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To plan or not to plan? That is the question
Brachytherapy 5 (2006) 216e217
Editorial
To plan or not to plan? That is the question In this issue of Brachytherapy, Symon et al. investigate the relative benefits of individual fraction optimization (IFO) versus first fraction optimization (FFO) in the application of vaginal cuff high-dose-rate (HDR) brachytherapy (1). IFO refers to the planning and optimization of each brachytherapy implant as compared to applying the first planning and optimization to subsequent fractions without replanning (FFO). I applaud the authors’ attempt to investigate optimal techniques to deliver vaginal cuff brachytherapy in endometrial cancer. Endometrial cancer is the most common gynecologic malignancy, with an estimated 41,200 cases in the United States in 2006 (2). Traditional therapy for early endometrial cancer includes hysterectomy, lymph node staging and, in selected cases, adjuvant external beam radiotherapy. Recent randomized trials of pelvic radiotherapy versus observation after hysterectomy note the dominant pattern of recurrence in observed patients to be vaginal, suggesting a role for vaginal brachytherapy alone as adjuvant therapy for endometrial cancer (3, 4). Recent institutional trials of vaginal cuff brachytherapy alone after hysterectomy have noted excellent local control rates with minimal toxicity (5e7). A recent survey performed by the American Brachytherapy Society (ABS) confirms that among American radiation oncologists there is an increasing trend toward recommending vaginal brachytherapy alone as an adjuvant therapy in endometrial cancer (8). The ABS survey also notes that the majority of radiation oncologists deliver HDR brachytherapy, as opposed to lowdose-rate (LDR) brachytherapy, with the most common fractionation pattern being 7 Gy prescribed to 0.5 cm from the vaginal surface. Greater than 90% of respondents use a single channel vaginal cylinder to deliver HDR vaginal cuff brachytherapy. The use of IFO versus FFO was not reported in the survey, but it can be assumed that many practitioners performed only FFO given that nearly 20% of respondents did not obtain localization films for each brachytherapy application. Most of the respondents (80%), although not all, calculate bladder and rectal doses. Symon et al. use a multichannel applicator and perform a comparison of the doses to the bladder and rectum with and without IFO. The results note no statistically significant difference in mean and maximum bladder and rectal doses between IFO and FFO. However, for FFO, maximum bladder or rectal doses were exceeded by 20% in O50% of patients. In addition, there was a significant correlation between treated volume optimization and mean bladder
and rectal doses for IFO, which was lost when FFO was applied implying fluctuating interfractional position of critical organs. The authors also noted that similar applicator spatial angle reduced critical organ dose variability. There is probably little applicability of these outcomes to patients treated with a single channel vaginal cylinder. It seems that the authors’ technique is to place the applicator in a comfortable position and then proceed with treatment planning. There seems to be no attempt in the second or subsequent applications to reproduce the first fraction position. The authors note that patient discomfort is increased by immobilizing the cylinder to the couch to improve reproducibility of the applicator position. As shown in Figure 1, there seems to be a significant difference in the position of the cylinder between applications. With a multichannel applicator and significant variation of cylinder position, repeat planning would make logical sense to reduce dose to critical structures. As we noted in the ABS survey, the mass majority or radiation oncologists in the United States use a single channel vaginal cylinder to deliver vaginal brachytherapy. Given the symmetric dose distribution of a line source, there would seem to be little room for dose optimization to improve the dose to critical structures, yet still deliver the planned prescribed dose. In our technique, we introduce a Foley catheter and rectal contrast during the first application of vaginal brachytherapy. The largest diameter cylinder that can be placed comfortably is generally positioned horizontally and for vaginal brachytherapy alone, without external beam radiotherapy, 700 cGy is prescribed to 0.5 cm from the surface of the cylinder for three fractions. The length of the vagina treated is altered based, in part, on the stage, histology, grade, cervical or lower uterine segment involvement, and length of the vagina. In general, we treat the upper 3e5 cm of the vagina. Longer regions of the vagina are treated for patients deemed to have a higher risk of suburethral recurrence and for patients with longer vaginas. With the first application, multiple dose points are calculated including vaginal mucosal dose, dose to the bladder and multiple rectal dose points. The rectal doses are calculated with the use of rectal barium with the attempt to also obtain a sigmoid colon dose. These doses are converted to LDR equivalent doses using the alpha/beta ratio as described by Nag and Gupta (9). If the LDR equivalent dose exceeds 75 Gy to the bladder or 70 Gy to the rectum, the implant is altered. The first alteration is an attempt to reposition the
