DNA or cell kinetics flow cytometry analysis of 33 small gastrointestinal cancers treated by photodynamic therapy.
BACKGROUND
Photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) is a new treatment for cancers of small volume undergoing Phase II or III clinical trials in various medical fields. However, there is a lack of prognostic criteria of efficacy as in other cancer treatment.


METHODS
Cell DNA content or cell kinetics throughout the cell cycle were analyzed by flow cytometry and propidium iodide staining before and after HPD-PDT in 33 patients with Tis or T1 cancers of the gastrointestinal tract. The authors compared results in near-diploid cancers with those obtained in normal corresponding tissue.


RESULTS
Complete local tumor destruction and negative histologic findings (complete response [CR]) were observed in 17 of 33 patients during a period averaging 15.7 months. Flow cytometry DNA analysis was feasible in 32 patients. Aneuploidy, found in 15 of the 32 indicated a poor prognosis because 5 of 15 patients with aneuploid tumors were classified as having CR, compared with 12 of 17 patients with near-diploid tumors (P < 0.05). Changes in ploidy after PDT in 11 patients consisted of a reduction in the number of aneuploid peaks in 8 patients and the appearance of one aneuploid peak in 3 patients. Percentages of cells in SG2M phase in near-diploid tumors differed from those observed in control subjects for adenocarcinomas, and there was no significant decrease after HPD-PDT. There was no correlation between the decrease of SG2M cells and the response to HPD-PDT.


CONCLUSIONS
Results obtained with PDT in this series of patients confirm previously published findings. Changes occurring in the ploidy of PDT-treated patients demonstrate that PDT acts directly on cancer cells in humans and not only on tumor vasculature. However, response to PDT varies from one cell population to another. The appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of aneuploid clones that initially are not detectable by flow cytometry.
Foultier
M T
MT
Faculté de Pharmacie, Nantes, France.
Vonarx-Coinsman
V
V
de Brito
L X
LX
Morlet
L
L
Robillard
N
N
Patrice
T
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis* / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods; D010865:Pilot Projects; D011003:Ploidies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012074:Remission Induction; D012811:Sigmoid Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; D017324:Hematoporphyrin Derivative