Overview

A few general observations can be made regarding conditional survival probabilities, long-term survival, and cure of GBM and other brain tumors:

• Favorable prognostic indicators include lower age, higher KPS, and MGMT promoter hypermethylation.
• Once patients have survived about 2 years after diagnosis, the conditional probability of surviving an additional year (or any other time interval) tends to increase the longer one has survived.  This is especially the case after having survived about 4 or 5 years, although recurrence can still occur even after having many years without clinically-detectable tumor (see Baehr et al 2009), so patients should remain vigilant regarding measures to prevent recurrence (diet, exercise, supplements, chemoprevention, etc.).
• A small but meaningful percentage of brain tumor patients have survived well over 10 years, even with GBM.  Historically, this was achieved with a variety of conventional treatments, without any particular treatment standing out in this regard.
• The percentage of long-term survivors has tended to increase in recent years with the availability of newer treatments, improvements in ability to achieve gross-total surgical resection (eg, via awake surgery and intraoperative MRI), increased use of combination and rotated treatments, and generally more proactive approaches to treatment.
• Cure of brain tumors is possible.
• Statistics, including survival curves, are derived from and apply to populations of patients.  Statistics therefore have limited applicability to individual patients and, at best, provide only general guidance on the "odds" of various possible outcomes.  No one can reliably predict the prognosis for an individual patient.  Patients should therefore seek the best treatments available for their circumstances and should allow room for hope.

Survival Curves

For an introduction to the concept of survival curves, see Survival Curves: The Basics.  For a discussion of how survival curves are generated, see Survival Curves: Accrual and the Kaplan-Meier Estimate.

For those who are mathematically inclined, note that if the conditional probability of surviving an additional increment of time is constant as a function of time, the survival curve will follow an exponential decay function.  Such an exponential decay function will have a constant half-life, and the half-life is the same as the median survival duration.  In other words, the median survival duration looking forward will remain constant as a function of time.  This situation can also be viewed as representing a constant failure rate or hazard function when the survival curve is viewed as a survival function. 

If the conditional probability of surviving an additional increment of time tends to increase as a function of time, that would indicate that the survival curve is "flattening faster" than exponential decay, which means that the half-life and median survival duration are also increasing as a function of time.  This can be mathematically modeled in various ways, such as with an exponential function by making the exponential coefficient a function of time, by a Gompertz-Makeham function, or by a power law function if the percentage of long-term survivors is sufficient to reflect a "long tail."

Abstracts

The following are a few key abstracts related to this topic.

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Brain. 2007 Oct;130(Pt 10):2596-606. Epub 2007 Sep 4.

Long-term survival with glioblastoma multiforme.

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M,
Steinbach JP, Heese O, Reifenberger G, Weller M, Schackert G; German Glioma
Network.

Department of Neurosurgery, Carl Gustav Carus University Hospital, University of 
Technology, Dresden, Germany. dietmar.krex@uniklinikum-dresden.de

The median survival of glioblastoma patients is approximately 12 months. However,
3-5% of the patients survives for more than 3 years and are referred to as
long-term survivors. The clinical and molecular factors that contribute to
long-term survival are still unknown. To identify specific parameters that might 
be associated with this phenomenon, we performed a detailed clinical and
molecular analysis of 55 primary glioblastoma long-term survivors recruited at
the six clinical centres of the German Glioma Network and one associated centre. 
An evaluation form was developed and used to document demographic, clinical and
treatment-associated parameters. In addition, environmental risk factors,
associated diseases and occupational risks were assessed. These patients were
characterized by young age at diagnosis and a good initial Karnofsky performance 
score (KPS). None of the evaluated socioeconomic, environmental and occupational 
factors were associated with long-term survival. Molecular analyses revealed MGMT
hypermethylation in 28 of 36 tumours (74%) investigated. TP53 mutations were
found in 9 of 31 tumours (29%) and EGFR amplification in 10 of 38 tumours (26%). 
Only 2 of 32 tumours (6%) carried combined 1p and 19q deletions. Comparison of
these data with results from an independent series of 141 consecutive unselected 
glioblastoma patients registered in the German Glioma Network revealed
significantly more frequent MGMT hypermethylation in the long-term survivor
group. Taken together, our findings underline the association of glioblastoma
long-term survival with prognostically favourable clinical factors, in particular
young age and good initial performance score, as well as MGMT promoter
hypermethylation.

Publication Types: 
 Multicenter Study
 Research Support, Non-U.S. Gov't
 Review

PMID: 17785346 [PubMed - indexed for MEDLINE]

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Can J Neurol Sci. 2007 Aug;34(3):339-42.

Coincidence vs cause: cure in three glioblastoma patients treated with
brachytherapy.

Dehdashti AR, Sharma S, Laperriere N, Bernstein M.

Division of Neurosurgery, Toronto Western Hospital, University of Toronto,
Toronto, Ontario, Canada.

BACKGROUND: Very long term survival after diagnosis of malignant glioma has been 
described in individual case reports. Survival of more than 10 years is extremely
rare, especially when identified in 3 out of 71 patients assigned to one arm of a
randomized controlled trial. PATIENTS: Three patients survived 11, 16, and 18
years following the diagnosis of glioblastoma and treatment with surgery,
conventional fractionated radiation, and high-activity iodine-125 boost
brachytherapy as part of a randomized controlled trial. CONCLUSION: Despite this 
apparent cause and effect relationship, statistical analysis shows no
relationship between these cures and treatment with brachytherapy. Cure of
glioblastoma remains rare.

Publication Types: 
 Case Reports

PMID: 17803034 [PubMed - indexed for MEDLINE]

_____________________
 

J Neurooncol. 2007 May;83(1):91-3. Epub 2006 Dec 13.

Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of
glioblastoma multiforme.

Martinez R, Schackert G, Yaya-Tur R, Rojas-Marcos I, Herman JG, Esteller M.

We have performed a methylation-specific PCR approach to comparatively analyze
the MGMT promoter methylation status in 186 glioblastomas (GBM) from patients
with classic survival and nine from patients with long-term survival (LTS GBM).
The methylation rate in LTS GBM was significantly higher (77.8% vs. 39.2%, P =
0.033) which suggests that MGMT hypermethylation is a frequent hallmark of LTS
GBM and contributes to characterize this intriguing GBM subtype.

Publication Types: 
 Letter

PMID: 17164975 [PubMed - indexed for MEDLINE]

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Surg Neurol. 2003 Nov;60(5):402-6; discussion 406.

The conditional probabilities of survival in patients with anaplastic astrocytoma
or glioblastoma multiforme.

Lin CL, Lieu AS, Lee KS, Yang YH, Kuo TH, Hung MH, Loh JK, Yen CP, Chang CZ,
Howng SL, Hwang SL.

Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan.

BACKGROUND: By the use of conditional probabilities of survival, we studied the
yearly survival rates for individual tumor survivors. METHODS: Conditional
survival rate was estimated in 114 consecutive patients with anaplastic
astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving
some years given survival to a specific period of time after craniotomy and 95%
confidence intervals were calculated in the individual tumor survivors. RESULTS: 
The estimated median survival was 30 months for 45 patients with anaplastic
astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The
conditional probabilities of surviving next one year given survival to 1 year, 2 
years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma
were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma
multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional
probability of surviving to 5 years given survival to 2 years after craniotomy
for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%,
which was better than observed 5-year survival rate (28.6%); for glioblastoma
multiforme it was 40.2%, which also was better than observed 5-year survival rate
(12.4%). CONCLUSIONS: The conditional probability of survival was a good method
to clinically predict yearly survival rate for individual tumor survivors. In
addition, the method can estimate the probabilities of surviving next some years 
given survival to a specific period of time after craniotomy. It also showed a
more encouraging result than observed survival rate in patients with
supratentorial malignant astrocytomas.

PMID: 14572960 [PubMed - indexed for MEDLINE]

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J Neurooncol. 2000 Dec;50(3):257-64.

The conditional survival statistics for survivors with primary supratentorial
astrocytic tumors.

Hwang SL, Yang YH, Lieu AS, Chuang MC, Chang SJ, Chang YY, Lin HJ, Howng SL.

Division of Neurosurgery, Kaohsiung Medical University Hospital, Taiwan, ROC.

