title: Therapeutic gain factors for fractionated radiation treatment of spontaneous murine tumors using fast neutrons, photons plus O2(1) or 3 ATA, or photons plus misonidazole.
abstract: Therapeutic gain factors (TGFs) have been determined for three spontaneous tumors of the C3H mouse treated by photons + normobaric oxygen (O2(1) ATA), photons + hyperbaric oxygen (O2 3 ATA), photons + misonidazole, or fast neutrons. The tumors were early generation isotransplants of spontaneous tumors: MCaIV, a mammary carcinoma; FSaII, a fibrosarcoma; and SCCVII, a squamous cell carcinoma. The tumors, transplanted to the right leg, were 6 mm at start of treatment. Normal tissue responses studied were acute reaction of normal skin (all treatment modalities) and LD50 following irradiation of the upper abdomen (in test of photons + O2 at 1 or 3 ATA). Thus both the tumor and normal tissues would be classified as "acute responding." All subject tissues were at congruent to 34.5-35 degrees C at irradiation. Treatments were based on d(25)Be or p(43)Be fast neutron beams, 60Co and 137Cs photon beams. Treatments were given in 5 or 15 equal doses in 5 days. For photon treatments, TGFs (air/O2 3 ATA) were substantially and significantly larger than 1 for all three tumor systems treated at small or large doses per fraction when related to skin or abdominal tissue responses. The TGFs (air/O2 1 ATA) were greater than 1 at small doses per fraction for MCaIV and FSaII for skin as the normal tissue; the TGFs for all three tumors and at all doses per fraction would be greater than 1 when related to upper abdominal tissues. TGFs (O2 1 ATA/O2 3 ATA) for photon irradiation greater than 1 were found only for SCCVII and that obtained for both large and small doses per fraction. Misonidazole achieved impressive TGFs (air/air + miso or air/O2 1 ATA + miso); the drug was tested only at 10-12 Gy/fraction and relative to skin. RBEs(FN) for the three tumors were lower at 1.5-2 Gy(FN)/fraction than at 5-6 Gy(FN)/fraction, i.e. the opposite to that reported for normal tissue (RBE increases with decreasing dose per fraction). A TGF (relative to skin reaction) greater than 1 for fast neutron therapy was found only for SCCVII when treated at large doses/fraction; this was true for air or O2 1 ATA conditions.
authors.affiliation: Edwin L. Steele Laboratory of Radiation Biology, Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
authors.forename: H D
authors.initials: HD
authors.lastname: Suit
authors.forename: R
authors.initials: R
authors.lastname: Sedlacek
authors.forename: G
authors.initials: G
authors.lastname: Silver
authors.forename: C C
authors.initials: CC
authors.lastname: Hsieh
authors.forename: E R
authors.initials: ER
authors.lastname: Epp
authors.forename: F Q
authors.initials: FQ
authors.lastname: Ngo
authors.forename: W K
authors.initials: WK
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Verhey
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005214:Fast Neutrons; D005260:Female; D005354:Fibrosarcoma / Q000532:radiotherapy*; D006931:Hyperbaric Oxygenation; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000627:therapeutic use; D011879:Radiotherapy Dosage
chemical_list: D008920:Misonidazole; D010100:Oxygen