Friday, August 30, 2013

How Old Is Old in PJS?


A recent discussion at the Peutz-Jeghers Syndrome Online Support Group – http://listserv.acor.org/archives/pjs.html on life expectancy in people with PJS led me to do a little research on the topic. Here’s what I found from the medical literature. Fortunately several “older” members shared their ages – causing me to eat my words. I’m 57 years old.



Dear PJS friends,

Well, I was ready to eat my words about how long people with PJS can and do live.

Am so grateful that many members shared their ages and that of their relatives with PJS. It’s good to remember that many do live past age 60 and even age 70 with PJS.

With the current life expectancy of 78 years in the USA, it’s great to imagine living that long, hopefully in relatively good health.

My problem is – I read too many medical journal articles.

Figuring my memory was at fault, I just reviewed over 30 articles and found them frustratingly incomplete for answering questions about our life expectancy.

The figure estimating death by age 57 is an old one from 1989 and the risk wasn’t a 100% chance, but a 48% chance. (reference 4, below)

There are two main types of articles on PJS people – case reports that tell the story of one person or one family and larger compilations of many patients (can be by institution, nation or international).

While statistics tell us nothing about how life will be for a single individual, they can give us a general sense of how the group of us might do. If we can trust the statistics.

Unfortunately, I’m caught between looking at tables of individuals or families that include ages and figures, graphs and charts that estimate statistical probabilities of cancer and mortality (survival) by age.

The patients included in the tables are mostly under the age of 60 years, many under the age of 20 years.

The graphs then use that data to guesstimate cancer and mortality risk.

The big problem is most of the groups calculating the data don’t:
A.) follow their patients over a long time;
B.) tell readers what the follow-up period is;
C.) include the ages of the participants (our cancer risk increases with age);
D.) many have too many young patients and not tell us much about older patients risk of cancer and chance of survival;
E.) the largest group studied was a pooling of 419 patients, so statistics are going to be shaky. We’re not going to get data from 10,000 PJS patients in our lifetimes. We can’t trust statistics.

Here are some excerpts from various articles about our risk of cancer and life expectancy –

Study of 133 PJS patients from the Netherlands, 2011:
“At the closing date of the study, two patients (1%) had been lost to follow-up, 42 (32% had died at a median age of 45 (range 3-76 years), and the median age of the 89 patients still alive was 34 years. 49 cancers were diagnosed in 42 of 133 included patients, including seven patients diagnosed with two primary carcinomas…The median age at cancer diagnosis was 45 years…” (1)

The Dutch group had the most reliable data – gathered over a long time on patients they kept track of and they included ages! But their patient population was still young. Will be interested to see what happens over the next decade.

Study of 54 patients from Mayo Clinic in the USA, 2010:
“… 21 malignancies were diagnosed and treated in 19 patients (35%)… Sixteen (30%) patients have died. The major cause of death was malignancy. The median age of death was premature at 51 years (IQR: 38-57).” (2)

Study of 31 patients from Germany, 2009:
“Seventy-seven percent of PJS patients had a positive family history for cancer as expected. A total of ten malignant tumours were detected in six (19%) of 31 PJS patients resulting in a cumulative cancer risk of 65% up to age 60…There was only one carcinoma at age 28, while all the other cancers occurred at age 40 or later.” (3)

A good piece of news in this article from Germany – many of the cancers were detected during routine surveillance – presumably early and while still treatable/curable.

From St. Mark’s in London, 1989:
“Among 72 patients with the Peutz-Jeghers syndrome malignant tumours have developed in 16 (22%) of whom al but one have died. There were nine gastrointestinal and seven non- gastrointestinal tumours. The relative risks of death from gastrointestinal cancer and all cancers were 13 (95%CI2.7-38.1) and 9 (95%CI4.2-173) respectively. The chance of dying of cancer by the age of 57 was 48%.” (4)

This is the source of the dying by age 57 years that we’ve heard about. But it’s a 48% chance, not a 100% chance!

Relative risk is the number of times more likely than a normal person. So our risk of gastrointestinal cancer in this report is 13 times that of a person who doesn't have PJS.

33 patients from the UK, 2003:
“The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27–73%) with elevated risks of both gastrointestinal and breast cancer.” (5)

In this article only 3 of the 33 patients included in the table were over age 60. So, I think it’s really hard to predict what will happen as they and the others age!

419 patients, international, 2006:
“Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively.” (6)

This article included patients from the prior article, so you can see how the estimates jumped from 47% risk of developing any cancer by age 65 years to 60% by age 60 years.

All we can really figure from these articles, tables and graphs is that we have an increased cancer risk over the general population and that the risk increases with age.

We know from our own experience, that a cancer diagnosis isn’t an immediate or even delayed death sentence. Many members have survived one or more cancer diagnoses in addition to the PJS diagnosis.

So, I’m happy to eat my words!

Happy to meet so many PJS people over the age of 60!

Happy that others too are living fully in spite of, or because of, a PJS diagnosis.

Sending warm, healing regards,
Stephanie
Who’s lived for over 20 years with advanced cancer – you just never, ever know how it’s going to go!

REFERENCES:
(1) High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome.
van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, Lemmens VE, Kuipers EJ, Mathus-Vliegen EM, van Leerdam ME. Gut. 2011
Feb;60(2):141-7. doi: 10.1136/gut.2010.223750. PubMed PMID: 21205875.

(2) Peutz-Jeghers syndrome: a study of long-term surgical morbidity and causes of mortality.
You YN, Wolff BG, Boardman LA, Riegert-Johnson DL, Qin R.
Fam Cancer. 2010 Dec;9(4):609-16. doi: 10.1007/s10689-010-9358-1. PubMed PMID:
20571886.

(3)  Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers.
Salloch H, Reinacher-Schick A, Schulmann K, Pox C, Willert J, Tannapfel A, Heringlake S, Goecke TO, Aretz S, Stemmler S, Schmiegel W.Int J Colorectal Dis. 2010 Jan;25(1):97-107. doi:
10.1007/s00384-009-0793-0. Epub 2009 Sep 2. PubMed PMID: 19727776.

(4) Cancer and the Peutz-Jeghers syndrome.
Spigelman AD, Murday V, Phillips RK.
Gut. 1989 Nov;30(11):1588-90. PubMed PMID: 2599445; PubMed Central PMCID:
PMC1434341.
Free full-text

(5) Further observations on LKB1/STK11 status and
cancer risk in Peutz-Jeghers syndrome.
Lim W, Hearle N, Shah B, Murday V, Hodgson SV, Lucassen A, Eccles D, Talbot I, Neale K, Lim AG, O'Donohue J, Donaldson A, Macdonald RC, Young ID, Robinson MH, Lee PW, Stoodley BJ, Tomlinson I, Alderson D, Holbrook AG, Vyas S, Swarbrick ET, Lewis AA, Phillips RK, Houlston RS.
Br J Cancer. 2003 Jul 21;89(2):308-13.
PubMed PMID: 12865922; PubMed Central PMCID: PMC2394252.
Free full-text

(6) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome.
Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller
JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB,
Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Möslein G, Royer-Pokora B,
Vogel T, Phillips RK, Spigelman AD, Houlston RS. Clin Cancer Res. 2006 May
15;12(10):3209-15. PubMed PMID: 16707622.





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