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Peritoneal Carcinomatosis

Peritoneal carcinomatosis (PC) is one of the most deadly and challenging complications of advanced GC and many other cancers. PC is present in more than 30% of GCs at diagnosis, and the peritoneum is also the most frequent site of metastasis and recurrence after treatment. The incidence of PC is increasing, and its prognosis is worse compared to other sites of metastasis. PC is associated with diffuse histology and the epithelial mesenchymal transition (EMT) molecular subtype of GC. Diffuse GC is common in Asians, and the EMT subtype that is dominant in Singapore is also associated with a lack of targetable oncogenic drivers. Furthermore, the symptoms associated with PC are often intractable to medical treatment and significantly affect patient's quality of life. Current treatment for PC is palliative systemic chemotherapy. However, the response is poor due to chemo-resistance and poor tolerability of treatment. Therefore, PC from GC is a key area of unmet need worldwide, and in Singapore. Approaches to achieve a better understanding and better treatment for this deadly disease is therefore required.

Ongoing Clinical Trials

  • First-in-human clinical trial of Combined PIPAC with Systemic Immunotherapy for GC with peritoneal carcinomatosis. We will assess the safety of PIPAC using oxaliplatin in combination with Pembrolizumab for advanced GC with resistance to standard chemotherapy. The primary endpoint will be assessed by surgery-related adverse events and by chemotherapy-related events. The secondary endpoints will include clinical response (PCI and Response Evaluation Criteria in Solid Tumours), pathological response (peritoneal regression grading score), PK profiling (Inductively Coupled Plasma Mass Spectrometry) and quality of life quality assessment (EORTC QLQ-C30).  NCT03172416
  • Targeting STAT3 pathway in malignant ascites as novel therapy for PC. PC patients have a much poorer prognosis if they have gross ascites detected intraoperatively [1, 2]. Our transcriptomic analysis of cells treated with ascites fluid obtained intraoperatively demonstrated significant upregulation of the STAT3 signalling pathway [3, 4], and inhibition of STAT3 signalling in a novel mouse model of PC dependent on paracrine signalling demonstrated promising clinical utility of IP instillation of STAT3 inhibitors. We will further characterise the potential of targeting this pathway.

 

  • Exosomes as biomarker for treatment response. We aim to develop a novel nanosensor for molecular profiling of exosomes in liquid biopsies. In this study, we will develop and employ a novel miniaturised sensor to enable fast and multiplexed exosome detection [5, 6], which will represent real-time non-invasive markers for PC.
  • Feasibility Study of Intraperitoneal Paclitaxel. This is a single arm phase 2 trial evaluating the efficacy and tolerability of intraperitoneal paclitaxel with oxaliplatin and capecitabine in advanced gastric cancer patients with peritoneal metastasis and/or cancer cells on peritoneal cytology. Twenty patients will be recruited into the study for an estimated period of two years. Paclitaxel will be administered intraperitoneally at 40mg/m2 on Day 1 and 8 in patients receiving standard intravenous oxaliplatin 130mg/m2 on Day 1 and capecitabine 1000mg/m2 on day 1-14. The study hypothesizes that the addition of intraperitoneal paclitaxel with chemotherapy will improve treatment efficacy. NCT01739894

 

Distinct advantages of PIPAC for Peritoneal Carcinomatosis:

  • More homogenous distribution
  • Deeper drug penetration
  • Minimally invasive & less side effects
  • Repeated dosing

Translational Research

  • Single-cell RNA/DNA sequencing,whole genome expression studies
  • Single-cell immune profiling
  • Peritoneal fluid exosome & cytokinesas biomarker and therapeutic targets
  • Generate organoids as model for carcinogenesis and precision therapy

Recent Publications

  • Extensive peritoneal lavage with saline after curative gastrectomy for gastric cancer (EXPEL): a multicentre randomised controlled trial.
    Yang HK, Ji J, Han SU, Terashima M, Li G, Kim HH, Law S, Shabbir A, Song KY, Hyung WJ, Kosai NR, Kono K, Misawa K, Yabusaki H, Kinoshita T, Lau PC, Kim YW, Rao JR, Ng E, Yamada T, Yoshida K, Park DJ, Tai BC, So JBY.
    Lancet Gastroenterol Hepatol. 2020 Nov 27: S2468-1253(20)30315-0.
    doi: 10.1016/S2468-1253(20)30315-0. Epub ahead of print.
    PMID: 33253659.
  • Anaesthesia considerations and techniques for Pleura Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC).
    Shree V, Lim TJ, Lean LL, So BYJ, Kim G.
    Pleura Peritoneum. 2020 Nov 17;5(4):20190013. doi: 10.1515/pp-2019-0013. PMID: 33575459; PMCID: PMC7823152.
  • PIPAC-OX: A Phase I study of Oxaliplatin-based Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Peritoneal Metastases
    Kim G, Tan HL, Sundar R, Lieske B, Chee CE, Ho J, Shabbir A, Babak MV, Ang WH, Goh BC, Yong WP, Wang L, So JBY.
    Clin Cancer Res. 2020 Nov 4:clincanres.2152.2020. doi: 10.1158/1078-0432.CCR-20-2152.
    Epub ahead of print. PMID: 33148667.
  • Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model
    Tan HL, Kim G, Charles CJ, Li RR, Jang CJ, Shabbir A, Chue KM, Tai CH, Sundar R, Goh BC, Bonney GK, Looi WD, Ch eow ES, So JB, Wang L, Yong WP.
    Eur J Surg Oncol. 2020 Jul 11:S0748-7983(20)30556-4. doi: 10.1016/j.ejso.2020.06.031.
    Epub ahead of print. PMID: 32800400.
  • Recent Advances in Intra-peritoneal Chemotherapy for Gastric Cancer
    Chia DKA, So JBY.
    J Gastric Cancer. 2020 Jun;20(2):115-126. doi: 10.5230/jgc.2020.20.e15. Epub 2020 Apr 10. PMID: 32595996; PMCID: PMC7311211.