Hyperthermic Intraperitoneal Chemotherapy

腹腔热化疗
  • 文章类型: Journal Article
    腹膜肉瘤病是一种罕见的恶性疾病,预后差,继发于腹盆腔软组织肉瘤的腹膜播散。它的稀有性,连同特征性的组织学异质性和历史上对全身治疗的不良反应,阻止了建立具有治愈意图的广泛接受的治疗标准。在这个意义上,根治性细胞减灭术(CRS)与周围切除术和腹腔热化疗(HIPEC),广泛用于腹膜癌,效果极佳,在腹膜肉瘤病患者中没有相同的进化发展。一个由肉瘤和腹膜肿瘤外科专家组成的多学科工作组根据当前的科学证据为腹膜肉瘤病的管理制定了一系列建议,考虑到腹盆腔肉瘤的不同组织学亚组,可根据其起源引起:腹膜后肉瘤,子宫肉瘤,GIST(胃肠道间质瘤)和非GIST起源的内脏/腹膜肉瘤。本文显示了肉瘤专家对在伊比利亚-美洲关于腹膜肉瘤病管理的共识中提出的建议进行投票的结果,这是在最近举行的第三届西班牙裔-葡萄牙肉瘤治疗更新会议的庆祝活动中举行的。
    Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts\' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.
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  • 文章类型: Journal Article
    Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the “The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the “ESMO Standardized Operating Procedures Consensus Conference” were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive “Arbeitsgemeinschaft Gynäkologische Onkologie – AGO” score or “I-model” positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.
    Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la “Conferencia de consenso de procedimientos operativos estandarizados de ESMO”. Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.
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  • 文章类型: Journal Article
    背景:细胞减灭术(CRS)和腹腔热化疗(HIPEC)的组合构成了腹膜假性黏液瘤患者的既定护理标准。然而,HIPEC的作用缺乏通过随机试验的验证,导致不同的治疗方案。这一共识旨在使HIPEC方案标准化,并确定研究重点,以提高清晰度。
    方法:指导委员会将患者,干预,比较器,和结果方法来制定关键的临床问题。对证据的评估遵循建议的分级,评估,发展,和评价体系。通过有国际专家参与的两轮德尔菲进程,寻求就HIPEC方案和研究优先事项达成共识。
    结果:在90名合格的小组成员中,71人(79%)参加了德尔福两轮比赛,在与HIPEC方案相关的7个问题中的6个问题上达成共识。压倒性的84%积极共识赞成将HIPEC与CRS结合使用,而在CRS不完整后,70%的微弱积极共识支持HIPEC。具体的HIPEC方案也获得了共识,53%支持奥沙利铂200mg/m2,51%支持顺铂(CDDP)与丝裂霉素-C(MMC)联合使用。高剂量MMC方案获得了89%的阳性推荐。在研究重点方面,61%的小组成员强调了比较CRS后HIPEC方案的研究的重要性。此类研究的优选方案是CDDP/MMC和高剂量MMC的组合。
    结论:根据现有证据,共识建议在CRS之后应用HIPEC。CDDP/MMC和大剂量MMC方案的组合在当前的临床实践和未来的研究工作中得到认可。
    BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity.
    METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts.
    RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC.
    CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.
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    背景:教科书肿瘤学结果(TOO)是一个复合指标,显示与治愈性肿瘤学程序后生存率的提高相关。尽管外科肿瘤学学科的使用越来越多,其定义在细胞减灭术(CRS)和腹腔热灌注化疗(HIPEC)中尚无共识.
