I've found great value in this blog and am posting for the first time.
I was diagnosed in march 2016 with grade 2 oligo. Its a somewhat larger tumor, about 7x6x5cm and unlike most oligo's is not in the frontal lobe, but is left parietal and overlapping motor, sensory and speech areas and nearing midline crossover. Because of all that it was considered a high risk surgery zone and so I have so far only had a biopsy and have been doing chemo. I'm IDH1 mt, mgmt meth, 1p19q codel, ATRX normal, p53 normal.
So the broad plan was chemo then RT. The hope was to shrink the tumor to be able to reduce the RT zone. So far 6 rounds of Temodar but I have now switched over and done 1 round of CCNU after having learned more about hypermutation risks with TMZ.
I've dug thru what published data there is and its all clear as mud. On the one hand the 2014 Science paper (Johnson et al from the Costello UCSF lab) that seems to have really launched this topic found very clear and scary linkages showing hypermutation and upgrading at recurrance to GBM in about half of the patients treated with TMZ vs none with only RT, on the other hand it was a very small data set, had mixed genetics, was clearly a selected dataset and not randomized, and only looked at TMZ alone or RT alone, not the more common RT+TMZ. The few other studies I have found add some implications that mutations in TP53 and mismatch repair genes increase the risk, though some data also shows TMZ driving mutations of TP53 and MSHx which then creates the path to hypermutation.
In simplified terms if chemo mutates the cancer to a point where the 'self check' mechanisms during cell division stop working then the next time the cell gets hit with chemo it will go ahead and replicate in spite of the genetic damage from chemo and create new set of mutations.
To further complicate the picture most of the historical data looking at different chemo options is comparing PCV to TMZ, but procarbazine is a monoalkylating agent that is quite similar to TMZ. So I've gotten some input from Doc's that CCNU alone may be less mutagenic because it is a bi-alkylating agent and will more effectively stop DNA replication thru double strand breaks.
So Steven or others who are into the science side of cancer, do you have any thoughts on how to unravel all this? Recommendations on other approaches to consider, or ways to enhance effectiveness of chemo for low grade cases?
SW edited this post to include the image below, from a presentation at the 2016 SNO conference in Phoenix Arizona: