- Email: [email protected]
Response to editorial by Harari and Fowler
216
1. J. Radiation Oncology 0 Biology 0 Physics
1. Allal, A.; Kurtz, J.; Pipard, G.; Marti, M. C.; Mirabeil, R.; Popowski, Y.; Egeli, R. Chemotherapy versus radiotherapy alone for anal cancer: A retrospective comparison. Int. J. Radiat. Oncol. Biol. Phys.. 27: 59-66; 1993. 2. Brunet, R.; Becouarn, V.; Pigneux, J.; Ravaud, A.: Faivre, J.: Jeandroz, V. Cisplatine et Fluorouracile en chimiothtrapie neoadjuvante des carcinomes Cpidermdides du canal anal. Lyon Chir. 87:77-78; 1991. 3. Cummings, B. J.; Keane. T. J.: O’Sullivan, B.: Wong. C. S.; Catton. C. N. Epidermoid anal cancer: Treatment by radiation alone or by radiation and 5 Fluorouracil with and without mitomycin c. Int. J. Radiat. Oncol. Biol. Phys. 21:115-l 125; 1991. 4. Flam. M. S.: John. M. J.: Peter. T.: Hoffman. J. Radiation and 5 FU vs radiation 5 FU-MMC in’the’ treatment of anal canal carcinoma. Preliminary results of a phase III randomized RTOG/ECOG trial. Proceeding ASCO, 12(no. 557) 192; 1993. 5. Gerard, J. P.; Romestaing, P.; Mahe, M. A.: Salerno, N. Cancer du canal anal: Role de I’association 5 FU-cisplatinum Lyon Chir. 87: 74-76; 1991. 6. Morgan, D.; Meadows, H. On behalf of the UKCCR anal cancer trial working party. UKCCR anal cancer trial. Bull. Cancer Radioth. 80:399; 1993. Papillon, J.; Montbarbon, J. F. Epidermoid carcinoma of the anal canal. A series of 276 cases. Dis. Colon Rectum. 30:324-333: 1987. Rich, T. A.; Ajani, J. A.; Morrison, W. H.; Ota, D.; Levitt, B. Chemoradiation therapy for anal cancer: Radiation plus continuous infusion of 5 Fluorouracil with or without cisplatin. Radiother. Oncol. 27:209-2 15; 1993. Schlienger, M.; Krzisch, C.: Pene, F.; Marin, J. L.; Gindrey, V. B., Mauban, S.; Barthelemy, N.; Habrand, J. L.; Socie, G.; Part, R.; Gallot, D.: Malafosse. M.; Laugier. A. Epidermoid carcinoma of the anal canal. Treatment results and prognostic variables in a series of 242 cases. Int. J. Radiat. Oncol. Biol. Phys., 17:1141-1151; 1989.
