bronchoscopy guided simulation of a bronchial neoplasm

2
Correspondence 1745 period from day 14-32. Mitotic index peaks at about 5% and labeling index at 50-60%, but they average about half these values over the regenerative period.2 These numbers are difficult to reconcile with doubling times as low as 14 hours. Other considerations are as Follows: I. After pulse labeling, the incidence of contiguous pairs of labeled cells peaked and then dropped off rapidly over a one or two day period.’ In a pipeline model the labeled pairs should persist for several days until the last component of the basal layer clears. 2. The wide variation observed in the size of regenerating islands suggests that different surviving basal cells can have much different proliferative rates. Such heterogeneity might also reflect a heterogeneity in radioresistance. 3. The number of giant islands changes only slightly with increasing single dose. The high Do this represents, coupled with the more rapid proliferation, suggests that these giant islands may derive from a particularly radioresistant subpopulation of basal cells.2 Hendry and Potten raise a few minor points that should be clarified. 1. Clone count survival estimates were taken as the mean of upper and lower limits only for the lowest dose used, 970 rad. This was done because some fields were fully regenerated during the observation period, and it was impossible to distinguish whether they represented a large number of small clonl:s, or a small number of large clones. Therefore, the error bars show the limits for these extreme possibilities. For the higher doses, no fields were regenerated, and the error bars shown are 95% confidence limits based directly on island counts for 8 animals at each dose. 2. The method used in our paper to derive survival curves from island count data included :I correction for the two-dimensional geometry of the islands as ‘described in Appendix A; hence the difference in results from the Iprevious publication.* It should also be mentioned that our calculated value of 250 rad for the island count survival data reflects data only for the higher three doses. We omitted the 970 rad data because of its lower reliability. Inclusion of that point increases the estimated D,, to 309 rad. 3. Hendry and Potten state that the discrepancy between island count survival estimates and those obtained by back-extrapolation of the cell population regeneration curves would disappear “if conventional cell doubling times are assumed and the surviving fractions for islands are increased. .” This is not so. The times to complete regeneration for the single dose irradiation were 28, 31, and 33 days. Starting from the observed (relative) survival levels, if doubling time were long, the times to complete regeneration would be more spread out. The close spacing of regeneration times requires rapid doubling of surviving cells, for any absolute level of survival. 4. Hendry and Potten suggest that counting colonies per unit area of epidermis may be more accurate than using sectional material to estimate those counts. While this is true in principle, in practice there are difficulties in making accurate counts by simply observing the skin surface after irradiation. Irradiated fields often have widespread areas of moist reaction or a scab covering so that regenerating islands cannot easily be identified. Counting of small islands is clearly a problem under such conditions. Our method of taking eight sections radially oriented within the circular fields and using the geometric correction to estimate the island counts is, we feel, at least as accurate as other methods where clones are counted on the skin surface. I. 2. R. M. SHYMKO, PH.D. Division ‘of Biology Beckman Research Institute of the City of Hope Duarte, CA 9 10 IO J. 0. AR(:HAMBEAU, PH.D. Dept. of ‘Radiation Oncology Loma Linda University Loma Linda, CA Archambeau, J.O., Bennett, G.W.: Quantification of morphologic, cytologic, and kinetic parameters of unirradiated swine skin: A histologic model. Radiat. Rex 98: 254-273, 1984. Archambeau, J.O., Bennett, G.W., Abata, J.J., Brenneis, H.J.: Response of swine skin to acute single exposures of X-rays: Quantification of the epidermal cell changes. Radiat. Res. 79: 298-337, 1979. Mackenzie, I.C., Zimmerman, K., Peterson, L.: The pattern of cellular organization of human epidermis. J. Invest. Dermatol. 76: 459-461, 1981. Potten, C.S.: Stem cells in epidermis from the back of the mouse. In Stem Cells: Their Iden@ation and Characterisation. C.S. Potten (Ed.). Edinburgh, Churchill-Livingstone. 1983, pp. 200- 232. Shymko, R.M., Hauser, D.L., Archambeau, J.O.: Lack of correlation between basal cell survival and gross response in irradiated swine skin. Int. J. Radiat. Oncol. Biol. Phys. 10: 1079-1085, 1984. BRONCHOSCOPY GUIDED SIMULATION OF A BRONCHIAL NEOPLASM To the Edilor: In the practice of radiotherapy it often becomes necessary to deliver high dose radiation to small volumes, mostly as boost doses. These ports are usually set up using anatomical landmarks with the aid of a simulator. In an effort to increase the precision placement of such small fields in the lung, we have used bronchoscopy during simulation to help place these fields with maximum precision and minimal radiation exposure to the personnel involved. It became necessary to re-irradiate a patient with locally recurrent lung cancer to his left main bronchus, 4 years after right pneumonectomy and 5000 cGy post operative radiation therapy to the mediastinum and hila for his primary disease. This recurrence was not demonstrated on routine chest X ray or CT scan and was only detected by bronchoscopy after the patient presented with hemoptysis. To spare as much normal remaining lung as possible, as well as avoiding spinal cord, necessitated using small fields precisely located over the docu- mented area of recurrence shown by bronchoscopy. The patient was placed on the treatment simulator in the supine position and prepared for bronchoscopy with local anesthetics to his Fig. I. A simulation film with bronchoscopc in place and field size set on the collimators.

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Page 1: Bronchoscopy guided simulation of a bronchial neoplasm

Correspondence 1745

period from day 14-32. Mitotic index peaks at about 5% and labeling index at 50-60%, but they average about half these values over the regenerative period.2 These numbers are difficult to reconcile with doubling times as low as 14 hours.

Other considerations are as Follows:

I. After pulse labeling, the incidence of contiguous pairs of labeled cells peaked and then dropped off rapidly over a one or two day period.’ In a pipeline model the labeled pairs should persist for several days until the last component of the basal layer clears.

2. The wide variation observed in the size of regenerating islands suggests that different surviving basal cells can have much different proliferative rates. Such heterogeneity might also reflect a heterogeneity in radioresistance.

3. The number of giant islands changes only slightly with increasing single dose. The high Do this represents, coupled with the more rapid proliferation, suggests that these giant islands may derive from a particularly radioresistant subpopulation of basal cells.2

Hendry and Potten raise a few minor points that should be clarified.

1. Clone count survival estimates were taken as the mean of upper and lower limits only for the lowest dose used, 970 rad. This was done because some fields were fully regenerated during the observation period, and it was impossible to distinguish whether they represented a large number of small clonl:s, or a small number of large clones. Therefore, the error bars show the limits for these extreme possibilities. For the higher doses, no fields were regenerated, and the error bars shown are 95% confidence limits based directly on island counts for 8 animals at each dose.

2. The method used in our paper to derive survival curves from island count data included :I correction for the two-dimensional geometry of the islands as ‘described in Appendix A; hence the difference in results from the Iprevious publication.* It should also be mentioned that our calculated value of 250 rad for the island count survival data reflects data only for the higher three doses. We omitted the 970 rad data because of its lower reliability. Inclusion of that point increases the estimated D,, to 309 rad.

3. Hendry and Potten state that the discrepancy between island count survival estimates and those obtained by back-extrapolation of the cell population regeneration curves would disappear “if conventional cell doubling times are assumed and the surviving fractions for islands are increased. .” This is not so. The times to complete regeneration for the single dose irradiation were 28, 31, and 33 days. Starting from the observed (relative) survival levels, if doubling time were long, the times to complete regeneration would be more spread out. The close spacing of regeneration times requires rapid doubling of surviving cells, for any absolute level of survival.

4. Hendry and Potten suggest that counting colonies per unit area of epidermis may be more accurate than using sectional material to estimate those counts. While this is true in principle, in practice there are difficulties in making accurate counts by simply observing the skin surface after irradiation. Irradiated fields often have widespread areas of moist reaction or a scab covering so that regenerating islands cannot easily be identified. Counting of small islands is clearly a problem under such conditions. Our method of taking eight sections radially oriented within the circular fields and using the geometric correction to estimate the island counts is, we feel, at least as accurate as other methods where clones are counted on the skin surface.

I.

2.

R. M. SHYMKO, PH.D. Division ‘of Biology Beckman Research Institute of the City of Hope Duarte, CA 9 10 IO

J. 0. AR(:HAMBEAU, PH.D. Dept. of ‘Radiation Oncology Loma Linda University Loma Linda, CA

Archambeau, J.O., Bennett, G.W.: Quantification of morphologic, cytologic, and kinetic parameters of unirradiated swine skin: A histologic model. Radiat. Rex 98: 254-273, 1984. Archambeau, J.O., Bennett, G.W., Abata, J.J., Brenneis, H.J.: Response of swine skin to acute single exposures of X-rays: Quantification of the epidermal cell changes. Radiat. Res. 79: 298-337, 1979.

