterogeneous, with biochemical relapse in 59 (25%); symptomatic relapse in 58 (24%); positive immunofixation/monoclonal protein rise not meeting relapse/progression criteria in 88 (37%) and abnormal free light chain ratio in LC MM in 34 (14%) patients. OS from start of first-line therapy was superior in patients starting second-line treatment for biochemical vs. symptomatic relapse (125 vs. 81 months, p = 0.001). This is likely attributable to underlying disease biology and prevention of end-organ damage by early treatment initiation, as benefit was independent of R-ISS stage.
Asunto(s)
Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/patología , Anciano , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/metabolismo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia , Resultado del TratamientoAsunto(s)
Amiloidosis/mortalidad , Amiloidosis/patología , Macroglobulinemia de Waldenström/mortalidad , Macroglobulinemia de Waldenström/patología , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/metabolismo , Femenino , Humanos , Inmunoglobulina M/metabolismo , Masculino , Persona de Mediana Edad , Macroglobulinemia de Waldenström/metabolismoRESUMEN
Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.
Asunto(s)
Citometría de Flujo , Cariotipificación , Mieloma Múltiple/mortalidad , Trisomía , Supervivencia sin Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Mieloma Múltiple/sangre , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Valor Predictivo de las Pruebas , Tasa de SupervivenciaRESUMEN
BACKGROUND: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use. METHODS: Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided. RESULTS: Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96.1% (49/51, 95% CI = 86.5% to 99.5%), and directly led to matched targeted therapy in 21.9% (46/210) with clinical response. CONCLUSIONS: Plasma ctDNA NGS detected a variety of oncogenic drivers with a shorter TAT compared with tissue NGS and matched patients to targeted therapy with clinical response. Positive findings on plasma NGS were highly concordant with tissue NGS and can guide immediate therapy; however, a negative finding in plasma requires further testing. Our findings support the potential incorporation of plasma NGS into practice guidelines.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/genética , Neoplasias Pulmonares/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/terapia , ADN Tumoral Circulante/sangre , Femenino , Técnicas de Genotipaje , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Biopsia Líquida , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Medicina de Precisión , Estudios ProspectivosRESUMEN
Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure. The data concerning the timing of ASCT (early in the disease course or at first relapse), single versus tandem (double) ASCT and the role and duration of consolidation and maintenance therapy post ASCT remain conflicting. This review aims to discuss the evolution of stem-cell transplant over the past 3 decades and its current role in the context of newer, safer and more effective therapeutic agents.
RESUMEN
We evaluated the prognostic impact of clonal circulating plasma cells (cPCs) detected by six-color multi-parametric flow cytometry (MFC) in light chain (AL) amyloidosis at diagnosis. Of the 154 patients who underwent MFC, cPCs were detected in 42% (n = 65) patients. Median number of cPCs was 81 per 150,000 events (range: 6-17,844). High bone marrow plasma cell percentage was an independent predictor of presence of cPCs. Presence of cPCs at diagnosis was associated with inferior overall survival (OS) (90 vs. 98 months, p = 0.003) and inferior progression free survival (PFS) (31 vs. 52 months, p = 0.02). Estimated 1, 2 and 5 year OS in the two groups was: 74, 64 and 57 and 89, 87, and 80%, respectively. Estimated PFS at 1, 2, and 5 years was: 69, 56, and 23% and 80, 74, and 37%, respectively. Furthermore, the presence of cPCs at diagnosis was an independent adverse predictor of OS in multivariable analysis. Achieving a very-good partial response, or better, was able to overcome the adverse impact of cPCs at diagnosis. Patients with cPCs at diagnosis may warrant closer monitoring post-treatment, especially if they do not achieve a deep hematologic response.