BACKGROUND: Relative survival rates can offer a general description of tumor
outcome and, traditionally, are used for surveillance and comparison purposes.
However, they are not informative for individual tumor survivors. Conditional
survival estimates can calculate the probability of surviving next some years
given survival to a specific period of time after craniotomy for individual tumor
survivors. However, clinically, they have not been used for predicting the tumor 
outcome. METHODS: We calculated conditional probabilities of survival within 6
years after craniotomy in 112 patients with primary supratentorial astrocytic
tumors and evaluated factors affecting the survival time more than 2 years after 
craniotomy. RESULTS: Our data showed that the conditional probability of survival
can predict yearly survival rate when patients survive for a specific period of
time. The conditional survival rates within 6 years after craniotomy were always 
higher than those evaluated by relative survival rates. Overall, the longer the
patients survived, the higher the conditional probabilities of surviving sixth
year postoperatively were. CONCLUSION: Our study demonstrates the conditional
probabilities of survival have good availability and are important estimates for 
individual tumor survivors.

PMID: 11263506 [PubMed - indexed for MEDLINE]

 
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Cancer. 1999 Jan 15;85(2):485-91.

The conditional probability of survival of patients with primary malignant brain 
tumors: surveillance, epidemiology, and end results (SEER) data.

Davis FG, McCarthy BJ, Freels S, Kupelian V, Bondy ML.

Division of Epidemiology and Biostatistics, University of Illinois at Chicago,
60612, USA.

BACKGROUND: Five-year survival estimates in standard cancer reports provide a
general description of disease outcome that is useful for surveillance and
comparison purposes. However, for cancer survivors these overall survival rates
may be discouraging, and the relevant question regarding an individual is this:
Once he or she has survived for a specified period of time, what is the
probability of survival over the next period of time? METHODS: To address this,
conditional survival rates by histology for malignant brain tumor survivors were 
estimated using the SEER public use data and the Portable Survival System, with
19,105 brain and other nervous system patients diagnosed between 1979 and 1993.
Given that the survival curve declines more rapidly in the first 2 years than in 
subsequent years, conditional probabilities of surviving 5 years given survival
to 2 years and 95% confidence intervals (CIs)were calculated. As age is a strong 
prognostic factor for these tumors, conditional probabilities were also estimated
by categories of age. RESULTS: Estimated 2- and 5-year relative survival rates
for patients with malignant brain and other CNS tumors were 36.2% and 27.6%;
however, the conditional probability of surviving to 5 years, given survival to 2
years, reaches 76.2% (95% CI: 74.8-77.6). Conditional probabilities varied by
histology and age at diagnosis. The conditional probability of surviving 5 years 
after surviving 2 years was 67.8% (95% CI: 62.6-73.1) for patients with
anaplastic astrocytomas, 36.4% (95% CI: 31.9-41.6) for patients with
glioblastomas, and 79.8% (95% CI:75.3-84.1) for patients with medulloblastomas.
CONCLUSIONS: Conditional probabilities provide important and encouraging
information for those who are brain tumor survivors. The utility of these
estimates for other time intervals and other cancers or diseases should be
considered.

Publication Types: 
 Research Support, Non-U.S. Gov't

PMID: 10023719 [PubMed - indexed for MEDLINE]

 
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Surg Neurol. 1992 Nov;38(5):359-63.

Long-term survival after the diagnosis of malignant glioma: a series of 22
patients surviving more than 4 years after diagnosis.

Vertosick FT Jr, Selker RG.

Center for Neuro-Oncology, West Penn Hospital, Pittsburgh, Pennsylvania.

Long-term survival after the diagnosis of malignant glioma is uncommon but not
rare. To define better the population of patients who have extended survival with
this disease, we reviewed the records of 22 of our patients who survived more
than 4 years after the biopsy-proven diagnosis of anaplastic astrocytoma,
malignant mixed glioma, or glioblastoma multiforme. Surprisingly, 21 of the 22
patients are still alive and being actively followed by the authors. The
long-term survivors were typically young and with minimal or no functional
impairment at the time of diagnosis. Survivals ranged from 4.2 to 15.8 years. The
quality of survival was generally good, with the surviving patients having a mean
Karnofsky Performance Score of 76. Three-quarters of the patients had no
enhancement or mass effect on their most recent computed tomography scans. A
review of the available literature, together with our own series, suggests that
death from recurrent disease is unusual in glioma patients who survive more than 
4 or 5 years.

Publication Types: 
 Research Support, U.S. Gov't, P.H.S.
 Review

PMID: 1336626 [PubMed - indexed for MEDLINE]