Binding affinity of antigen-antibody complexes at clinically relevant hyperthermic temperatures: A proposed model

Prooeedingsofthe32ndAnnualASTRO

Meeting

249

1048 CORRECTION Ramesh

FOR OFF-AXIS PHOTON

C. Tailor,

Department

Ph.D.,

of Radiation

BEAM ENERGY

CHANGE

B. Schroy,

Ph.D.,

Carter Physics,

University

and William

F. Hanson,

of Texas M.D. Anderson

Cancer

Ph.D. Center,

Houston,

TX 77030

The Radiological Physics Center (RPC) provides quality assurance (QA) for several radiotherapy Part of this QA is verifying that doses stated in the treatment records are accurate. study groups. The task of maintaining beam profiles for This frequently requires dose calculations to off-axis points. Consequently, the each photon energy of more than 750 institutions that participate would be unwieldy. RPC opts to calculate dose at the point in question using the equation: Dp = Dfs x OAF(B)

x [TARQ(d)

+ SAR

(w,d)]

where Dp = Dose at point p; D f;" = dose in free space on the central axis (tax) at the distance from the target to point p; OAF(B) is t e off-axis factor at angle 8 from the tax; TARO(d) is the TAR for a 0 x 0 field size at depth d; and SAR (w,d) is the scatter-air ratio for depth d and a field size with an equivalent-square of w. One factor that has not been routinely accounted for is the change in TARQ as a function of angle 8. The beam passes through thinner parts of the flattening filter as 8 increases and thus is less Consequent changes in TAR0 and half-valug layers (HVL) of water are evident and hardened by the filter. can be quantified by the ratio of HVL at 8 vs that on the tax (HVLO). TARO(=

TMRO)

varies

by: TARO(B)

= exp ([-ln2][d-dmax]/HVL(e))

= exp ([ln TARO(O)]/HVLg)

We measured HVL vs B for a number of newer As can be seen. TARn(8) can be determined from HVL!. Analysis of this linacs (6-20 MV) by'usini‘the narrow beam water HVL m&hod of Hanson et al. (1980). data and similar ore-existinq data for older linacs indicate a straiqht line (r = 0.95) would orovide a This universal fit (with acceptable limits of uncertainty) regardless of linac‘model and energy. equation is: HVLI = 1.018 - 0.012 8

It can be calculated, for example, that at a depth of 10 cm the TMR of an 8 cm diameter effective field 11 cm off axis (8 = 7.B"), treated with an 80 cm SAD 4 MV machine, would be decreased 3.5% using (This assumes that the SAR component does not change significantly with the change in the correction. beam energy.) This correction would increase the accuracy of an off-axis dose calculation and improve QA methodology accordingly. This work was supported

in part by PHS grant

CA 10953 awarded

by the National

Cancer

Institute,

DHHS.

1049 BINDING AFFINITY OF ANTIGEN-ANTIBODY TEMPERATURES:A PROPOSED MODEL

COMPLEKES

AT CLINICALLY

RELEVANT

HYPERTHERMIC

Pon N. Yi, Ph.D., Alan A. Alfieri, M-S., Massimo Temponi, Ph.D., Soldano Ferrone, M.D., Department of Radiation Medicine, Ph.D., Chitti Moorthy, M.D. and Basil S. Hilaris, M.D. New York Medical College, Valhalla, New York 10595 Department of Microbiology, Immunological participation in the cytotoxic response of tumors to localized and whole body hyperthermia was speculated with the first observations that treatment of one of multiple lesions resulted in the regression of both treated and untreated lesions. These observations had biological basis only when heat induced structural and functional These proteins have been changes of cellular membranes and proteins were demonstrated. as a stimulant to implicated in the expression of membrane-bound antigens, and postulated antibody production. Recent findings have shown enhanced expression of tumor associated after acute exposure, peaks at the 4th day and antigens in heated cells. This modulation If combined hyperthermia and antibody may have both temperature and duration dependence. therapy results in the amplification of existing concomitant immunity, then the importance of temperature sequencing and local tumor temperature are of clinical relevance. However, a concern is whether the binding affinity between antigen-antibody is modified by hyperthermic temperatures during treatment. The rise in kinetic energy at elevated temperatures would support a reduced affinity A reduction in the affinity implies detachment of bound between antigen-antibody. The avidity constant, Ka is related to the temperature and free energy of complexes. binding A F by: - AF/RT Ka = e Example: a where R is the gas constant (2 cal/deg mole) and T the absolute temperature. anti-high molecular weight-melanoma associated Scatchard plot of the binding of the antigen [mAB 225.281 for Co10 38 melanoma target cells exhibits an avidity constant of Ka = 10ES liters/mole at 37 C. Thereby, the free energy of binding can be expressed ae 0. F

250

Radiation Oncology, Biology, Physics

October 1990, Volume 19, Supplement

= -12 K&l/mole. Substituting this value in the equation dependence of the avidity constant can be found. At 43C,

1

above, the temperature the avidity is reduced

by 30% from the 37C value. This calculation assumes that the receptors of proteins involved are not irreversibly damaged. Thereby, the effects of local hyperthermia to the Ag-Ab binding is small and most likely limited to the duration of thermal sessions but not affected by the timing between hyperthermia and antibody induction. This model should allow optimal temperature-time determination and sequence of Ab administration to enhance Ab mediated cytotoxicity for tumors exhibiting antigenic expression. The potential applications of this model and its requirements for other cell types will be presented.

