6’th Annual SPAEN Conference

Proud to represent Friends of Max in the 6’th Annual SPAEN (Sarcoma Patients Euronet) in November 2015 in Chantilly, Paris.
Sarcoma Patients EuroNet Association (SPAEN), the European Network ofSarcoma, GIST and Desmoid Patient Advocacy Groups, was founded in April 2009 with the aim of extending information services, patient support and advocacy to patient organisations for the benefit of sarcoma patients across the whole of Europe. Acting in partnership with clinical experts, scientific researchers, industry and other stakeholders SPAEN is working to improve the treatment and care of sarcoma patients in Europe through improving information and support, and by increasing the visibility ofsarcoma with policymakers and the public.

Highlight was Friends of Max being recognized as a Associate Member of SPAEN.

Meeting was conducted in the beautiful forest region of Chantilly near Paris from 19’th to 21’st November.

It was attended by experts of Sarcoma ,GIST & Desmoids. Advocacy groups from Europe attended the Conference.

Various GIST and Sarcoma experts attended the meet including Dr Sebastian Bauer ,Dr Anette Duensing , Dr Janet Shipley , Dr Silvie Rusakiewicz , Dr Sarah Durmont ,Dr Alessandro Gronchi

Interesting presentation were done by the Mitigate project on newer cutting edge treatment for GIST .

Markus Wartenberg in his Welcome address as Chairman emphasized on the importance of updating and being aware of the the latest treatment modalities in GIST and also networking world wide between GIST advocacy groups to bring out best for GIST support.

Dr.Janet Shipley talked on trends and challenges in cancer research .The key points she talked on

1. Treatment were supposed to More effective,less Toxic & more personalized.
2. This can be achieved after studying the molecular biology of the tumour.
The biology of the normal cell followed by mutation and rapid growth of Cancer cells was explained .
She talked on the importance of getting surgical tissue samples for Sample based research which would lead further to Model focused Molecular Biology ie Molecular characterization of tumours leading to ultimately better targeted drugs for the patient and a more effective and lesser toxic treatment.

Dr Silvie R. talked on Immune system and Immune-oncology .
Natural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of innate immune system.
Natural killer (NK) cells play important roles in innate immunity by lysing tumor and virally infected cells and by producing cytokines including interferon-gamma.
The importance is to get the NK cells to actively target and kill the tumour cells.
Imatinib acts on c-Kit expressed by dendritic cells to promote the DC/NK cells cross talk in mice and humans.
In Exon 11 mutation the GIST cells also have a receptor on which NK Cells attach and destroy the GIST cell along with Glivec .So it is 2 receptors attacked and on the GIST cell one is by Imatinib and the other by NK cells .Therefore you have a more efficient death of the GIST cells and GIST tumor.
In some GIST mutations it is observed the NK cells are also have defective functions hence disease control is affected.
Therefore active NK cells are important in disease control in GIST and for progression free survival.
Immunity is important.
So in future a role of combination Immune Oncology and Glivec will be the key for cure for GIST.

Dr Anette Duensing spoke on Personalized Medicine for GIST

Precision Medicine : Identifying specific mutations and developing specific drugs targeting that mutation.
Having a Diagnostic Marker and a Therapeutic target.
For this reason it is important to do Molecular testing/Mutational analysis for each patient .
KIT has a important role in Oncogenesis and diagnosis.Common mutations detected in GIST are Exon 9,11,13,17.
Exon 11 has the best response to Glivec 400 mg. Exon 9 will require 800 mg Glivec
In SDH mutations Sunitinib will work.
In BRAF mutation BRAF inhibitors will work not Imatinib.
GIST diagnosis starts with basic H&E stain followed by Immunohistochemistry staining and Mutational Analysis.
Future of diagnosis is Liquid Biopsy to study circulating tumor DNA ,which is free DNA circulating in the blood obtained from dead tumor cells
Liquid biopsy can be used for judging tumor response,selection of therapies,novel drug targets,predictive and prognostic biomarkers,and for early detection.

Sean Swarner an living legend gave an inspirational talk on Life.

Sean has survived 2 cancers in his early years , he lost 1 lung to radiation treatment .But he fought on and achieved the impossible Dream of being the First Cancer Survivor to climb Mt.Everest .
He has climbed all the major mountain peaks in the world for the cause of creating awareness for Cancer research.
He used the analogy of a mountain ie to climb from the base camp(difficult situation of us in life) to eventually the peak (our goal in life).
He urged us never to loose HOPE and to take One Step at a time .
After all we all should live a life that matters !!

Dr Sebastian Bauer talked Topics for Prognosis and Survival for GIST.

