RESUMEN
OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.
Asunto(s)
Proteína BRCA1 , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Anciano , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Persona de Mediana Edad , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Proteína BRCA1/genética , Proteína BRCA2/genética , Anciano de 80 o más Años , Factores de Edad , Adulto , Recombinación Homóloga , Estadificación de Neoplasias , Clasificación del Tumor , Pruebas Genéticas/métodosRESUMEN
PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.
Asunto(s)
Quimioradioterapia , Cisplatino , Neoplasias Endometriales , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/terapia , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Anciano , Estudios Prospectivos , Quimioradioterapia/métodos , Supervivencia sin Progresión , Adulto , Braquiterapia/métodos , Braquiterapia/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
PURPOSE: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION: While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.
Asunto(s)
Neoplasias Endometriales , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/diagnóstico por imagen , Valor Predictivo de las Pruebas , Tamizaje Masivo , Ultrasonografía , Antígeno Ca-125RESUMEN
BACKGROUND: Little is known about the risks and benefits of cannabis use in the context of cancer care. This study characterized the prevalence, reasons for use, and perceived benefits of cannabis and compared symptoms and perceived risks between those who reported past 30-day cannabis use and those who did not. METHODS: Adults undergoing cancer treatment at a National Cancer Institute-designated cancer center completed measures of sociodemographic characteristics, cannabis use, use modalities, reasons for use, perceived harms/benefits of use, physical and psychological symptoms, and other substance/medication use. Analyses compared patients who used or did not use cannabis in the past 30 days. RESULTS: Participants (N = 267) were 58 years old on average, primarily female (70%), and predominantly White (88%). Over a quarter of respondents (26%) reported past 30-day cannabis use, and among those, 4.5% screened positive for cannabis use disorder. Participants who used cannabis most often used edibles (65%) or smoked cannabis (51%), and they were younger and more likely to be male, Black, and disabled, and to have lower income and Medicaid insurance than participants who did not use cannabis. Those who used cannabis reported more severe symptoms and perceived cannabis as less harmful than those who did not use cannabis. The most common medical reasons for cannabis use were pain, cancer, sleep problems, anxiety, nausea/vomiting, and poor appetite. Participants reported the greatest cannabis-related symptom relief from sleep problems, nausea/vomiting, headaches, pain, muscle spasms, and anxiety. CONCLUSIONS: Patients with cancer who used cannabis perceived benefits for many symptoms, although they showed worse overall symptomatology. PLAIN LANGUAGE SUMMARY: Among adults undergoing cancer treatment, 26% reported cannabis use in the past 30 days. Those who used cannabis were more likely to be male and disabled and to have lower income and Medicaid insurance than those who did not use cannabis. Participants most commonly reported using cannabis for pain, cancer, sleep, anxiety, and nausea/vomiting and reported the greatest perceived benefits for sleep, nausea/vomiting, headaches, pain, muscle spasms, and anxiety, yet participants who used cannabis also reported feeling worse physically and psychologically compared to those who did not use cannabis. Participants who used cannabis were more likely to report that cannabis was less risky to their health than alcohol, smoking, and opioids than those who did not use cannabis.
Asunto(s)
Dolor en Cáncer , Cannabis , Marihuana Medicinal , Neoplasias , Trastornos del Sueño-Vigilia , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Marihuana Medicinal/efectos adversos , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/epidemiología , Náusea/inducido químicamente , Náusea/epidemiología , Vómitos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Dolor , Espasmo/tratamiento farmacológico , CefaleaRESUMEN
This study sought to describe and relate the factors associated with complications and delays in adjuvant chemotherapy in patients with ovarian cancer treated with primary cytoreductive surgery. Serum from patients diagnosed with ovarian cancer scheduled for primary cytoreductive surgery were analyzed for prealbumin, 25-OH Vitamin D, intracellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), monocyte chemoattractant protein 2 (MCP-2), macrophage derived chemokine (MDC). Postoperative complications were identified using common terminology criteria for adverse events 4.0 and 30 day after surgery. Delays in adjuvant chemotherapy were defined as >1 week interval between surgery and initiation. Patients with postoperative complications (39.6%) were significantly older, had lower serum prealbumin levels, and higher serum IL-6 and IL-8 than those without. Univariate logistic regression found that age (OR: 1.12, 95%CI: 1.00-1.35) and IL-6 (OR: 1.02, 95%CI: 0.99-1.05) were associated with postoperative complications, whereas age remained significant after multivariate analysis (OR:1.14, 95%CI: 1.00-1.29). Patients with delays in chemotherapy exhibited greater BMI and lower 25-OH Vitamin D than those without. Multivariate analysis found that increasing levels of 25-OH Vitamin D were associated with a lower risk of delayed chemotherapy initiation after controlling for age, body mass index, and tumor grade (OR: 0.93, 95%CI:0.87-0.99). This work suggests that in addition to age being predictive of postoperative complications, serum 25-OH Vitamin D may a provide insight into a patient's risk for postsurgical delays in chemotherapy initiation. These findings should, however, be confirmed in a larger study including robust survival analysis.
In a small cohort, increasing age was associated with postsurgical complications in patients with ovarian cancer following primary cytoreductive surgery.In patients with ovarian cancer following primary cytoreductive surgery delays in adjuvant chemotherapy initiation were inversely associated with serum 25-OH vitamin D status.
Asunto(s)
Neoplasias Ováricas , Prealbúmina , Humanos , Femenino , Proyectos Piloto , Interleucina-8 , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Interleucina-6 , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Quimioterapia Adyuvante , Complicaciones Posoperatorias/etiología , Biomarcadores , Vitamina D/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC). OBJECTIVE: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC. STUDY DESIGN: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate. RESULTS: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]). CONCLUSIONS: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Recurrencia Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Combinación de Medicamentos , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Estradiol , Estriol , Estrona , Everolimus/uso terapéutico , Femenino , Humanos , Letrozol/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Fosfatidilinositol 3-QuinasasRESUMEN
PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
Asunto(s)
Recurrencia Local de Neoplasia/patología , Nomogramas , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Neoplasias del Cuello Uterino/cirugíaRESUMEN
PURPOSE: This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma. PATIENTS AND METHODS: This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21-24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response. RESULTS: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008). CONCLUSIONS: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/terapia , Histerectomía , Acetato de Medroxiprogesterona/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas/administración & dosificación , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/etiología , Femenino , Humanos , Histerectomía/métodos , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Piridinas/administración & dosificación , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
PURPOSE: To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions. METHODS: Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017. RESULTS: Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group (P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group (P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group (P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18). CONCLUSION: In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.
Asunto(s)
Recurrencia Local de Neoplasia/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
OBJECTIVES: Chemotherapy is the standard treatment in stage IVB cervical cancer (CC). However, given that many women have a significant pelvic disease burden, whole pelvic radiation (WPR) in addition to chemotherapy for primary treatment may have utility. The aim of this study was to compare the overall survival (OS) and complication rates between women who received both WPR and chemotherapy (CT) versus CT alone in the management of stage IVB CC. METHODS: A multi-institutional, IRB-approved, retrospective review of patients (pts) with stage IVB CC, diagnosed between 2005 and 2015, was performed. Descriptive statistics of the demographic, oncologic, and treatment characteristics were performed. OS was estimated using the Kaplan Meier method. RESULTS: A total of 126 pts met inclusion criteria. Thirty one patients elected for hospice care at diagnosis and were excluded from further analysis. In the remaining population, median age was 53 yrs. The majority (72%) had squamous cell carcinoma and 82% had FIGO grade 2 or 3 tumors. Thirty four patients (35.8%) received WPR in addition to CT as a part of planned primary therapy and 64.2% (n = 61) received CT alone, with 88.2% and 80.3% receiving a cisplatin-based chemotherapy regimen, respectively. The OS was significantly longer in the WPR with CT group (41.6 vs 17.6 mo, p < 0.01). The rates of ureteral obstruction, vaginal bleeding, pelvic infection, pelvic pain, and fistula were not significantly different between the 2 groups (all p > 0.05). CONCLUSION: This study found WPR in addition to CT gives a significant OS benefit. Further study is warranted to determine which subgroups may benefit the most from this novel treatment strategy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Cisplatino/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pelvis/efectos de la radiación , Supervivencia sin Progresión , Radioterapia/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
OBJECTIVES: To assess whether comprehensive genomic profiling (CGP) in the setting of routine clinical care allows molecular classification of recurrent endometrial cancer (EC) into the four Cancer Genome Atlas (TCGA) categories: POLE ultramutated, microsatellite instable, copy-number low, and copy-number high and whether this approach can identify genomic alterations (GAs) which inform treatment decisions. METHODS: Archival tissues from 74 patients diagnosed with recurrent EC were prospectively analyzed using hybrid-capture-based genomic profiling. Tumor mutational burden and microsatellite instability were measured. Clinically relevant GAs (CRGAs) were defined as GAs associated with targeted therapies available on-label or in mechanism-driven clinical trials. RESULTS: Using POLE mutational analysis, mismatch repair status, and p53 mutational analysis as surrogate for 'copy-number' status CGP segregated all cases into four TCGA molecular subgroups. While recurrent serous ECs were predominantly copy-number high, we found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors. Every tumor sample had at least one GA and 91% (67/74) had at least one CRGA. In this series 32% (24/74) of patients received a matched therapy based on the results of CGP. Objective responses to the matched therapy were seen in 25% (6/24) of patients with an additional 37.5% (9/24) achieving stable disease leading to a clinical benefit rate of 62.5% with a median treatment duration of 14.6â¯months (range 4.3-69â¯months). CONCLUSIONS: CGP allows molecular classification of EC into four TCGA categories and allows identification of potential biomarkers for matched therapy in the setting of routine clinical care.
Asunto(s)
Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Neoplasias Endometriales/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inestabilidad de Microsatélites , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
The case of a 36-yr-old woman with a pituitary adenoma who was found to have bilateral ovarian masses is reported. The right ovary was removed, measured 15 cm in maximum dimension, and contained multiple cysts which on microscopic examination had the typical morphology of follicle cysts. The left ovary was grossly similar intraoperatively. Subsequent excision of the pituitary adenoma was followed â¼3 mo later by a return to normal size of the left ovary. The case represents an example of multiple luteinized follicle cysts, analogous to the phenomenon seen occasionally in pregnancy, but with a different clinical background. Periodic documentation of this phenomenon is present in the literature, predominantly the clinical literature with limited pathologic documentation of the nature of the process in many reports. As pertains to the evaluation of follicle cysts encountered during pregnancy the differential diagnosis is with a cystic granulosa cell tumor of either adult or juvenile types, more likely the latter. The cyst lining is identical to that of standard follicle cysts and contrasts with the immature mitotically active nuclei seen in a juvenile granulosa cell tumor. That neoplasm also usually shows follicular differentiation typically absent in follicle cysts. Pathologists should be aware of the rare occurrence of luteinized follicle cysts in patients with a pituitary adenoma to enable correct intraoperative and standard pathologic evaluation.
Asunto(s)
Adenoma/diagnóstico , Tumor de Células de la Granulosa/diagnóstico , Quistes Ováricos/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenoma/complicaciones , Adenoma/patología , Adenoma/cirugía , Adulto , Diagnóstico Diferencial , Femenino , Tumor de Células de la Granulosa/complicaciones , Tumor de Células de la Granulosa/patología , Tumor de Células de la Granulosa/cirugía , Humanos , Luteinización , Quistes Ováricos/complicaciones , Quistes Ováricos/patología , Quistes Ováricos/cirugía , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovario/patología , Ovario/cirugía , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , EmbarazoRESUMEN
This retrospective observational study examined trends, characteristics, and survival of women with synchronous endometrial and ovarian cancer (SEOC) in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Among 235,454 women with primary endometrial cancer, synchronous ovarian cancer was seen in 4,082 (1.7%) women with the proportion being decreased from 2.0% to 1.6% between 1983 and 2013 (P=0.049); and the proportion of concurrent endometrioid tumors in the two cancer sites has increased from 24.2% to 49.9% among SEOC women (P<0.001). When compared to endometrial cancer without synchronous ovarian cancer, endometrioid histology in the two cancer sites was associated with improved cause-specific survival while non-endometrioid histology in the ovarian cancer was associated with decreased cause-specific survival (adjusted-P<0.01). Among 110,063 women with primary epithelial ovarian cancer, synchronous endometrial cancer was seen in 3,940 (3.6%) women with the proportion being increased from 2.2% to 4.4% between 1973 and 2013 (P<0.001); and the proportion of concurrent endometrioid tumors in the two cancer sites had increased from 24.3% to 50.2% among SEOC women (P<0.001). When compared to primary epithelial ovarian cancer without synchronous endometrial cancer, SEOC was associated with better cause-specific survival if ovarian cancer is endometrioid type or if endometrial cancer is endometrioid type (adjusted-P<0.001). Across the two cohorts, the proportion of SEOC reached to the peak in the late-40 years of age and then decreased significantly (P<0.001). In conclusion, our study suggests that synchronous ovarian cancer has decreased among endometrial cancer whereas synchronous endometrial cancer has increased among epithelial ovarian cancer.
