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Regarding “longer survival and higher doses of thoracic radiotherapy in patients with limited non-small lung cancer”
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Correspondence 3. Perez, C. A.; Hanks, G. E.; Leibel, S. A.; Zietman, A. L.; Fuks, Z.; Lee, W. R. Localized carcinoma of the prostate (Stage Ti , Tz, and Ts): Review of management with radiation therapy. Cancer 72:3 l563173; 1993. 4. Russell, K. J.; Dunatov, C.; Haferman, M. D.; Griffith, J. T.; Polissar, L.; Pelton, J.; Cole, S. B.; Taylor, E. W.; Wiens, L. W.; Koh, W. J.; Austin-Seymour, M. M.; Griffin, B. R.; Russell, A. H.; Laramore, G. E.; Griffin, T. W. Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. J. Urol. 146: lO46- 1052; 1991. 5. Stein, A.; DeKemion, J. B.; Smith, R. B.; Dorey, F.; Pate], H. Prostate specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer. J. Urol. 147: 942-946; 1992. 6. Zagars, G. K.; von Eschenbach, A. C. Prostate-specific antigen. An important marker for prostate cancer treated by external beam radiation therapy. Cancer 72:538-548; 1993. 7. Zietman, A. L.; Coen, J. J.; Shipley, W. U.; Authausen, A. F. Adjuvant irradiation after radical prostatectomy for prostate adenocarcinoma: An analysis of freedom from PSA failure. Urology 42: 292-298; 1993. 8. Zincke, H.; Blute, M. L.; Fallen, M. J.; Farrow, G. M. Radical prostatectomy for stage A adenocarcinoma of the prostate: Staging errors and their implications for treatment recommendations and disease outcome. J. Urol. 146:1053-1058; 1991.
REGARDING “LONGER SURVIVAL AND HIGHER DOSES OF THORACIC RADIOTHERAPY IN PATIENTS WITH LIMITED NON-SMALL LUNG CANCER” To the Editor: We are surprised that Ball and his. colleagues’ can be so confident in their conclusion that the longer survival in their group of patients with non-small cell lung cancer can largely be attributed to the higher dose of radiotherapy. They gloss over the “possible influence of tumor size and TNM staging (which were not recorded)” without any further discussion. They state that the patients who received 60 Gy were selected on the basis of tumor size (“primary tumor less than 6 cm in maximum diameter”), which implies that those who were treated with palliative doses almost certainly had disease that was more bulky. The radically treated group of patients were also intensively staged by bone scan, computed tomography (CT) of chest and upper abdomen and, for some histologies, CT brain scan. It is not clear whether the other patients were staged in this way, but it seems unlikely that they were. The group treated with lower radiation doses almost certainly included patients with more advanced local disease (probably including bulky nodal disease) and some with subclinical metastases. These factors might of themselves account for the observed survival differences, because it is well known from surgical series what important prognostic factors they are. It is also not clear how many of those given 60 Gy were inoperable because of tumor extent or because of age and intercurrent medical problems. These constitute two rather different groups which may have different outcomes. This report, therefore, does not offer credible evidence to justify the use of radical radiotherapy in inoperable nonsmall cell lung cancer, and until a proper, modem, randomized study is carried out, we will continue to be treating on the basis of hunch and tradition.
RESPONSE TO MACBETH AND GREGOR To the Editor: In their opening sentence, Macbeth and Gregor have paraphrased our conclusion in such a way that it no longer represents either what we wrote or the manner in which it was written. We cautiously concluded that our data “support the hypothesis that the increased survival . with higher dose radiotherapy is not due purely to patient selection” and that based on our results “we see no reason to change our policy of offering high dose thoracic irradiation to selected patients with inoperable NSCLC confined to the primary site and mediastinum.” While we accept that the patients treated with lower radiation doses may have had more advanced local disease than those treated with higher radiation doses, some of the influence of a difference in stage of disease would have been accounted for already in the multivariate analyses adjusting for performance status and weight loss. Even though there were considerable differences in the distribution of these two factors in the patients treated with 60 Gy and those treated with 20 Gy, the relative death rate for these two groups of patients only changed from a value of 0.44 (95% confidence interval (CI): 0.37-0.52, p < 0.0001) in the univariate analysis to 0.53 (CI: 0.44-0.65, p < 0.0001) after adjusting for these two major prognostic factors. It is difficult to believe that further adjustment by inclusion of stage would have altered the relative death rate to the extent that it was no longer significant (upper limit of the confidence interval greater than I). Your correspondents also attribute prognostic significance to the intensity of staging, implying that more vigorous investigation in the lower dose groups may have produced a sufficiently large stage shift to alter our results by excluding patients with subclinical metastases. We are unable to say what percentage of our patients who had no symptoms or signs of metastatic disease might have had a positive result on multiorgan scanning, but in a study of patients being worked up for sutgical resection it was only 3% (I). In his book “Intellectuals,” Paul Johnson alleges that there is no evidence that Karl Marx ever set foot inside a factory; this did not however deter Marx from telling the world how it should be changed to change the lot of the working classes. We on the other hand have been inside the factory; we have carefully documented and analyzed our observations and prefer to use the best information from our own practice as the basis for the future management of our patients rather than leaving them to the fate of “hunch and tradition.” DAVID BALL, FRACR Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia JANE MATTHEWS,PH.D. Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia VALENTINAWOROTNIUK B. Appl. SC. Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia ELIZABETHCRENNAN,FRACR Royal Prince Alfred Hospital Camperdown
1. Grant, D.; Edwards, D.; Goldstraw, P. Computed tomography of the brain, chest and abdomen in the preoperative assessment of non-small cell lung cancer. Thorax 43:883-886; 1988.
FERGUS MACBETH
Beatson Oncology Centre Western Infirmary Glasgow ANNA GREGOR
Western General Hospital Edinburgh 1. Ball, D.; Matthews, J.; Worotniuk, V.; Crennan, E. Longer survival and higher doses of thoracic radiotherapy in patients with limited non-small lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 25:599604; 1993.
G-CSF TREATMENT OF LEUCOPENIA DURING FRACTIONATED RADIOTHERAPY To the Editor: Recently Mac Manus et al. reported on the use of recombinant granulocyte-colony stimulating factor (G-CSF) to treat neutropenia in four consecutive patients receiving craniospinal irradiation (3). In our institution, we have used G-CSF injections to treat neutropenia in patients undergoing fractionated radiotherapy ( 1, 5). Eligibility criteria including white blood cell counts (WBC) less than 2OOO/pLand platelet
Correspondence 3. Perez, C. A.; Hanks, G. E.; Leibel, S. A.; Zietman, A. L.; Fuks, Z.; Lee, W. R. Localized carcinoma of the prostate (Stage Ti , Tz, and Ts): Review of management with radiation therapy. Cancer 72:3 l563173; 1993. 4. Russell, K. J.; Dunatov, C.; Haferman, M. D.; Griffith, J. T.; Polissar, L.; Pelton, J.; Cole, S. B.; Taylor, E. W.; Wiens, L. W.; Koh, W. J.; Austin-Seymour, M. M.; Griffin, B. R.; Russell, A. H.; Laramore, G. E.; Griffin, T. W. Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. J. Urol. 146: lO46- 1052; 1991. 5. Stein, A.; DeKemion, J. B.; Smith, R. B.; Dorey, F.; Pate], H. Prostate specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer. J. Urol. 147: 942-946; 1992. 6. Zagars, G. K.; von Eschenbach, A. C. Prostate-specific antigen. An important marker for prostate cancer treated by external beam radiation therapy. Cancer 72:538-548; 1993. 7. Zietman, A. L.; Coen, J. J.; Shipley, W. U.; Authausen, A. F. Adjuvant irradiation after radical prostatectomy for prostate adenocarcinoma: An analysis of freedom from PSA failure. Urology 42: 292-298; 1993. 8. Zincke, H.; Blute, M. L.; Fallen, M. J.; Farrow, G. M. Radical prostatectomy for stage A adenocarcinoma of the prostate: Staging errors and their implications for treatment recommendations and disease outcome. J. Urol. 146:1053-1058; 1991.
REGARDING “LONGER SURVIVAL AND HIGHER DOSES OF THORACIC RADIOTHERAPY IN PATIENTS WITH LIMITED NON-SMALL LUNG CANCER” To the Editor: We are surprised that Ball and his. colleagues’ can be so confident in their conclusion that the longer survival in their group of patients with non-small cell lung cancer can largely be attributed to the higher dose of radiotherapy. They gloss over the “possible influence of tumor size and TNM staging (which were not recorded)” without any further discussion. They state that the patients who received 60 Gy were selected on the basis of tumor size (“primary tumor less than 6 cm in maximum diameter”), which implies that those who were treated with palliative doses almost certainly had disease that was more bulky. The radically treated group of patients were also intensively staged by bone scan, computed tomography (CT) of chest and upper abdomen and, for some histologies, CT brain scan. It is not clear whether the other patients were staged in this way, but it seems unlikely that they were. The group treated with lower radiation doses almost certainly included patients with more advanced local disease (probably including bulky nodal disease) and some with subclinical metastases. These factors might of themselves account for the observed survival differences, because it is well known from surgical series what important prognostic factors they are. It is also not clear how many of those given 60 Gy were inoperable because of tumor extent or because of age and intercurrent medical problems. These constitute two rather different groups which may have different outcomes. This report, therefore, does not offer credible evidence to justify the use of radical radiotherapy in inoperable nonsmall cell lung cancer, and until a proper, modem, randomized study is carried out, we will continue to be treating on the basis of hunch and tradition.
RESPONSE TO MACBETH AND GREGOR To the Editor: In their opening sentence, Macbeth and Gregor have paraphrased our conclusion in such a way that it no longer represents either what we wrote or the manner in which it was written. We cautiously concluded that our data “support the hypothesis that the increased survival . with higher dose radiotherapy is not due purely to patient selection” and that based on our results “we see no reason to change our policy of offering high dose thoracic irradiation to selected patients with inoperable NSCLC confined to the primary site and mediastinum.” While we accept that the patients treated with lower radiation doses may have had more advanced local disease than those treated with higher radiation doses, some of the influence of a difference in stage of disease would have been accounted for already in the multivariate analyses adjusting for performance status and weight loss. Even though there were considerable differences in the distribution of these two factors in the patients treated with 60 Gy and those treated with 20 Gy, the relative death rate for these two groups of patients only changed from a value of 0.44 (95% confidence interval (CI): 0.37-0.52, p < 0.0001) in the univariate analysis to 0.53 (CI: 0.44-0.65, p < 0.0001) after adjusting for these two major prognostic factors. It is difficult to believe that further adjustment by inclusion of stage would have altered the relative death rate to the extent that it was no longer significant (upper limit of the confidence interval greater than I). Your correspondents also attribute prognostic significance to the intensity of staging, implying that more vigorous investigation in the lower dose groups may have produced a sufficiently large stage shift to alter our results by excluding patients with subclinical metastases. We are unable to say what percentage of our patients who had no symptoms or signs of metastatic disease might have had a positive result on multiorgan scanning, but in a study of patients being worked up for sutgical resection it was only 3% (I). In his book “Intellectuals,” Paul Johnson alleges that there is no evidence that Karl Marx ever set foot inside a factory; this did not however deter Marx from telling the world how it should be changed to change the lot of the working classes. We on the other hand have been inside the factory; we have carefully documented and analyzed our observations and prefer to use the best information from our own practice as the basis for the future management of our patients rather than leaving them to the fate of “hunch and tradition.” DAVID BALL, FRACR Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia JANE MATTHEWS,PH.D. Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia VALENTINAWOROTNIUK B. Appl. SC. Peter MacCallum Cancer Institute Melbourne Victoria 3000, Australia ELIZABETHCRENNAN,FRACR Royal Prince Alfred Hospital Camperdown
1. Grant, D.; Edwards, D.; Goldstraw, P. Computed tomography of the brain, chest and abdomen in the preoperative assessment of non-small cell lung cancer. Thorax 43:883-886; 1988.
FERGUS MACBETH
Beatson Oncology Centre Western Infirmary Glasgow ANNA GREGOR
Western General Hospital Edinburgh 1. Ball, D.; Matthews, J.; Worotniuk, V.; Crennan, E. Longer survival and higher doses of thoracic radiotherapy in patients with limited non-small lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 25:599604; 1993.
G-CSF TREATMENT OF LEUCOPENIA DURING FRACTIONATED RADIOTHERAPY To the Editor: Recently Mac Manus et al. reported on the use of recombinant granulocyte-colony stimulating factor (G-CSF) to treat neutropenia in four consecutive patients receiving craniospinal irradiation (3). In our institution, we have used G-CSF injections to treat neutropenia in patients undergoing fractionated radiotherapy ( 1, 5). Eligibility criteria including white blood cell counts (WBC) less than 2OOO/pLand platelet