RESUMO
OBJECTIVES: To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies. METHODS: A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease. RESULTS: One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10-5). CONCLUSIONS: PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response.
RESUMO
STUDY OBJECTIVE: To compare outcomes of advanced ovarian cancer patients who had minimally invasive surgery (MIS) with outcomes of advanced ovarian cancer patients who had laparotomy for interval cytoreduction after neoadjuvant chemotherapy (NACT). DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: One large teaching hospital with a tertiary referral function for gynecologic oncology and MIS. PATIENTS: All consecutive patients with stages III to IV epithelial ovarian, tubal, or peritoneal cancer who underwent MIS or laparotomy for interval cytoreduction after at least 1 NACT cycle from 2006 to 2017 at 1 institution. INTERVENTIONS: Patients underwent either MIS or laparotomy for interval cytoreduction after at least 1 cycle of NACT. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed and data abstracted and analyzed. Survival was estimated by the Kaplan-Meier method, and outcomes were compared with Fisher's exact test, Student's t test, Wilcoxon rank sum test, and the log-rank test. In total, 157 assessable patients underwent interval cytoreductive surgery through MIS (nâ¯=â¯53) or laparotomy (nâ¯=â¯104). MIS was completed without conversion in 44 of 53 patients (83%), of whom 20 required a hand port and/or mini-laparotomy. R-zero and optimal resections were achieved in 60.4% and 96.3% of MIS patients respectively, compared with 42.3% and 82.7% of laparotomy patients (pâ¯=â¯.02). MIS patients had lower estimated blood loss (EBL; 156 vs 278 mL, p <.001), fewer intraoperative transfusions (2% vs 17%, pâ¯=â¯.006), and shorter hospital stay (3.0 vs 5.7 days, p < .001). Operative time was longer (171 vs 150 minutes, pâ¯=â¯.007), but complications, intensive care unit stay, readmission, median progression-free survival (27 vs 29 months, pâ¯=â¯.45), and median overall survival (37 vs 35 months, pâ¯=â¯.74) were similar. CONCLUSION: MIS is feasible and effective for interval cytoreduction after NACT in advanced ovarian cancer patients. MIS is associated with less EBL, lower transfusion rate, and shorter length of hospital stay with no difference in patient outcomes.
Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Laparotomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Progressão da Doença , Feminino , Humanos , Laparotomia/efeitos adversos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Terapia Neoadjuvante , Duração da Cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To compare the outcomes after intraperitoneal (IP) chemotherapy in patients with and without pathogenic BRCA mutations. METHODS: Patients with high grade ovarian cancer who were treated with adjuvant IP chemotherapy in the initial setting between 2005 and 2016 were identified. Outcomes were compared between patients with pathogenic mutations in BRCA (BRCA+) and those who tested negative or were unknown (BRCA-). RESULTS: A total of 100 eligible patients were identified. The median follow-up was 47.0â¯months (range, 6.6-144.1â¯months). Of these 100 patients, 77 patients underwent BRCA testing; 25 patients (32%) were BRCA+ (23 germline, 2 somatic). No differences were noted between groups with respect to number of IP cycles, stage, or residual disease after surgery. The median progression-free survival (PFS) was longer in the BRCA+ group; median PFS was not reached in the BRCA+ group compared to 17.3â¯months in the BRCA- group (HRâ¯=â¯0.38; 95% CI 0.20-0.73, Pâ¯=â¯0.003). Median overall survival (OS) was longer in the BRCA+ group at 110.4â¯months versus 67.1â¯months (HRâ¯=â¯0.28, 95% CI 0.11-0.73, Pâ¯=â¯0.009). CONCLUSIONS: Pathogenic BRCA mutations are more common than expected in optimally resected ovarian cancer patients selected for IP therapy. IP therapy was associated with a dramatic improvement in PFS and OS in BRCA+ patients compared with BRCA- patients. This improvement is greater than has been reported for BRCA+ patients with IV chemotherapy. The magnitude of this benefit suggests that patients with pathogenic mutations in BRCA may benefit from IP therapy.
Assuntos
Quimioterapia Adjuvante/métodos , Genes BRCA1/fisiologia , Genes BRCA2/fisiologia , Neoplasias Ovarianas/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/patologia , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to demonstrate the utility of a comprehensive program involving management-based evidence, telemedicine, and patient navigation to provide genetic counseling services for patients with ovarian and breast cancer across a geographically large health care system. METHODS: We identified all patients with newly diagnosed ovarian and breast cancer in our health care system from January 2013 to December 2015 through the cancer registry. Referral characteristics and testing outcomes were recorded for each year and compared using the χ or Fisher exact test. RESULTS: Because the implementation of this program, the number of new ovarian cancer cases remained constant (109-112 cases/year) but patients referred for genetic counseling increased annually from 37% to 43% to 96% (P < 0.05). The percentage of ovarian cancer patients who underwent genetic testing increased annually from 24% to 27% to 53% (P < 0.05). The number of new breast cancer patients was constant (1543-1638 cases/year). The percentage of patients with triple negative breast cancer referred for genetic counseling rose from 69% in 2013 to 91% in 2015; the percentage of patients who underwent testing increased annually from 59% to 86% (P < 0.05). Of women with breast cancer diagnosed at less than 45 years of age, 78% to 85% were referred for genetic counseling across this period; the percentage of patients who underwent testing increased annually from 66% to 82% (P < 0.05). Patient navigation was initiated and was available to all patients in the system during this period. Telemedicine consults were performed in 118 breast/ovarian patients (6%) during this period. CONCLUSIONS: A comprehensive program may improve access to effective genetic counseling services in patients with ovarian and breast cancer despite geographic barriers.
Assuntos
Neoplasias da Mama/genética , Aconselhamento Genético/organização & administração , Neoplasias Ovarianas/genética , Feminino , Aconselhamento Genético/estatística & dados numéricos , Humanos , Navegação de Pacientes , Programas Médicos Regionais/estatística & dados numéricos , Telemedicina/estatística & dados numéricosRESUMO
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response. RESULTS: Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension. CONCLUSIONS: Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.
Assuntos
Alanina/análogos & derivados , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Triazinas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/efeitos adversos , Alanina/provisão & distribuição , Alanina/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/provisão & distribuição , Carcinoma/terapia , Progressão da Doença , Intervalo Livre de Doença , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Critérios de Avaliação de Resposta em Tumores Sólidos , Retratamento , Taxa de Sobrevida , Triazinas/efeitos adversos , Triazinas/provisão & distribuição , Neoplasias do Colo do Útero/terapiaRESUMO
PURPOSE: A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients. PATIENTS AND METHODS: Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m2) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4. RESULTS: Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p<0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p=0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p=0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p=0.008) and toxicity, with the odds ratio (OR) of grade 3+ toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72-0.96; p=0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p=0.019) for patients receiving CP. CONCLUSION: Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologiaRESUMO
OBJECTIVE: To identify potential cost savings in gynecologic oncology care without sacrificing quality. METHODS: Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines. RESULTS: Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care. RECOMMENDATIONS: ⢠Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. ⢠Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. ⢠Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. ⢠Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. ⢠Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end.
Assuntos
Neoplasias dos Genitais Femininos/economia , Neoplasias dos Genitais Femininos/terapia , Ginecologia/economia , Ginecologia/normas , Oncologia/economia , Oncologia/normas , Adulto , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Ginecologia/métodos , Humanos , Programas de Rastreamento , Oncologia/métodos , Cuidados Paliativos , Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Sociedades MédicasRESUMO
BACKGROUND: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. METHODS: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. CONCLUSIONS: Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment.
Assuntos
Antineoplásicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Análise Custo-Benefício , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/economia , Paclitaxel/economia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/economia , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Neoplasias Ovarianas/psicologia , Paclitaxel/administração & dosagem , Platina/uso terapêutico , Qualidade de Vida , Recidiva , Taxoides/administração & dosagem , Taxoides/economiaRESUMO
BACKGROUND: The aim of this randomized clinical trial was to evaluate the efficacy and safety of combination (cDC) and sequential (sDC) weekly docetaxel and carboplatin in women with recurrent platinum-sensitive epithelial ovarian cancer (EOC). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2) on days 1 and 8 and carboplatin area under the curve (AUC) = 6 on day 1, every 3 weeks or docetaxel 30 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles followed by carboplatin AUC = 6 on day 1, every 3 weeks for 6 cycles or until disease progression. The primary endpoint was measurable progression-free survival (PFS). RESULTS: Between January 2004 and March 2007, 150 participants were enrolled. The response rate was 55.4% and 43.2% for those treated with cDC and sDC, respectively. The median PFS was 13.7 months (95% confidence interval [CI], 9.9-16.8) for cDC and 8.4 months (95% CI, 7.1-11.0) for sDC. On the basis of an exploratory analysis, patients treated with sDC were at a 62% increased risk of disease progression compared to those treated with cDC (hazard ratio = 1.62; 95% CI, 1.08-2.45; P = .02). The median overall survival time was similar in both groups (33.2 and 30.1 months, P = .2). The incidence of grade 2 or 3 neurotoxicity and grade 3 or 4 neutropenia was higher with cDC than with sDC (11.7% vs 8.5%; 36.8% vs 11.3%). The sDC group demonstrated significant improvements in the Functional Assessment for Cancer Therapy-Ovarian, Quality of Life Trial Outcome Index scores compared with the combination cohort (P = .013). CONCLUSIONS: Both cDC and sDC regimens have activity in recurrent platinum-sensitive EOC with acceptable toxicity profiles. The cDC regimen may provide a PFS advantage over sDC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Platina/uso terapêutico , Qualidade de Vida , Recidiva , Taxoides/efeitos adversosRESUMO
Background: A pure ovarian dysgerminoma in a postmenopausal female is a rare phenomenon. Case: A 65-year-old female presented with a large pelvic mass. Following surgical debulking, the patient was diagnosed with FIGO Stage IIB ovarian dysgerminoma. She was treated with three cycles of etoposide and cisplatin and has been disease-free for 12 months. Conclusion: Dysgerminomas in postmenopausal females are uncommon. Gynecologic oncologists should be familiar with the pathological diagnosis and treatment recommendations to achieve optimal outcomes.
RESUMO
OBJECTIVES: A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer. This manuscript reports prospectively collected health-related quality of life (HRQL). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel 30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was assessed as an intent-to-treat analysis. The secondary HRQL endpoints included the FACT-O total score, the FACT-General, and several domain scores of the FACT-O instrument (physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and the ovarian cancer specific (OCS) module). The FACT-O was administered at randomization, prior to each of 6 cycles of treatment, and at study endpoint. RESULTS: One hundred forty-eight participants were randomized to each group. Sequential docetaxel followed by carboplatin (sDC) was associated with significant improvements in the FACT-O TOI (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the combination docetaxel and carboplatin group (cDC). CONCLUSIONS: Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC. The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/fisiopatologia , Neoplasias das Tubas Uterinas/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/psicologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/fisiopatologia , Neoplasias Peritoneais/psicologia , Estudos Prospectivos , Qualidade de Vida , Recidiva , Índice de Gravidade de Doença , Taxoides/administração & dosagem , Taxoides/efeitos adversosRESUMO
BACKGROUND: Use of immune checkpoint inhibitors in treatment of gynecologic malignancies is increasing. Rare, but potentially fatal, immune-related neurologic adverse events may occur as a result of treatment. CASE: A 72 year old female with recurrent metastatic uterine adenocarcinoma received pembrolizumab and lenvatinib combination therapy. Following her second dose of pembrolizumab, the patient developed multiple neurologic symptoms. She was ultimately diagnosed with Guillain-Barre Syndrome based on neurologic evaluation with imaging, serum studies, and cerebrospinal fluid analysis. The patient was successfully treated with high-dose intravenous corticosteroids and intravenous immunoglobulin. CONCLUSION: Neurologic complications related to immune checkpoint inhibitor therapy are rare. It is imperative for gynecologic oncologists to be familiar with potentially fatal hazards of therapy to allow for rapid diagnosis and treatment.
