Improving the palliative-procedure decision-making process for patients with peritoneal carcinomatosis: A secondary analysis.

BACKGROUND: Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers. METHODS: We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute hospitalization and palliative procedure. Participants in both study arms described their experiences in semi-structured interviews. We re-analyzed coded qualitative data with a focus on understanding decision-making experiences surrounding palliative surgery and procedures using conventional content analysis. RESULTS: Interviews from 32 participants, 23 patients and 9 caregivers, were analyzed. Participants reported their decision-making was complicated by illness uncertainty and a desire for clear, effective communication with surgical and medical oncology teams. Participants requested more information about the impact of palliative procedures on their daily life. Several also noted that, without improved understanding, a misalignment between patient and family caregiver goals and palliative procedures may inadvertently increase suffering. CONCLUSION: Discussions related to patients' goals and preferences can improve the quality of treatment decision-making in patients with PC and their caregivers. Future research should test interventions to improve advanced cancer patients' illness understanding and decision-making surrounding palliative surgery and procedures.

Feasibility and acceptability of a nurse-led telehealth intervention (BOLSTER) to support patients with peritoneal carcinomatosis and their caregivers: A pilot randomized clinical trial.

OBJECTIVE: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP). METHODS: Pilot feasibility RCT. Recently hospitalized adults with advanced GYN and GI cancers, PC, and a new complex care need and their caregivers were randomized 1:1 to BOLSTER or enhanced discharge planning (EDP). We defined feasibility as a ≥ 50% approach-to-consent ratio and acceptability as ≥70% satisfaction with BOLSTER. We assessed patients' HRQoL and self-efficacy at baseline and six weeks, then compared the proportion experiencing meaningful improvements by arm. ACP documentation was identified using natural language processing. RESULTS: We consented 77% of approached patients. In the BOLSTER arm, 91.0% of patients and 100.0% of caregivers were satisfied. Compared to EDP, more patients receiving BOLSTER experienced improvements in HRQoL (68.4% vs. 40.0%) and self-efficacy for managing symptoms (78.9% vs. 35.0%) and treatment (52.9% vs. 42.9%). The BOLSTER arm had more ACP documentation. CONCLUSIONS: BOLSTER is a feasible and acceptable intervention with the potential to improve patients' HRQoL and promote ACP. An efficacy trial comparing BOLSTER to usual care is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03367247; PI: Wright.

Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

PURPOSE: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Geographical Health District and Distance Traveled Influence on Clinical Status at Admission of Patients with Gestational Trophoblastic Disease / A influência do distrito de saúde e da distância viajada sobre o estado clínico na apresentação de pacientes com doença trofoblástica gestacional

Abstract Objective To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). Methods This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I-XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. Results This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (β = 2.38 [0.87-3.88], p = 0.002) and XVI (β = 0.78 [0.02-1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (β = 3.32, 95% CI = 0.78-5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). Conclusion Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

Resumo Objetivo Avaliar a possível relação entre estado clínico na apresentação e distância percorrida a partir do distrito de saúde em mulheres com doença trofoblástica gestacional. Métodos Estudo transversal incluindo mulheres com doença trofoblástica gestacional dos 17 distritos de saúde do estado de São Paulo (I-XVII), Brasil, encaminhadas ao Centro de Doenças Trofoblásticas de Botucatu (distrito VI), entre 1990 e 2018. Na admissão, avaliaram-se mola hidatiforme pelo sistema de pontuação de risco de Berkowitz et al. e neoplasia trofoblástica gestacional pelo escore de risco/estadiamento Federação Internacional de Ginecologia e Obstetrícia / Organização Mundial da Saúde (FIGO/OMS). Coletaram-se dados demográficos, clínicos e distância percorrida e análises de regressão múltipla foram realizadas. Resultados Este estudo incluiu 366 mulheres (335 mola hidatiforme, 31 neoplasia trofoblástica gestacional). O estado clínico na apresentação e distância percorrida diferiram significativamente entre o centro especializado e demais distritos. Nas pacientes encaminhadas pelos distritos IX (β = 2,38 [0,87-3,88], p = 0,002) e XVI (β = 0,78 [0,02-1,55], p = 0,045), os escores de mola hidatiforme foram maiores que no centro especializado. As pacientes com neoplasia trofoblástica gestacional do distrito XVI apresentaram escores FIGO 3,32 vezes maior que no centro especializado (β = 3,32, 95% CI = 0,78-5,87, p = 0,010). A distância percorrida pelas pacientes dos distritos IX (200km) e XVI (203,5km) foi significativamente maior do que a percorrida pelas pacientes do centro especializado (76km). Conclusão Pacientes de distritos de saúde fora da cobertura do centro especializado apresentaram escores de risco mais alto para mola hidatiforme e para neoplasia trofoblástica gestacional na admissão. Longas distâncias (>80 km) pareceram influenciar negativamente o estado clínico da doença trofoblástica gestacional na apresentação, indicando barreiras no acesso a centros especializados.

Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia - systematic review with a presentation of the first 4 Brazilian cases

Abstract Objective To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. Methods Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board. Results Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab. Conclusion Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment.

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia / Apresentação clínica, resultados do tratamento e fatores relacionados à resistência em mulheres sul-americanas com neoplasia trofoblástica gestacional pós-molar de baixo risco

Abstract Objective There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Methods Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. Results A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p= 0.019). Conclusion 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Resumo Objetivo Existem poucos estudos multinacionais sobre os resultados do tratamento da neoplasia trofoblástica gestacional (NTG) na América do Sul. O objetivo deste estudo foi avaliar a apresentação clínica, os resultados do tratamento e os fatores associados a casos de quimiorresistência em NTG pós-molar de baixo risco tratados com quimioterapia de agente único de primeira linha em três centros sul-americanos. Métodos Estudo multicêntrico de coorte histórica incluindo mulheres com NTG pós-molar de baixo risco com estadiamento International Federation of Gynecology and Obstetrics (FIGO) em centros de atendimento na Argentina, Brasil e Colômbia entre 1990 e 2014. Foram obtidos dados sobre as características do paciente, apresentação da doença e resposta ao tratamento. A regressão logística foi usada para avaliar a relação entre fatores clínicos e resistência ao tratamento de primeira linha com agente único. Foi realizada uma análise multivariada dos fatores clínicos significativos na análise univariada. Resultados Cento e sessenta e três mulheres com NTG de baixo risco foram incluídas na análise. A taxa global de resposta completa à quimioterapia de primeira linha foi de 80% (130/163). As taxas de resposta completa ao metotrexato ou actinomicina-D como tratamento de primeira linha e actinomicina-D como tratamento de segunda linha após falha do metotrexato foram 79% (125/157), 83% (⅚) e 70% (23/33), respectivamente. A mudança para o tratamento de segunda linha por quimiorresistência ocorreu em 20,2% dos casos (33/163). A análise multivariada demonstrou que pacientes com pontuação de risco FIGO de 5 a 6 foram 4,2 vezes mais propensos a desenvolver resistência ao tratamento com agente único de primeira linha (p= 0,019). Conclusão 1) Na apresentação, a maioria das mulheres demonstrou características clínicas favoráveis a um bom resultado, 2) a taxa geral de remissão completa sustentada após o tratamento de primeira linha com agente único foi comparável à de países desenvolvidos, 3) um escore de risco FIGO de 5 ou 6 está associado ao desenvolvimento de resistência à quimioterapia de agente único de primeira linha.

Association between antioxidant vitamins and oxidative stress among patients with a complete hydatidiform mole

OBJECTIVES: This study aimed to evaluate the potential relationship between oxidative stress, dietary intake, and serum levels of antioxidants in patients with a complete hydatidiform mole (CHM) compared with controls. METHODS: This was an observational cross-sectional study conducted in Rio de Janeiro, Brazil. A total of 140 women were enrolled in this study and divided into four groups: 43 patients with CHM, 33 women who had had an abortion, 32 healthy pregnant women, and 32 healthy non-pregnant women. All participants underwent blood sampling, assessment using a semiquantitative food frequency questionnaire, and anthropometric measurement. Blood samples were collected after overnight fasting (10-12 h). Vitamin levels (A, C, and E) were determined by ultra-performance liquid chromatography, and gamma-glutamyl transferase levels were assessed using an automated quantitative analysis system (Dimension®, Siemens). RESULTS: Although all groups showed sufficient serum vitamin A and E levels, the participants had inadequate dietary intake of these vitamins. Conversely, all groups had an insufficient serum level of vitamin C, despite adequate intake. The gamma-glutamyl transferase values did not differ significantly among the groups. However, elevated serum levels of this enzyme were observed in several patients. CONCLUSIONS: All groups exhibited high levels of oxidative stress, as evaluated by gamma-glutamyl transferase levels, and had inadequate intake of antioxidant vitamins. Therefore, the high exposure to oxidative stress found in our study, even in healthy pregnant and non-pregnant women, may increase the incidence of CHM in this region.