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PURPOSE: To determine the feasibility and acceptability of using a patient decision aid (DA) for women with elevated breast cancer risk who are considering MRI screening. METHODS: This pilot study employed a mixed methods design to develop, modify, and test an interactive DA. The DA was administered among a consecutive patient sample with an estimated Tyrer-Cuzick v.8 lifetime breast cancer risk of 20% or greater and without a pathologic genetic mutation. The decisional conflict scale was used to measure decisional conflict. Post-intervention provider and patient feedback evaluated shared decision-making, feasibility, and acceptability. RESULTS: Twenty-four patients participated, with a median age of 44 years. Prior to DA use, sixteen patients (67%) were unsure whether to add MRI to their screening, six patients elected MRI (25%), and two patients declined MRI (8%). Following DA use, thirteen of sixteen of the initially undecided participants (81%) established a preference, with eleven electing to add MRI screening. Of participants with an initial preference, all maintained the same decision following use of the DA. Prior to the DA, the median decisional conflict score among participants was 25% (range 0-60%) compared with 0% (range 0-25%) after the DA. Healthcare providers reported that the DA was useful and easily incorporated into clinical workflow. CONCLUSIONS: This pilot study shows that there may be a benefit to DA utilization in the high-risk breast cancer clinic to guide shared decision-making in establishing a screening preference. The findings warrant further research to test the use of the DA in a larger, multi-site trial.
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Neoplasias de la Mama , Adulto , Femenino , Humanos , Neoplasias de la Mama/genética , Toma de Decisiones , Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer , Proyectos Piloto , Persona de Mediana EdadRESUMEN
INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a standard practice for staging cutaneous melanoma. High false-negative rates have an increased interest in adjunctive techniques for localizing SLNs. Mobile gamma cameras (MGCs) represent potential tools to enhance SLNB performance. METHODS: An institutional review board approval was obtained for this study (ClinicalTrials.gov ID NCT01531608). After obtaining informed consent, 20 eligible melanoma patients underwent 99mTc sulfur colloid injection and standard lymphoscintigraphy with a fixed gamma camera (FGC). A survey using a 20 cm square MGC, performed immediately preoperatively by the study surgeon, was used to establish an operative plan while blinded to the FGC results. Subsequently, SLNB was performed using a gamma probe and a novel 6 cm diameter handheld MGC. RESULTS: A total of 24 SLN basins were detected by FGC. Prior to unblinding, all 24 basins were identified with the preoperative MGC and the operative plan established by preoperative MGC imaging was confirmed accurate by review of the FGC images. All individual sentinel lymph nodes were identified during intraoperative MGC imaging, and in 5/24 (21%) cases, surgeon-reported additional clinically useful information was obtained from the MGC. CONCLUSIONS: Preoperative MGC images provide information consistent with FGC images for planning SLNB and in some cases provide additional information that aided in surgical decision-making.
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Melanoma , Neoplasias Cutáneas , Humanos , Cámaras gamma , Ganglios Linfáticos/patología , Linfocintigrafia , Melanoma/patología , Radiofármacos , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/patología , Azufre Coloidal Tecnecio Tc 99mRESUMEN
INTRODUCTION: Inguinal complete lymph node dissection (CLND) for metastatic melanoma exposes the femoral vein and artery. To protect femoral vessels while preserving the sartorius muscle, we developed a novel sartorius and adductor fascial flap (SAFF) technique for coverage. METHODS: The SAFF technique includes dissection of fascia off sartorius and/or adductor muscles, rotation over femoral vasculature, and suturing into place. Patients who underwent inguinal CLND with SAFF for melanoma at our institution were identified retrospectively from a prospectively-collected database. Patient characteristics and post-operative outcomes were obtained. Multivariate logistic regression assessed associations of palpable and non-palpable disease with wound complications. RESULTS: From 2008 to 2019, 51 patients underwent CLND with SAFF. Median age was 62 years, and 59% were female. Thirty-one (61%) patients were presented with palpable disease and 20 (39%) had non-palpable disease. Fifty-five percent (95% confidence interval CI: 40%-69%) experienced at least one wound complication: wound infection was most common (45%; 95% CI: 31%-60%), while bleeding was the least (2%; 95% CI: 0.05%-11%). Complications were similar, with and without palpable disease. CONCLUSIONS: The SAFF procedure covers femoral vessels, minimizes bleeding, preserves the sartorius muscle, and uses standard surgical techniques easily adoptable by surgeons who perform inguinal CLND.