RESUMO
Ovarian cancer is the fourth leading cause of gynecological cancer death among women in the United States. Early detection is a critical prerequisite to initiating effective cancer therapy. Gene microarray technology and proteomics have provided much of the biomarkers with potential use for diagnosis. However, more research is needed to fully understand disease onset and progression. To this end, we have performed microarray analysis with the goal of identifying molecular interaction networks defining tumor growth. Microarray analysis was performed on a limited set of ovarian tissues with various pathological diagnoses using Human Genome Focus Array (HGFA) for the detection of approximately 8500 human transcripts. Hierarchical clustering identified groups of ovarian tissues reflective of low malignant potential/early cancer onset and possible pre-cancerous stages involving small molecule, cytokine and/or hormone-dependent feed-back responses specific to the pelvic reproductive system and a priori initiated tumor suppression mechanisms. ANOVA followed by post hoc Scheffe confirmed our hypotheses. Moreover, we established a protein/protein interaction database associated with HGFA probe sets. This database was used to build and visualize molecular networks integrating small but significant changes in gene expression. In conclusion, we were able for the first time to delineate an intersecting genetic pattern linking ovarian tissues reflective of low potential malignancy/early cancer onset stages via long distance signaling between tissues of gynecological origin.
Assuntos
Transformação Celular Neoplásica/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Análise por Conglomerados , Bases de Dados de Proteínas , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Estatística como AssuntoRESUMO
BACKGROUND: While performance feedback and assessment are hallmarks of surgical training, they abruptly cease after training is completed. In their absence, performance may stagnate and poor habits persist. Our aim was to develop a coaching mechanism for practicing surgeons with feedback provision based on objective performance assessment. METHODS: Technical and nontechnical intraoperative video recordings from laparoscopic or robotic cholecystectomies, colectomies, and hysterectomies were assessed by a blinded surgeon and a human factors expert, respectively. Aspects of performance in need of improvement were noted, and a coaching session was developed for feedback provision to participating surgeons. This 4-hour coaching session consisted of a didactic lecture with video review and hands-on practice using procedural and mannequin-based simulation. RESULTS: Thirty-two practicing surgeons (18 general; 14 gynecologists) from 6 different hospitals were assessed, and 9 of them participated in coaching. Technical aspects identified for performance improvement included suboptimal trocar placement, inadequate critical view achievement during laparoscopic cholecystectomies, poor visualization of the operating field, bimanual dexterity, and dissection techniques, while nontechnical aspects included inappropriate handling of distractions and interruptions, poor ergonomic positioning and situational awareness, and inadequate mitigation of delays. Most surgeons appropriately accomplished some of the objectives of the distraction scenario, but none was able to achieve expert levels on Fundamentals of Laparoscopy tasks. Participants perceived the coaching sessions as highly valuable. CONCLUSION: Our study identified several technical and nontechnical skill sets of practicing surgeons in need of improvement and provided support for the implementation of coaching programs for surgeons on an ongoing basis.
Assuntos
Colecistectomia Laparoscópica/educação , Colectomia/educação , Feedback Formativo , Histerectomia/educação , Tutoria/métodos , Procedimentos Cirúrgicos Robóticos/educação , Competência Clínica , Humanos , Estudos Prospectivos , Melhoria de Qualidade , Gravação em VídeoRESUMO
OBJECTIVES: The objectives were to determine the acute toxicities of concurrent carboplatin and radiation therapy in the primary treatment of cervix cancer and to ascertain the antitumor activity of this regimen. METHODS: Patients with stage IB-1 to IVA untreated primary cervix cancers were eligible for enrollment into this study. Carboplatin was administered on a weekly basis with external radiation therapy (ERT). Low-dose brachytherapy was given after completion of ERT. Acute toxicities and response to treatment were assessed. RESULTS: Thirty-one evaluable patients were enrolled. The majority of patients had early stage disease. Carboplatin was successfully administered in 175 out of 186 (94%) planned treatments. All patients completed the prescribed course of radiation therapy. The mean treatment time was 50 days (36-73). There were no treatment delays for neutropenia or gastrointestinal toxicity. No patient was hospitalized for treatment related toxicities. Gastrointestinal toxicity equivalent to grade 3 or 4 was not reported. The objective tumor response based on physical exam findings and computed tomography measurements was 90%. CONCLUSION: Patients with cervix cancer can be treated on schedule with concurrent carboplatin and pelvic radiation therapy. This regimen is well tolerated and produces excellent response rates.
Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos/efeitos adversos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/efeitos adversos , Feminino , Humanos , Estadiamento de Neoplasias , Radioterapia/efeitos adversosRESUMO
OBJECTIVE: The goal of this study was to determine the clinical implications of a progressively rising serum CA-125 level in the normal (< 35 U/ml) range in ovarian cancer patients with complete response to therapy. METHODS: A multi-institutional investigation was undertaken to identify patients with CA-125-producing epithelial ovarian cancers who experienced progressively rising antigen levels in the normal (<35 U/ml) range after completion of therapy. All patients had (1) histologic documentation of epithelial ovarian cancer and (2) complete clinical remission (CR) as defined by negative imaging studies, normal clinical examination, and a normal (<35 U/ml) serum CA-125 value. All patients had serum CA-125 determinations at 1- to 3-month intervals after treatment. A rising serum CA-125 level was defined as a progressive increase in at least three CA-125 values above the coefficient of variation (CV) for the assay. No patient had a known episode of pelvic or gastrointestinal inflammatory disease during the period when the progressive rise in serum CA-125 took place. RESULTS: Eleven patients with rising serum CA-125 levels in the normal range were identified. Original stage of disease was as follows: stage IIA, 1; stage IIIC, 10. Cell type was as follows: endometrioid adenocarcinoma, 4; serous adenocarcinoma, 6; clear cell carcinoma, 1. Of the 11 patients identified, all developed recurrent ovarian cancer. Tumor recurrence was documented either by new lesions appearing on imaging studies (6/11) or by histologic confirmation (5/11). The mean time from CR to recurrence was 21 months (median = 22, range = 12-33). The mean time from the third early rising serum CA 125 value to clinical or radiographic confirmation of recurrence was 189 days (range = 84-518). All recurrences were intraabdominal with the exception of one axillary recurrence. CONCLUSION: In patients with a history of ovarian cancer, three progressively rising serum CA-125 values in the normal range (< 35 U/ml) at 1- to 3-month intervals are associated with a high likelihood of tumor recurrence. Patients with such a pattern should undergo immediate investigation to rule out and/or identify recurrent cancer.
Assuntos
Antígeno Ca-125/sangue , Neoplasias Ovarianas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapiaRESUMO
OBJECTIVES: The purpose of this study was to determine the recurrence rate, survival, and pregnancy outcome in patients with Stage IA and Stage IC invasive epithelial ovarian cancer treated with unilateral adnexectomy. METHODS: A multi-institutional retrospective investigation was undertaken to identify patients with Stage IA and IC epithelial ovarian cancer who were treated with fertility-sparing surgery. All patients with ovarian tumors of borderline malignancy were excluded. Long-term follow-up was obtained through tumor registries and telephone interviews. The time and sites of tumor recurrence, patient survival, and pregnancy outcomes were recorded for every patient. RESULTS: Fifty two patients with Stage I epithelial ovarian cancer treated from 1965 to 2000 at 8 participating institutions were identified. Forty-two patients had Stage IA disease, and 10 had Stage IC cancers. Cell type was distributed as follows: mucinous, 25; serous, 10; endometrioid, 10; clear cell, 5; and mixed, 2. Histologic differentiation was as follows: grade 1, 38; grade 2, 9; and grade 3, 5. Twenty patients received adjuvant chemotherapy (mean 6 courses, range 3-12 courses). Patients received the following chemotherapeutic agents: cisplatin/taxol or carboplatin/taxol, 11; melphalan, 5; cisplatin and cyclophosphamide, 3; and single-agent cisplatin, 1. Eight patients had second-look laparotomies and all were negative. Duration of follow-up ranged from 6 to 426 months (median 68 months). Five patients developed tumor recurrence 8-78 months after initial surgery. Sites of recurrence were as follows: contralateral ovary, 3; peritoneum, 1; and lung, 1. Nine patients underwent subsequent hysterectomy and contralateral oophorectomy for benign disease. At present, 50 patients are alive without evidence of disease and 2 have died of disease 13 and 97 months after initial treatment. The estimated survival was 98% at 5 years and 93% at 10 years.Twenty-four patients attempted pregnancy and 17 (71%) conceived. These 17 patients had 26 term deliveries (no congenital anomalies noted) and 5 spontaneous abortions. CONCLUSION: The long-term survival of patients with Stage IA and IC epithelial ovarian cancer treated with unilateral adnexectomy is excellent. Fertility-sparing surgery should be considered as a treatment option in women with Stage I epithelial ovarian cancer who desire further childbearing.