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New Horizons GIST May 2019 – New Jersey, USA

Thank you Friends of Max for the opportunity to represent you at this conference. This is an Annual global GIST conference for GIST treatment updates and advocacy. This conference was organised by the Life Raft group USA

Representatives from 18 countries were present.

Dr Ping Chi (USA) spoke about “GIST research updates”

  • 5000 new cases are diagnosed every year in USA
  • GIST originates from Interstitial cells of Cajal
  • KIT / PGDFRA mutation causes cells to grow into tumour
  • KIT 75-80%, PGDFRA 5-8%, Wild type 12-15%
  • Imatinib is still the first line of drug
  • Resistance to Imatinib happens due to secondary mutations
  • Polyclonal resistance may also be present in a large tumour
  • New Drug trials are on: PLX9486+ PLX3397, IMATINIB+BINIMETINIB, BLU 285, DCC 2618
  • Precision therapy along with combination therapy is the new way forward
  • Molecular biomarkers drive novel therapies in GIST like MEK162(BINIMETINIB), PLX3397(PEXIDARTINIB)
  • Developing Liquid biopsies to more predictable results.

Dr Ciara Kelly (USA) talked on “GIST TREATMENT UPDATES”

  • BLU-285 & DCC-2618 are new promising drugs for resistant GIST which have a good response rate and are likely to be in the market as approved drugs soon.

Dr Ping, Dr Kelly and Dr Sicklick presented various cases of GIST treatment.

  • Imatinib + BINIMETINIB was used in some cases with good results.

Dr Ciara Kelly talked about “Liquid Biopsy in GIST”

Liquid biopsy is a blood test used to determine the presence of tumour cell DNA in the blood and to confirm the mutation and activity of the GIST tumour. It eliminates the need of an open biopsy for the tumour. It relies on the ctDNA shed by the tumour cells for diagnosis.

  1. It helps in identifying mutations and hence the specific target drug
  2. Helps monitor response to a particular drug, example in a good disease control there will be absence on ctDNA.
  3.  Identifies other mutations not picked up initially like in tumour heterogenicity.
  4. Helps identify novel therapeutic strategy.

Dr Jason Sicklick (USA) spoke on “Precision Oncology”

  • Personalised medicine is individual drug dosing and managing side effects judiciously.
  • Precision medicine is about a specific drug for a specific target like a specific key will only fit a particular lock, hence such a drug will be more effective and cause lesser side effects.
  • Combination therapy is needed in multiple target (mutation) cases.

SDH deficient GIST- Vandetanib and Linsitinib trials were carried out with 45% benefit rate. TMZ (Temozolomide) trials are going on. Rare GIST subtypes: NTRK fusion-Larotrectinib is used. Next generation sequencing (NGS) Mutational analysis is important to study all mutations.

Becky Owens spoke about “Pediatric & SDH- deficient GIST consortium”

11 institutes along with NIH are working together.

Denisse Montoya from LRG spoke about increase in number of SDH tissue being made available in their tissue bank.

Denisse also spoke on GIST prime/ GIST registry- 1900 patients from 67 countries are registered. Youngest diagnosed is at 5 years and oldest is at 98 years, average age being 51.

52% patients had mutational testing done in the registry out of which- KIT was 78%, PGDFRA 8%, Rest 14% This registry helps in Real World Evidence for demographics of the disease and also helps in research

Lucinda Orsini spoke about “Real World Evidence”

RWE is obtained from electronic health records, Hospital data, Insurance claims, Drug trial data. It provides information about demographics of a disease, its history, efficacy of drugs, side effect management and treatment protocols.

RWE is used in

  1. Drug development
  2. FDA safety monitoring
  3. Regulatory approvals

Artificial intelligence can used for arranging the RWE in a faster organised manner.

Dr Joseph Erinjeri (USA) spoke about “Interventional radiology approaches to treat recurrent GIST”

Transarterial Methods for treating GIST lesions are                               

  1. Hepatic artery embolization  
  2. Chemo-embolization      
  3. Drug eluting bead Chemo-embolization.

RFA ( Radio frequency ablation) uses alternating electric current to generate heat and destroy the tumour.

MA (Microwave ablation) uses a needle antennae that emits microwaves to heat tissues.

MA causes greater thermal damage to tissues than RFA

Cryoablation is used for lesions to close to nerve, it causes freezing of the tumour and reduces pain.

Survival of patients improved when these local procedures are done as they are minimal invasive patient has a better Quality of life.

Rodrigo Salas spoke about “Real World Evidence in Mexico”

He showed how creating a cancer patient registry helps in research, pharmacovigilance, more research papers on GIST, approaching the government health authorities with data for drug approvals or modification of regulations.

Piga Fernandez spoke about “Real World Evidence in Chile”

Her passion for working for helping the needy patients came from the following quote

Health is a human right. No one should get sick and die just because they are poor, or because they cannot access the health services they need

RWE presented to the government helped in modification of laws and drug approvals. Working with health authorities for developing treatment protocols and guidelines for GIST.

Sara Rothschild of LRG USA spoke about “Pediatric and SDH-deficient GIST consortium”.

It is a collaboration between USA and UK groups for more scientific research, tissue samples and patient registry data is shared for better research.

Peter Knox of LRG talked about “mysideeq.org”

Online platform for patients to register and enter the side effects they have with various drugs. Other registered patients offer solutions to the side effects and better management of medicines. Collected data is also used for further studies and research.

Jayne Bressington of UK spoke about “UK national GIST tissue bank”

Tissue bank is based in Royal Marsden hospital in London, collects fresh frozen tissue and blood samples for research.

Conclusions:

  • Imatinib still remains the first line of drug for GIST
  • Precision therapy along with combination therapy is the new way  forward
  • New Drug trials are on: PLX9486+ PLX3397, IMATINIB+BINIMETINIB, BLU 285, DCC 2618
  • Molecular biomarkers drive novel therapies in GIST like
    • MEK162 (BINIMETINIB), PLX3397(PEXIDARTINIB)
  • Liquid biopsies are becoming more predictable are being used for diagnosing the disease, monitoring the drug response, identifying recurrences not detected on Imaging.
  • SDH deficient GIST- Vandetanib and Linsitinib trials are on along with TMZ (Temozolomide) trials.
  • Rare GIST subtypes: NTRK fusion-Larotrectinib is used
  • Next generation sequencing (NGS) Mutational analysis is important to study all mutations
  • For isolated metastatic lesions the following modalities are useful
    • Hepatic artery embolization
    • Chemo-embolization
    • Drug eluting bead Chemo-embolization
    • Radiofrequency ablation (RFA)
    • Microwave ablation
    • Cryoablation
  • Important to maintain Real World Evidence, GIST registry and tissue banks are important for better research and drug development, Cooperation between countries is important to share information and tissue samples.

Report by Nikhil Guhagarkar [ gdental99@gmail.com ]

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