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Melanoma , Neoplasias Cutáneas , Femenino , Ingle/patología , Ingle/cirugía , Humanos , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Masculino , Melanoma/patología , Persona de Mediana Edad , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Colgajos Quirúrgicos/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Lymphatic drainage from subcostal nodes, along the costal groove, have not previously been characterized as sites for melanoma drainage and metastasis. This study reports a series of patients with subcostal nodes draining primary melanomas, with characterization of the sites of primary melanomas that drain to these nodes. METHODS: Patients who presented to our institution between 2005 and 2020 with documented cutaneous melanoma and sentinel lymph node biopsy of a subcostal node (sentinel = S), or metastases to subcostal nodes later in clinical management (recurrent = R) were included. Patient demographics, melanoma pathology, nodal features, imaging information, surgical approaches, and outcomes data were collected. RESULTS: Six patients had subcostal sentinel nodes (SNs). Primary sites included the posterior trunk and lateral chest wall. Subcostal nodes were found under ribs 10-12. Subcostal SNs had at least one dimension measuring 3 mm or less. There were no surgical complications related to removing the subcostal SN. CONCLUSIONS: Melanoma can metastasize to subcostal lymph nodes and be found at the time of SN biopsy or identified at recurrence. These small nodes are fed by lymphatic channels that run in the neurovascular bundle under the ribs. When lymphatic mapping identifies a subcostal SN, it should be excised.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Metástasis Linfática/patología , Cintigrafía , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/métodos , Escisión del Ganglio Linfático , Melanoma Cutáneo MalignoRESUMEN
INTRODUCTION: Optimal approaches to induce T cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T cell recruitment and may be induced by IFN. This study tests the hypothesis that intratumoral administration of IFNγ will induce CXCL9-11 and will induce T cell recruitment and anti-tumor immune signatures in melanoma metastases. PATIENTS AND METHODS: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides and received IFNγ intratumorally. Effects on the tumor microenvironment were evaluated in sequential tumor biopsies. Adverse events (AEs) were recorded. T cell responses to vaccination were assessed in PBMC by IFNγ ELISPOT assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression, and gene expression. RESULTS: Vaccination and intratumoral administration of IFNγ were well tolerated. Circulating T cell responses to vaccine were detected in six of nine patients. IFNγ increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone, nor the addition of IFNγ promoted immune cell infiltration or induced anti-tumor immune gene signatures. CONCLUSION: The melanoma vaccine induced circulating T cell responses, but it failed to infiltrate metastases, thus highlighting the need for combination strategies to support T cell infiltration. A single intratumoral injection of IFNγ induced T cell-attracting chemokines; however, it also induced secondary immune regulation that may paradoxically limit immune infiltration and effector functions. Alternate dosing strategies or additional combinatorial treatments may be needed to promote trafficking and retention of tumor-reactive T cells in melanoma metastases.
