RESUMEN
Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy.
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Antineoplásicos Inmunológicos/uso terapéutico , Antígeno CD24/antagonistas & inhibidores , Inmunoterapia/métodos , Lectinas/metabolismo , Macrófagos/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Antineoplásicos Inmunológicos/inmunología , Antineoplásicos Inmunológicos/farmacología , Antígeno CD24/deficiencia , Antígeno CD24/genética , Antígeno CD24/inmunología , Línea Celular Tumoral , Humanos , Lectinas/antagonistas & inhibidores , Lectinas/genética , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Neoplasias/inmunología , Neoplasias/patología , Fagocitosis/efectos de los fármacos , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/genética , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunologíaRESUMEN
OBJECTIVE: To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin. METHODS: We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint 4.9.1.0 was used to characterize log-linear time trends. RESULTS: The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC -1.2%, p < 0.001), including that of high-grade (2006-2019: APC -1.2%, p < 0.05) and low-grade (2003-2019: APC -2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers. CONCLUSION: There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum.
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Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Neoplasias Peritoneales , Programa de VERF , Humanos , Femenino , Neoplasias Peritoneales/epidemiología , Neoplasias Peritoneales/mortalidad , Neoplasias de las Trompas Uterinas/epidemiología , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Incidencia , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/epidemiología , Carcinoma Epitelial de Ovario/patología , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Administración Oral , Adulto , Anciano , Carcinoma Epitelial de Ovario/patología , Femenino , Humanos , MAP Quinasa Quinasa 1/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Supervivencia sin Progresión , Nivel de Atención , Resultado del Tratamiento , Reino Unido , Estados UnidosRESUMEN
BACKGROUND: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). PATIENTS AND METHODS: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. RESULTS: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. CONCLUSIONS: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.
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Neoplasias de la Mama , Neoplasias Ováricas , Humanos , Femenino , Estudios Retrospectivos , Mutación , Resultado del Tratamiento , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugíaRESUMEN
OBJECTIVE: The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes. METHODS: We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier. RESULTS: Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence. CONCLUSIONS: Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.
RESUMEN
OBJECTIVES: Emerging data suggests that abnormal (nuclear) ß-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal ß-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control. METHODS: We identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with ß-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. RESULTS: Median follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal ß-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal ß-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal ß-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal ß-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal ß-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03). CONCLUSION: Use of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal ß-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences.
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Neoplasias Endometriales , beta Catenina , Femenino , Humanos , Radioterapia Adyuvante/métodos , Estadificación de Neoplasias , Histerectomía , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Recurrencia , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
OBJECTIVE: Aberrant ß-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer. METHODS: This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed. RESULTS: 297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant ß-catenin distribution was found in 135 patients (45.5%) and wild type membranous ß-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant ß-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between ß-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected. CONCLUSIONS: Aberrant ß-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts.
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Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Persona de Mediana Edad , beta Catenina/genética , Cateninas , Estudios Retrospectivos , Estudios de Cohortes , Recurrencia Local de Neoplasia/patología , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patologíaRESUMEN
Densely O-glycosylated mucin domains are found in a broad range of cell surface and secreted proteins, where they play key physiological roles. In addition, alterations in mucin expression and glycosylation are common in a variety of human diseases, such as cancer, cystic fibrosis, and inflammatory bowel diseases. These correlations have been challenging to uncover and establish because tools that specifically probe mucin domains are lacking. Here, we present a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. By mutating catalytic residues of two such enzymes, we engineered mucin-selective binding agents with retained glycoform preferences. StcEE447D is a pan-mucin stain derived from enterohemorrhagic Escherichia coli that is tolerant to a wide range of glycoforms. BT4244E575A derived from Bacteroides thetaiotaomicron is selective for truncated, asialylated core 1 structures commonly associated with malignant and premalignant tissues. We demonstrated that these catalytically inactive point mutants enable robust detection and visualization of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry. Application of our enzymatic toolkit to ascites fluid and tissue slices from patients with ovarian cancer facilitated characterization of patients based on differences in mucin cleavage and expression patterns.