1538-4721/06/$ e see front matter Ó 2006 American Brachytherapy Society. All rights reserved. doi:10.1016/j.brachy.2006.08.002
Editorial / Brachytherapy 5 (2006) 216e217
implant to reduce the dose to the organ that seems to be receiving excessive radiotherapy. In our experience, this is always the rectum or sigmoid colon. If repositioning of the implant fails to improve the calculated doses, the fractionation is changed to increase the number of fractions and reduce the dose/fraction. Finally, if the doses continue to be significantly above tolerance, we may not proceed with radiotherapy. In our first 66 patients treated in this manner, including patients treated with a vaginal cuff boost, 9% underwent treatment alteration including one patient who did not receive therapy related to the close proximity of the sigmoid colon (10). The implant is secured to the treatment table and the patient is not moved from the time of treatment planning to actual delivery of the radiotherapy with the help of an integrated brachytherapy unit. Symon et al. note that rigid immobilization of the multichannel Wright applicator to the couch increases patient discomfort and pain. In fact, the authors routinely deliver muscle relaxants and mild analgesia. We have not found this to be the case. In fact, in approximately 500 fractions of vaginal cuff brachytherapy over the last 5 years, we have never used any medication and have never not proceeded with therapy because of discomfort. Most patients tolerate the implant extremely well. In our technique, treatment planning is not accomplished for the second or subsequent fractions of brachytherapy. Under fluoroscopic guidance, the applicator is placed in a position identical to that in the first application and the same treatment plan is used with appropriate decay constants recalculated. It is presumed with this technique that the doses to critical structures, bladder and rectum, are unchanged between radiotherapy fractions. Symon et al. do note that similar, !10 , differences in angle between fractions result in reduced differences in doses supporting this technique. Currently, in patients whom we have recommended and treated with vaginal cuff brachytherapy alone with the use of the described technique, there has been no local recurrence and no significant bladder or rectal complications. The use of this technique allows us to place a Foley catheter and rectal contrast with only the first fraction of radiotherapy reducing patient discomfort and potential for a urinary tract infection. In addition, because no planning is achieved for subsequent implants, the procedure is completed relatively quickly, also improving patient tolerance and the costs of the therapy are reduced.
217
In conclusion, I applaud the attempts of Symon et al. to study vaginal cuff brachytherapy. Vaginal brachytherapy is a commonly prescribed treatment with a relative paucity of technical data. With the authors’ techniques, IFO planning does seem to reduce dose to nearby critical normal structures. The need for IFO for single channel vaginal cylinders is yet to be determined. William Small, Jr., MD Department of Radiation Oncology Robert H. Lurie Comprehensive Cancer Center of Northwestern University Chicago, IL
References [1] Symon Z, Menhal J, Alezra D, et al. Individual fraction optimization for multi-channel applicator vaginal brachytherapy. Brachytherapy 2006;5:211e215. [2] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106e130. [3] Creutzberg C, van Putten WLJ, Kooper PCM, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage I endometrial carcinoma: Multicentre randomized trial. Lancet 2000; 355:1404e1411. [4] Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744e751. [5] Small W Jr, Zeytinoglu M, Keh R, et al. Endometrial adenocarcinoma invasive to <½ the myometrial thickness: Analysis of prognostic variables for recurrence and survival. Int J Radiat Oncol Biol Phys 2001;51(3, Suppl.):35e36. [6] Anderson JM, Stea B, Hallum AV, et al. High dose rate postoperative vaginal cuff irradiation alone for stage IB and IC endometrial cancer. Int J Radiat Oncol Biol Phys 2000;46:417e425. [7] Chadha M, Nanavati PJ, Liu P, et al. Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 1999;75:103e107. [8] Small W Jr, Erickson B, Kwakwa F. An American Brachytherapy Society survey regarding the practice patterns of post-operative irradiation for endometrial cancer. Int J Radiol Oncol Biol Phys 2005;63:1502e1507. [9] Nag S, Gupta N. A simple method of obtaining equivalent doses for use in HDR brachytherapy. Int J Radiat Oncol Biol Phys 2000;46: 507e513. [10] Small W Jr, Marshall I, Lurain J, et al. Does pretreatment calculation of bladder and rectal doses in HDR vaginal radiation alter therapy? Brachytherapy 2003;2:41.
