Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

Driel, Willemien J. van; Koole, Simone N.; Sikorska, Karolina; Leeuwen, Jules H. Schagen van; Schreuder, Henk W.R.; Hermans, R; Hingh, Ignace H. J. T. de; Velden, J. van der; Arts, Henriëtte J.G.; Massuger, Leon F.A.G.; Aalbers, Arend G. J.; Verwaal, Victor J.; Kieffer, Jacobien M.; Vijver, Koen K. Van de; Tinteren, Harm van; Aaronson, Neil K.; Sonke, Gabe S.

doi:10.1056/nejmoa1708618

Cited by 1,019 publications

(676 citation statements)

References 21 publications

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“…For ovarian PM, large phase III studies and meta-analyses demonstrated a survival benefit of intraperitoneal chemotherapy over traditional chemotherapy when combined with complete cytoreduction [11-14]. Recent evidence, including a randomized controlled trial and a meta-analysis, demonstrated similar results for PM of colorectal origin with a significant survival benefit in HIPEC patients [15-17].…”

Section: Discussionmentioning

confidence: 99%

Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Grass¹,

Martin²,

Montemurro³

et al. 2018

Chemotherapy

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Aims of the Study: The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. Methods: This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d’Oncologie including 101 members of various oncological specialties. Participants’ demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. Results: Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4–7) for ovarian, 5/10 (IQR 3–7) for colorectal, and 3/10 (IQR 1–3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6–10). Conclusion: Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities.

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Section: Discussionmentioning

confidence: 99%

Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Grass¹,

Martin²,

Montemurro³

et al. 2018

Chemotherapy

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“…Two randomized clinical trials have recently investigated the feasibility and benefit from adding a cycle of IP therapy during surgery. 90,91 A 245-patient, multicenter, randomized, phase 3 trial demonstrated that HIPEC was feasible and tolerable. 90 Specifically, there was a significant improvement in outcome among women who underwent cytoreductive surgery with HIPEC (the surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% CI, 0.50-0.87; P = .003).…”

Section: Chemotherapymentioning

confidence: 99%

“…90,91 A 245-patient, multicenter, randomized, phase 3 trial demonstrated that HIPEC was feasible and tolerable. 90 Specifically, there was a significant improvement in outcome among women who underwent cytoreductive surgery with HIPEC (the surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% CI, 0.50-0.87; P = .003). The median recurrencefree survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group.…”

Section: Chemotherapymentioning

confidence: 99%

“…The median OS was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. 90 Although debate remains regarding the use of HIPEC, 92 more research on this technology seems warranted and might be considered in the frontline setting for ovarian cancer. • Treatment after recurrence follows a complex algorithm based on initial benefit, judged by the platinumfree interval from the last dose of platinum-based chemotherapy, which has used a period of 6 months as a guide.…”

Section: Chemotherapymentioning

confidence: 99%

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Epithelial ovarian cancer: Evolution of management in the era of precision medicine

Lheureux

Braunstein

Oza

2019

CA A Cancer J Clinicians

863

726

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Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum‐based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP‐ribose) polymerase (PARP) molecules involved in the DNA damage‐repair process, which have been approved in a recurrent setting and recently in a first‐line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence‐based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.

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“…The added value of HIPEC after CRS has recently been questioned in light of results from the Prodige 7 RCT 12 , which showed that adding oxaliplatin-based HIPEC to CRS provided no survival benefit 12 . However, clinical proof that HIPEC after CRS can effectively target minimal residual disease in the peritoneum has been provided by a large phase III study in ovarian cancer 13 . Rather than omitting HIPEC from the treatment of PMs from colorectal cancer, efforts should be made to improve the efficacy of intraperitoneal chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

Ubink

Bolhaqueiro

Elias

et al. 2019

British Journal of Surgery

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Background Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create a preclinical platform for the development of more effective intraperitoneal chemotherapy strategies. Methods Using organoid technology, five tumour cultures were generated from malignant ascites and resected peritoneal metastases. These were used in an in vitro HIPEC model to assess sensitivity to mitomycin C (MMC) and oxaliplatin, the drugs used most commonly in HIPEC. The model was also used to test a rational combination treatment involving MMC and inhibitors of the checkpoint kinase ATR. Results MMC was more effective in eliminating peritoneal metastasis‐derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines for oxaliplatin, indicating a general resistance to monotherapy. ATR inhibition increased the sensitivity of all peritoneal metastasis‐derived organoids to MMC, as the IC50 decreased 2·6–12·4‐fold to well below concentrations commonly attained in clinical practice. Live‐cell imaging and flow cytometric analysis showed that ATR inhibition did not release cells from MMC‐induced cell cycle arrest, but caused increased replication stress and accelerated cell death. Conclusion Peritoneal metastasis‐derived organoids can be used to evaluate existing HIPEC regimens on an individual‐patient level and for development of more effective treatment strategies. Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has improved prognosis of patients with peritoneal metastases from colorectal cancer, but disease recurrence is common. More effective and personalized HIPEC is urgently needed. Organoid technology is frequently used for drug screens, as patient‐derived organoids can accurately predict clinical therapeutic response in vitro.A panel of organoids was established from peritoneal metastases from colorectal cancer and used to develop a model for testing HIPEC regimens in vitro. Patient‐derived organoids differed in sensitivity to commonly used chemotherapeutics, in line with variable clinical outcomes following cytoreductive surgery–HIPEC. Combining MMC with an ATR inhibitor improved the efficacy of MMC.Peritoneal metastasis‐derived organoids can be used as a platform to test novel (combination) strategies that increase HIPEC efficacy. In the future, organoids could be used to select patent‐tailored HIPEC regimens.

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Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

Cited by 1,019 publications

References 21 publications

Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Epithelial ovarian cancer: Evolution of management in the era of precision medicine

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

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