Title: In vitro chemoresistance testing in well differentiated carcinoid tumors. Authors
|Lyons, John - LSUHSC DEPT. OF SURGERY|
|Abergel, Jeffrey - MOUNT SINAI SCH. OF MED.|
|Anthony, Cathy - LSUHSC DEPT. OF SURGERY|
|Wang, Yi-Zarn - LSUHSC DEPT. OF SURGERY|
|Anthony, Lowell - LSUHSC DEPT. OF SURGERY|
|Boudreaux, J Philip - LSUHSC DEPT. OF SURGERY|
|Strauchen, James - MOUNT SINAI SCH. OF MED.|
|Idrees, Muhammad - MOUNT SINAI SCH. OF MED.|
|Warner, Richard - MOUNT SINAI SCH. OF MED.|
Submitted to: Annals of Surgical Oncology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 28, 2008
Publication Date: March 1, 2009
Citation: Lyons, J., Abergel, J., Thomson, J.L., Anthony, C.T., Wang, Y., Anthony, L.B., Boudreaux, J., Strauchen, J., Idrees, M., Warner, R.P. 2009. In vitro chemoresistance testing in well differentiated carcinoid tumors. Annals of Surgical Oncology. 16(3):649-655. Interpretive Summary: Chemotherapy treatment options for patients with typical (rare and slow-growing) carcinoid tumors are limited. Even if a tumor responds to chemotherapy, the response is often short-lived and rarely results in prolonged survival for the patient. To obtain a more complete understanding of carcinoid tumors response to treatment, we tested a group of carcinoid tumor specimens against a variety of chemotherapy drugs in the laboratory. Contrary to results obtained in the clinical setting, we found that a surprising proportion (81%) of the carcinoid tumors showed good response to at least two chemotherapy drugs. Two drugs in particular, 5-FU and doxorubicin, were effective in stopping growth in over 65% of the tumors tested. These results indicate that chemotherapy drugs may be more effective in treating carcinoid tumors than previously thought. Further, the results imply that assay-guided selection of chemotherapy drugs may be a more effective means for providing treatment to patients with typical carcinoid tumors than the current method based upon physician choice.
Technical Abstract: Well-differentiated, “typical” carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. Methods: 98 typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. 3H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. Results: 70 specimens generated results. Each was tested with an average of 6 drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0 to 1), 0.34 (range 0 to 1), and 0.18 (range 0 to 0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2,respectively. 57 (81%) of 70 of specimens had LDR to at least 2 drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by Doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids while EDR was comparatively infrequent. Conclusions: This implies that there may be less clinical chemoresistance and more hemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.