Editorial
To plan or not to plan? That is the question In this issue of Brachytherapy, Symon et al. investigate the relative benefits of individual fraction optimization (IFO) versus first fraction optimization (FFO) in the application of vaginal cuff high-dose-rate (HDR) brachytherapy (1). IFO refers to the planning and optimization of each brachytherapy implant as compared to applying the first planning and optimization to subsequent fractions without replanning (FFO). I applaud the authors’ attempt to investigate optimal techniques to deliver vaginal cuff brachytherapy in endometrial cancer. Endometrial cancer is the most common gynecologic malignancy, with an estimated 41,200 cases in the United States in 2006 (2). Traditional therapy for early endometrial cancer includes hysterectomy, lymph node staging and, in selected cases, adjuvant external beam radiotherapy. Recent randomized trials of pelvic radiotherapy versus observation after hysterectomy note the dominant pattern of recurrence in observed patients to be vaginal, suggesting a role for vaginal brachytherapy alone as adjuvant therapy for endometrial cancer (3, 4). Recent institutional trials of vaginal cuff brachytherapy alone after hysterectomy have noted excellent local control rates with minimal toxicity (5e7). A recent survey performed by the American Brachytherapy Society (ABS) confirms that among American radiation oncologists there is an increasing trend toward recommending vaginal brachytherapy alone as an adjuvant therapy in endometrial cancer (8). The ABS survey also notes that the majority of radiation oncologists deliver HDR brachytherapy, as opposed to lowdose-rate (LDR) brachytherapy, with the most common fractionation pattern being 7 Gy prescribed to 0.5 cm from the vaginal surface. Greater than 90% of respondents use a single channel vaginal cylinder to deliver HDR vaginal cuff brachytherapy. The use of IFO versus FFO was not reported in the survey, but it can be assumed that many practitioners performed only FFO given that nearly 20% of respondents did not obtain localization films for each brachytherapy application. Most of the respondents (80%), although not all, calculate bladder and rectal doses. Symon et al. use a multichannel applicator and perform a comparison of the doses to the bladder and rectum with and without IFO. The results note no statistically significant difference in mean and maximum bladder and rectal doses between IFO and FFO. However, for FFO, maximum bladder or rectal doses were exceeded by 20% in O50% of patients. In addition, there was a significant correlation between treated volume optimization and mean bladder
and rectal doses for IFO, which was lost when FFO was applied implying fluctuating interfractional position of critical organs. The authors also noted that similar applicator spatial angle reduced critical organ dose variability. There is probably little applicability of these outcomes to patients treated with a single channel vaginal cylinder. It seems that the authors’ technique is to place the applicator in a comfortable position and then proceed with treatment planning. There seems to be no attempt in the second or subsequent applications to reproduce the first fraction position. The authors note that patient discomfort is increased by immobilizing the cylinder to the couch to improve reproducibility of the applicator position. As shown in Figure 1, there seems to be a significant difference in the position of the cylinder between applications. With a multichannel applicator and significant variation of cylinder position, repeat planning would make logical sense to reduce dose to critical structures. As we noted in the ABS survey, the mass majority or radiation oncologists in the United States use a single channel vaginal cylinder to deliver vaginal brachytherapy. Given the symmetric dose distribution of a line source, there would seem to be little room for dose optimization to improve the dose to critical structures, yet still deliver the planned prescribed dose. In our technique, we introduce a Foley catheter and rectal contrast during the first application of vaginal brachytherapy. The largest diameter cylinder that can be placed comfortably is generally positioned horizontally and for vaginal brachytherapy alone, without external beam radiotherapy, 700 cGy is prescribed to 0.5 cm from the surface of the cylinder for three fractions. The length of the vagina treated is altered based, in part, on the stage, histology, grade, cervical or lower uterine segment involvement, and length of the vagina. In general, we treat the upper 3e5 cm of the vagina. Longer regions of the vagina are treated for patients deemed to have a higher risk of suburethral recurrence and for patients with longer vaginas. With the first application, multiple dose points are calculated including vaginal mucosal dose, dose to the bladder and multiple rectal dose points. The rectal doses are calculated with the use of rectal barium with the attempt to also obtain a sigmoid colon dose. These doses are converted to LDR equivalent doses using the alpha/beta ratio as described by Nag and Gupta (9). If the LDR equivalent dose exceeds 75 Gy to the bladder or 70 Gy to the rectum, the implant is altered. The first alteration is an attempt to reposition the
