I am posting the information below so that we may more fully understand the
colon cancer, Stage I to Stage III nomograms available on the MSK website:
There are two
colon cancer nomograms listed the MSK website, and I will call them
MSK-nomogram and
SEER-nomogram, respectively:
- MSK-nomogram
https://www.mskcc.org/nomograms/colorectal/disease_free_probability
This nomogram is based on a sample of 1,320 Stage I, II, III colon cancer patients, all from MSK, who had all cancer removed by surgery and were observed from 1990 though 2000. During this period, the only available adjuvant chemo regimen was raw 5-FU monotherapy. The outcome variables for this nomogram were "5-year and 10-year Disease-Free Probability Following Surgery" i.e., the probability of being disease free at the end of the 5-year or 10-year observation periods.
. - SEER-nomogram,
https://www.mskcc.org/nomograms/colorectal/overall_survival_probability
This nomogram is based on a sample of 128,853 Stage I, II, III colon cancer patients, from various hospitals nationwide, who had all cancer removed by surgery and were observed from 1994 until 2005. During this period several different adjuvant chemo regimens became available as they were approved by FDA, including: 5-FU monotherapy, 5-FU/Leucovorin, Irinotecan, FOLFIRI, FOLFOX, XELOX/CAPEOX, Erbitux, FOLFOX+Avastin. The outcome variable for this nomogram was "5-year Overall Survival Following Surgery"
FDA Approv.
========
1962-06-01 Adrucil (5-FU)
<<<< 2000 Cut-off date for MSK nomogram: " Disease-Free Probability Following Surgery" (1,320 patients) >>>>
2000-05-01 Camptosar (Irinotecan Hydrochloride)
2001-08-01 Xeloda (Capecitabine)
2002-02-12 Leucovorin (Folinic acid)
2002-08-09 Eloxatin (Oxaliplatin)
2004-02-12 Erbitux (Cetuximab)
2004-02-26 Avastin (Bevacizumab)
<<<< 2005 Cut-off date for SEER nomogram: "Overall Survival Probability Following Surgery " (128,853 patients) >>>>
2006-09-27 Vectibix (Panitumumab)
2012-08-03 Zaltrap (Ziv-Aflibercept)
2012-09-27 Stivarga (Regorafenib)
2015-04-24 Cyramza (Ramucirumab)
2015-08-22 Lonsurf (Trifluridine and Tipiracil Hydrochloride)
2017-05-23 Keytruda (Pembrolizumab)
2017-08-01 Opdivo (Nivolumab)
2018-07-10 Yervoy (Ipilimumab)
There are a number of questions that could be posed concerning these two nomograms. For example:
DATA TOO OLD?
Old, out-of-date chemo regimens?
Old surgical techniques? no laparoscopy; no robotic?
Old technology? old staplers; old suture technology?
Old radiation protocols?
SAMPLING FRAME ADEQUATE?
- Biased sample?
- Small sample?
SCOPE TOO NARROW?
- Location of tumor: Only colon tumors included; rectal tumors not included
- Staging: Stage I, II or III only; no Stage IV/mCRC
- Resectability: Only R0 (totally resectable) cases included; no partial resections included
METHODOLOGY?
-Cox proportional hazards model appropriate? Was "proportional hazards assumption" met?
PREDICTOR VARIABLES APPROPRIATELY CHOSEN?
- Too few biomarkers? CEA only; no CA-19-9; no KRAS/NRAS/BRAF bio-markers; no MSI status
- No chemo regimen details for SEER; No info on time spent on chemo.
- No details on type of surgery.
- No details on possible co-morbidities (e.g., diabetes; heart condition, etc.)
- No details on possible additional risk factors (e.g., smoking; obesity, etc.)
- Overlapping or intercorrelated predictors? (absence of orthogonality/independence of predictors, etc.)
OUTCOME VARIABLES APPROPRIATELY CHOSEN?
- etc.
Any thoughts?