RESPONSE
TO EDITORIAL
BY HARARI AND FOWLER
To the Editor: Local and regional control of disease remains a significant problem in many patients with advanced head and neck cancers. The scientific analysis of time-dose relationships for radiotherapy alone in the treatment of head and neck cancer has provided insight into the disease process. Time-dose relationships for local control of head and neck cancer is becoming well defined for those patients receiving radiotherapy alone. In general, the shorter the overall treatment time, the better the chance of local disease control. Based on the poor local control in advanced disease with conventional fractionation schemes and timedose analysis, some investigators have elected to pursue altered fractionation schemes with twice daily (b.i.d.) or three times daily (t.i.d.) radiation therapy in an effort to improve control and outcome. Other investigators have chosen to study the addition of chemotherapy, either in a neoadjuvant or concomitant setting, to achieve better results. Altered fractionation schemes and the addition of concomitant chemotherapy are attempts to increase the dose-intensity of treatment. Both have potential advantages and disadvantages. While time-dose relationships for radiation therapy alone are better understood in the treatment of head and neck cancer, there has been no detailed investigation of time-dose relationships for concomitant chemoradiotherapy. Our report is the first attempt to quantitate this complex issue and illustrate the fact that current time-dose relationships do not apply to concomitant chemotherapy and radiation. Our results also show that chemotherapy given concomitantly with radiation can at least compensate for planned treatment breaks in radiation treatment. In a recently published study with the participation of several centers. 2 15 patients with locally advanced head and neck cancer were randomized to either concomitant radiation and chemotherapy consisting of 5-fluorouracil and cisplatin given on an alternate week schedule (i.e., 1 week of treatment with both modalities alternating with I week of break), or neoadjuvant chemotherapy with the same drugs for three cycles followed by 70 Gy of radiation given once daily (1). The locoregional failure rate in the concomitant group was less than that in the sequential group (39% vs. 55%, respectively). Overall survival was similar between the treatment arms. but significantly more patients in the sequential group died oftheir
Volume 29. Number 1, 1994 cancer than those in the concomitant group. This study provides further support that chemotherapy can compensate for prolongation of treatment duration when given concomitantly with radiation. In a detailed analysis of survival, the institution where the patient received treatment was a significant prognostic variable on disease-free survival. Patients treated in institutions with more experience in concomitant chemoradiotherapy had better outcome than those treated in institutions with less experience. This observation suggests that experience with this intensive regimen may be important for optimal results. We agree to the comment by Harari and Fowler that the optimal drugs, schedules, and fractionation methods for combined chemoradiotherapy in head and neck cancers remain to be determined. However, we also believe that the same vigorous analysis of time-dose relationships should be used for concomitant chemoradiotherapy as well as radiation alone. Until we have more convincing evidence that combined chemoradiotherapy is a superior treatment than radiation alone, we feel that these regimens should be given in a research setting in centers that have experience with these regimens and can provide the intensive support for these patients. WILLIAM W. WONG,
M.D. Mayo Clinic Scottsdale, Scottsdale, AZ 85259 DANIEL J. HARAF, M.D. RALPH R. WEICHSELBAUM,M.D. ROSEMARIEMICK, M.S. EVERETTE. VOKES, M.D.
University of Chicago, Chicago, IL 60637 Taylor IV. S. G.: Murthy, A. K.; Vannetzel, J.-M. et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J. Clin. Oncol. 12:383-395; 1994.
EQUATION
FOR CALCULATING OVERALL TREATMENT TIME IN RADIOTHERAPY
To fhe Editor: In calculating various treatment schedules using the linear-quadratic formula one must determine the overall treatment time in days. Until recently I have used a calendar to count the days or a chart which had various total days depending on the number of treatment days and day of the week treatment was started. Here is an equation available to almost anyone with a computer which will do this calculation quite nicely. Such an equation will be convenient, perhaps even necessary, for certain computer manipulations to optimize new schedules.
Total time = (INT [(A + C + F - 2)/B])*(7 - B) + (A + F - I) + (D - l):(E/24). Total time = The total number of days it takes to complete treatment. It includes the total number of treatment days, weekend days, and any break days. It also depends on what day of the week treatment is started and if more than one treatment is given per day. A = Number of treatment days. For example, 30 fractions given once a day would be equal to 30 treatment days. Thirty fractions given twice a day would be equal to 15 treatment days. B = Number of treatment days per week. C = Day treatment is started (i.e., Monday = 1, Tuesday = 2, Wednesday = 3 and so forth). D = Number of treatments per day. E = Time between multiple treatments per day in hours. F = Number of break days. Break days are treatment days in which no treatment was given. Weekend days do not count as break days. For example, if a person was on a 5 day per week treatment schedule and they took a Friday, Saturday, Sunday, and Monday off then that would only count as 2 break days because Saturday and Sunday are weekend days. INT: This function takes the integer of a number (i.e., 2.9 becomes 2. 3.2 becomes 3). Example: A patient is treated with 60 fractions given twice a day (30 treatment days). They are treated 5 days a week and begin treatment on Monday. There are 6 hours between fractions and the patients completes treatment without any break days.
