RESUMO
Ovarian cancer continues to have a high mortality rate despite therapeutic advances. Traditionally, treatment has focused on surgery followed by systemic platinum- based chemotherapy. Unfortunately, most patients develop resistance to platinum agents, highlighting the need for targeted therapies. PARP inhibitors and anti-angiogenic agents, such as bevacizumab, have more recently changed upfront therapy. Unfortunately, other targeted therapies including immunotherapy have not seen the same success. Emerging therapeutic targets and modalities such as small molecule tyrosine kinase inhibitors, lipid metabolism targeting agents, gene therapy, ribosome targeted drugs as well as several other therapeutic classes have been and are currently under investigation. In this review, we discuss targeted therapies in high grade serous ovarian cancer from preclinical studies to phase III clinical trials.
RESUMO
Objective: We aimed to assess the impact of preoperative steroid administration and perioperative glycemic control on postoperative complications in diabetic gynecologic oncology patients undergoing laparotomy. Methods: This retrospective cohort study included gynecologic oncology patients with Type I and Type II diabetes (DM) undergoing laparotomy for any gynecologic indication at a single academic center from 10/2017 to 09/2020. The primary outcome was the rate of postoperative complications. Preoperative steroid administration and 24-hour postoperative average serum blood glucose (BG) ≥ 180 mg/dL were the studied exposures. Data was analyzed with SPSS Statistics v.28. Results: 225 patients met inclusion criteria; 47.6 % had postoperative complications. Patient demographics were similar between patients with and without postoperative complications. Patients with complications had higher BMIs (36.8 vs. 34.0; p = 0.03), bowel surgery (33.0 % vs. 17.1 %; p = 0.008), operative time ≥ 240 min (14.2 % vs. 5.1 %; p = 0.02) and average BG ≥ 180 (63.6 % vs. 40.2 %; p < 0.01). On multivariate analysis, bowel surgery (OR 2.4 (1.2-4.8); p = 0.01) and average BG ≥ 180 (OR 2.8 (1.6-4.9); p < 0.01) remained significant predictors of postoperative complications. There were no differences in complication rates (42.3 % vs. 42.6 %; p = 1.0) between patients who received preoperative steroids and those who did not. When stratified by average postoperative BG < 180 mg/dL vs. BG ≥ 180 mg/dL, there was no difference in Clavien-Dindo classification, 30-day readmission rate (28.2 % vs. 22.1 %; p = 0.49) or 30-day mortality rate (2.9 % vs. 0.0 %; p = 0.53). Conclusion: The administration of preoperative steroids did not increase complication rates. Perioperative hyperglycemia was associated with an increased risk of postoperative complications. Optimizing perioperative glycemic control is imperative to decrease postoperative complications.
RESUMO
OBJECTIVE: To evaluate the impact of a mobile health patient engagement technology (PET) on postoperative outcomes in gynecologic oncology patients. METHODS: All gynecologic oncology patients undergoing laparotomy on an enhanced recovery program (ERP) were approached from July 2019 to May 2021 to enroll in a PET, which can be accessed by computer, tablet, or smart phone. This platform provides enhanced pre- and postoperative patient education and remote patient monitoring. Patients who elected to participate were provided with targeted education based on their age and comorbidities and were asked to complete daily health checks during the postoperative period. Participants in the PET were compared to patients who opted out as well as to a historical cohort from prior to PET implementation. Patient and procedure-level factors were recorded. The primary outcomes were length of stay (LOS) and 30-day readmission rate. Analysis was performed using SPSS v.26. RESULTS: 682 women met inclusion criteria during the study time; 347 in the PET group and 335 in the control group. Demographic and other factors including race, BMI (kg/m2), Charlson Comorbidity Index (CCI), surgical complexity, and insurance status were not different between the PET and control group; however, patients in the PET cohort were slightly younger (55.0 yo vs. 57.2 yo; p = 0.04). Patients in the PET group had a significantly shorter LOS (2.9 days vs. 3.6 days; p < 0.01) and lower readmission rate (4.3% vs. 8.6%; p < 0.01) when compared with the control group. CONCLUSIONS: Use of a PET in our gynecologic oncology patients decreased LOS by nearly one day despite an absence of differences in other demographic and surgical factors other than age. Furthermore, there was a 50% reduction in readmission rates in the PET group. The use of a PET allows for healthcare professionals to engage, evaluate, and treat patients in a way that improves perioperative care.