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Vacunas contra el Cáncer/inmunología , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/metabolismo , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Interferón gamma/uso terapéutico , Melanoma/terapia , Linfocitos T/inmunología , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/inmunología , Movimiento Celular , Células Cultivadas , Ensayo de Immunospot Ligado a Enzimas , Femenino , Estudios de Seguimiento , Humanos , Linfocitos Infiltrantes de Tumor/patología , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Fragmentos de Péptidos/inmunología , Análisis de Supervivencia , Vacunas de Subunidad/inmunologíaRESUMEN
BACKGROUND: The extent to which ACOSOG Z0011 findings are applicable to patients undergoing breast-conserving therapy (BCT) is uncertain. We prospectively assessed how often axillary dissection (ALND) was avoided in an unselected, consecutive patient cohort meeting Z0011 eligibility criteria and whether subgroups requiring ALND could be identified preoperatively. METHODS: Patients with cT1,2cN0 breast cancer undergoing BCT were managed without ALND for metastases in <3 sentinel nodes (SNs) and no gross extracapsular extension (ECE). Patients with and without indications for ALND were compared using Fisher's exact and Wilcoxon rank sum tests. RESULTS: From August 2010 to November 2012, 2,157 invasive cancer patients had BCT. A total of 380 had histologic nodal metastasis; 93 did not meet Z0011 criteria. Of 287 with ≥1 H&E-positive SN (209 macrometastases), 242 (84 %) had indications for SN only. ALND was indicated in 45 for ≥3 positive SNs (n = 29) or ECE (n = 16). The median number of SNs removed in the SN group was 3 versus 5 in the ALND group (p < 0.0001). Age, hormone receptor and HER2 status, and grade did not differ between groups; tumors were larger in the ALND group (p < 0.0001). Of ALND patients, 72 % had additional positive nodes (median = 1; range 1-19). No axillary recurrences have occurred (median follow-up, 13 months). CONCLUSIONS: ALND was avoided in 84 % of a consecutive series of patients having BCT, suggesting that most patients meeting ACOSOG Z0011 eligibility have a low axillary tumor burden. Age, ER, and HER2 status were not predictive of ALND, and the criteria used for ALND (≥3 SNs, ECE) reliably identified patients at high risk for residual axillary disease.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Adulto , Anciano , Anciano de 80 o más Años , Axila , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
The critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.
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Vacunas contra el Cáncer , Melanoma , Humanos , Masculino , Adyuvantes Inmunológicos , Linfocitos T CD8-positivos , Melanoma/tratamiento farmacológico , Péptidos , FemeninoRESUMEN
BACKGROUND: Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. MATERIALS AND METHODS: Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0-5, >5-15, >15-30, and >30 mm. Images were scored on a scale from -1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. RESULTS: IR imaging was able to determine the malignancy of small (0-5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5-15 mm, sensitivity was 58% and specificity 98%. For lesions >15-30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%-100% across all strata, and the negative predictive value was 95% for >15-30 mm lesions and 80% for >30 mm lesions. CONCLUSIONS: Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies.
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Melanoma/diagnóstico , Melanoma/secundario , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/secundario , Termografía , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Rayos Infrarrojos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Seguridad del Paciente , Proyectos Piloto , Sensibilidad y EspecificidadRESUMEN
Nipple discharge is the third most common breast-related complaint but is rarely the presenting symptom of breast cancer. Distinguishing patients with physiologic versus pathologic nipple discharge, and treating the later according to the underlying pathologic condition is of utmost importance. Nipple discharge is categorized as lactational, physiologic, or pathologic. Physiologic nipple discharge (galactorrhea) is typically caused by hyperprolactinemia due to medications (ie, antipsychotics), pituitary tumors, and endocrine disorders. When a suspicious radiologic lesion is identified, pathologic assessment of the lesion is indicated. Patients with pathologic nipple discharge should be referred to a breast surgeon for definitive treatment and follow-up.
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Enfermedades de la Mama , Neoplasias de la Mama , Galactorrea , Secreción del Pezón , Femenino , Embarazo , Humanos , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/etiología , Enfermedades de la Mama/terapia , Mama/patología , Galactorrea/diagnóstico , Galactorrea/etiología , Galactorrea/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapiaRESUMEN
OBJECTIVES: To determine the feasibility and acceptability of using a decision aid (DA) in a breast surgery clinic. SAMPLE & SETTING: 42 patients with minimally suspicious mammograms and two physicians participated in this study at an outpatient breast specialty clinic in Virginia. METHODS & VARIABLES: A quasiexperimental single group pilot study was conducted to determine the feasibility of DecisionKEYS, a theory-based, interactive DA intervention. Patients with minimally suspicious mammogram results chose between breast biopsy or close imaging follow-up. The Decisional Conflict Scale was used to measure decisional conflict. The Decision-Making Quality Scale was used to evaluate the overall decision process. Postintervention physician and patient feedback evaluated feasibility and acceptability. RESULTS: Participants and physicians rated the DA as helpful. Decisional Conflict Scale scores were low before and after the intervention. Physicians reported the DA was feasible for workflow, and the majority reported using the DA in making final recommendations. Management recommendation (breast biopsy, close imaging follow-up) changed in 26 of 42 cases from pre- to postintervention. The majority of participants underwent breast biopsy. IMPLICATIONS FOR NURSING: The feasibility and acceptability of the DA were beneficial to patients and clinic workflow.
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Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer , Humanos , Toma de Decisiones , Mamografía , Proyectos PilotoRESUMEN
BACKGROUND: A vaccine containing 6 melanoma-associated peptides to stimulate helper T cells (6MHP) is safe, immunogenic, and clinically active. A phase I/II trial was designed to evaluate safety and immunogenicity of 6MHP vaccines plus programmed death 1 (PD-1) blockade. PARTICIPANTS AND METHODS: Participants with advanced melanoma received 6MHP vaccines in an incomplete Freund's adjuvant (6 vaccines over 12 weeks). Pembrolizumab was administered intravenously every 3 weeks. Tumor biopsies at baseline and day 22 were analyzed by multiplex immunohistochemistry. Primary end points were safety (Common Terminology Criteria for Adverse Events V.4.03) and immunogenicity (ex vivo interferon-γ ELISpot assay). Additional end points included changes in the tumor microenvironment (TME) and clinical outcomes. RESULTS: Twenty-two eligible participants were treated: 6 naïve to PD-1 antibody (Ab) and 16 PD-1 Ab-experienced. Median follow-up was 24.4 months. Most common treatment-related adverse events (any grade) included injection site reactions, fatigue, anemia, lymphopenia, fever, elevated aspartate aminotransferase, pruritus, and rash. Treatment-related dose-limiting toxicities were observed in 3 (14%) participants, which did not cross the study safety bound. A high durable T cell response (Rsp) to 6MHP was detected in only one participant, but twofold T cell Rsps to 6MHP were detected in 7/22 (32%; 90% CI (16% to 52%)) by week 13. Objective clinical responses were observed in 23% (1 complete response, 4 partial responses), including 4/6 PD-1 Ab-naïve (67%) and 1/16 PD-1 Ab-experienced (6%). Overall survival (OS) was longer for PD-1 Ab-naïve than Ab-experienced participants (HR 6.3 (90% CI (2.1 to 28.7)). In landmark analyses at 13 weeks, OS was also longer for those with T cell Rsps (HR 6.5 (90% CI (2.1 to 29.2)) and for those with objective clinical responses. TME evaluation revealed increased densities of CD8+ T cells, CD20+ B cells, and Tbet+ cells by day 22. CONCLUSIONS: Treatment with the 6MHP vaccine plus pembrolizumab was safe, increased intratumoral lymphocytes, and induced T cell Rsps associated with prolonged OS. The low T cell Rsp rate in PD-1 Ab-experienced participants corroborates prior murine studies that caution against delaying cancer vaccines until after PD-1 blockade. The promising objective response rate and OS in PD-1 Ab-naïve participants support consideration of a larger study in that setting.
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Vacunas contra el Cáncer , Melanoma , Linfocitos T CD8-positivos , Humanos , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Vacunas de Subunidad/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the sensitivity and clinical utility of intraoperative mobile gamma camera (MGC) imaging in sentinel lymph node biopsy (SLNB) in melanoma. BACKGROUND: The false-negative rate for SLNB for melanoma is approximately 17%, for which failure to identify the sentinel lymph node (SLN) is a major cause. Intraoperative imaging may aid in detection of SLN near the primary site, in ambiguous locations, and after excision of each SLN. The present pilot study reports outcomes with a prototype MGC designed for rapid intraoperative image acquisition. We hypothesized that intraoperative use of the MGC would be feasible and that sensitivity would be at least 90%. METHODS: From April to September 2008, 20 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and SLNB was performed with use of a conventional fixed gamma camera (FGC), and gamma probe followed by intraoperative MGC imaging. Sensitivity was calculated for each detection method. Intraoperative logistical challenges were scored. Cases in which MGC provided clinical benefit were recorded. RESULTS: Sensitivity for detecting SLN basins was 97% for the FGC and 90% for the MGC. A total of 46 SLN were identified: 32 (70%) were identified as distinct hot spots by preoperative FGC imaging, 31 (67%) by preoperative MGC imaging, and 43 (93%) by MGC imaging pre- or intraoperatively. The gamma probe identified 44 (96%) independent of MGC imaging. The MGC provided defined clinical benefit as an addition to standard practice in 5 (25%) of 20 patients. Mean score for MGC logistic feasibility was 2 on a scale of 1-9 (1 = best). CONCLUSIONS: Intraoperative MGC imaging provides additional information when standard techniques fail or are ambiguous. Sensitivity is 90% and can be increased. This pilot study has identified ways to improve the usefulness of an MGC for intraoperative imaging, which holds promise for reducing false negatives of SLNB for melanoma.