    方法:一项基于国际共识的研究采用Delphi方法达成共识。来自腹膜表面恶性肿瘤领域的54名高级外科医生收到了一份问卷,该问卷由TOO参数组成,分为3个手术领域:手术,术后短期和长期结果。与与会者举行的两次在线会议定义了新标准。当达成75%的协议率时,就达成了共识。收集2010-2022年在一个指定中心(SMC)接受CRS/HIPEC治疗结直肠腹膜转移(CPM)的患者的临床资料,应用共识定义并分析结果。
    结果:38名外科医生(70%)参加。CPM-CRS/HIPEC的专家共识TOO参数包括:手术后30天的计划外再手术,严重的术后并发症(Clavien-Dindo≥III),手术后30天内计划外再入院,术后90天死亡率,术后12周内化疗禁忌症,并包括实现完全细胞减少(CC-0)。研究队列包括251例患者;151例患者(60%)符合TOO标准。达到TOO的患者总生存期明显更好(中位数为67.5个月,CI95%)与未达到TOO的患者(中位数44.6个月,CI95%,p值<0.001),并显著提高无病生存率(中位数,12个月,CI95%,vs.9个月,CI95%,p值=0.01)。
    结论:达成共识声明所定义的TOO与生存率提高相关。
    BACKGROUND: Textbook oncologic outcome (TOO) is a composite metric shown to correlate with improved survival after curative intent oncologic procedures. Despite increasing use among disciplines in surgical oncology, no consensus exists for its definition in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
    METHODS: An international consensus-based study employed a Delphi methodology to achieve agreement. Fifty-four senior surgeons from the peritoneal surface malignancies field received a questionnaire comprising TOO parameters divided into 3 surgical domains: operative, short-term, and long-term postoperative outcomes. Two online meetings with participants defined the new criteria. Consensus was achieved when 75% of agreement rate was reached. Clinical data of patients who underwent CRS and HIPEC for colorectal peritoneal metastasis between 2010 and 2022 from 1 designated center (Sheba Medical Center) were collected, the consensus definition applied and outcomes analyzed.
    RESULTS: Thirty-eight surgeons (70%) participated. Expert consensus TOO parameters for colorectal peritoneal metastasis CRS and HIPEC included the absence of unplanned reoperations during 30 days postoperation, absence of severe postoperative complications (Clavien-Dindo ≥III), absence of unplanned readmissions during 30 days postoperation, 90-day postoperative mortality, and absence of contraindications for chemotherapy within 12 weeks from operation, and included the achievement of complete cytoreduction (CC0). The study cohort consisted of 251 patients, and 151 (60%) met TOO criteria. Patients who achieved TOO had significantly better overall survival (median 67.5 months, 95% CI) vs patients who did not achieve TOO (median 44.6 months, 95% CI, p < 0.001) and significantly improved disease-free survival (median, 12 months, 95% CI, vs 9 months, 95% CI, p = 0.01).
    CONCLUSIONS: Achievement of TOO as defined by consensus statement is associated with improved survival.
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    背景:选定的结直肠癌腹膜转移(PM-CRC)患者可以从潜在治愈性细胞减灭术(CRS)±腹腔热化疗(HIPEC)中受益,中位总生存期(OS)超过40个月。
    目的:这一循证共识的目的是确定HIPEC的适应症,为了选择首选的HIPEC方案,并确定将HIPEC用于PM-CRC的研究重点。
    方法:共识指导委员会根据PICO(患者,干预,比较器,结果)方法,并根据建议分级评估证据,评估,发展,和评估(等级)框架。标准化的证据表提交给一个国际专家小组,以达成共识(4点,弱和强的积极/消极)通过两轮德尔菲过程对HIPEC方案和研究重点。共识定义为4点共识分级≥50%或两种组合中的任一种≥70%。
    结果:9/10个临床问题的证据较弱或非常弱。总的来说,70/90合格的小组成员回答了德尔福两轮(78%),就HIPEC方案的10/10问题达成共识。关于持续时间短,有强烈的负面共识,大剂量奥沙利铂(OX)方案(55.7%),和微弱的正面投票(53.8-64.3%)赞成基于丝裂霉素C(MMC)的HIPEC(首选:荷兰方案:35mg/m2,90分钟,三个分数),原发性细胞减少和复发。确定CRS后HIPEC的作用被认为是最重要的研究问题,被85.7%的小组成员认为是必不可少的。此外,超过90%的专家建议在初次和继发性CRS复发后进行HIPEC,治疗初次手术后1年以上复发.