1. J. Radiation Oncology 0 Biology 0 Physics
1. Allal, A.; Kurtz, J.; Pipard, G.; Marti, M. C.; Mirabeil, R.; Popowski, Y.; Egeli, R. Chemotherapy versus radiotherapy alone for anal cancer: A retrospective comparison. Int. J. Radiat. Oncol. Biol. Phys.. 27: 59-66; 1993. 2. Brunet, R.; Becouarn, V.; Pigneux, J.; Ravaud, A.: Faivre, J.: Jeandroz, V. Cisplatine et Fluorouracile en chimiothtrapie neoadjuvante des carcinomes Cpidermdides du canal anal. Lyon Chir. 87:77-78; 1991. 3. Cummings, B. J.; Keane. T. J.: O’Sullivan, B.: Wong. C. S.; Catton. C. N. Epidermoid anal cancer: Treatment by radiation alone or by radiation and 5 Fluorouracil with and without mitomycin c. Int. J. Radiat. Oncol. Biol. Phys. 21:115-l 125; 1991. 4. Flam. M. S.: John. M. J.: Peter. T.: Hoffman. J. Radiation and 5 FU vs radiation 5 FU-MMC in’the’ treatment of anal canal carcinoma. Preliminary results of a phase III randomized RTOG/ECOG trial. Proceeding ASCO, 12(no. 557) 192; 1993. 5. Gerard, J. P.; Romestaing, P.; Mahe, M. A.: Salerno, N. Cancer du canal anal: Role de I’association 5 FU-cisplatinum Lyon Chir. 87: 74-76; 1991. 6. Morgan, D.; Meadows, H. On behalf of the UKCCR anal cancer trial working party. UKCCR anal cancer trial. Bull. Cancer Radioth. 80:399; 1993. Papillon, J.; Montbarbon, J. F. Epidermoid carcinoma of the anal canal. A series of 276 cases. Dis. Colon Rectum. 30:324-333: 1987. Rich, T. A.; Ajani, J. A.; Morrison, W. H.; Ota, D.; Levitt, B. Chemoradiation therapy for anal cancer: Radiation plus continuous infusion of 5 Fluorouracil with or without cisplatin. Radiother. Oncol. 27:209-2 15; 1993. Schlienger, M.; Krzisch, C.: Pene, F.; Marin, J. L.; Gindrey, V. B., Mauban, S.; Barthelemy, N.; Habrand, J. L.; Socie, G.; Part, R.; Gallot, D.: Malafosse. M.; Laugier. A. Epidermoid carcinoma of the anal canal. Treatment results and prognostic variables in a series of 242 cases. Int. J. Radiat. Oncol. Biol. Phys., 17:1141-1151; 1989.
RESPONSE
TO EDITORIAL
BY HARARI AND FOWLER
To the Editor: Local and regional control of disease remains a significant problem in many patients with advanced head and neck cancers. The scientific analysis of time-dose relationships for radiotherapy alone in the treatment of head and neck cancer has provided insight into the disease process. Time-dose relationships for local control of head and neck cancer is becoming well defined for those patients receiving radiotherapy alone. In general, the shorter the overall treatment time, the better the chance of local disease control. Based on the poor local control in advanced disease with conventional fractionation schemes and timedose analysis, some investigators have elected to pursue altered fractionation schemes with twice daily (b.i.d.) or three times daily (t.i.d.) radiation therapy in an effort to improve control and outcome. Other investigators have chosen to study the addition of chemotherapy, either in a neoadjuvant or concomitant setting, to achieve better results. Altered fractionation schemes and the addition of concomitant chemotherapy are attempts to increase the dose-intensity of treatment. Both have potential advantages and disadvantages. While time-dose relationships for radiation therapy alone are better understood in the treatment of head and neck cancer, there has been no detailed investigation of time-dose relationships for concomitant chemoradiotherapy. Our report is the first attempt to quantitate this complex issue and illustrate the fact that current time-dose relationships do not apply to concomitant chemotherapy and radiation. Our results also show that chemotherapy given concomitantly with radiation can at least compensate for planned treatment breaks in radiation treatment. In a recently published study with the participation of several centers. 2 15 patients with locally advanced head and neck cancer were randomized to either concomitant radiation and chemotherapy consisting of 5-fluorouracil and cisplatin given on an alternate week schedule (i.e., 1 week of treatment with both modalities alternating with I week of break), or neoadjuvant chemotherapy with the same drugs for three cycles followed by 70 Gy of radiation given once daily (1). The locoregional failure rate in the concomitant group was less than that in the sequential group (39% vs. 55%, respectively). Overall survival was similar between the treatment arms. but significantly more patients in the sequential group died oftheir