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Cámaras gamma , Ganglios Linfáticos/diagnóstico por imagen , Melanoma/patología , Biopsia del Ganglio Linfático Centinela/instrumentación , Neoplasias Cutáneas/patología , Adulto , Anciano , Intervalos de Confianza , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Cuidados Intraoperatorios/métodos , Ganglios Linfáticos/patología , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Cintigrafía/instrumentación , Cintigrafía/métodos , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/cirugía , Estadísticas no Paramétricas , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Peptide vaccines designed to stimulate melanoma-reactive CD4+ T cells can induce T cell and antibody (Ab) responses, associated with enhanced overall survival. We hypothesized that adding toll-like receptor 3 agonist polyICLC to an incomplete Freund's adjuvant (IFA) would be safe and would support strong, durable CD4+ T cell and Ab responses. We also hypothesized that oral low-dose metronomic cyclophosphamide (mCy) would be safe, would reduce circulating regulatory T cells (T-regs) and would further enhance immunogenicity. PARTICIPANTS AND METHODS: An adaptive design based on toxicity and durable CD4+ T cell immune response (dRsp) was used to assign participants with resected stage IIA-IV melanoma to one of four study regimens. The regimens included a vaccine comprising six melanoma peptides restricted by Class II MHC (6MHP) in an emulsion with IFA alone (Arm A), with IFA plus systemic mCy (Arm B), with IFA+ local polyICLC (Arm C), or with IFA+ polyICLC+ mCy (Arm D). Toxicities were recorded (CTCAE V.4.03). T cell responses were measured by interferon γ ELIspot assay ex vivo. Serum Ab responses to 6MHP were measured by ELISA. Circulating T-regs were assessed by flow cytometry. RESULTS: Forty-eight eligible participants were enrolled and treated. Early data on safety and dRsp favored enrollment on arm D. Total enrollment on Arms A-D were 3, 7, 6, and 32, respectively. Treatment-related dose-limiting toxicities (DLTs) were observed in 1/7 (14%) participants on arm B and 2/32 (6%) on arm D. None exceeded the 25% DLT threshold for early closure to enrollment for any arm. Strong durable T cell responses to 6MHP were detected ex vivo in 0%, 29%, 67%, and 47% of participants on arms A-D, respectively. IgG Ab responses were greatest for arms C and D. Circulating T-regs frequencies were not altered by mCy. CONCLUSIONS: 6MHP vaccines administered with IFA, polyICLC, and mCy were well tolerated. The dRsp rate for arm D of 47% (90% CI 32 to 63) exceeded the 18% (90% CI 11 to 26) rate previously observed with 6MHP in IFA alone. Vaccination with IFA+ polyICLC (arm C) also showed promise for enhancing T cell and Ab responses.