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Mucinas/análisis , Polisacárido Liasas/metabolismo , Adenocarcinoma/química , Secuencias de Aminoácidos , Western Blotting , Femenino , Citometría de Flujo , Humanos , Neoplasias Ováricas/química , Mutación Puntual , Polisacárido Liasas/química , Polisacárido Liasas/genéticaRESUMEN
BACKGROUND: Macrophages are an important component of the tumour immune microenvironment (TME) and can promote tumour growth and metastasis. Macrophage-secreted chemokine-ligand-23 (CCL23) induces ovarian cancer cell migration via chemokine-receptor 1 (CCR1). However, the effect of CCL23 on other immune cells in the TME is unknown. METHODS: CCL23 levels were measured by ELISA. The expression of surface markers in exhaustion assays was quantified by flow cytometry. Signalling pathways were identified by phosphokinase array and validated by western blot. RESULTS: Ascites from patients with high-grade serous ovarian cancer (HGSC) contain high levels of CCL23. Similarly, significantly higher CCL23 levels were found in plasma from HGSC patients compared to healthy individuals. RNA-seq analysis of ovarian cancer tissues from TCGA showed that expression of CCL23 correlated with the presence of macrophages. In tissues with high levels of CCL23 and macrophage content, the fraction of CD8 + T cells expressing exhaustion markers CTLA-4 and PD-1 were significantly higher compared to low-level CCL23 tissues. In vitro, CCL23 induced upregulation of immune checkpoint proteins on CD8 + T cells, including CTLA-4, TIGIT, TIM-3 and LAG-3 via phosphorylation of GSK3ß in CD8 + T cells. CONCLUSIONS: Our data suggest that CCL23 produced by macrophages contributes to the immune-suppressive TME in ovarian cancer by inducing an exhausted T-cell phenotype.
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Quimiocinas CC/metabolismo , Macrófagos/metabolismo , Neoplasias Ováricas , Microambiente Tumoral , Antígeno CTLA-4 , Carcinoma Epitelial de Ovario/metabolismo , Quimiocina CCL22/metabolismo , Femenino , Humanos , Ligandos , Neoplasias Ováricas/metabolismoRESUMEN
The comprehensive genomic analysis of endometrial carcinoma (EC) by The Cancer Genome Atlas (TCGA) led to the discovery of four distinct and prognostically significant molecular subgroups. Molecular classification has the potential to improve risk-stratification when integrated with clinicopathologic features and has recently been included in national and international patient management EC guidelines. Thus, the adoption of molecular classification into routine pathologic and clinical practice is likely to grow significantly in the upcoming years. Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Here we describe our effort to implement rapid and routine molecular classification on all ECs diagnosed at our institution. To this effect, we performed immunohistochemistry as a surrogate marker for identifying genetic and/or epigenetic alterations in DNA mismatch repair (e.g., MLH1, PMS2, MSH6, MSH2), and TP53 genes. In addition, we have developed and employed a single-gene POLE SNaPshot assay, which is a rapid and analytically sensitive method for detecting select POLE exonuclease domain mutations (EDMs). We report our molecular testing workflow and integrative reporting system as well as the clinicopathologic and molecular features of 310 ECs that underwent routine molecular classification at our institution. The 310 ECs were molecularly classified as follows: 15 (5%) POLE mutant (POLEmut), 79 (25%) mismatch repair-deficient (MMRd), 135 (44%) no specific molecular profile (NSMP), and 81 (26%) p53 abnormal (p53abnl). This work provides an initial framework for implementing routine molecular classification of ECs.
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Neoplasias Endometriales , Biomarcadores de Tumor/genética , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/patología , Femenino , Genes p53 , Humanos , Inmunohistoquímica , Mutación , Estudios ProspectivosRESUMEN
BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach. OBJECTIVE: Our study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery. STUDY DESIGN: Firstly, "In silico" analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing. Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns. RESULTS: The Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC Ø0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of Ø0.797. CONCLUSION: The tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Bancos de Muestras Biológicas , Biomarcadores , Carcinoma Epitelial de Ovario , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirugía , Femenino , Humanos , Neoplasia Residual , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: This review provides an update on recent developments in cell-based immunotherapy in gynecologic cancers. RECENT FINDINGS: Chimeric antigen receptor (CAR) technology has made significant progress allowing now for not only expressing CARs on T-cells, but also on other immune effector cells, such as natural killer cells and macrophages. Cell-based vaccines have started to show promising results in clinical trials. SUMMARY: Cell-based immunotherapies in gynecologic cancers continue to evolve with promising clinical efficacy in select patients.