    结论:根据现有证据,尽管PRODIGE7的结果为阴性,但HIPEC可以有条件地推荐给CRS后PM-CRC患者.虽然更多的临床前和临床数据急切地等待进一步协调的程序,基于MMC的荷兰方案仍然是主要和次要CRS后的首选方案.
    BACKGROUND: Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months.
    OBJECTIVE: The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC.
    METHODS: The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations.
    RESULTS: Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8-64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m2, 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery.
    CONCLUSIONS: Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    目的:我们报告了上皮性卵巢癌(EOC)腹腔热化疗(HIPEC)方案的国际共识结果,其目标如下:定义HIPEC的适应症确定EOC中每个适应症的最合适的HIPEC方案确定HIPEC的未来研究领域为HIPEC方法的围手术期护理的某些方面提供建议:使用了两轮投票技术。有三类问题:基于证据的建议[使用建议等级,评估,发展,与患者的评估(等级)系统,干预,比较器,和结果(PICO)方法],意见调查,和研究建议。
    结果:108位受邀专家中有73位(67.5%)在第一轮中做出了回应,第二轮为68人(62.9%)。对34/38(94.7%)的问题达成了共识。然而,只有6/38(15.7%)的问题达成了将导致纳入常规护理的强烈积极共识.除了间隔细胞减灭术(CRS)外,HIPEC还获得了强烈的积极建议,值得纳入常规护理。单药顺铂是唯一推荐用于常规护理的药物,OVHIPEC-1是最优选的方案.小组建议执行HIPEC至少60分钟,建议最低腹内温度为41°C。顺铂HIPEC应使用硫代硫酸钠的肾脏保护。
    结论:这一共识的结果应指导HIPEC适应症的临床决策以及HIPEC方案的选择和各种参数,并可以填补目前的知识空白。这些结果应该是设计未来EOC中HIPEC临床试验的基础。
    OBJECTIVE: We report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals: To define the indications for HIPEC To identify the most suitable HIPEC regimens for each indication in EOC To identify areas of future research on HIPEC To provide recommendations for some aspects of perioperative care for HIPEC METHODS: The Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations.
    RESULTS: Seventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC.
    CONCLUSIONS: The results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.
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  • 文章类型: Journal Article
    背景:弥漫性恶性腹膜间皮瘤(DMPM)是一种罕见且侵袭性的原发性腹膜疾病,推荐的治疗方法,在符合条件的患者中,完全细胞减灭术(CRS)和腹腔热化疗(HIPEC)的组合。由于治疗是多模式的,HIPEC方案存在广泛的异质性,排除了明确的比较.需要国际一级的标准化。
    方法:国际腹膜表面肿瘤学组织(PSOGI)指定了一个指导委员会,为HIPEC方案提出共识建议,适应每个病因。推荐等级,评估,发展,使用评估(等级)方法,基于针对DMPM患者和患者与HIPEC方案相关的主要结局的系统评价,干预,比较器,和结果(PICO)方法来阐述主要问题。添加了意见调查。此外,Delphi过程是在国际专家小组的投票下进行的。
    结果:阐述了11个问题,包括两项用于未来研究要求,三项用于评估小组的HIPEC方案偏好。问题背后的证据水平在全球范围内很低。总的来说,87名受邀专家中有75名(86%)和67名(77%)在第一轮和第二轮投票中完成了投票,分别。完整的CRS之后的HIPEC得到了88%的选民的大力支持,无需计划仅对61.2%的选民进行CRS的比较研究。双药方案似乎优于单药方案,顺铂在全球范围内受到青睐。意见调查证实顺铂和多柔比星的组合是推荐的方案。
    结论:国际共识确认了DMPM患者完全CRS后HIPEC的适应症,并推荐顺铂-阿霉素作为一线HIPEC方案。
    BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and aggressive primary peritoneal disease, with recommended treatment, in eligible patients, of a combination of complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). As treatment is multimodal, there is a wide heterogeneity of HIPEC protocols precluding clear comparisons. Standardization at an international level is required.