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Carboximetilcelulosa de Sodio/análogos & derivados , Ciclofosfamida/administración & dosificación , Adyuvante de Freund/administración & dosificación , Lípidos/administración & dosificación , Melanoma/tratamiento farmacológico , Poli I-C/administración & dosificación , Polilisina/análogos & derivados , Vacunas de Subunidad/administración & dosificación , Administración Metronómica , Administración Oral , Anticuerpos/sangre , Linfocitos T CD4-Positivos/metabolismo , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Carboximetilcelulosa de Sodio/administración & dosificación , Carboximetilcelulosa de Sodio/efectos adversos , Terapia Combinada , Ciclofosfamida/efectos adversos , Femenino , Adyuvante de Freund/efectos adversos , Humanos , Lípidos/efectos adversos , Masculino , Melanoma/inmunología , Melanoma/patología , Estadificación de Neoplasias , Poli I-C/efectos adversos , Polilisina/administración & dosificación , Polilisina/efectos adversos , Linfocitos T Reguladores/metabolismo , Resultado del Tratamiento , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunologíaRESUMEN
BACKGROUND: Large centers have described triangular intermuscular space (TIS) sentinel nodes (SNs) for some melanomas of the back. However, their management remains controversial and poorly characterized, especially as related to the ipsilateral axillary node basin. The aim of this study was to summarize our experience with TIS SN, which may contribute to defining their appropriate surgical management. METHODS: We performed a retrospective review on surgical patients from January 1993 to April 2009. Among 293 patients with upper back melanoma, data were collected on those with TIS SN. RESULTS: Fourteen patients (5%) with melanoma of the upper back had a TIS SN, 6 of whom (43%) were incorrectly identified at lymphoscintigraphy as axillary, and 11 of whom (79%) had a concurrent axillary SN. Micrometastatic disease was identified in TIS SN in two patients (14%) and in an axillary SN in one (9%). We found direct lymphatic drainage independently to the TIS and to the axilla, as well as a more typical pattern of drainage first to the TIS node and then to axillary nodes. CONCLUSIONS: We defined three patterns of lymphatic drainage to TIS and axillary nodes. The TIS and axilla are anatomically linked; patients with SN in both locations should undergo biopsies of both for optimal nodal staging. We recommend directed evaluation for TIS SN in patients with upper back melanomas and recommend clearing the TIS at the time of TIS SN biopsy. Melanoma can metastasize to TIS SN, and we discuss considerations for management of the axilla in patients with positive TIS nodes.
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Drenaje , Ganglios Linfáticos/patología , Vasos Linfáticos/patología , Melanoma/secundario , Neoplasias de los Músculos/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Axila , Femenino , Humanos , Metástasis Linfática , Vasos Linfáticos/diagnóstico por imagen , Vasos Linfáticos/cirugía , Masculino , Melanoma/diagnóstico por imagen , Melanoma/cirugía , Persona de Mediana Edad , Neoplasias de los Músculos/diagnóstico por imagen , Neoplasias de los Músculos/cirugía , Estadificación de Neoplasias , Pronóstico , Cintigrafía , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugíaRESUMEN
Successful management of epithelial skin cancers with imiquimod 5% cream (Aldara), an immunomodulatory agent, led to speculation that it may promote an immune response against melanoma. Studies, mostly case reports, have assessed the value of imiquimod as a topical treatment for dermal melanoma metastases that prove difficult to manage surgically. The precise value of imiquimod, however, in treatment of dermal and subcutaneous metastases remains unclear. A case at our institution elucidates histopathologically that subcutaneous metastases may progress despite excellent treatment of superficial dermis in the same location. In preparation for a clinical trial using imiquimod to treat patients with dermal melanoma metastases, we have treated several patients off protocol. We present a case report in which the observed changes are documented photographically and histologically. The patient experienced dramatic improvement in the locally treated dermis with concurrent regional treatment failure in the subcutaneous space. Our experience supports growing evidence that imiquimod for some provides an effective option for dermal disease. The unique histological documentation we provide regarding the differential effectiveness of imiquimod in treating various tissue components may help guide future investigations regarding optimal clinical application of imiquimod therapy for melanoma metastases.
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Aminoquinolinas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Dermis/efectos de los fármacos , Dermis/patología , Femenino , Neoplasias de Cabeza y Cuello/secundario , Humanos , Imiquimod , Melanoma/secundario , Persona de Mediana Edad , Neoplasias Cutáneas/secundario , Tejido Subcutáneo/efectos de los fármacos , Tejido Subcutáneo/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Assessment of lymphatic status via sentinel lymph node (SLN) biopsy is an integral and crucial part of melanoma surgical oncology. The most common technique for sentinel node mapping is preoperative planar scintigraphy of an injected gamma-emitting lymphatic tracer followed by intraoperative node localization using a non-imaging gamma probe with auditory feedback. In recent years, intraoperative visualization of SLNs in 3D has become possible by coupling the probe to an external system capable of tracking its location and orientation as it is read out, thereby enabling computation of the 3D distribution of the tracer (freehand SPECT). In this project, the non-imaging probe of the fhSPECT system was replaced by a unique handheld gamma camera containing an array of sodium iodide crystals optically coupled to an array of silicon photomultipliers (SiPMs). A feasibility study was performed in which preoperative SLN mapping was performed using camera fhSPECT and the number of detected nodes was compared to that visualized by lymphoscintigraphy, probe fhSPECT, and to the number ultimately excised under non-imaging probe guidance. RESULTS: Among five subjects, SLNs were detected in nine lymphatic basins, with one to five SLNs detected per basin. A basin-by-basin comparison showed that the number of SLNs detected using camera fhSPECT exceeded that using lymphoscintigraphy and probe fhSPECT in seven of nine basins and five of five basins, respectively. (Probe fhSPECT scans were not performed for four basins.) It exceeded the number excised under non-imaging probe guidance for seven of nine basins and equaled the number excised for the other two basins. CONCLUSIONS: Freehand SPECT using a prototype SiPM-based gamma camera demonstrates high sensitivity for detection of SLNs in a preoperative setting. Camera fhSPECT is a potential means for efficiently obtaining real-time 3D activity distribution maps in applications such as image-guided percutaneous biopsy, and surgical SLN biopsy or radioguided tumor excision.