RESUMEN
OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47â¯years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40â¯years for BRCA1 and age 45â¯years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (Pâ¯<â¯0.0001) and RRSO (Pâ¯=â¯0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (Pâ¯=â¯0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Ovariectomía/métodos , Salpingectomía/métodos , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Femenino , Humanos , Neoplasias Ováricas/patología , Proyectos Piloto , Estudios Prospectivos , Conducta de Reducción del RiesgoRESUMEN
OBJECTIVES: Patient navigation programs have been shown to positively impact cancer outcomes for minority populations. Little is known regarding the effects of these programs on American Indian (AI) populations. The purpose of this study is to characterize the impact of a patient navigation program on AI cervical cancer patients at a tertiary care center. METHODS: A retrospective review of all AI cervical cancer patients receiving navigation services and a cohort of AI patients treated prior to navigation services was performed. Additional comparisons were made between those with and without Indian Health Service (IHS) funding. Summary statistics were used to describe demographic, clinical characteristics, treatment, and survivorship across groups. RESULTS: Of 55 patients identified, 34 received navigation and 21 did not. In navigated patients, median age was 46years (27-80years) compared with 42years (17-68years) in pre-navigation patients (p=0.53). There was no difference between stage at diagnosis (p=0.73). No difference was noted in treatment received between groups (p=0.48). Distance traveled for treatment between groups did not differ (p=0.46). Median time to initiation of treatment was not different between groups, 30.5days vs. 27.5days (p=0.18). Among patients with IHS funding, navigation services did not alter time to initiation of treatment (p=0.57), and there was no difference in completion of prescribed therapy between groups (92% navigated vs 100% pre-navigation). CONCLUSIONS: Navigation services for AI cervical cancer patients did not alter initiation or completion of treatment. Navigation programs may provide less tangible benefits to AI cervical cancer patients and further study is warranted.
Asunto(s)
Indígenas Norteamericanos , Navegación de Pacientes/métodos , United States Indian Health Service , Neoplasias del Cuello Uterino/etnología , Neoplasias del Cuello Uterino/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Cooperación del Paciente , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
PURPOSE: The goal of this study was to compile a review of topics pertinent to the use of immune checkpoint inhibitors in gynecologic malignancies, including foundation for use, current agents available and trials in gynecologic cancers, special populations of interest, identification and management of toxicities, and considerations in predictive biomarkers and response assessment. METHODS: A literature review of selected topics in reference to immune checkpoint inhibitors and gynecologic cancers was conducted on PubMed and the US Food and Drug Administration drug search application. A review of current and ongoing clinical trials was performed in clinicaltrials.gov, and selected preliminary results reported in PubMed abstracts and through the American Society of Clinical Oncologists were compiled. FINDINGS: Although immunotherapy in gynecologic malignancy is relatively new, 7 agents are currently approved for use in other oncologic indications, and a multitude of trials in gynecologic cancer are ongoing. Immunotherapy has a specific set of drug toxicities that manifest and are managed unlike traditional cytotoxic therapies. IMPLICATIONS: Application of the knowledge of immune checkpoint inhibitor use in gynecologic cancers will improve care for women with cancers of the female reproductive tract. As more complex and newer immunotherapies evolve, it will be vital to accurately characterize each specific drug class and management thereof.
Asunto(s)
Neoplasias de los Genitales Femeninos/terapia , Inmunoterapia/métodos , Femenino , HumanosRESUMEN
OBJECTIVES: The study objective was to analyze the impact of prognostic factors, including treatment modality, on outcome in patients with advanced-stage uterine serous carcinoma (USC). METHODS: A retrospective review of patients diagnosed with stage III or IV USC between 1993 and 2012 was performed. Summary statistics were used to describe demographic and clinical characteristics. Overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier analysis. Cox proportional hazards regression was used to model the association of potential prognostic factors with OS and RFS. RESULTS: The study included 260 patients with median follow-up of 26.6months (range 1-172.8). Median age was 63years (range 30-88) and 52.3% had stage III disease. In all, 60% were treated with surgery followed by chemotherapy, 18.1% received surgery, chemotherapy, and radiotherapy, 11.5% had surgery and radiotherapy, and 10.4% had neoadjuvant chemotherapy. The overall complete response rate was 68.9%, and the cumulative incidence of recurrence was 82.7%. Treatment that included surgery, chemotherapy, and radiation and stage III disease were associated with improved RFS on multivariate analysis. For OS, therapy with surgery, chemotherapy, and radiation, mixed histology, and stage III disease were associated with better OS on multivariate analysis. CONCLUSIONS: Patients with advanced-stage USC have a poor prognosis, regardless of clinical factors or treatment received. However, combination therapy that includes chemotherapy and radiation appears to be associated with improved survival in these women.
Asunto(s)
Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapiaRESUMEN
BACKGROUND: Fallopian tube involvement by cervical carcinoma has rarely been documented, with literature reports focusing primarily on squamous cell carcinoma. CASE PRESENTATION: In this report, we present the case of a 50 year old woman who presented with an abnormal Pap test with atypical squamous and glandular cells. A loop electrosurgical excision procedure (LEEP) was performed and led to the diagnosis of stage IB1 endocervical adenocarcinoma. Subsequent radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic lymph node dissection showed a well-differentiated endocervical adenocarcinoma of usual type with superficial spread to the endometrium and right fallopian tube. The patient received no adjuvant therapy and has remained without evidence of disease. CONCLUSIONS: While the advent of more extensive fallopian tube sampling has led to increased discovery and discussion of fallopian tube involvement by metastatic carcinoma, its impact on treatment and prognosis remains to be seen.
Asunto(s)
Adenocarcinoma/patología , Endometrio/patología , Trompas Uterinas/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/química , Adenocarcinoma/cirugía , Biomarcadores de Tumor/análisis , Biopsia , Endometrio/química , Endometrio/cirugía , Trompas Uterinas/química , Trompas Uterinas/cirugía , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Escisión del Ganglio Linfático , Persona de Mediana Edad , Membrana Mucosa/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Ovariectomía , Salpingectomía , Resultado del Tratamiento , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/cirugíaRESUMEN
OBJECTIVE: Women with primary platinum resistant (PPR) high grade serous ovarian cancer (HGSOC) are known to have a poor prognosis. Less is known regarding outcomes in patients with acquired platinum resistance (APR). The goal of this study was to evaluate survival in both PPR and APR patients. METHODS: A retrospective review of HGSOC patients diagnosed between 2000 and 2010 was performed. Descriptive statistics summarized clinical characteristics and demographics. The Kaplan-Meier method estimated progression free survival (PFS) and overall survival (OS). The association of OS and clinical factors was modeled using Cox proportional-hazards. RESULTS: Of the 330 patients identified, 81 (25%) had PPR. Of the remaining women, 55 (22%) developed APR. Median PFS of PPR patients was 4.2months and median OS was 17.8months. On multivariate analysis, the number of biologic agents received was the only predictor of OS. Patients with APR had a median PFS of 14.2months and a median OS of 56months. OS from the date of platinum resistance was 21.9months, though this was not different than PPR patients (p=0.19). Multivariate analysis found cancer stage and clinical trial participation to be associated with OS. CONCLUSIONS: Platinum resistance confers a poor prognosis in the APR and PPR setting. The number of biologic agents received is the strongest predictor of OS among women with PPR. Cancer stage and clinical trial participation predicts OS in patients with APR. Providing opportunities to participate in clinical trials, especially those involving targeted therapy, should be a priority in these populations.