Factors affecting Prognosis are Size ,Site ,Mitosis ,Type of Mutation ,non rupture of tumor.
He talked on various syndromes associated with GIST like Carney-Strataski ,NF1.
Prognosis of SDH -deficient GIST was favorable ,while that of NF associated GIST was variable.
Imatinib improves chances of Progression free survival.
SDH deficient GIST have to consider the following points for Clinical management.
2.Life long followup MRI
3.Genetic testing.
4.No Adjuvant treatment.
To summarize
GIST patients should be treated in GIST/Sarcoma centers.
Mutational analysis is a must.
Surgery is the final curative & Compliance in taking drugs is a must.

Dr Sarah Dumont spoke on Long term side effects of drugs.

Side effects of Imatinib are Anemia –solution Iron supplements/Iron rich diet
,Oedema-Solution Diuretics.
,Fatigue,- Solution good healthy diet ,Vitamin supplements .
Muscular cramps-Solution Calcium ,Mg supplements ,Coconut water/Banana
,Nausea-Solution anti emetics ,twice a day tablet,eat with a decent quantity of food.
,Skin rash-Topical creams/Sunblock
,Bone and joint pain-Solution Crocin.
,Hepatitis –Consult physician
and Bleeding-Solution reassurance .
Decrease in pigmentation-Fairness of skin.
Should consult an Physician to overcome these side effects.
Hypothyroidism causes decrease bowel movements ,constipation and depression.

Sunitinib :
causes Hand foot syndrome –solution use cotton socks,cream,open shoes.
,Diarrea,mucositis,Cardiac problems,yellowish skin,voice disruption.
Despite side-effects it is important to adhere to compliance in taking the drugs regularly.
Stoppage of drugs may lead to Tumor progression and Resistance.
In a shocking study in was shown that on a average patient skips 109 days of drug a year ie 1/3’rd of his treatment.
Important to educate the patient on compliance,reduce his side effects
Long term side effects of Imatinib include.
Bleeding in the eye ,headache ,dizziness ,insomnia,altered bone metabolism,rarely cardian toxicity.
Hypothyroidism can happen in patients on Sunitinib /Sorafenib not on Imatinib.
Pregnancy avoid any TKI’s
It can affect the immune system and may cause gynecomastia.
Conclusions : Early recognition and proper management of treatment-associated side effects may help GIST patients maintain Imatinib therapy and ultimately achieve optimal clinical efficiency.

Markus Wartenberg talked on Generic drugs and stressed the importance of Bioequivalency test to compare the properties and efficacy of Generic and the Original drug.
If it is Generic drug ,then it should be approved by EMA/FDA.

Michelle Duburow from Life Raft group USA gave an detailed presentation about the extensive work carried out by Life Raft group for GIST research & support.

Dr Dario Callegaro spoke on the Surgical management of GIST.
Surgery is the final and only curative in localized GIST, it is important to supplement with Adjuvant Imatinib for PFS (progression free survival ) and OS (overall survival).
15% of GIST patients are diagnosed with Metastatic disease. Imatinib produces tumor regression and control in 80 % cases.

Surgery is important in Metastatic GIST as Imatinib is not curative and there are chances of resistance developing after 2 years in patients with large tumors who have not undergone surgery and are only on Imatinib.
Only 20 % of Metastatic GIST patients remain disease free after 5 years being on Imatinib alone.

Aims of Surgery are :
Reduce the tumor burden.
Prevent secondary mutations.
Prolong time to progression.
Increase PFS and OS.

Role of surgery is limited in resistant and Progressive GIST .
In Focal (limited) Progression ( progressive growth in isolated lesion but drug responsiveness in most tumor deposits) we should Continue drug therapy and do surgery to eliminate resistant clones.
Patients who recurred after complete resection of metastatic lesions seemed to do so because of discontinuing adjuvant therapy rather than acquiring new mutations.

Some more pointers on GIST Surgery:
Patients operated on residual disease do better than patients operated on progressive disease.
Ideal candidates to surgery should be patients responsive to Imatinib.
Surgery should be offered to patients with limited progression.
No Surgery for generalized progression.
Surgery is helpful to responsive patients with metastatic lesions to Peritoneum and Liver.

Role of Surgery under Sunitinib :
Completeness of resection did not correlate with preoperative response to Sunitinib.
Complication rate was 54%
Reoperations were needed in 16 % cases.
Younger age was prognostic of survival.

During Surgery following points are to be noted.
-Expect more than what you see on CT.
-Carefully look at critical sites.
-Be ready for multivisceral resection.
-Avoid tumor rupture if possible.
-Avoid major surgical procedure if possible.
-Aim : gain time.