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Neoplasias de los Genitales Femeninos , Receptores Quiméricos de Antígenos , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Inmunoterapia/métodos , Células Asesinas Naturales , Linfocitos TRESUMEN
Mucin domains are densely O-glycosylated modular protein domains that are found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. Here, we demonstrate that secreted protease of C1 esterase inhibitor (StcE), a bacterial protease from Escherichia coli, cleaves mucin domains by recognizing a discrete peptide- and glycan-based motif. We exploited StcE's unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Finally, using StcE, we discovered that sialic acid-binding Ig-type lectin-7 (Siglec-7), a glycoimmune checkpoint receptor, selectively binds sialomucins as biological ligands, whereas the related receptor Siglec-9 does not. Mucin-selective proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of mucin domain structure and function.
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Antígenos CD/química , Antígenos de Diferenciación Mielomonocítica/química , Proteínas de Escherichia coli/química , Escherichia coli/enzimología , Lectinas/química , Metaloendopeptidasas/química , Mucinas/química , Proteínas de Neoplasias/química , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/química , Secuencias de Aminoácidos , Humanos , Espectrometría de Masas , Especificidad por SustratoRESUMEN
BACKGROUND: Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors. METHODS: Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months. RESULTS: The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005). CONCLUSIONS: Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.
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Carcinoma Endometrioide/rehabilitación , Neoplasias Endometriales/rehabilitación , Ejercicio Físico , Monitores de Ejercicio , Sistemas Recordatorios , Adulto , Anciano , Supervivientes de Cáncer , Carcinoma Endometrioide/terapia , Neoplasias Endometriales/terapia , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Envío de Mensajes de Texto , Caminata/fisiologíaRESUMEN
PURPOSE OF REVIEW: To provide an update on cell-based immunotherapies in solid tumors particularly in gynecological cancers. RECENT FINDINGS: Recent clinical trial results demonstrate safety and tolerability of different cell therapies in gynecological cancers. Novel approaches, such as harnessing the cells of the innate immune system are also under investigation in a phase I trial. SUMMARY: Cell-based therapies are gaining widespread attention as evidenced by the increasing number of clinical trials encompassing both, innate and adaptive cells to target gynecological cancers. A majority of these therapeutic approaches are well tolerated and show promising results in early trials.
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Tratamiento Basado en Trasplante de Células y Tejidos , Neoplasias de los Genitales Femeninos/terapia , Inmunoterapia , Femenino , HumanosRESUMEN
OBJECTIVE: Vulvar cancers account for 5% of all gynecologic malignancies; only 1%-3% of those vulvar cancers are primary vulvar sarcomas. Given the rarity of vulvar sarcomas, outcome data specific to histopathologic subtypes are sparse. The aim of this study was to identify clinical and pathologic factors of primary vulvar sarcomas that are associated with survival and may inform treatment decisions. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched for women diagnosed with vulvar sarcoma between 1973 and 2018. We identified 315 patients and reviewed their demographic, clinicopathologic, surgical, and survival information. Statistical analyses included χ2 and t-tests, Kaplan-Meier survival, and Cox regression analyses. RESULTS: The most common histopathologies of vulvar sarcomas were dermatofibrosarcomas (85/315, 27%) and leiomyosarcomas (72/315, 22.9%). Rhabdomyosarcomas (18/315, 5.7%), liposarcomas (16/315, 5.1%), and malignant fibrous histiocytomas (16/315, 5.1%) were less frequent. The majority of patients underwent surgery (292/315, 92.7%), which included lymph node dissections in 21.6% (63/292). Survival and lymph node involvement varied significantly with histologic subtype. The 5-year disease-specific survival for dermatofibrosarcomas, liposarcomas, and fibrosarcomas was 100% and only 60.3% and 62.5% for malignant fibrous histiocytomas and rhabdomyosarcomas, respectively. None of the patients with (dermato)fibrosarcomas, liposarcomas, or leiomyosarcomas had positive lymph nodes, in contrast to rhabdomyosarcomas and malignant fibrous histiocytomas with 77.8% and 40% positive lymph nodes, respectively. The 5-year disease-specific survival for women with positive lymph nodes was 0%. CONCLUSIONS: Vulvar sarcomas are heterogeneous with survival highly dependent on the histopathologic subtype. While surgical excision is the mainstay of treatment for all vulvar sarcomas, staging lymphadenectomy should be deferred for (dermato)fibrosarcomas, liposarcomas, and leiomyosarcomas as there were no cases of lymph nodes metastases.
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Sarcoma/mortalidad , Sarcoma/secundario , Neoplasias de la Vulva/mortalidad , Neoplasias de la Vulva/patología , Antineoplásicos/uso terapéutico , Dermatofibrosarcoma/mortalidad , Dermatofibrosarcoma/secundario , Femenino , Histiocitoma Fibroso Maligno/mortalidad , Histiocitoma Fibroso Maligno/secundario , Humanos , Estimación de Kaplan-Meier , Leiomiosarcoma/mortalidad , Leiomiosarcoma/secundario , Liposarcoma/mortalidad , Liposarcoma/secundario , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Radioterapia , Rabdomiosarcoma/mortalidad , Rabdomiosarcoma/secundario , Programa de VERF , Sarcoma/terapia , Tasa de Supervivencia , Estados Unidos/epidemiología , Neoplasias de la Vulva/terapia , VulvectomíaRESUMEN
STUDY OBJECTIVE: To evaluate practice patterns among gynecologic oncologists with regard to sentinel lymph node injection and biopsy in endometrial cancer. DESIGN: An observational study with no control group. SETTING AND PATIENTS: Active members of the Society of Gynecologic Oncology. INTERVENTIONS: After institutional review board approval, we performed an online survey among active members of the Society of Gynecologic Oncology. Members were contacted via e-mail and their answers anonymously captured. Study data were collected using REDCap (REDCap developed by Vanderbilt University, Nashville TN). MEASUREMENTS AND MAIN RESULTS: Three hundred eighteen of 1216 listed members completed the online survey. The majority of respondents (82.7%) perform sentinel lymph node sampling for endometrial cancer staging. Most technical aspects of sentinel lymph node sampling were consistently applied by the vast majority of respondents, including the choice of indocyanine green as a lymphatic tracer (97.3%) and its injection into the cervix (100%). Other technical aspects of sentinel lymph node sampling, such as the depth of injection, varied among respondents. Although 50.9% of the respondents perform an intraoperative assessment of the uterus by frozen section, only 17.9% assess sentinel lymph nodes by frozen section and/or touch prep. Some of the respondents' approaches are based on limited data, including (1) the use of sentinel lymph node injection and biopsy for high-risk histologies (performed by 69%-75% of the respondents dependent on the histology), (2) omitting side-specific completion lymphadenectomy in the absence of sentinel node mapping (in up to 57.8%), or (3) when lymph node metastases are present (in 39.9%). CONCLUSION: In summary, despite the growing use of sentinel lymph node injection and biopsy in endometrial cancer, practice patterns vary considerably among providers sampled by this survey. Some of the decisions are based on limited evidence and, in some instances, deviate from current published guidelines.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Endometriales/patología , Ginecología/estadística & datos numéricos , Oncólogos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Adenocarcinoma/epidemiología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Periodo Intraoperatorio , Escisión del Ganglio Linfático/estadística & datos numéricos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela/métodos , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
Asunto(s)
Oncología Médica/normas , Infecciones por Papillomavirus/terapia , Neoplasias del Cuello Uterino/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/métodos , Braquiterapia/normas , Cuello del Útero/diagnóstico por imagen , Cuello del Útero/patología , Cuello del Útero/virología , Quimioradioterapia Adyuvante/normas , Femenino , Preservación de la Fertilidad/métodos , Preservación de la Fertilidad/normas , Humanos , Histerectomía/normas , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Oncología Médica/métodos , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano/métodos , Tratamientos Conservadores del Órgano/normas , Prueba de Papanicolaou/normas , Papillomaviridae/aislamiento & purificación , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Sociedades Médicas/normas , Estados Unidos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.
Asunto(s)
Enfermedad Trofoblástica Gestacional , Femenino , Humanos , Embarazo , Oncología MédicaRESUMEN
PURPOSE OF REVIEW: To provide an update on cell-based immunotherapies in solid tumors particularly in gynecological cancers. RECENT FINDINGS: Improvements have been made in engineering T cells to overcome the immunosuppressive environment in ovarian cancer. Significant efforts are underway to create 'off the shelf' cell therapies which leverage natural killer (NK) cells and would not rely on engineering a patient's T cells. SUMMARY: Efforts to target solid tumors using cell-based therapies are expanding into cell types other than T cells (NK cells and macrophages) which may have a lower risk of significant side effects and higher efficacy in solid tumors than chimeric antigen receptor T cells.