====== Tumor recurrence ======

see [[Glioblastoma recurrence]].

===== Etiology =====

[[Glioma stem cell]]s (GSC) contribute to the tumor’s heterogenous nature, therapeutic resistance, and, thereby, inevitable [[tumor recurrence]]
((Calabrese C, Poppleton H, Kocak M, et al. A perivascular
niche for brain tumor stem cells. Cancer Cell.
2007;11(1):69-82.))
((Cheng L, Huang Z, Zhou W, et al. Glioblastoma
stem cells generate vascular pericytes to support vessel
function and tumor growth. Cell. 2013;153(1):139-
152.)).

===== Diagnosis =====

Ancillary criteria to identify tumor recurrence such as [[MacDonald criteria]] or [[RANO criteria]] may provide false diagnoses. [[Perfusion MRI]] imaging has been proposed to differentiate post-treatment changes from recurrence.


An increase in [[FLAIR]] signal of the fluid within the resection cavity might be a highly specific and early sign of local [[tumor recurrence]]/[[tumor progression]] also for [[brain metastases recurrence]]. 
((Bette S, Gempt J, Wiestler B, Huber T, Specht H, Meyer B, Zimmer C, Kirschke
JS, Boeckh-Behrens T. Increase in FLAIR Signal of the Fluid Within the Resection 
Cavity as Early Recurrence Marker: Also Valid for Brain Metastases? Rofo. 2017
Jan;189(1):63-70. doi: 10.1055/s-0042-119686. PubMed PMID: 28002859.
)).


===== Outcome =====

[[Tumor]] [[recurrence]] is a leading cause of [[cancer]] [[mortality]]. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, Johnson et al., sequenced the [[exome]]s of 23 initial [[Low-grade glioma]]s and recurrent tumors resected from the same patients. In 43% of cases, at least half of the [[mutation]]s in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis
((Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, Fouse SD, Yamamoto
S, Ueda H, Tatsuno K, Asthana S, Jalbert LE, Nelson SJ, Bollen AW, Gustafson WC, 
Charron E, Weiss WA, Smirnov IV, Song JS, Olshen AB, Cha S, Zhao Y, Moore RA,
Mungall AJ, Jones SJ, Hirst M, Marra MA, Saito N, Aburatani H, Mukasa A, Berger
MS, Chang SM, Taylor BS, Costello JF. Mutational analysis reveals the origin and 
therapy-driven evolution of recurrent glioma. Science. 2014 Jan
10;343(6167):189-93. doi: 10.1126/science.1239947. Epub 2013 Dec 12. PubMed PMID:
24336570; PubMed Central PMCID: PMC3998672.
)).


Tumor recurrence remains the major clinical complication of [[meningioma]]s, the majority of recurrences occurring among WHO grade I/benign tumors.