Article Review: Most Acoustic Neuroma tumors stop growing within 5 years?

[ANSydney]

“Regardless of tumor localization or size, growth occurs only within the first 5 years after diagnosis”

This interesting quote is from “The Natural History of Vestibular Schwannoma” by Sven-Eric Stangerup et al from 2006. http://acusticusneurinom.dk/wp-content/uploads/2015/10/natural-history-of-vs.pdf

Interesting snippets are:
* 552 prospectively registered patients were followed (1975 to 2004)
* 28.9% of extrameatal tumors grew
* an increase of more than 2 mm in the largest extrameatal diameter was defined as growth
* a decrease of more than 2 mm in the largest extrameatal diameter was defined as shrinkage
* Of the 322 extrameatal tumors, over the entire observation period:
      - 0.9% decreased in size (n = 3)
      - 70.2% was unchanged in size (n = 226)
      - 28.9% increased in size (n = 93)
            - 58 (62% of 93) during first year
            - 24 patients (26% of 93) during the second year
            - 9 patients (10% of 93) during the third year
            - 2 patients (2% of 93) during the fourth year
            - No tumor growth occurred after the fourth year of observation
* There was no significant difference in number of patients with growth between male and female
patients, different age groups, or small (<10 mm) and larger (>10 mm) extrameatal tumors
* Of the 93 patients (intrameatal) with tumor growth:
         - 58 patients were operated on
         - 5 patients were irradiated
         - 10 patients died as a result of unrelated reasons
         - 20 patients were either waiting for operation or radiotherapy, or continued observation due to specific patient choice, old age, or significance concurrent disease
* The data are additionally strengthened by the prospective and consecutive one-center registration of all patients diagnosed during the period from 1976 to 2004 in Denmark, with a population of 5.2 million inhabitants. The data are thus without patient referral bias.
* All previous studies on VS growth have been subject to considerable referral bias and additional patient selection bias

All of this is interesting. I wondered if the findings reported here have changed over the years, so I searched for contemporary articles by the same lead author. The most recent, regarding this topic is “Active Treatment is Not Indicated in the Majority of Patients Diagnosed with a Vestibular Schwannoma: A review on the Natural History of Hearing and Tumor Growth” 2014 http://www.bhtinformatie.nl/pdf/ingrijpen.pdf .

Interesting snippets are:
* In order to justify invasive treatment either by surgery or radiotherapy for these smaller tumors the outcome should be superior to that resulting from the natural history of the disease
* the occurrence of significant growth in 20-45% after 3-5 years of observation.
* Tumor regression or shrinkage is reported in 4-22%
* tumor growth occurring beyond the fifth year of observation is very rare, but is, however, still observed
* a larger percentage [of extrameatal tumors] exhibited growth, ranging between 29 and 54%
* hearing will deteriorate faster in patients with growing, as opposed to stable or regressing tumors
* On average, 60% of patients presenting with good hearing at diagnosis will maintain a good hearing level after 5 years of observation
* patients with a normal SD [speech discrimination] at diagnosis will maintain a good hearing level which is markedly better than patients with only a small discrimination loss, and it is especially noteworthy that 75% maintain good hearing after 10 years.
* the main arguments in favor of primary active treatment (surgery or radiotherapy) is to preserve hearing function.
* Hearing preservation by both surgery and radiotherapy show that on average, around 50% of patients preserve good or serviceable hearing short-term by both modalities

Of the few papers that observed tumor growth after 5 years, “Conservative Management of Vestibular Schwannoma: Expectations Based on the Length of the Observation Period”
https://www.ncbi.nlm.nih.gov/pubmed/24914786 [abstract only]

Interesting snippets are:
* 37.7% of tumors (n = 43) showed growth of at least 2 mm.
* Among the patients in the current study, an MRI negative for growth at 2 years of observation yielded only a 12% chance of future growth.
* Of those with a negative MRI at 5 years, only 4% grew by later follow-up
* Not all tumors that grew necessitated further treatment.
* We found that 85.7% of patients who started with an initial AAO-HNS hearing Class A were able to retain a Class A or B (serviceable hearing) at an average follow-up time of 4.8 years.

Summary: Tumor growth occurring beyond the fifth year of observation is very rare.

[keithmac]

very interesting indeed

I hope you won't mind my having taken the liberty of posting your piece on BANA (UK association) and attributing it here.

[ANSydney]

Good to see my efforts are spreading Keith. That's great. Hope to get some discussion going on this topic.

[caryawilson]

Tough to grasp the data, perhaps my experience is clouding my judgement.   

"70.2% was unchanged in size".  Sounds like the overwhelming majority of AN do NOT grow.

"tumor growth occurring beyond the fifth year of observation is very rare".  Appears to support your position, but would NOT have been my initial assumption.  I had assume the majority of ANs were slow growing at 2mm per year, so all of the surgeries on 2.0cm and above, would have assumed a tumor for around 10 years or more.  But based on this data, it would appear ANs agressively grow for several years and then remain in a stable state. 

Are these fair conclusions?

[keithmac]

Tough to grasp the data, perhaps my experience is clouding my judgement.   

"70.2% was unchanged in size".  Sounds like the overwhelming majority of AN do NOT grow.

"tumor growth occurring beyond the fifth year of observation is very rare".  Appears to support your position, but would NOT have been my initial assumption.  I had assume the majority of ANs were slow growing at 2mm per year, so all of the surgeries on 2.0cm and above, would have assumed a tumor for around 10 years or more.  But based on this data, it would appear ANs agressively grow for several years and then remain in a stable state. 

Are these fair conclusions?

fair conclusions?  What do YOU think?

[ANSydney]

caryawilson,

Your assessments appear correct regarding "70.2% was unchanged in size" and "tumor growth occurring beyond the fifth year of observation is very rare", however the 2 mm per year concept is the problem. If we average the growth rate over the five years, that figure is correct, but the growth rate varies with time as per Table 1 of the first article, which is reproduced below:

TABLE 1. Mean Annual Growth Rate in Intrameatal and Extrameatal VS, Related to Tumor Size and Year of Established Growth after Diagnosis

          Intrameatal (n = 39),       Extrameatal (n = 93)
          mm/yr                             mm/yr

1st yr        10.32                            4.90
2nd yr         3.83                            2.79
3rd yr          2.17                            1.15
4th yr          0.92                            0.75

Here are my interpretations. These figures are for growing tumors. Some would grow faster and some smaller. Some would be observed late in their growth phase. It would appear that growth is most rapid straight after genesis; let's say a possible average for extrameatal tumors is 10 mm in the first year, 5 mm in the second year (1 year after diagnosis), 2.5 mm in the third, 1.25 mm in the fourth, 0.75 mm in the fifth, 0.375 mm in the sixth, etc. In this case, the tumor would eventually grow to 20 mm. However, I suspect that once a tumor has grown for a few years it can no longer sustain itself and growth either ceases or even shrinkage can occurs in "4-22%" of cases [my current best guess is ~12.5%, on average, shrink]

Understanding the findings (for us) and understanding the mechanics (for the authors) is an important step in unraveling the mystery of an acoustic neuroma.

[sharonov]

I've been "watch and wait" for the past twelve years based on the assumption that my small tumor would not grow, and actually it's only grown a tiny bit (from 1.4 x 1.3 x 1.1 to 1.7 x 1.3 x 1.1).  At one of the conventions I attended, a panel of doctors said that many people die with the tumors still in their head.  This heartened me.  But.......at age 74, with what the doctors call a "slow growing AN", I'm having the dreaded retro-sigmoid surgery.  Why?  My tumor has grown just enough to encroach on my trigeminal nerve, causing excruciating pain, and the meds don't work anymore.  So I guess they can grow a little.  Sometimes. And that tiny bit of growth can wreak havoc.  Sometimes. 

[ANSydney]

sharonov, sad to hear you have excruciating pain. Regardless of size change, unbearable symptoms need to be addressed. Did you do your MRI and measurement interpretation at the same place by the same person? I askthis as there are measurement variations, even if the same place and person does them, but this variation increases if another center or person is doing the interpretation.

How long have you had trigeminal nerve pain?

A 2 mm growth in 12 years is consistent with the findings reported in the papers.

[sharonov]

During my last flareup of trigeminal pain, in 2012, I sent my MRI to four doctors.  They disagreed as to whether it was caused by my AN.  Then the pain stopped so I chose to forget about it.  When the current pain started it was different--more intense, more electrical, truly unbearable.  And the medication sometimes no longer touches it,  So I sent my MRI to 3 different top surgeons--one who was recommended by the president of the Trigeminal Neuralgia Association and two that were highly recommended on this site.  All agreed that the pain was caused by the AN.  This time it's not going away, and I fear that even if it does, the next round may make me think about the name "suicide disease", which is TN's nickname.  By then I may be too old to operate aggressively, as I'm even pushing it at 74 for a retrosigmoid.  Anyhow, my big regret is that I didn't have either radiation or cyberknife when it was first diagnosed. 

[v357139]

AN Sydney,
Mine grew from 2.7cm to 3.5cm in nine months after diagnosis.  Was that covered in any of your articles?
Rich

[ANSydney]

Rich,

That's a rapid growth. I don't think I've come across anywhere near 8 mm growth in 9 months. And your tumor was large to start with.

Did your tumor have a cystic component (they appear to have sudden growth spurts)?

Did you get the MRI done at the same place and interpreted by the same operator? Some include the IAC component and others do not. Did you take a look at the MRI scans and see anything unusual?

[ANSydney]

Rich,

I read through your posts to get an understanding of your growth. Your first post on 22 January 2013 you said it was 2.5 cm. On 1 October 2013 you said it was 2.7 cm. You had tranlab microsurgery on 20 November 2013. Couldn't see a post for 3.5 cm tumor.

[sharonov]

BTW, I had my MRI done at the same place each time, at a large facility in Chicago.  It was evaluated by whatever radiologist was on duty and sent to the neurosurgeon with whom I was working at the time. 

[ANSydney]

The first paper presented in this topic was http://acusticusneurinom.dk/wp-content/uploads/2015/10/natural-history-of-vs.pdf [Ref. 1]. An interesting article http://link.springer.com/article/10.1007/s00405-008-0791-9 [Ref. 2] supports the first paper.

Ref 2’s Fig. 1 is remarkably similar to Ref 1’s Fig. 3, but not at first glance. Ref 2 shows a probability of growth about twice that of Ref. 1. Ref 2 also shows significant growth probability continuing past the fourth year. Are they showing the same information?

Ref 1 defines growth as more than 2 mm, while Ref 2 defines growth as more than 1 mm. This results in long term growth for Ref 1 at 28.9% for extrameatal tumors and for Ref. 2 at 73% for extrameatal tumors. Changing the growth definition explains most of this difference.

Ref 2, considering extrameatal tumors, has a high degree of drop out (patients that were lost to follow-up). In year 4 there are only 6 remaining patients, in year 5 only 4 patients and in year 6 only one patient. These are statistically small samples and due to the inferences made from the few remaining patients for the entire study population, just one growth beyond 1 mm has a large effect on the graph. This is evident by the smoothness of Ref 2’s Fig 1 in the early years, but large stepwise changes in the later years. The steps seen beyond year 3 appear to be single patient incidence of tumor growth beyond 1 mm. If we ignore the later years, the extrameatal growth probabilities could plateau at about 60%.

So, given the different definitions of growth and Ref 2’s very small number of patients in the later years, the two graphs show remarkably the same thing.

What is perplexing is that Ref 2, which was published in 2008, did not reference Ref 1, which was published in 2006. They are basically both examining untreated growth of vestibular schwannoma tumors!

Ref 2 has some additional interesting pertinent information. As already stated, for extrameatal tumors, the paper states growth probability is 73%. However, if there is long duration of hearing loss, no unsteadiness/vertigo and hearing loss, when it did occur, was sudden, then the probability of growth drops to 12.7% within the first two years.

What the authors don’t consider is that long term hearing loss and absence of unsteadiness/vertigo both point to a lengthy period since inception of symptoms. The long term hearing loss speaks for itself. If the tumor has been growing (slowly) for an extended period, the vestibular system is expected to compensate. That all supports the summary of “Tumor growth occurring beyond the fifth year of observation is very rare”.

[sharonov]

Thanks for posting the research. It's always interesting to read about ones illnesses!  And there will always be exceptions to whatever study is done.