After much intense data scrutiny and soul-searching, we have decided to pursue Jackson’s treatment at Sloan. We are skipping cheese steaks and transplants and heading to NYC for some pizza and 3F8!
From a purely risk-adjusted mathematical basis, MSKCC and CHOP are about equal.
- MSKCC (2.5% * 30% EFS with no antibodies and no transplant) + (97.5% * 63% EFS with 3F8) = 62.2% risk adjusted EFS
- CHOP (3.0% * 0% EFS with transplant death) + (97.0% * 63% EFS with transplant and ch14.18) = 61.1% risk adjusted EFS
However, this comes down to much more than math as there is only one statistic that matters in this case! So why would we choose to pursue MSKCC when the COG and most institutions in the world believe stem cell transplant is beneficial? Our rationale is that while Jackson has Stage IV neuroblastoma, he is in a rare subset that all of his doctors (except for MSKCC) ignore. Most doctors are focused on fixing the problems of the larger group of a rare disease and not the very rare subset (~5 kids per year). When the limited data on Jackson’s particular case is analyzed, we believe the risk/reward favors skipping the transplant.
- Most of the rationale for ASCT vs. no ASCT is from a study (CCG3891) which clearly shows an advantage for ASCT. However, in sorting through the data on the precursor study (1996 JCO – CCG321) the 4 year EFS percentages for patients with transplant and without is no different for all of the subsets in which Jackson falls: 1-2 years old (no difference in %), absent bone metastases (marginal difference in %), absent bone marrow metastases (no difference in %). CCG3891 didn’t cut the data into comparable subsets and only 11 patients out of 434 Stage IV patients in the CCG3891 (2.5%) had a similar diagnosis to Jackson (Stage IV-N, distant lymph node involvement only) (3891 metastatic subsets). Under the COG treatment protocol, all patients in a particular staging are treated equally. We believe Jackson’s case is different. The counter arguement is that Jackson’s tumor is N-myc amplified and prior COG studies show that these types of patients, as a whole, benefit from transplant.
- The CCG3891 study was administered without antibodies. Up until 2001, the only place antibodies were available was through MSKCC. As part of the COG ANBL0032 study, the COG began testing the use of antibodies (all with transplants). There has never been a test of transplant vs. no transplant with antibodies (except in Sloan’s internal data and in the 2005 German Cooperative Results (NB97 trial) which showed a difference in EFS but not OS). Sloan’s internal data shows no benefit from using 3F8 with a stem cell transplant (MSKCC used stem cell transplants as part of their treatment from 1980-1989 and 1999-2003). Slides from MSKCC’s 2007 presentation from ASCO show their survival curves for patients with and without stem cell transplant. Sloan’s latest published survival statistics (2010 MSKCC EFS) has very similar (although not directly comparable) results to the latest COG data from ANBL0032 with antibodies. The counter arguement is that Sloan’s data is unpublished, not from a randomized trial, and not segmented into subsets such as MYCN amplification.
- 3F8 without the transplant is a far less toxic process. Eliminating the transplant removes the 3% risk of death from the transplant process (CCG3891 data actually had a 7% mortality rate) and lowers but doesn’t eliminate the risk that Jackson will become sterile from his treatment (there is already a 40-50% risk that he is sterile from the chemotherapy he has received so far). The counter arguement is that there is a risk that Jackson develops early HAMA and won’t get enough antibodies to protect against MRD (less than 10% risk of developing HAMA if 3F8 is started within 90 days of chemotherapy) and he will still be exposed to additional chemotherapy if he develops HAMA (MSKCC uses rituximab and low dose cyclophosphamide to reduce HAMA).
- Relapse rates from neuroblastoma is 40-50%. For patients who have undergone stem cell transplants in CCG3891, the time from relapse to death was quicker. Some would argue that it’s due to the toxicity of the process and the body’s inability to fight from a weakened state (takes 6-12 months to fully recover) while others would argue its simply due to the fact that it’s a more aggressive cancer that can survive through the stem cell transplant. For Jackson, his tumor is N-myc amplified and most relapses are seen within the first 12 months (at a time when his body would be weakened from a transplant) and we would rather fight from a position of strength (although we are praying we never have to face this).
For us – the risk of Jackson dying in the next month + becoming sterile is too high to pay for something that only “potentially” has value. We’re headed to NYC – bring on the pizza!
We love you Jackson and pray that we have made the right decision! FUCK YOU CANCER!