Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases.
BACKGROUND
Progress in the treatment of hepatic colorectal metastases (HCRM) demands pathologic indicators of therapy response. We observed that a majority of residual tumor cells are seen at the tumor-normal interface (TNI) in resected HCRM specimens and hypothesized that tumor thickness at the TNI correlates with radiologic and pathologic response and recurrence-free survival (RFS).


METHODS
This study included 103 patients with HCRM resected after preoperative chemotherapy with or without bevacizumab. Imaging response was assessed by response evaluation criteria in solid tumors (RECIST) and recently described CT morphology criteria by Chun et al. The pathologic response was categorized as complete (no tumor cells), major (<50% residual tumor cells), or minor (> or =50% residual tumor cells). The maximum thickness of uninterrupted layers of tumor cells was measured perpendicular to the TNI by 2 pathologists independently, followed by consensus review for discrepant cases. For specimens containing >1 tumor, the average tumor thickness at the TNI was used.


RESULTS
Sixty-five patients received oxaliplatin-based chemotherapy, 38 received irinotecan-based chemotherapy, and 75 received concurrent bevacizumab. A complete pathologic response was seen in 9 patients, a major response in 44, and a minor response in 50. Median tumor thickness at the TNI was 2.8 mm (interquartile range, 0.5 to 6 mm). Tumor thickness correlated better with radiologic response as determined by Chun et al (P<0.0001) than by RECIST criteria (Spearman r=0.35, P<0.001). Tumor thickness correlated with pathologic response (Spearman r=0.80, P<0.0001). Greater thickness predicted shorter recurrence-free survival, and this correlation remained in multivariate analysis (P=0.015). Tumor thickness was smaller in patients treated with bevacizumab than in patients not given bevacizumab (P=0.03).


CONCLUSIONS
Tumor thickness measured at the TNI is potentially a new prognostic factor for therapy response and survival outcome in patients with resected HCRM.
Maru
Dipen M
DM
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. dmaru@mdanderson.org
Kopetz
Scott
S
Boonsirikamchai
Piyaporn
P
Agarwal
Atin
A
Chun
Yun Shin
YS
Wang
Huamin
H
Abdalla
Eddie K
EK
Kaur
Harmeet
H
Charnsangavej
Chusilp
C
Vauthey
Jean-Nicolas
JN
Loyer
Evelyne M
EM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011300:Preoperative Care; D012189:Retrospective Studies
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin