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Is radiation therapy a viable alternative to surgery in early stage lung cancer?
Inl. J Radialion Oncology Bml t’hys Vol. Printed in the U.S.A. All rights reserved.
0360-3016/W $3.00 + .M) copyright 0 1990 Per$amon Pm.5 plc
19, pp. 223-224
0 Editorial
IS RADIATION THERAPY A VIABLE ALTERNATIVE TO SURGERY IN EARLY STAGE LUNG CANCER? BRUCE G. HAFFTY,
M.D.
Department of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 065 10 Lung cancer, Radiation therapy.
are difficult, one might ask the question how radical ra-
Surgical resection is the standard treatment modality for technically operable non-small cell carcinoma of the lung. While radiation therapy is generally reserved for more advanced unresectable non-small cell lung carcinoma, there are occasional patients with early stage operable lung carcinoma who are either unwilling or unable to undergo thoracotomy and are offered radical radiation therapy as a treatment option. One of the earlier reports in the literature analyzing the results of radiation therapy in this group of patients was by Hilton and Smart nearly 30 years ago (2,4). Utilizing orthovoltage equipment and applying “variable daily radiation doses according to the patients’ general condition, pulse rate, respiration rate and temperature chart” to a total dose in the range of 4500-5000 cGy they achieved a 22.5% 5-year survival rate in 40 patients. Although selection criteria were not clearly specified, these patients reportedly were otherwise reasonable surgical candidates with no clinical evidence of nodal or distant metastases. The survival rate achieved was not significantly different from a cohort of patients treated surgically in the same time interval. Over the ensuing 30 years there have been limited additional reports addressing the results of radical radiation therapy in this group of otherwise operable early stage non-small cell lung cancer patients. In a recent analysis from Yale (l), we achieved a similar 2 1% 5-year survival in 43 clinical Stage I patients treated with radical radiation therapy. In that analysis we had noted that this patient population did not undergo extensive pretreatment staging with only 2 of 43 patients having had a pretreatment CT scan. This, along with the generally poor medical condition of these patients, makes comparisons with surgical series difficult since surgically treated patients generally undergo much more aggressive preoperative staging, and are in better medical condition. Thus, while comparisons with surgically treated patients
diation therapy compares with surgery in patients undergoing similar pretreatment staging procedures. In this issue, Sandler et al. present some interesting data addressing this issue. While the overall survival and disease-free survival of their patients treated with radical radiation appears to be inferior to surgically treated patients, in a small group of patients undergoing “excellent pretreatment staging” including CT scanning to adequately evaluate the extent of the primary lesion and regional lymph nodes, they achieved a 3-year overall survival of 40% and a disease-specific survival of 77%. While one must recognize significant problems associated with subset analyses of retrospective data, these results appear to approach the results in some surgical series and raise some interesting questions regarding how radical radiation therapy compares with surgical resection in patients with early stage operable lung cancer. Sandler’s paper, however, provides us with some additional, although discouraging data regarding local control. They note an overall local failure rate of 56%. Even in the group of patients with tumors < 3 cm, local progression-free survival was only 50%. These local control figures are consistent with the overall 39% thoracic failure rate noted in our series from Yale. Due to the narrow range of doses used, no dose response data are available from Sandler’s study. In a recent analysis by Zhang et al. (5), patients who received doses of 69-70 Gy appeared to have a lower local recurrence rate ( 18%) and a higher 5year survival rate (36%) than patients treated with lower doses of 55-6 1 Gy. Similarly, the Yale analysis suggested both higher local control rates and superior survival in patients treated with a continuous course technique compared with a split course technique. In another recent retrospective analysis from the Netherlands,3 Noordijk et al. demonstrated improved survival (42%) in TI-zNO pa-
Reprint requests to: Bruce G. HafFty,M.D.
Accepted for publication 223
10 April 1990.
224
I. J. Radiation
Oncology
0 Biology
0 Physics
tients achieving a complete radiographic response, compared with less than 5% survival among partial and nonresponders. Even among the complete response subset, however, local failure was 25%. While these recent analyses provide some interesting observations, we are still left with relatively low overall local control rates, and 5year survival rates which are not significantly different than the results 1950s.
obtained
by Hilton
and Smart
in the
Again recognizing the difficulties inherent in comparisons to surgical series, the local failure rates reported in these recent radiotherapy series exceed local failure rates in surgically treated Stage I and II patients. Even with limited resections (wedge resection/segmentectomy) failure rates rarely exceed lo- 15%. In considering
local radia-
tion therapy as an alternative to surgery, we must ognize that the cardiac and pulmonary complications
recas-
sociated with local failure often directly contribute to patient demise, accounting for the apparent relationship
July
1990.
Volume 19, Number 1
between local control and survival in this group of patients. Whether careful treatment planning with the cautious escalation of doses, alternate fractionation schemes, or employment of concomitant adjuvant chemotherapy will improve on the local control rates achieved with radical radiation therapy remains to be seen. It is prudent to apply our efforts in this direction, however, since it is this group of early stage lung cancer patients, where disease may be truly localized, who would derive the greatest benefit from improvements in local control. Currently, it is apparent that surgical resection remains the treatment of choice for early stage non-small cell carcinoma of the lung. It is important, however, that we stress results such as those reported by Sandler et al. to our surgical, pulmonary and medical oncology colleagues which demonstrate that radical radiation therapy does provide an alternative for those patients unwilling or unable to undergo thoracotomy, and that such treatment does offer a realistic possibility of longterm survival.
REFERENCES Haffty, B. G.: Goldberg, N. B.; Gerstley, J.; Fischer, D. B.: Peschel, R. E. Results of radical radiation therapy in clinical Stage I, technically operable non-small cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 15:69-73; 1988. Hilton, G. Present position relative to cancer of the lung. results with radiotherapy alone. Thorax 15: 17- 18; 1960. Noordijk, E. M.; Poest Clement, E.: Hermans. J.; Wever, A. M. J.; Leer, J. W. H. Radiotherapy as an alternative to
surgery diother. 4. Smart. alone? 5. Zhang, Z. X.; therapy diother.
in elderly patients with resectable lung cancer. RaOncol. 13:83-89; 1988. J. Can lung cancer be cured by radiation therapy JAMA 195:158-161; 1966. H. X.: Yin, W. B.; Zhang, L. J.; Yang, Z. Y.; Zhang, Wang, M.; Chen, D. F.; Gu, X. Z. Curative radioof early operable non-small cell lung cancer. RaOncol. 14:89-94; 1989.
0360-3016/W $3.00 + .M) copyright 0 1990 Per$amon Pm.5 plc
19, pp. 223-224
0 Editorial
IS RADIATION THERAPY A VIABLE ALTERNATIVE TO SURGERY IN EARLY STAGE LUNG CANCER? BRUCE G. HAFFTY,
M.D.
Department of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 065 10 Lung cancer, Radiation therapy.
are difficult, one might ask the question how radical ra-
Surgical resection is the standard treatment modality for technically operable non-small cell carcinoma of the lung. While radiation therapy is generally reserved for more advanced unresectable non-small cell lung carcinoma, there are occasional patients with early stage operable lung carcinoma who are either unwilling or unable to undergo thoracotomy and are offered radical radiation therapy as a treatment option. One of the earlier reports in the literature analyzing the results of radiation therapy in this group of patients was by Hilton and Smart nearly 30 years ago (2,4). Utilizing orthovoltage equipment and applying “variable daily radiation doses according to the patients’ general condition, pulse rate, respiration rate and temperature chart” to a total dose in the range of 4500-5000 cGy they achieved a 22.5% 5-year survival rate in 40 patients. Although selection criteria were not clearly specified, these patients reportedly were otherwise reasonable surgical candidates with no clinical evidence of nodal or distant metastases. The survival rate achieved was not significantly different from a cohort of patients treated surgically in the same time interval. Over the ensuing 30 years there have been limited additional reports addressing the results of radical radiation therapy in this group of otherwise operable early stage non-small cell lung cancer patients. In a recent analysis from Yale (l), we achieved a similar 2 1% 5-year survival in 43 clinical Stage I patients treated with radical radiation therapy. In that analysis we had noted that this patient population did not undergo extensive pretreatment staging with only 2 of 43 patients having had a pretreatment CT scan. This, along with the generally poor medical condition of these patients, makes comparisons with surgical series difficult since surgically treated patients generally undergo much more aggressive preoperative staging, and are in better medical condition. Thus, while comparisons with surgically treated patients
diation therapy compares with surgery in patients undergoing similar pretreatment staging procedures. In this issue, Sandler et al. present some interesting data addressing this issue. While the overall survival and disease-free survival of their patients treated with radical radiation appears to be inferior to surgically treated patients, in a small group of patients undergoing “excellent pretreatment staging” including CT scanning to adequately evaluate the extent of the primary lesion and regional lymph nodes, they achieved a 3-year overall survival of 40% and a disease-specific survival of 77%. While one must recognize significant problems associated with subset analyses of retrospective data, these results appear to approach the results in some surgical series and raise some interesting questions regarding how radical radiation therapy compares with surgical resection in patients with early stage operable lung cancer. Sandler’s paper, however, provides us with some additional, although discouraging data regarding local control. They note an overall local failure rate of 56%. Even in the group of patients with tumors < 3 cm, local progression-free survival was only 50%. These local control figures are consistent with the overall 39% thoracic failure rate noted in our series from Yale. Due to the narrow range of doses used, no dose response data are available from Sandler’s study. In a recent analysis by Zhang et al. (5), patients who received doses of 69-70 Gy appeared to have a lower local recurrence rate ( 18%) and a higher 5year survival rate (36%) than patients treated with lower doses of 55-6 1 Gy. Similarly, the Yale analysis suggested both higher local control rates and superior survival in patients treated with a continuous course technique compared with a split course technique. In another recent retrospective analysis from the Netherlands,3 Noordijk et al. demonstrated improved survival (42%) in TI-zNO pa-
Reprint requests to: Bruce G. HafFty,M.D.
Accepted for publication 223
10 April 1990.
224
I. J. Radiation
Oncology
0 Biology
0 Physics
tients achieving a complete radiographic response, compared with less than 5% survival among partial and nonresponders. Even among the complete response subset, however, local failure was 25%. While these recent analyses provide some interesting observations, we are still left with relatively low overall local control rates, and 5year survival rates which are not significantly different than the results 1950s.
obtained
by Hilton
and Smart
in the
Again recognizing the difficulties inherent in comparisons to surgical series, the local failure rates reported in these recent radiotherapy series exceed local failure rates in surgically treated Stage I and II patients. Even with limited resections (wedge resection/segmentectomy) failure rates rarely exceed lo- 15%. In considering
local radia-
tion therapy as an alternative to surgery, we must ognize that the cardiac and pulmonary complications
recas-
sociated with local failure often directly contribute to patient demise, accounting for the apparent relationship
July
1990.
Volume 19, Number 1
between local control and survival in this group of patients. Whether careful treatment planning with the cautious escalation of doses, alternate fractionation schemes, or employment of concomitant adjuvant chemotherapy will improve on the local control rates achieved with radical radiation therapy remains to be seen. It is prudent to apply our efforts in this direction, however, since it is this group of early stage lung cancer patients, where disease may be truly localized, who would derive the greatest benefit from improvements in local control. Currently, it is apparent that surgical resection remains the treatment of choice for early stage non-small cell carcinoma of the lung. It is important, however, that we stress results such as those reported by Sandler et al. to our surgical, pulmonary and medical oncology colleagues which demonstrate that radical radiation therapy does provide an alternative for those patients unwilling or unable to undergo thoracotomy, and that such treatment does offer a realistic possibility of longterm survival.
REFERENCES Haffty, B. G.: Goldberg, N. B.; Gerstley, J.; Fischer, D. B.: Peschel, R. E. Results of radical radiation therapy in clinical Stage I, technically operable non-small cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 15:69-73; 1988. Hilton, G. Present position relative to cancer of the lung. results with radiotherapy alone. Thorax 15: 17- 18; 1960. Noordijk, E. M.; Poest Clement, E.: Hermans. J.; Wever, A. M. J.; Leer, J. W. H. Radiotherapy as an alternative to
surgery diother. 4. Smart. alone? 5. Zhang, Z. X.; therapy diother.
in elderly patients with resectable lung cancer. RaOncol. 13:83-89; 1988. J. Can lung cancer be cured by radiation therapy JAMA 195:158-161; 1966. H. X.: Yin, W. B.; Zhang, L. J.; Yang, Z. Y.; Zhang, Wang, M.; Chen, D. F.; Gu, X. Z. Curative radioof early operable non-small cell lung cancer. RaOncol. 14:89-94; 1989.