Local –regional therapies for Liver progression are :

-Trans-arterial (Hepatic artery) Chemoembolization .
-Radioembolization ( SIRT)
Microsphere ( 90 Y spheres ) injected in the hepatic artery become trapped within the tumor microvasculature selectively delivering radiation to tumor whilst sparing normal tissue.
-Radiofrequency ablation (RFA)
Rate of local control after RFA was found to be equal to that of resection with lower morbidity and mortality rates.
Used in smaller lesions of 3 cms or smaller,used after Imatinib therapy for stable /residual lesions and some times for local progressing lesions.
RFA works best along with Imatinib therapy.

Radiotherapy for GIST :

Latest reports suggest that some GIST respond to Radiotherapy .
In some cases this treatment was used only palliative for bone metastasis.

Conclusions :

GIST is not a single disease.
Multidisciplinary approach is important for a successful outcome.
A Experienced team is needed for
-To Select the proper patient for Neo-adjuvant treatment.
-To Select the proper patient for surgery of metastasis.
-To Interpret response
-To Treat the few complications promptly
-To Select the proper patient for Loco- regional therapy
Lastly Molecular sub typing will be critical for Surgical decision .

Prof Stefan S spoke on the MITIGATE Project

Goal : Develop novel protocols & guidelines to diagnose and treat patients with Metastatic GIST resistant to current treatment.
-Innovative strategy for biopsy inline tissue analysis
-Molecular tumor analysis
-PET & MRI imaging
-Assesment of biodistribution,dose calculation & measurement of therapeutic effectivesness
-Synergestic concept of minimal invasive treatments.

Expected outcomes of this project are :

-Optimised biopsy and tissue preparation
-Make a tumor bank
-Molecular imaging probes for GIST indicating drug resistance,early therapeutic response or progression.
-Targetted agents as endoradiopharmaceuticals
-Minimal invasive ,personalized treatment options with minimal side effects
-Non invasive monitoring of treatment in clinical routine

Minimally invasive therapies :

-Patients with metastatic GIST
-Reduce pain and discomfort of patient and allow faster recovery
-Selective Internal Radiation Therapy (S I R T) : can treat lesions on 7cms size which RFA cant.
-Irreversible electroporation (I R E) : more needles surround the tumor creating electric field causing death of tumor.advantage is it can be used in tumors next to important blood vesels.
-Microwave ablation
-Percutaneous ablation for GIST liver metastasis : needles are placed near the tumor emitting microwaves which kill tumor tissue.
-Robotic assistance and imaging feedback for more accurate safe and fast intervention with minimal damage to surrounding tissues

Dr Anette Duensing Spoke on Update on research in GIST

-Presence of Micro-GIST in large number of normal population which may progress to Proliferating GIST or Invasive metastatic GIST in some patients.
-DMD (Dystrophin) is important for proper muscle function, it is expressed in GIST .It is inactivated by deletion in Metastatic GIST .Its inactivation is linked to Metastatic behavior of GIST.
-“Cell sleep” as a therapeutic target in GIST based on the observation that GIST kills only a subset of GIST cells ,the remaining cells are sleeping which are potential reservoirs for resistant clones. Dream complex.
Cell sleep can be targeted to enhance effect of Imatinib .
The dream complex is a new therapeutic target in GIST.
New drugs like Mithramycin A ,Mitoxantrone are being tried for treatment of GIST.

Dr Sebastian Bauer spoke on the latest Clinical Trials in GIST

Talked on targeting each Individual mutation ie a drug targeting each specific mutation of GIST improving accuracy of treatment and more predictable response.
Strategies to overcome Imatinib –resistance .
-Direct Kit inhibition
-indirect Kit inhibition
-KIT independent targets

Sure -trial (rapid alternating Sunitinib and Regorafenib) 3 days of Sunitinib and 4 days of Regorafenib.
Ponatinib (POETIG) trial.
Masotinib / Pazopanib (PAGIST trial)
Cabozatinib Trial
Crenolanib Trial
BLU -285 /Midostaurin Trial.
Imatinib plus MEK 162 trial
Imatinib plus BYL trial
Dasitinib plus Ipilumumab trials

In the Sarcoma UK Research group presentation ,they talked on a novel idea of giving all GP’s a golfball and asking them to report any lesion equal or larger than the size of a Golf ball to a Sarcoma centre .thereby improving the early diagnosis and treatment.
A tribute was paid to Hans Keulen who was a pioneer in Sarcoma support in Europe.
It was a fruitful conference with a lot of new knowledge on GIST treatment and latest Advances .

ARTIS-Uli Deck// 19.11.- 21.11.2015 6. SPAEN Annual Conference, Dolce Hotel Chantilly - Paris www.artis-foto.de  -ARTIS-ULI DECK Werrabronner Strasse 19  76229 KARLSRUHE  TEL:  0049 (0) 721-84 38 77  FAX:  0049 (0) 721 84 38 93   Mobil: 0049 (0) 172 7292636 E-Mail:  deck@artis-foto.de

Report by Dr. Nikhil Guhagarkar- FOM Mumbai