Assuntos
Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/etiologia , Estudos Retrospectivos , Participação do Paciente , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Assistência Perioperatória , Tempo de Internação , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: Distress screening and management is a recommended component of oncology care. Our objective was to evaluate distress rate, sources, and compliance with psychosocial follow-up among ovarian cancer patients receiving chemotherapy. METHODS: We reviewed patient distress surveys completed by ovarian cancer patients receiving chemotherapy from 10/2017-6/2019. Lay or nurse navigators conducted screening with the NCCN Distress Thermometer from 0 (none) to 10 (highest distress). A distress score ≥ 4 (moderate/severe) was considered a positive screen. A recommendation for psychosocial follow-up was automatically generated in the treatment care plan based upon a yes response to any depression-related concern, independent of distress score. Documentation of referral to a mental health professional or social worker for counseling was considered compliant with psychosocial follow-up. We performed descriptive statistics and bivariate analyses. RESULTS: 97/211 (46%) ovarian cancer patients screened positive for distress. Average score was 6.1 for those who screened positive and 3.3 for the entire cohort (range 0-10). Unmarried status (p < 0.01) was associated with positive screen, whereas non-white race (p = 0.26) and recurrent disease (p = 0.21) were not. Median age was older for patients with a positive distress screen (p < 0.01). Among screened patients, the most frequent sources of distress were: cognitive/physical (87%), psychosocial (62%), practical (84%), and family concerns (40%). Of 50 patients recommended to have psychosocial referral, 4 (8%) patients had documented psychiatric follow-up and 19 (38%) patients had documented psychosocial counseling by a social worker. CONCLUSIONS: Nearly half of ovarian cancer patients screened positive for moderate/severe distress. Cancer/treatment-related cognitive/physical symptoms were the most frequent sources. Improved methods of symptom monitoring and management during treatment and resources to address psychosocial concerns are needed to improve distress management of ovarian cancer patients.
Assuntos
Neoplasias , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/complicações , Feminino , Humanos , Programas de Rastreamento , Oncologia , Neoplasias/terapia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/terapia , Encaminhamento e Consulta , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Estresse Psicológico/psicologiaRESUMO
OBJECTIVE: To evaluate the effects of an environmentally friendly drug deactivation bag on opioid disposal among patients undergoing gynecologic surgery. METHODS: This prospective cohort study included patients undergoing gynecologic procedures requiring an opioid prescription from March 2020 to December 2020. Patients were managed on a restrictive opioid prescribing algorithm and given an opioid disposal bag. The carbon drug deactivation bag neutralizes the opioid medication and can be discarded safely in the trash. Patients were educated about pain management goals and the disposal bag. Patients were surveyed at their postoperative visit to evaluate satisfaction, number of leftover pills, and disposal methods. Statistical analysis was performed using SPSS Statistics 26. RESULTS: Two hundred patients were asked to complete the survey, with a response rate of 78%. The most common procedures were exploratory laparotomy (50%) and minimally invasive hysterectomy (41%). Most patients (91%, 95% CI 91-97) filled their opioid prescription and 64 (41%, 95% CI 34-48) had leftover opioid pills. Most patients with leftover opioid pills (73%, 95% CI 67-79) discarded them; 78%, 95% CI 69-80 used the disposal bag. Patients undergoing an exploratory laparotomy most commonly used the disposal bag. All patients who used the disposal bag stated they would use it again. CONCLUSION: Despite a restrictive opioid prescribing algorithm, 41% of gynecologic surgical patients had leftover opioid pills. This study demonstrated that leftover opioid pills were safely discarded 73% of the time when patients were provided an opioid disposal bag and preoperative education.
Assuntos
Analgésicos Opioides , Procedimentos Cirúrgicos em Ginecologia , Eliminação de Resíduos de Serviços de Saúde/instrumentação , Alabama , Algoritmos , Estudos de Coortes , Meio Ambiente , Feminino , Humanos , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the utility of a society-based robotic surgery training program for fellows in gynecologic oncology. METHODS: All participants underwent a 2-day robotic surgery training course between 2015-2017. The course included interactive didactic sessions with video, dry labs, and robotic cadaver labs. The labs encompassed a wide range of subject matter including troubleshooting, instrument variation, radical hysterectomies, and lymph node dissections. Participants completed a pre- and post-course survey using a 5-point Likert scale ranging from "not confident" to "extremely confident" on various measures. Statistical analysis was performed using SPSS Statistics v. 24. RESULTS: The response rate was high with 86% of the 70 participants completing the survey. Sixteen (26.7%) of these individuals were attending physicians and 44 (73.3%) were fellows. In general, there was a significant increase in confidence in more complex procedures and concepts such as radical hysterectomy (p=0.01), lymph node dissection (p=0.01), troubleshooting (p=0.001), and managing complications (p=0.004). Faculty comfort and practice patterns were cited as the primary reason (58.9%) for limitations during robotic procedures followed secondarily by surgical resources (34.0%). CONCLUSION: In both gynecologic oncology fellows and attendings, this educational theory-based curriculum significantly improved confidence in the majority of procedures and concepts taught, emphasizing the value of hands-on skill labs.
Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Currículo , Feminino , Humanos , Histerectomia , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
OBJECTIVE: Enhanced recovery protocols are now established as the standard of care leading to improved perioperative outcomes and associated cost-benefits. The objective of this study was to evaluate the impact of an enhanced recovery program on complication rates in high-risk gynecologic oncology patients undergoing surgery. METHODS: This retrospective cohort study included gynecologic oncology patients with pathology-proven malignancy undergoing non-emergent laparotomy from October 2016 to December 2018 managed on an enhanced recovery protocol, and a control group from October 2015 through September 2016 prior to enhanced recovery protocol implementation. The primary outcome was complication rates in a high-risk population pre- and post-enhanced recovery protocol. High-risk patients were defined as those with obesity (body mass index >30 kg/m2) and/or age ≥65 years. Analysis was performed using Statistical Package for Social Sciences (SPSS) v.24. RESULTS: A total of 363 patients met the inclusion criteria: 104 in the control group and 259 in the enhanced recovery protocol group. Patient demographics, including age, body mass index, diagnosis, and performance status, were similar. Overall complication rates were less in the enhanced recovery protocol group (29% vs 53.8%; p<0.0001). The enhanced recovery protocol group had a shorter length-of-stay compared with control (3.3 vs 4.2 days; p<0.0001). The 30-day readmission rates were similar between the groups (9.6% vs 13.5%; p=0.19). In the enhanced recovery protocol group compared with control, complication rates were less in obese patients (29.4% vs 57.8%; p<0.0001), morbidly obese patients (20.9% vs 76.2%; p<0.0001), and age ≥65 (36.1% vs 57.1%; p<0.0001). The most common complications in the enhanced recovery protocol group were ileus (9.7%), pulmonary complications (2.7%), and blood transfusions (10.8%). CONCLUSIONS: Implementation of an enhanced recovery protocol decreases complication rates and length-of-stay in morbidly obese and geriatric patients with gynecologic malignancy without an increase in readmission rates.
Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias dos Genitais Femininos/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Readmissão do Paciente/estatística & dados numéricos , Estudos RetrospectivosRESUMO
OBJECTIVE: Patients with epithelial ovarian cancer (EOC) typically present with late-stage disease, posing a significant challenge to treatment. Although taxane and platinum-based chemotherapy plus surgical debulking are initially effective, EOC is marked by frequent recurrence with resistant disease. Immunotherapy represents an appealing treatment paradigm given the ability of immune cells to engage metastatic sites and impede recurrence; however, response rates to checkpoint blockade in ovarian cancer have been disappointing. Here, we tested whether class I HDAC inhibition can promote anti-tumor T cell responses in a spontaneous and nonspontaneous murine model of EOC. METHODS: We used the spontaneous Tg-MISIIR-Tag and nonspontaneous ID8 models of murine ovarian cancer to test this hypothesis. Whole tumor transcriptional changes were assessed using the nCounter PanCancer Mouse Immune Profiling Panel. Changes in select protein expression of regulatory and effector T cells were measured by flow cytometry. RESULTS: We found that treatment with the class I HDAC inhibitor entinostat upregulated pathways and genes associated with CD8 T cell cytotoxic function, while downregulating myeloid derived suppressor cell chemoattractants. Suppressive capacity of regulatory T cells within tumors and associated ascites was significantly reduced, reversing the CD8-Treg ratio. CONCLUSIONS: Our findings suggest class I HDAC inhibition can promote activation of intratumoral CD8 T cells, potentially by compromising suppressive networks within the EOC tumor microenvironment. In this manner, class I HDAC inhibition might render advanced-stage EOC susceptible to immunotherapeutic treatment modalities.