New study regarding AN growth

[notaclone13]

Hot off the presses,

J Neurosurg. 2019 Aug 2:1-7. doi: 10.3171/2019.5.JNS1923. [Epub ahead of print]
Volumetric growth rates of untreated vestibular schwannomas.
Schnurman Z1, Nakamura A1, McQuinn MW1, Golfinos JG1, Roland JT2, Kondziolka D1.

Abstract
OBJECTIVE:
There remains a large discrepancy among surgeons in expectations of vestibular schwannoma (VS) growth. The anticipated growth rate of a VS and its potential clinical impact are important factors when deciding whether to observe the lesion over time or to intervene. Previous studies of VS natural growth remain limited, mostly confined to linear measurements, often without high-resolution, thin-sequence imaging. The present study comprehensively assessed natural tumor growth rates using volumetric measurements.
METHODS:
Between 2012 and 2018, 212 treatment-naïve patients diagnosed with a unilateral VS were evaluated. A total of 699 MR images were assessed, with a range of 2-11 MR images per patient. All MR images preceded any intervention, with patients subsequently being observed through completion of data analysis (36%) or treated with stereotactic radiosurgery (32%) or microsurgical resection (32%). To determine precise tumor volumes, the tumor area was outlined on every slice, and the products of the area and slice thickness were summed (99% of scans were ≤ 1-mm slice thickness). A multilevel model with random effects was used to assess the mean volume change over time. Each tumor was categorized as one of the following: growing (volume increase by more than 20% per year), fast growing (volume increase by more than 100% per year), stable (volume change between 20% decrease and 20% increase per year), and shrinking (volume decrease by more than 20% per year).
RESULTS:
The mean VS volumetric growth rate was 33.5% per year (95% CI 26.9%-40.5%, p < 0.001). When assessing the frequencies of individual tumor annual growth rates, 66% demonstrated growth (30% fast growing), 33% were stable, and 1% exhibited shrinking over an average interval of 25 months. Larger tumors were associated with increased absolute growth, but there was no relationship between tumor size and proportional growth rate. There was also no relationship between patient age and tumor growth rate.
CONCLUSIONS:
This study comprehensively assessed VS volumetric growth rates using high-resolution images and was conducted in a large and diverse patient sample. The majority of the tumors exhibited growth, with about one-third growing at a rate of 100% per year. These findings may contribute to a consensus understanding of tumor behavior and inform clinical decisions regarding whether to intervene or observe.

[ANSydney]

Thanks for that very recent article. The findings surprise me as they are not consistent with other studies. Hopefully this study initiates debate among the profession. And I bet it will.

The study findings may be academic since what really matters is, is it still growing in your case. Waiting for 2 followup MRIs 6 months apart may prevent surgery in some cases since "33% were stable". If it growing rapidly and threatening to exceed 2 cm diameter, you probably want to act.

My examination of studies on what percentage of vestibular schwannoma tumors grow is at https://www.anausa.org/smf/index.php?topic=23404.msg979773728#msg979773728 . My summary of the papers is that about 13% of tumors grow more than 2 mm.

[PaulW]

And if your tumour grows 19% by volume per year it is still considered to be no growth according to that study.
I read the W&W studies. Often they don’t follow patients for long enough. Sometimes they use linear measurements which are less accurate, or patients lost to follow up are excluded from the stats... while the patient went off to have surgery or radiation because they were tired of W&W.


From my observations with many people I have met on W&W the number that grow is closer to the upper estimates of the published results not the lower.

Yes the growth rate is often 0.5mm or less per year, but after 10 or 20 years this becomes significant especially if you are younger.

[ANSydney]

From reading the literature, yes there is a 0.5 mm, or 1 mm or 2 mm growth, but this only in the early yes post diagnosis. Growth generally slows down over time. "tumor growth occurring beyond the fifth year of observation is very rare, but is, however, still observed" https://link.springer.com/article/10.1007/s40136-014-0064-7

[Greece Lover]

These are interesting studies. I think the headline here is "There's still a lot we don't know about VS."  But, these statistics seem to show pretty clearly: 1/3 grow quickly; 1/3 grow slowly; 1/3 don't grow.  That's helpful for people who are in a decision making process. thanks for posting.

[ANSydney]

The big question is, should the 1/3 that grow slowly be treated? Also, how many of those keep growing?

[PaulW]

tumor growth occurring beyond the fifth year of observation is very rare, but is, however, still observed" https://link.springer.com/article/10.1007/s40136-014-0064-7
I read the paper, it provides 4 references to this fact, and none of them instill any confidence in that statement.   Small sample size 31 patients, median follow up 31 months. Maximum followup of 84 months.
Below is one of the reference articles, the other 3 are no better..



Abstract
OBJECTIVE:
Periodic observation with imaging is an acceptable option for patients with small vestibular schwannomas (VSs). The objective of this study was to evaluate the outcome of conservative management of intracanalicular VSs (ICVSs).

METHODS:
We reviewed 31 patients who were followed up for more than 1 year among patients diagnosed as having VS limited to the internal auditory canal. The median follow-up period was 31 months (range, 12-84 mo). We analyzed the patients' clinical features, clinical courses, and audiologic changes.

RESULTS:
The most frequent initial presenting symptom in patients with ICVS was hearing loss, and one-half of the patients (8 of 16) had a history of sudden hearing loss. Seven patients (22.5%) showed tumor growth during the follow-up period. When we considered the initial tumor size in ICVS, the patients larger in size than the median showed a significantly higher rate of tumor growth. In terms of the initial hearing levels of ICVS according to the Consensus Meeting Guidelines, five patients were classified as Class A (normal hearing) and six patients were classified as Class B. Only one patient among patients with useful hearing (Classes A and B) showed tumor growth. The follow-up hearing levels of all Class A patients were preserved; however, all Class B patients deteriorated to Class C.

CONCLUSION:
Patients with ICVS showed favorable results with conservative management. Among them, patients with small tumors and normal hearing showed a good prognosis.

[ANSydney]

I main paper regarding growth after the fourth year from diagnosis appears to be:

https://acusticusneurinom.dk/wp-content/uploads/2015/10/natural-history-of-vs.pdf with 552 patients "No tumor growth occurred after the fourth year of observation"

What are the references to the four papers?

[PaulW]

Unfortunately I feel that paper is flawed largely because of their patient sampling.
Page 2 Figure 2.
The number of patients being observed is highly skewed towards the first 5 years.
So skewed it makes you wonder where did all the patients go after 3 years.
From 550 at year 1, 300 at year 3, and about 175 at year 5.

I suspect like many watch and wait studies, a significant proportion of people get frustrated with W&W and seek other specialists and options. They are then lost to follow up and excluded from the stats.
When you look at this paper and see how many patients they have lost to follow up by 5 years, it skews the results. I think the rule of thirds... one third are stable or shrink, one third grow slowly, and one third grow more rapidly is closer to reality. With the number of people lost to follow up by 5 years, it certainly makes me wonder whether the authors of this paper were actually left with the one third that are suitable for W&W.

The four references are listed directly after this statement on this paper "tumor growth occurring beyond the fifth year of observation is very rare, but is, however, still observed" https://link.springer.com/article/10.1007/s40136-014-0064-7

I am not sure how they can make that claim based on the references they have provided.

I think a more suitable statement would have been, people with growing tumors rarely stay with our institution beyond 5 years, but we do have some.

Please understand I am not anti W&W. I have noticed however there are biases built into so many papers.
Length of the study, Sample Sizes, Patient Selection, Age, Tumor Size, Tumor location, and the criteria they use to measure success or failure. When it comes to surgery, many of the stats come from the worlds best, and that may not reflect what happens locally. Radiosurgery, tumor sizes, age, location, affect results significantly.