1538-4721/06/$ e see front matter Ó 2006 American Brachytherapy Society. All rights reserved. doi:10.1016/j.brachy.2006.08.002
Editorial / Brachytherapy 5 (2006) 216e217
implant to reduce the dose to the organ that seems to be receiving excessive radiotherapy. In our experience, this is always the rectum or sigmoid colon. If repositioning of the implant fails to improve the calculated doses, the fractionation is changed to increase the number of fractions and reduce the dose/fraction. Finally, if the doses continue to be significantly above tolerance, we may not proceed with radiotherapy. In our first 66 patients treated in this manner, including patients treated with a vaginal cuff boost, 9% underwent treatment alteration including one patient who did not receive therapy related to the close proximity of the sigmoid colon (10). The implant is secured to the treatment table and the patient is not moved from the time of treatment planning to actual delivery of the radiotherapy with the help of an integrated brachytherapy unit. Symon et al. note that rigid immobilization of the multichannel Wright applicator to the couch increases patient discomfort and pain. In fact, the authors routinely deliver muscle relaxants and mild analgesia. We have not found this to be the case. In fact, in approximately 500 fractions of vaginal cuff brachytherapy over the last 5 years, we have never used any medication and have never not proceeded with therapy because of discomfort. Most patients tolerate the implant extremely well. In our technique, treatment planning is not accomplished for the second or subsequent fractions of brachytherapy. Under fluoroscopic guidance, the applicator is placed in a position identical to that in the first application and the same treatment plan is used with appropriate decay constants recalculated. It is presumed with this technique that the doses to critical structures, bladder and rectum, are unchanged between radiotherapy fractions. Symon et al. do note that similar, !10 , differences in angle between fractions result in reduced differences in doses supporting this technique. Currently, in patients whom we have recommended and treated with vaginal cuff brachytherapy alone with the use of the described technique, there has been no local recurrence and no significant bladder or rectal complications. The use of this technique allows us to place a Foley catheter and rectal contrast with only the first fraction of radiotherapy reducing patient discomfort and potential for a urinary tract infection. In addition, because no planning is achieved for subsequent implants, the procedure is completed relatively quickly, also improving patient tolerance and the costs of the therapy are reduced.
217
In conclusion, I applaud the attempts of Symon et al. to study vaginal cuff brachytherapy. Vaginal brachytherapy is a commonly prescribed treatment with a relative paucity of technical data. With the authors’ techniques, IFO planning does seem to reduce dose to nearby critical normal structures. The need for IFO for single channel vaginal cylinders is yet to be determined. William Small, Jr., MD Department of Radiation Oncology Robert H. Lurie Comprehensive Cancer Center of Northwestern University Chicago, IL
References [1] Symon Z, Menhal J, Alezra D, et al. Individual fraction optimization for multi-channel applicator vaginal brachytherapy. Brachytherapy 2006;5:211e215. [2] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106e130. [3] Creutzberg C, van Putten WLJ, Kooper PCM, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage I endometrial carcinoma: Multicentre randomized trial. Lancet 2000; 355:1404e1411. [4] Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744e751. [5] Small W Jr, Zeytinoglu M, Keh R, et al. Endometrial adenocarcinoma invasive to <½ the myometrial thickness: Analysis of prognostic variables for recurrence and survival. Int J Radiat Oncol Biol Phys 2001;51(3, Suppl.):35e36. [6] Anderson JM, Stea B, Hallum AV, et al. High dose rate postoperative vaginal cuff irradiation alone for stage IB and IC endometrial cancer. Int J Radiat Oncol Biol Phys 2000;46:417e425. [7] Chadha M, Nanavati PJ, Liu P, et al. Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 1999;75:103e107. [8] Small W Jr, Erickson B, Kwakwa F. An American Brachytherapy Society survey regarding the practice patterns of post-operative irradiation for endometrial cancer. Int J Radiol Oncol Biol Phys 2005;63:1502e1507. [9] Nag S, Gupta N. A simple method of obtaining equivalent doses for use in HDR brachytherapy. Int J Radiat Oncol Biol Phys 2000;46: 507e513. [10] Small W Jr, Marshall I, Lurain J, et al. Does pretreatment calculation of bladder and rectal doses in HDR vaginal radiation alter therapy? Brachytherapy 2003;2:41.