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Ovarianas/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Apoptose , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/patologia , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The objective of this study was to evaluate the impact of a post-surgical restrictive opioid prescribing algorithm (ROPA) in gynecologic oncology patients. METHODS: This cohort study included gynecologic oncology patients undergoing any surgical procedure from 08/2018-7/2019 after implementation of a ROPA. Patients were compared to historical controls managed without a ROPA from 10/2016-9/2017. Patients were educated preoperatively about pain management goals, the ROPA, and opioid disposal. A 4-tiered system was developed to standardize prescriptions at discharge based on surgical complexity and inpatient opioid requirements. Patients were surveyed at their postoperative visit to assess home opioid use and satisfaction. Statistical analysis was performed using SPSS Statistics v.24. RESULTS: 2549 patients met inclusion criteria; 1321 in the historical control group and 1228 in the ROPA group. Demographics, including age, BMI, and performance status were similar. Compared with the control group, the average number of opioid pills prescribed was significantly lower in the ROPA group (30.5 vs 11.3; p < 0.001) along with the morphine milligram equivalents (MME) (152.5 MME vs. 83.3 MME; p < 0.001). The percentage of patients requiring opioid refill within 30 days was similar (13.0% vs. 12.6%; p = 0.71). 95.7% of patients surveyed were satisfied with their pain regimen. The total number of pills prescribed annually decreased from 34,130 in the control group to 13,888 in the ROPA group. CONCLUSIONS: A restrictive prescribing practice allows for a significantly lower number of opioids to be prescribed to postoperative patients while maintaining patient satisfaction. There was no increase in opioid refill requests using a ROPA in patients undergoing surgery.
Assuntos
Analgésicos Opioides/administração & dosagem , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Ginecologia/organização & administração , Ginecologia/normas , Ginecologia/estatística & dados numéricos , Implementação de Plano de Saúde , Humanos , Oncologia/organização & administração , Oncologia/normas , Oncologia/estatística & dados numéricos , Pessoa de Meia-Idade , Epidemia de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/etiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Dor Pós-Operatória/etiologia , Satisfação do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.
Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Indazóis/economia , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas/economia , Inibidores de Poli(ADP-Ribose) Polimerases/economia , Carcinoma Epitelial do Ovário/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Neoplasias Ovarianas/economia , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVES: The objective of this quality improvement (QI) project was to decrease the rate of low-value computed tomography (CT) imaging in established gynecologic oncology patients presenting to the emergency department (ED). METHODS: This was a cohort study with a before and after design that evaluated implementation of a QI project designed to decrease CT utilization in established gynecologic oncology patients in the ED. The pre-intervention cohort included patients admitted through the ED from 4/1/17 to 5/31/18, while the post-intervention cohort was from 6/1/18 to 5/31/19. The intervention included gynecologic oncology consultation before CT on patients who had imaging within the prior 3 weeks. Details regarding CT, ED length of stay (LOS), and oncologic history were abstracted. The value of CT was determined by consensus from 2 reviewers. Prospective data monitoring evaluated for patient safety. RESULTS: Prior to intervention, there were 129 unique ED encounters in gynecologic oncology patients leading to admission. CT scans were performed in 101 (78.3%) encounters, 57.7% of which were deemed to be of low-value. Following implementation, the CT utilization rate decreased significantly from median monthly rate of 75.2% to 49.1% (p < 0.00001), and the ED LOS decreased from 8.1 to 6.9 h (p = 0.0102). The number of CT scans deemed to be low-value in the post-intervention group decreased to 2 (3.8%). CONCLUSIONS: Implementation of an early consultation policy and imaging guidelines led to a significant decrease in unnecessary CT utilization and shorter ED LOS in gynecologic oncology patients presenting to the ED.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Estudos de Coortes , Serviço Hospitalar de Emergência/normas , Feminino , Neoplasias dos Genitais Femininos/terapia , Fidelidade a Diretrizes , Humanos , Pessoa de Meia-Idade , Melhoria de Qualidade , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normasRESUMO