Volume 29. Number 1, 1994 cancer than those in the concomitant group. This study provides further support that chemotherapy can compensate for prolongation of treatment duration when given concomitantly with radiation. In a detailed analysis of survival, the institution where the patient received treatment was a significant prognostic variable on disease-free survival. Patients treated in institutions with more experience in concomitant chemoradiotherapy had better outcome than those treated in institutions with less experience. This observation suggests that experience with this intensive regimen may be important for optimal results. We agree to the comment by Harari and Fowler that the optimal drugs, schedules, and fractionation methods for combined chemoradiotherapy in head and neck cancers remain to be determined. However, we also believe that the same vigorous analysis of time-dose relationships should be used for concomitant chemoradiotherapy as well as radiation alone. Until we have more convincing evidence that combined chemoradiotherapy is a superior treatment than radiation alone, we feel that these regimens should be given in a research setting in centers that have experience with these regimens and can provide the intensive support for these patients. WILLIAM W. WONG,
M.D. Mayo Clinic Scottsdale, Scottsdale, AZ 85259 DANIEL J. HARAF, M.D. RALPH R. WEICHSELBAUM,M.D. ROSEMARIEMICK, M.S. EVERETTE. VOKES, M.D.
University of Chicago, Chicago, IL 60637 Taylor IV. S. G.: Murthy, A. K.; Vannetzel, J.-M. et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J. Clin. Oncol. 12:383-395; 1994.
EQUATION
FOR CALCULATING OVERALL TREATMENT TIME IN RADIOTHERAPY
To fhe Editor: In calculating various treatment schedules using the linear-quadratic formula one must determine the overall treatment time in days. Until recently I have used a calendar to count the days or a chart which had various total days depending on the number of treatment days and day of the week treatment was started. Here is an equation available to almost anyone with a computer which will do this calculation quite nicely. Such an equation will be convenient, perhaps even necessary, for certain computer manipulations to optimize new schedules.
Total time = (INT [(A + C + F - 2)/B])*(7 - B) + (A + F - I) + (D - l):(E/24). Total time = The total number of days it takes to complete treatment. It includes the total number of treatment days, weekend days, and any break days. It also depends on what day of the week treatment is started and if more than one treatment is given per day. A = Number of treatment days. For example, 30 fractions given once a day would be equal to 30 treatment days. Thirty fractions given twice a day would be equal to 15 treatment days. B = Number of treatment days per week. C = Day treatment is started (i.e., Monday = 1, Tuesday = 2, Wednesday = 3 and so forth). D = Number of treatments per day. E = Time between multiple treatments per day in hours. F = Number of break days. Break days are treatment days in which no treatment was given. Weekend days do not count as break days. For example, if a person was on a 5 day per week treatment schedule and they took a Friday, Saturday, Sunday, and Monday off then that would only count as 2 break days because Saturday and Sunday are weekend days. INT: This function takes the integer of a number (i.e., 2.9 becomes 2. 3.2 becomes 3). Example: A patient is treated with 60 fractions given twice a day (30 treatment days). They are treated 5 days a week and begin treatment on Monday. There are 6 hours between fractions and the patients completes treatment without any break days.