1050 Torrisi, 3; Rustgi, S.; Spitzer, T; Popescu,

Cottler-Fox,

G; Deeg, Y.;

M; Kyler,

R; Rogers,

J.

Georgetown University

TOTAL BODY IRRADIATION:

COMPARISON

OF DIRECT

IN VIVO DOSE MEASUREMENT

WITH CALCULATED

DOSE

Total body irradiation (TBI) is an integral part of many bone marrow transplantation preparatory attention may be directed With increasing patient survival following transplantation, regimens. Possible factors contributing to toward decreasing late effects attributable to radiotherapy. To gain further insight late toxicity include total dose, fractionation and dose inhomogeneity. in vivo dosimetry was performed on 20 consecutive patients into the degree of dose inhomogeneity, who received TBI as part of their bone marrow transplantation preparatory regimen since January, 1988. All patients were treated using a multifractionated treatment scheme and technique similar to that popularized by Memorial Sloan-Kettering.1 All patients received 13.2 Gy whole body dose in 11 Regions of the chestwall shielded by the lung blocks fractions with 50% transmission lung blocks. To investigate the dose distribution and were given an electron boost of 6 Gy in two fractions. Correlation of significant structures were performed. accuracy of this approach, diode measurements with the prescribed dose was excellent and yielded measured fractional doses at the prescription point (central axis) within .75% of 1.2 Gy. The area shielded by the lung blocks received an average of An approximate 10% higher dose was noted .61 Gy confirming the adequacy of the lung blocking system. for peripheral sites (fraction size of 1.36, 1.31, and 1.34 Gy for the arm, leg, and neck respectfully). Our results The outer canthus of the eye (lens) received on average 118% of the prescribed dose. suggest that radiation dose to crucial central structures may be delivered within a relatively narrow Possible correlation of these tolerance but that dose inhomogeneity increases in peripheral areas. findings with reported late complications are explored. 1. B. Shank

et al, Int. J Rad One Biol Phys

9:1925,

1983.

1051 THE ROLE OF SURGICAL STAGING IN ENDOMETRIAL CARCINOMA

IN

DETERMINING

PROGNOSIS

AND

THE

NEED

FOR

ADJUNCTIVE

THERAPY

Aaron H. WolfFon, M.D.l, Sterling E. Sightier, l4.D.2, Arnold M. Markoe, W.D.1, James G. Schwade, M.D. , and Hervy E. Averette, M.D. Department of Radiation Oncology', Department of Obstetrics and Gynecology', University of Miami School of Medicine, Miami, Florida 33101 This study is a retrospective review of 156 patients with endometrial cancer from 1978 through 1984 who underwent primary surgical evaluation. The pre-operative FIGD clinical stage distribution for this study was as follows: 121 (77.6%) Stage I, 23 (14.7%) Stage II 5 (3.2%) Stage III, 2 (1.3%) Stage IV, and 5 (3.2%) unstaged patients. Most patients had TAH-BSO with peritoneal washings and retroperitoneal lymph node sampling. Post-operative FIG0 surgical staging revealed 122 (78%) Stage I, 9 (6%) Stage II, 12 (7.7%) Stage III, and 13 (8.3%) Stage IV patients. Surgery upstaged 12% of Clinical Stage I patients. 52.3% of Clinical Stage II patients were downstaged while 34.7% were upstaged. Sixty percent of Clinical Stage III patients were upstaged, but no downstaging occurred. Patients in Clinical Stage IV were managed palliatively without surgical intervention. All patients were followed until death or a minimum of five years (60-139 months, median 87 months) with the exception of 12 patients who were lost to follow-up (2-58 months, median 36 months). These patients were scored as having died of their disease at the time of last follow-up. Crude disease-free survival by clinical stage was as follows: 89/121 (74%) Stage I, 17/23 (74%) Stage II, O/5 Stage III, and O/2 Stage IV. Surgically staged patients had the following crude disease-free survival: 95/122 (78%) Stage I, 6/9 (67%) Stage II, 6/12 (50%) Stage III, and l/13 (8%) Stage IV. Ninety-six surgically staged patients received no adjuvant therapy. Their crude disease-free survival was as follows: 66/83 (80%) Stage I, 4/7 (57%) Stage II, O/2 Stage III, and O/4 Stage IV. Sixty patients received adjuvant