Mackenzie, I.C., Zimmerman, K., Peterson, L.: The pattern of cellular organization of human epidermis. J. Invest. Dermatol. 76: 459-461, 1981. Potten, C.S.: Stem cells in epidermis from the back of the mouse. In Stem Cells: Their Iden@ation and Characterisation. C.S. Potten (Ed.). Edinburgh, Churchill-Livingstone. 1983, pp. 200- 232. Shymko, R.M., Hauser, D.L., Archambeau, J.O.: Lack of correlation between basal cell survival and gross response in irradiated swine skin. Int. J. Radiat. Oncol. Biol. Phys. 10: 1079-1085, 1984.

BRONCHOSCOPY GUIDED SIMULATION OF A BRONCHIAL NEOPLASM

To the Edilor: In the practice of radiotherapy it often becomes necessary to deliver high dose radiation to small volumes, mostly as boost doses. These ports are usually set up using anatomical landmarks with the aid of a simulator. In an effort to increase the precision placement of such small fields in the lung, we have used bronchoscopy during simulation to help place these fields with maximum precision and minimal radiation exposure to the personnel involved.

It became necessary to re-irradiate a patient with locally recurrent lung cancer to his left main bronchus, 4 years after right pneumonectomy and 5000 cGy post operative radiation therapy to the mediastinum and hila for his primary disease. This recurrence was not demonstrated on routine chest X ray or CT scan and was only detected by bronchoscopy after the patient presented with hemoptysis. To spare as much normal remaining lung as possible, as well as avoiding spinal cord, necessitated using small fields precisely located over the docu- mented area of recurrence shown by bronchoscopy.

The patient was placed on the treatment simulator in the supine position and prepared for bronchoscopy with local anesthetics to his

Fig. I. A simulation film with bronchoscopc in place and field size set on the collimators.

Page 2: Bronchoscopy guided simulation of a bronchial neoplasm

1746 Radiation Oncology 0 Biology 0 Physics

otal and nasal mucosa. The table height was then set so that an SAD technique could be used with the level initially set at the patient’s midline. A 5 X 5 cm field was set on the collimator and, using surface anatomical landmarks, was placed in the approximate area where the tumor would be. Once this was accomplished, the bronchoscope was passed and the tumor area visualized. The bronchoscopist then placed the tip of the tube on the lesion, which was briefly viewed under fluoroscopy to check the tube’s location in relation to the field. The field was then adjusted so that the bronchoscope’s tip was centered in the 5 X 5 cm area, which was observed under fluoroscopy again for confirmation. An X ray film was then taken (Figure I) and the field was marked on the skin with castaderm.

With the bronchoscope still in place, the simulator was rotated to a direct lateral position, and the tip of the bronchoscope was located under fluoroscopy. The table was then raised so that the tip of the tube was again in the center of the field, thus insuring a precise SAD technique. The level was then marked on the patient and the broncho- scope withdrawn.

Appropriate contours were taken for computerized dosimetry and in this particular case oblique fields, anterior and posterior, were chosen with the axis of rotation being on the tumor.

The whole procedure took less than 30 minutes with less than two minutes actual fluoroscopy time being used, thus minimizing the risk to the bronchoscopist who had appropriate lead apron shielding on.

September 1985, Volume 11, Number 9

The patient tolerated the procedure well and returned home that same day.

Resimulation was done the following day without the bronchoscope to insure reproducibility of the previous set-up, which was confirmed. Weekly portal films on the machine confirmed reproducibility of the small field.

This procedure was found to be a relatively quick and extremely accurate method for localizing a small lesion and delivering high dose radiation therapy with minimal morbidity to the patient during set-up and the ensuing treatment. We were able to deliver 6170 cGy to a previously irradiated volume with no side effects to the patient to date (over 1 year). The procedure would be most applicable to locally recurrent tumor in the major airways or small boost volumes in which maximal tissue sparing would be called for, either because of the patient’s condition or previous treatment, as in our case.

CHARLES ANDREW& M.D.’ ROBERT PROMISLOFF, D.0.’ MARY LANSU, B.S.’ ARNOLD M. MARKOE, M.D., Sc.D.’ ’ Department of Radiation Oncology & Nuclear Medicine 2 Division of Pulmonary Medicine Hahnemann University, Philadelphia PA