Conference 2008 Roskilde

Saturday Report

See also Abstracts -- Thursday report -- Friday report

Joyce Graff gave the presentation for Dr. Paul Zeltzer, a neurosurgeon from UCLA who has written extensively about how to survive a brain tumor.  She spoke about the change in the doctor-patient relationship that has come about in the last 20 years, facilitated to a large extent by the internet.  The information which used to be in the realm of the doctor and handed down to the patient, is now accessible to the patient as well.  Often the patient arrives in the doctor’s office having read reams of information about the diagnosis.

Joyce likened this to the change in the doctor-patient relationship around childbirth.  Before the 1970’s in the U.S. it was normal for the mother to be given anesthesia early in the labor and to wake up and be presented with her child.  Fathers were banned from the labor and delivery process.  But by the 1960’s in Europe and the 1980’s in the U.S., doctors were realizing that anesthesia was not good for babies, and that having educated parents participating in the process was good for all of them, and actually helpful to the medical team. 

A similar transition is occurring more broadly in medical care.  While patients can read a great deal of information about their condition on the internet, what they need the doctor to do for them is to put all that into context – what is relevant to me, in my situation, with my particular genotype and progression of disease, right now?  We need to develop partnership.

Yin Hunang from Dr. Nakamura’s lab in Kyoto, presented a three-gene expression signature which he has determined can predict the clinical outcome of clear cell renal cell carcinoma (ccRCC).  By evaluating the levels of VCAM1, EDNRB, and RGS5 they have been able to predict the outcome for people with ccRCC.  They are evaluating additional candidate genes in an effort to improve their scoring model.

Thoshinari Yamasaki, also from Kyoto, showed us that the existence of endothelial fenestrations in tumor vasculature associated with VHL are a potent predictive marker for the success of anti-VEGF therapy in ccRCC.  They examine the tumor tissue with an electron microscope.  ccRCC tumors with a VHL mutation have more abundant VEGF dependent tumor vessels, which are responsive to VEGF inhibition.  Early loss of endothelial fenestrations in these tumors is a clue that the vessel phenotype may be predictive of sensitivity to VEGF signaling inhibition.

Marie-Louise Molgaard Poulson reported on the experience of the Danish group with preventive screening.  They wanted to evaluate the cost/benefit of doing prophylactic screening.  They follow a screening protocol similar to that in the VHL Handbook but with a 2-year internal between CNS scans.  After examining the medical records of the 59 patients in the study, they determined that the risk of CNS manifestations was twice as great (6%) after 24 months than after 12 (2%) or 15.5 (3%) months.

Mette Bertelsen presented her study of the Danish National clinical guidelines.  They recommend beginning screening at age 15.  They reviewed the cases of  27 individuals who have followed these guidelines since 2002.  Two people were screened from earlier ages (13 and 14) because of symptoms suggestive of VHL. 

Eye examinations were being conducted about three times a year.  They concluded that these could be less frequent and still prevent vision loss.

24-hour catecholamine assay was being performed once every three years.  They concluded that they should go to the recommended once a year to monitoring responsibly.  The interval might also be varied based on the genotype.  They are changing to plasma free metanephrines test, which they believe will be more often complied with, as the procedure for the 24-hour urine is inconvenient for the patient.

MRI’s of the CNS were being performed about once every two years.  They recommend a greater frequency of these scans.  4% of the scans showed manifestations without previous symptoms, and 19% of the scans influenced treatment decisions.

The annual scans of the abdomen were deemed to be appropriate.  6% of scans had an influence on treatment, and it is clear that earlier detection gives better prognosis.

Dr. Neumann posed the question whether we need the catecholamine assay at all?  If we have an MRI, and if most pheos occur near the adrenal glands, would they not be picked up on the scan?  Joyce said that while that might be a good model for his practice, where the radiologist is accustomed to looking for pheos, she does not trust every radiologist in every hospital to spot a pheo on a scan.

Frauke Pelz, geneticist from South Wales, UK, reported on the 20 years of VHL surveillance in her catchment area, where sheep outnumber humans.  The first VHL family was identified there in 1981.  By the mid-1980’s they had a number of families.

In her clinic, one day a week is devoted to VHL.  They coordinate clinical screening to that one day, and provide telephone support throughout the work week.  They often seek a second opinion on films from Dr. Maher’s group in Birmingham.

She is currently monitoring 37 patients, half men, half women.  Four are over 60, 6 are between 50 and 59, 18 are in their 30’s and 40’s, 5 in their 20’s, and 4 are teenagers.  93% of the patient are fully compliant with the screening protocol through the clinic.

Lesley Andrews from Prince of Wales Hospital in Sydney, Australia, shared with us a progress report on her effort to identify psychological and unmet support needs among individuals affected with VHL and MEN2A.  It is difficult to extrapolate findings from other hereditary cancer syndromes to these two because of some key differences: early onset of disease, rarity, and the fact that these are highly penetrant.

She has developed and is piloting an international survey to examine emotional, cognitive, and behavioral experiences of families affected by these diseases, including unaffected caregivers; to identify the demographic, clinical, and psychological correlates of distress among patients and caregivers; and to determine the unmet information, support, and service needs of these families.

So far there are 19 participants in the pilot group.  She is hoping to enlist participation by people in a number of countries, possibly different language groups, to see what is the same or different internationally.

Even in the pilot group, there is a wide range of opinion:
VHL is always on my mind, dominates my life – woman 41
The way I see it, it’s a very, very tiny part of our lives – woman 25

Many people talked about the importance of having a secure base at home.  Frustration with doctors has been a common theme.  There is an intense thirst for knowledge, and great frustration when they can’t get answers to questions that are important to them.  For example, one woman who had had a miscarriage said it was very hard to find information about pregnancy and VHL.

Groups who are willing to help enroll more patients in the study are asked to contact Dr. Andrews.

Chantal Lammens of the Netherlands presented her study of compliance with the recommended surveillance programs for VHL the Netherlands, and the psychsocial impact of VHL.

She recruited patients through the clinical genetics center.  156 members of 37 families in the Netherlands are participating in the study.  The questionnaire includes 250 questions.

Among people with VHL and their caregivers, they found that 39% of the participants have moderate/high distress, twice as high as among people with FAP (familial adenomatous polyposis)

Attitudes toward prenatal diagnosis:
Would you use it? 33% yes, 26% don’t know, 41% no

They wondered what correlations they might find.  When they correlated with desire to have a child at this time, half of those responding would consider it.

Employment
            Many were fully or partially disabled
            15% had problems with obtaining life insurance – 9 denied, 3 pay higher premium
            9% had problems getting a mortgage

She would appreciate the participation of other countries in her research. c.lammens@nki.nl. +31 20 5126098

Dr. Leif Wiklund of Sweden provided a summary of the morning’s presentations, which included two papers evaluating screening protocols and two papers evaluating psychsocial aspects.  It is good to see that these are being monitored and evaluated so that they can evolve and improve.

Dr. Marie Luise Bisgaard closed the meeting with thanks to all the participants and the volunteers who made this meeting possible.  She noted that the news in the press is that Denmark has been declared the world’s happiest country (on a scale from 0-10, Denmark earned an 8), and she feels that much of this happiness stems from the commitment of the health care system to truly care for all its people.  While no one can guarantee health, the the people of Denmark are clear that their nation cares about them and about their health and well-being.

In a similar way, it is clear that all the researchers and professionals who took the time and expense to attend this meeting care deeply for their patients.  

Best wishes to everyone, and we’ll see you in 2010 in Rio!

See also Abstracts -- Thursday report -- Friday report