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The early release of surfactant as a predictor of later lethal radiation pneumonitis
1282
137
Radiation Oncology 0 Bioiogy 0 Physics
September 1981. Volume 7, Number 9
LATE EFFECTS OF RADIOTHERAPY ON TASTE AND SALIVARY FUNCTION IN MAN Kenneth L. Mossman Allan R. Shatzman Judith D. Chencharick
Georgetown University Medical Center Washington, D.C. 20007 Taste and salivary dysfunction are frequent complications of the radiotherapy of head and neck cancer. Since the severity of these effects following radiotherapy remain unclear, we studied taste and salivary function in thirteen patients treated by radiation (5000-7000 cGy (rad) in 7-8 weeks ) one to seven years previously for tumors of the head and neck. Taste function was quantitatively evaluated using a standard forced-choice three stimulus drop technique for the determination of detection and recognition thresholds and a forced scaling technique for the determination of taste intensity responsiveness . Parotid salivary function was quantitatively evaluated by determining flow rate and protein secretion rate. Parotid saliva was collected using Lashley cups. Nine of thirteen patients (69%) had measurable taste loss. Taste loss was as severe in patients 6-7 years after therapy as in patients 1-2 years after therapy. The most severely affected taste qualities were salt and bitter and the least affected were sweet and sour. Patients as a group had thresholds for NaCl, sucrose, HCl and urea three times higher that thresholds measured in normal volunteers. Every patient who had radiotherapy including the parotid glands (12/13) had measurable salivary dysfunction. In seven patients, no saliva could be collected; in the other five patients parotid function was reduced to about 10% of normal. Salivary dysfunction was as severe in patients 6-7 years after therapy as in patients l-2 years after therapy. Based on these data and results from previously published studies (1,2), the TD 50/5 (3) for xerostomia is probably 4000-6500 cGy (this is lower than the usually accepted value of 7000 cGy (4)); the TD 50/5 for taste loss is probably 5000-6500 cGy. Thus in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury. Though this injury is not considered life-threatening,many patients may suffer di&comfort with compromised oral health and nutrition. REFERENCES AND NOTES :: 3. 4.
Eneroth, C., C. Henrikson and P. Jakobson, Cancer 30: 1147-1153 (1972). Mossman, K. et -.' al Int. J. Rad. One. 9iol.Vhys.T: 521-528 (1979). The maximum tolerance dose to which a given populatTon of patients is exposed resulting in a 50% complication rate 5 years after treatment Rubin, P. and G. Casarett, Frontiers of Rad Ther. One, & 1-6 (1972).
This work was supported in part by grant number CA-18865 from the National Cancer Institute, DHHS.
THE EARLY RELEASE OF SURFACTANT AS A PREDICTOR OF LATER LETHAL RADIATION PNEUMONITIS Philip Rubin, Dietmar Siemann, Donald Shapiro, Jacob Finkelstein, and David Penney University of Rochester Cancer Center, Rochester, New York 14642 Surfactant, a normal secretory product of Alveolar Type II cells, has been evaluated as an early marker for radiation pneumonitis. The immediate release of surfactant into the alveoli of lung following irradiation has been studied as a potential indicator for the later development of radiation pneumonitis. Utilizing single dose radiation exposures to the whole thorax in male LAFl/J mice, ranging from 5 to 18 Gy, a steep dose response curve for lavaged alveolar surfactant products was identified at day 7 after exposure.
1283
Proceedings of the 23rd Annual ASTR Meeting
There was no elevation with doses up to 12 Gy, above which a detectable The radiation pulmonary increase occurred with increasing radiation dose. lethality dose response curve assessed four months later indicated no lethality up to 12 Gy and an LD50 value of -13 Gy. The close correlation of the earlv biochemical effect and the later radiation oneumonitis lethality dose response curves is a remarkable coincidence of events. The evidence strongly indicates alveolar surfactant release is the first early biochemical marker uncovered hours to days after exposure that predicts for subsequent pneumonitis radiation injury.
8
RJ
60
I
I
I
800
139
THE
INFLUENCE
I
1000
I
I
I,,,,,
I
1200
.
1400 1600 Dose bad)
OF THE DOSE RATE OF IRRADIATION MAMMALIAN CELLS
H. Weiss,
A. Santomasso,
1800
ON THE SURVIVAL
B. Djordjevicl
OF CULTURED
and R. Fleischman
Memorial Sloan-Kettering Cancer Center New York, New York 10021
Chinese hamster V79 cells were irradiated at room temperature by 450 keV electrons in single intense pulses of 3 nsec duration or by 60~0 garnna rays from a radiotherapy unit. Dose rates were about 109 Gy/sec and 0.07 Gylsec, respectively. Approximately 105 log phase cells in 1 ml of medium were plated onto glass cover slips in plastic dishes and let stand for a few hours to permit attachment. Prior to irradiation the dishes were filled with a few ml of medium, then drained completely and gassed with water saturated ultra high purity nitrogen or air for 15 min while in the sample chamber. The dish with the cover slip was irradiated in a vertical position with either source, and the time the sample was in the chamber was kept the same with both sources. All fittings, connections and tubing from the nitrogen tank were made of glass, metal or nylon. After irradiation the dishes were refilled and held at room temperature for two hours. The cells were then trypsinized and plated into new tissue culture dishes for colony formation at 370~. Similar experiments were conducted with cells in plateau phase. The resulting curves obtained by a least square fit to the data of a multi-target model or a linear quadratic model show that under oxygenated conditions there is no effect due to dose rate. Whereas the curves for anoxic cells have the same shape but there is about a twenty percent reduction in O.E.R. for the pulsed irradiations. Dosimetry considerations, and the implication of these results will also be discussed. Supported
in part by American
Cancer
Society
Grant
No. PDT-59
NC1 Grant No. 18179. 1Present
address:
Mt. Sinai
Med. Ctr.;
New York,
N. Y. 10029.
and in part by
137
Radiation Oncology 0 Bioiogy 0 Physics
September 1981. Volume 7, Number 9
LATE EFFECTS OF RADIOTHERAPY ON TASTE AND SALIVARY FUNCTION IN MAN Kenneth L. Mossman Allan R. Shatzman Judith D. Chencharick
Georgetown University Medical Center Washington, D.C. 20007 Taste and salivary dysfunction are frequent complications of the radiotherapy of head and neck cancer. Since the severity of these effects following radiotherapy remain unclear, we studied taste and salivary function in thirteen patients treated by radiation (5000-7000 cGy (rad) in 7-8 weeks ) one to seven years previously for tumors of the head and neck. Taste function was quantitatively evaluated using a standard forced-choice three stimulus drop technique for the determination of detection and recognition thresholds and a forced scaling technique for the determination of taste intensity responsiveness . Parotid salivary function was quantitatively evaluated by determining flow rate and protein secretion rate. Parotid saliva was collected using Lashley cups. Nine of thirteen patients (69%) had measurable taste loss. Taste loss was as severe in patients 6-7 years after therapy as in patients 1-2 years after therapy. The most severely affected taste qualities were salt and bitter and the least affected were sweet and sour. Patients as a group had thresholds for NaCl, sucrose, HCl and urea three times higher that thresholds measured in normal volunteers. Every patient who had radiotherapy including the parotid glands (12/13) had measurable salivary dysfunction. In seven patients, no saliva could be collected; in the other five patients parotid function was reduced to about 10% of normal. Salivary dysfunction was as severe in patients 6-7 years after therapy as in patients l-2 years after therapy. Based on these data and results from previously published studies (1,2), the TD 50/5 (3) for xerostomia is probably 4000-6500 cGy (this is lower than the usually accepted value of 7000 cGy (4)); the TD 50/5 for taste loss is probably 5000-6500 cGy. Thus in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury. Though this injury is not considered life-threatening,many patients may suffer di&comfort with compromised oral health and nutrition. REFERENCES AND NOTES :: 3. 4.
Eneroth, C., C. Henrikson and P. Jakobson, Cancer 30: 1147-1153 (1972). Mossman, K. et -.' al Int. J. Rad. One. 9iol.Vhys.T: 521-528 (1979). The maximum tolerance dose to which a given populatTon of patients is exposed resulting in a 50% complication rate 5 years after treatment Rubin, P. and G. Casarett, Frontiers of Rad Ther. One, & 1-6 (1972).
This work was supported in part by grant number CA-18865 from the National Cancer Institute, DHHS.
THE EARLY RELEASE OF SURFACTANT AS A PREDICTOR OF LATER LETHAL RADIATION PNEUMONITIS Philip Rubin, Dietmar Siemann, Donald Shapiro, Jacob Finkelstein, and David Penney University of Rochester Cancer Center, Rochester, New York 14642 Surfactant, a normal secretory product of Alveolar Type II cells, has been evaluated as an early marker for radiation pneumonitis. The immediate release of surfactant into the alveoli of lung following irradiation has been studied as a potential indicator for the later development of radiation pneumonitis. Utilizing single dose radiation exposures to the whole thorax in male LAFl/J mice, ranging from 5 to 18 Gy, a steep dose response curve for lavaged alveolar surfactant products was identified at day 7 after exposure.
1283
Proceedings of the 23rd Annual ASTR Meeting
There was no elevation with doses up to 12 Gy, above which a detectable The radiation pulmonary increase occurred with increasing radiation dose. lethality dose response curve assessed four months later indicated no lethality up to 12 Gy and an LD50 value of -13 Gy. The close correlation of the earlv biochemical effect and the later radiation oneumonitis lethality dose response curves is a remarkable coincidence of events. The evidence strongly indicates alveolar surfactant release is the first early biochemical marker uncovered hours to days after exposure that predicts for subsequent pneumonitis radiation injury.
8
RJ
60
I
I
I
800
139
THE
INFLUENCE
I
1000
I
I
I,,,,,
I
1200
.
1400 1600 Dose bad)
OF THE DOSE RATE OF IRRADIATION MAMMALIAN CELLS
H. Weiss,
A. Santomasso,
1800
ON THE SURVIVAL
B. Djordjevicl
OF CULTURED
and R. Fleischman
Memorial Sloan-Kettering Cancer Center New York, New York 10021
Chinese hamster V79 cells were irradiated at room temperature by 450 keV electrons in single intense pulses of 3 nsec duration or by 60~0 garnna rays from a radiotherapy unit. Dose rates were about 109 Gy/sec and 0.07 Gylsec, respectively. Approximately 105 log phase cells in 1 ml of medium were plated onto glass cover slips in plastic dishes and let stand for a few hours to permit attachment. Prior to irradiation the dishes were filled with a few ml of medium, then drained completely and gassed with water saturated ultra high purity nitrogen or air for 15 min while in the sample chamber. The dish with the cover slip was irradiated in a vertical position with either source, and the time the sample was in the chamber was kept the same with both sources. All fittings, connections and tubing from the nitrogen tank were made of glass, metal or nylon. After irradiation the dishes were refilled and held at room temperature for two hours. The cells were then trypsinized and plated into new tissue culture dishes for colony formation at 370~. Similar experiments were conducted with cells in plateau phase. The resulting curves obtained by a least square fit to the data of a multi-target model or a linear quadratic model show that under oxygenated conditions there is no effect due to dose rate. Whereas the curves for anoxic cells have the same shape but there is about a twenty percent reduction in O.E.R. for the pulsed irradiations. Dosimetry considerations, and the implication of these results will also be discussed. Supported
in part by American
Cancer
Society
Grant
No. PDT-59
NC1 Grant No. 18179. 1Present
address:
Mt. Sinai
Med. Ctr.;
New York,
N. Y. 10029.
and in part by