RESUMEN
BACKGROUND: Metastatic melanoma to abdominal and retroperitoneal viscera carries a poor prognosis possibly resulting in reluctance to offer surgical management. There is value in defining the morbidity of such surgery. METHODS: Review of a prospectively maintained database identified patients with metastatic melanoma to abdominal or retroperitoneal viscera who underwent surgery from 9/99 to 8/06. RESULTS: Nineteen patients underwent surgery for metastasis to abdominal or retroperitoneal viscera detected by clinical symptoms (80%), or imaging (20%). The median length of stay was 7 days. There was no perioperative mortality. Surgical complications occurred in four patients. At initial follow-up, 13 patients (68%) had returned to baseline function, 7 of which reported improvement. Four patients (21%) had minimal symptoms, and only two patients (11%) had significantly limited function. Median follow-up was 35 months, at which time 9 of the 19 patients (47%) were still alive, with 3- and 5-year Kaplan-Meier survival estimates of 53% (SE 12) and 45% (SE 12), respectively, and 2 of the 19 patients are alive at over 8 years since surgery. CONCLUSION: In selected cases, surgery may have both palliative benefit and curative potential for patients with visceral metastases of melanoma. Surgical management of such patients should be encouraged in appropriate clinical settings.
Asunto(s)
Neoplasias del Sistema Digestivo/cirugía , Tiempo de Internación , Melanoma/cirugía , Recuperación de la Función , Neoplasias Retroperitoneales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/secundario , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Melanoma/secundario , Persona de Mediana Edad , Complicaciones Posoperatorias , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/secundarioRESUMEN
BACKGROUND: Identifying factors that impact progression of surgery trainees into academic versus non-academic practices may permit tailoring residency experiences to promote academic careers in institutions charged with the training of future surgeon scientists. The aim of this study was to identify factors associated with progression of surgery trainees into academic versus non-academic practice. METHODS: A survey was distributed to 135 surgeons graduating from the University of Virginia residency program from 1964-2016, a single academic institution. Questions addressed practice type, research productivity, work/life balance, mentorship, and overall sentiment toward research and academic surgery. A 5-point Likert scale measured career satisfaction and influence of factors in practice setting choice. RESULTS: Of the 135 surveys that were electronically distributed, 69 participants responded (response rate: 51%). Of the 54 with known current practice types, 34 (63%) were academic and 20 (37%) non-academic. Academic surgeons reported more publications by the conclusion of surgery training (56% vs 25% with >10 publications, Pâ¯=â¯.02). More academic surgeons reported >$100,000 in student debt at graduation (44% vs 25%, P < .05). Factors encouraging an academic career were similar for both types of surgeons, including involvement in education of trainees and access to mentorship. Both groups were discouraged from an academic practice by requirements of grant-writing and funding responsibilities. Surgeons in academic practice were more likely to recommend surgery as a career to a current medical student (100% vs 70%, Pâ¯=â¯.001). CONCLUSION: This knowledge may help to tailor training experiences to promote academic careers. By supporting funding mechanisms and grant-writing programs, while encouraging mentorship and productive research experiences, current surgical trainees may be more enthusiastic about a career in academic practice.