OBJECTIVE: To determine the financial impact of an enhanced recovery after surgery (ERAS) protocol in gynecologic oncology patients. METHODS: This study identified gynecologic oncology patients who were placed on the ERAS protocol after elective laparotomy from 10/2016-6/2017. A control group was identified from the year prior to ERAS implementation. Financial experts assisted in procuring data for these patient encounters, including payer status, direct and indirect costs, contribution margin, and length of stay (LOS). SPSS Statistics v. 24 was used for statistical analysis. RESULTS: 376 patients met criteria for inclusion: 179 in the ERAS group and 197 in the control group. Patient demographics were similar between the two cohorts. Payer status across the groups was not statistically significant in patients with private insurance (control 43.7% vs. ERAS 41.3%), Medicare (38.1% vs. 31.8%), or self-pay patients (12.2% vs. 15.1%). There was a significantly higher number of Medicaid patients in the ERAS group (6.1% vs. 11.7%; p = 0.05). Hospital direct costs ($5596 vs. 5346) and indirect costs ($5182 vs. $4954) per encounter were similar between groups. However, overall contribution margin per encounter decreased in the ERAS group ($11,619 vs. $8528; p = 0.01). LOS was significantly lower in the ERAS group (4.1 vs. 2.9 days; p = 0.04). CONCLUSIONS: Implementation of the ERAS protocol in gynecologic oncology patients does not lead to increased costs for the patient or hospital system. The decreased contribution margin is likely due to a reduction in per diem payments caused by the reduction in LOS. On a per-patient-day basis, contribution margin was the same for both groups ($2877 vs $2857). The reduction in LOS also created capacity for additional cases, the financial impact of which was not evaluated.
Assuntos
Neoplasias dos Genitais Femininos/economia , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/economia , Procedimentos Cirúrgicos em Ginecologia/métodos , Estudos de Casos e Controles , Estudos de Coortes , Recuperação Pós-Cirúrgica Melhorada , Feminino , Procedimentos Cirúrgicos em Ginecologia/normas , Gastos em Saúde/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Humanos , Seguro Saúde , Tempo de Internação/economia , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Assistência Perioperatória/economia , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Cuidados Pós-Operatórios/economia , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/normas , Estudos Retrospectivos , Estados UnidosRESUMO
Poly-ADP ribose polymerase inhibitors (PARPi) are a promising new treatment option for patients with ovarian cancer and are moderately emetogenic. Tolerance of therapy is paramount, and uncontrolled nausea and vomiting may limit use. Although most patients will experience improvement in nausea and vomiting after one to two months, approximately one in twenty patients will discontinue therapy due to unrelieved symptom burden. Three cases of olaparib-related nausea and vomiting mitigated by primary pyridoxine use are reported. Case 1 demonstrates successful use of pyridoxine in breakthrough nausea. Case 2 details the use of pyridoxine following refractory nausea and vomiting requiring hospitalization. Case 3 describes a prophylactic approach for a patient with significant anticipatory nausea. All three patients tolerated olaparib after starting and continuing pyridoxine. Vitamin B6, or pyridoxine, was successful as both a therapeutic and prophylactic option for significant treatment-related nausea and vomiting with PARPi use.
RESUMO
OBJECTIVE: To determine the cost-effectiveness of pembrolizumab in patients with recurrent endometrial cancer that have failed first-line chemotherapy. METHODS: We created a model to evaluate the cost-effectiveness of pembrolizumab compared to pegylated liposomal doxorubicin (PLD) or bevacizumab for the treatment of women with recurrent endometrial cancer who have failed carboplatin and paclitaxel. Microsatellite instability-high (MSI-H) and non-microsatellite instability-high (non-MSI-H) tumors were evaluated. We included 4400 patients in the model; 800 patients were assumed to have MSI-H tumors. Drug costs were calculated using 2016-2017 wholesale acquisition costs, and cost of Grade III-IV toxicities was estimated from clinical experience. Effectiveness was calculated as 2-year overall survival (OS). We calculated incremental cost-effectiveness ratios (ICERs) to determine the cost per 2-year survivor. Univariate sensitivity analyses were performed. The willingness to pay threshold was $100,000 per year of OS. RESULTS: The cost of therapy with PLD and bevacizumab were $33.2 million (M) and $167.9â¯M, respectively. The cost of pembrolizumab therapy was $318.3â¯M for non-MSI-H patients compared to $57.9â¯M for MSI-H patients. For non-MSI-H patients, bevacizumab was cost-effective relative to PLD with an ICER of $153,028, while pembrolizumab was not cost-effective relative to bevacizumab with an ICER of $341,830. For MSI-H patients, pembrolizumab was cost-effective compared to PLD with an ICER of $147,249, while bevacizumab was subjected to extended dominance. Sensitivity analysis revealed that for non-MSI-H patients, one cycle of pembrolizumab would need to cost $7253 or less to be cost-effective. CONCLUSIONS: For patients with MSI-H recurrent endometrial cancers who have failed first-line chemotherapy, pembrolizumab is cost-effective relative to other single agent drugs. To be cost-effective in non-MSI-H patients, the cost of pembrolizumab should decrease substantially.
Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/economia , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/economia , Bevacizumab/uso terapêutico , Estudos de Coortes , Análise Custo-Benefício , Doxorrubicina/análogos & derivados , Doxorrubicina/economia , Doxorrubicina/uso terapêutico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Instabilidade de Microssatélites , Recidiva Local de Neoplasia/economia , Recidiva Local de Neoplasia/genética , Polietilenoglicóis/economia , Polietilenoglicóis/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Ovarian cancer is poorly immunogenic; however, increased major histocompatibility complex class II (MHCII) expression correlates with improved immune response and prolonged survival in patients with ovarian cancer. The authors previously demonstrated that the histone deacetylase inhibitor entinostat increases MHCII expression on ovarian cancer cells. In the current study, they evaluated whether entinostat treatment and resultant MHCII expression would enhance beneficial immune responses and impair tumor growth in mice with ovarian cancer. METHODS: C57BL/6 mice bearing intraperitoneal ID8 tumors were randomized to receive entinostat 20 mg/kg daily versus control. Changes in messenger RNA (mRNA) expression of 46 genes important for antitumor immunity were evaluated using NanoString analysis, and multicolor flow cytometry was used to measure changes in protein expression and tumor-infiltrating immune cells. RESULTS: Entinostat treatment decreased the growth of both subcutaneously and omental ID8 tumors and prolonged survival in immunocompetent C57BL/6 mice. NanoString analysis revealed significant changes in mRNA expression in 21 of 46 genes, including increased expression of the MHCI pathway, the MHCII transactivator (CIITA), interferon γ, and granzyme B. C57BL/6 mice that received entinostat had increased MHCII expression on omental tumor cells and a higher frequency of tumor-infiltrating, CD8-positive T cells by flow cytometry. In immunocompromised mice, treatment with entinostat had no effect on tumor size and did not increase MHCII expression. CONCLUSIONS: In the current murine ovarian cancer model, entinostat treatment enhances beneficial immune responses. Moreover, these antitumor effects of entinostat are dependent on an intact immune system. Future studies combining entinostat with checkpoint inhibitors or other immunomodulatory agents may achieve more durable antitumor responses in patients with ovarian cancer.
Assuntos
Benzamidas/administração & dosagem , Antígenos de Histocompatibilidade Classe II/genética , Inibidores de Histona Desacetilases/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Piridinas/administração & dosagem , Regulação para Cima , Imunidade Adaptativa , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Hospedeiro Imunocomprometido , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Medicina de Precisão , Piridinas/farmacologia , Distribuição Aleatória , Transativadores/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Many of the enhanced recovery after surgery principles initially developed for colorectal surgery can be successfully applied to gynecologic oncology and lead to significant improvements in perioperative care. Enhanced recovery after surgery guidelines specific to gynecologic oncology were published in 2016 and provide a framework for the development and implementation of institutional protocols. Identification of key stakeholders and a multidisciplinary approach are critical to identifying which principles are best suited for implementation at a particular institution and for ensuring success of the protocol. Herein, we review our experience with protocol development and implementation on a gynecologic oncology service.