    METHODS: The Peritoneal Surface Oncology Group International (PSOGI) designated a steering committee to produce consensus recommendations for HIPEC regimens, adapted to each etiology. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology was used, based on a systematic review focused on main outcomes related to HIPEC regimens in DMPM patients and on the patient, intervention, comparator, and outcome (PICO) method to elaborate main questions. An opinion survey was added. Furthermore, a Delphi process was performed with voting from a panel of international experts.
    RESULTS: Eleven questions were elaborated, including two for future research requirements and three to assess the HIPEC regimen preference of the panel. The level of evidence underlying questions was globally low. Overall, 75 (86%) and 67 (77%) of the 87 invited experts completed the vote at the first and second round, respectively. HIPEC following complete CRS was strongly supported by 88% of voters with no need to plan comparative studies with CRS alone for 61.2% of voters. Bi-drug regimens appeared to be preferred to mono-drug ones and cisplatin was globally favored. The opinion survey confirmed the combination of cisplatin and doxorubicin as the recommended regimen.
    CONCLUSIONS: International consensus confirmed the indication of HIPEC following complete CRS in DMPM patients and recommended cisplatin-doxorubicin as the first-line HIPEC regimen.
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  • 文章类型: Journal Article
    背景:来自国际腹膜表面肿瘤学组织(PSOGI)和BIG-RENAPE小组的专家组在世界各地有治疗腹膜恶性肿瘤经验的外科医生中达成了共识,以得出关于腹膜内高温化疗(HIPEC)适应症的建议,HIPEC方案的选择和细节,以及未来研究的领域。本手稿描述了实现这一共识的方法以及专家的参与程度。
    方法:使用德尔菲技术,问卷包括三类:使用GRADE(推荐等级,评估,发展,和评估)系统与PICO(患者,干预,比较,和结果)方法,意见调查,和研究建议。如果任何一个选择的票数超过50%,就达成了共识,或正面或负面建议加起来的票数>70%。
    结果:在征求的145位专家中,第一轮71.1%和第二轮72.2%参加了调查。在治疗胃肠道和妇科恶性肿瘤的外科医生中,参与率最高。在113个问题中,在我轮之后,就72个(63.7%)问题达成共识,第二轮之后,另外22个(19.4%)问题达成共识,共提出94个(83.1%)问题,达成共识。
    结论:这项共识是通过对文献的全面审查和对证据的可靠评级来进行的。并包括来自世界各地的关键专家和意见领袖。结果可以指导临床医生使用HIPEC,在日常临床实践和设计临床试验中。
    BACKGROUND: A group of experts from the Peritoneal Surface Oncology Group International (PSOGI) and the BIG-RENAPE group carried out a consensus among surgeons experienced in treating peritoneal malignancies from around the world to derive recommendations on indications of hyperthermic intraperitoneal chemotherapy (HIPEC), choice and details of HIPEC regimens, and areas for future research. This manuscript describes the methodology of achieving this consensus and the degree of participation of experts.
    METHODS: The Delphi technique was used and the questionnaire comprised three categories: evidence-based recommendations using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system with the PICO (patient, intervention, comparison, and outcome) method, an opinion survey, and research recommendations. A consensus was achieved if any one option had >50% of votes, or positive or negative recommendations combined had > 70% of votes.
    RESULTS: Of the 145 experts solicited, 71.1% in round I and 72.2% in round II took the survey. Participation was highest among surgeons treating both gastrointestinal and gynecological malignancies. Of 113 questions, after round I, a consensus was achieved for 72 (63.7%) questions, and after the second round, consensus was achieved for another 22 (19.4%) questions, making a total of 94 (83.1%) questions for which a consensus was achieved.
    CONCLUSIONS: This consensus was carried out using a thorough review of literature and robust rating of evidence, and included key experts and opinion leaders from across the world. The results could guide clinicians on the use of HIPEC, both in their day-to-day clinical practice and in designing clinical trials.
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  • 文章类型: Practice Guideline
    BACKGROUND: This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).
    METHODS: All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence.
    RESULTS: AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies.
    CONCLUSIONS: These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.
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