Assuntos
Ginecologia , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica , Oncologia Cirúrgica , Feminino , HumanosRESUMO
OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients. METHODS: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation. The primary outcome was rate of postoperative ileus, defined as nausea and vomiting requiring nothing-per-mouth status or nasogastric tube (NGT) placement. Secondary outcomes included length of stay (LOS) and 30-day readmission. RESULTS: 376 patients met inclusion criteria; 197 in the control group and 179 in the ERAS group. Patient demographics were similar between groups. Ileus rate was significantly lower in the ERAS group (2.8% vs. 15.7%; pâ¯<â¯0.001), and fewer patients in the ERAS group required NGT placement (2.2% vs. 7.1%; pâ¯=â¯0.06). ERAS remained independently associated with decreased ileus rates when controlling for other patient and surgical factors (OR 0.2; pâ¯=â¯0.01). Epidural use was correlated with a significant increase in ileus risk (OR 2.6; pâ¯=â¯0.03), as was increased Charlson Comorbidity Index (OR 1.2; pâ¯<â¯0.01). LOS was significantly decreased in the ERAS group (2.9 vs. 4.0â¯days; pâ¯=â¯0.04), while 30-day readmission rates were similar (10.1% vs. 10.7%; pâ¯=â¯0.62). CONCLUSIONS: Implementation of an ERAS protocol significantly decreases the risk of postoperative ileus in gynecologic oncology patients undergoing laparotomy. ERAS also reduced LOS compared to pre-ERAS controls.
Assuntos
Neoplasias dos Genitais Femininos/fisiopatologia , Neoplasias dos Genitais Femininos/cirurgia , Íleus/etiologia , Íleus/fisiopatologia , Estudos de Coortes , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Íleus/prevenção & controle , Laparotomia , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
OBJECTIVES: The aim of this study was to determine preoperative risk factors associated with unplanned reoperation within 30 days for patients undergoing major surgery for primary ovarian cancer using the National Surgical Quality Improvement Program database. METHODS: We conducted a retrospective cohort study utilizing the National Surgical Quality Improvement Program database to identify patients undergoing primary ovarian cancer surgery from 2012 to 2014. Patients who had a reoperation within 30 days of their primary surgery were identified. Demographics and clinical covariates were calculated. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate logistic regression approaches to assess the association. RESULTS: A total of 4260 patients were identified during the study period. One hundred forty-eight patients (3.5%) underwent a reoperation within 30 days of their primary surgery. In univariate analysis, preoperative creatinine 1.5 mg/dL or greater (P = 0.010), smoking (P = 0.003), and both insulin-dependent (P = 0.029) and non-insulin-dependent diabetes mellitus (P = 0.048) were predictive of a reoperation. Multivariate analysis noted that smoking (OR, 1.94; 95% CI, 1.26-2.99), insulin-dependent diabetes mellitus (OR, 2.18; 95% CI, 1.08-4.40), non-insulin-dependent diabetes mellitus (OR, 1.65; 95% CI, 1.01-2.72), and preoperative creatinine (OR, 2.65; 95% CI, 1.26-5.58) were predictive of a reoperation. Age 50 to 60 years was protective against reoperation when compared with age younger than 50 years (OR, 0.54; 95% CI, 0.32-0.90). CONCLUSIONS: Efforts to reduce reoperation rates should focus on identifying high-risk patients by utilizing objective preoperative data. Optimizing their medical status prior to surgery may decrease the reoperation rate in patients with ovarian cancer, thereby improving outcomes and providing a probable cost benefit.
Assuntos
Neoplasias Ovarianas/cirurgia , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Laparotomia/métodos , Laparotomia/estatística & dados numéricos , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Oncologia Cirúrgica/normas , Oncologia Cirúrgica/estatística & dados numéricosRESUMO
A 32â¯year-old nulligravid woman with a uterine mass underwent exploratory laparotomy with myomectomy. Final pathology revealed a low-grade endometrial stromal sarcoma (ESS) with positive margins. She subsequently underwent definitive robotic hysterectomy and bilateral salpingectomy with ovarian preservation. She was diagnosed with a stage IB low-grade ESS. She is currently undergoing observation. Discussion of classification, surgical options, and adjuvant therapy is presented.
Assuntos
Neoplasias do Endométrio/terapia , Tumores do Estroma Endometrial/terapia , Tratamentos com Preservação do Órgão/métodos , Adulto , Biópsia , Quimioterapia Adjuvante/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Tumores do Estroma Endometrial/diagnóstico por imagem , Tumores do Estroma Endometrial/patologia , Tubas Uterinas/diagnóstico por imagem , Tubas Uterinas/cirurgia , Feminino , Preservação da Fertilidade/métodos , Humanos , Histerectomia , Laparoscopia/métodos , Margens de Excisão , Estadiamento de Neoplasias , Ovário/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Salpingectomia , Miomectomia Uterina , Útero/diagnóstico por imagem , Útero/patologia , Útero/cirurgiaRESUMO
While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n = 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC. Mol Cancer Res; 16(5); 813-24. ©2018 AACR.