Practical Radiation Oncology (2012) 2, 279–281
www.practicalradonc.org
Commentary
Regional treatment of vulvar cancer; lessons from the past and lessons for the future Patricia J. Eifel MD ⁎ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Received 13 April 2012; accepted 13 April 2012
As a radiation oncology resident in the early 1980s, I recall seeing only 1 vulvar cancer during the entire 3 years of my clinical training—a woman referred for palliative treatment of a massive locoregional recurrence. At the time, we were taught that radiation therapy had little or no role in the curative management of vulvar cancer, surgery was considered the only definitive treatment, and clinicians generally believed that the side effects of radiation therapy prohibited delivery of meaningful doses to the vulva. In contrast, today it is widely recognized that the best overall outcomes are achieved through careful application of a multidisciplinary treatment approach and that radiation therapy can play an integral role in curative treatment of many patients, particularly those who have locoregionally advanced disease. The path between then and now was marked by some remarkable highs but also by a few equally remarkable blunders. In 1986, Homesley et al 1 proved that in patients with vulvar cancer, adjuvant postoperative radiation therapy could improve survival by preventing regional disease recurrences. At about the same time, Cummings et al 2 published data demonstrating the power of concurrent chemoradiation as a tool for organ preservation in anal cancer. Clinicians were emboldened by these findings to take a second look at the potential for concurrent chemoradiation in women with locally advanced vulvar
See Related Article on page 274. Conflicts of interest: None. ⁎ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcolmbe Blvd, Unit 1202, Houston, TX 77030. E-mail address: [email protected].
cancers, arguing that in some cases vulvar cancers were distinguished from anal margin cancers as much by the door through which patients entered the hospital as by the location of the primary lesion. Encouraged by these developments, clinicians began to explore ways of reducing the morbidity of the treatments that had been standard for decades (radical vulvectomy and total inguinal lymphadenectomy) through the use of less radical surgical approaches and broader use of radiation therapy. Unfortunately, there were also some major setbacks during these early years. Nearly all of these resulted from clinicians' overconfidence in their understanding of the anatomy of the region and particularly in their understanding of the regional drainage of the vulva. Early attempts to reduce the side effects of treatment in patients with clinically node negative groins by lessening the radicality of lymph node dissection 3 or by replacing groin dissection with groin irradiation 4 resulted in unacceptable rates of recurrence in the groin. Early trials of limited dissections in women with early vulvar cancers probably failed not because a full dissection of the deep inguinal nodes was necessary but because surgeons had underestimated the importance of the medial inguinofemoral nodes as sentinels for lymph node involvement. 5 An early Gynecologic Oncology Group (GOG) randomized trial that questioned whether radical groin dissection could be replaced with groin irradiation in women who had clinically node negative groins (GOG 88) failed for a similar reason. The trial had accrued only 50 patients of a planned 400 when the investigators noted an alarming rate of groin recurrence in the radiation therapy arm. The trial was terminated early, and many clinicians abandoned the use of prophylactic irradiation in this
1879-8500/$ – see front matter © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.04.006
280
P.J. Eifel
setting. However, publication of the trial results was swiftly followed by articles criticizing the radiation therapy technique used. In one of these articles, Koh et al 6 pointed out that the prescription point (3-cm depth) did not adequately encompass the inguinal nodes. Unlike the earlier Homesley et al trial, 1 which employed anterior-posteriorposterior-anterior photon fields, GOG 88 specified treatment using appositional fields of combined photons and 9- to 12MeV electrons. This approach undoubtedly resulted in serious underdosage of critical lymph nodes, particularly in the medial femoral region—nodes that routinely fall beyond the range of 12-MeV electrons. The story of GOG 88 begs the question: How could such an error be made, particularly in a multi-institutional trial that involved so many experienced clinicians? More importantly, could we be making similar errors today as we find ourselves in the midst of a new era of rapid technologic expansion? I believe the answer to the first question suggests an affirmative answer to the second and yields important lessons for the modern era of inverse planning and intensity modulated radiation therapy (IMRT). In the early 1980s, before publication of the Homesley trial in vulvar cancer and the chemoradiation trials in anal cancer, the only major indication for groin irradiation was in patients with lymphoma. The dose prescribed at that time (40-44 Gy) was undoubtedly higher than necessary, and the “superficial” beams used to spare the underlying femoral heads were kilovoltage X-rays (which had a relatively gradual fall-off in dose) rather than electrons. Although a prescription point of 3 cm was traditional and the femoral nodes undoubtedly received less than the prescribed dose, the treatment was probably still adequate to sterilize microscopic nodal involvement with lymphoma. Then, in the late 1980s, electron beams began to be widely available. Clinicians were thrilled with the ability to “conform” treatment more tightly to superficial target volumes and began to replace orthovoltage beams with electrons when treating relatively superficial targets in the groin, neck, and elsewhere. At the time, the quality of abdominal computed tomography (CT) was still poor, and CT-based planning was rare. Clinicians who had been taught for decades to prescribe treatment at 3-cm depth continued to do so, perhaps never realizing that 3 cm had originally been intended as a reference point, not a target volume. An error in perception that had been relatively unimportant when lymphomas were being treated with kilovoltage beams was disastrous when carcinomas (which really required the prescribed dose) were treated with 9- to 12-MeV electron beams (which contributed a negligible dose beyond 3-4 cm). What had for decades served fairly well as a surrogate for the actual target volume proved to be wholly inadequate in a new era with new technology and new applications. During the past decade, the rapidly expanding use of inverse planning and IMRT has required clinicians to review their understanding of anatomy and locoregional patterns of tumor progression. Thousands of radiation oncologists,
Practical Radiation Oncology: October-December 2012
trained to use standard treatment fields and boney landmarks as surrogates for primary and regional target volumes, must now understand precisely which tissues within those traditional fields were really important. In the late 1980s, we were making this kind of transition only for a few relatively superficial tumor sites amenable to electron treatment. Today, we are in the midst of a technology revolution that requires us to completely rethink our understanding of every facet of radiation treatment. The potential for tissue sparing is clear. However, at the same time, the complexity and potential for error are substantial. In the early 1990s, erroneous interpretations of the regional target volume for vulvar cancer led to unnecessary recurrences and deaths. In this issue of Practical Radiation Oncology, Kim et al 7 demonstrate how poorly informed target volume designation could again lead to critical errors and unnecessary recurrences. I completely agree with the authors' argument that the groin needs to be contoured with an understanding of the vascular tissue compartment and not with a fixed radial margin around the major vessels. The regional drainage of the vulva terminates not only in nodes immediately adjacent to the femoral and saphenous vessels but also in nodes that lie along less prominent tributaries of the major vessels that are not easily appreciated on CT and do not lie within a fixed radial margin around the major vessels. However, I disagree with the authors' suggestion that, in this respect, the inguinofemoral target volume is different from pelvic or other regional target volumes. The habit radiation oncologists have developed of using a fixed margin around major vessels as a surrogate for a regional target volume implies that only vessels that are easily appreciated on tomographic imaging are associated with potential sites of regional metastasis. This approach is just as dangerous as was the use of a 3-cm reference depth for groin irradiation in 1990. For example, I have seen cervical cancer patients treated with conformal or IMRT fields that entirely excluded primary drainage sites in the internal iliac or presacral nodes, presumably because the treating physician only contoured around vessels that were easily appreciated on CT. The lesson to be learned from GOG-88 and the work of Kim et al 7 is that we should be very suspicious of any simple surrogates for regional target volumes. Optimal use of modern treatment (whether image-based 3-dimensional conformal radiation therapy or IMRT) requires careful study, humility, a willingness to learn from our failures, and many more studies of the sort published in this issue of Practical Radiation Oncology.
References 1. Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol. 1986;68:733-740.
Practical Radiation Oncology: October-December 2012 2. Cummings BJ, Keane TJ, O'Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys. 1991;21:1115-1125. 3. Stehman FB, Bundy BN, Dvoretsky PM, Creasman WT. Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstet Gynecol. 1992;79:490-497. 4. Stehman FB, Bundy BN, Thomas G, et al. Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic
Regional treatment of vulvar cancer
281
Oncology Group study. Int J Radiat Oncol Biol Phys. 1992;24: 389-396. 5. Levenback C, Morris M, Burke TW, Gershenson DM, Wolf JK, Wharton JT. Groin dissection practices among gynecologic oncologists treating early vulvar cancer. Gynecol Oncol. 1996;62:73-77. 6. Koh WJ, Chiu M, Stelzer KJ, et al. Femoral vessel depth and the implications for groin node radiation. Int J Radiat Oncol Biol Phys. 1993;27:969-974. 7. Kim CH, Olson AC, Kim H, Beriwal S. Contouring inguinal and femoral nodes; how much margin is needed around the vessels? Practical Radiat Oncol. 2012;2:274-278.
www.practicalradonc.org
Commentary
Regional treatment of vulvar cancer; lessons from the past and lessons for the future Patricia J. Eifel MD ⁎ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Received 13 April 2012; accepted 13 April 2012
As a radiation oncology resident in the early 1980s, I recall seeing only 1 vulvar cancer during the entire 3 years of my clinical training—a woman referred for palliative treatment of a massive locoregional recurrence. At the time, we were taught that radiation therapy had little or no role in the curative management of vulvar cancer, surgery was considered the only definitive treatment, and clinicians generally believed that the side effects of radiation therapy prohibited delivery of meaningful doses to the vulva. In contrast, today it is widely recognized that the best overall outcomes are achieved through careful application of a multidisciplinary treatment approach and that radiation therapy can play an integral role in curative treatment of many patients, particularly those who have locoregionally advanced disease. The path between then and now was marked by some remarkable highs but also by a few equally remarkable blunders. In 1986, Homesley et al 1 proved that in patients with vulvar cancer, adjuvant postoperative radiation therapy could improve survival by preventing regional disease recurrences. At about the same time, Cummings et al 2 published data demonstrating the power of concurrent chemoradiation as a tool for organ preservation in anal cancer. Clinicians were emboldened by these findings to take a second look at the potential for concurrent chemoradiation in women with locally advanced vulvar
See Related Article on page 274. Conflicts of interest: None. ⁎ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcolmbe Blvd, Unit 1202, Houston, TX 77030. E-mail address: [email protected].
cancers, arguing that in some cases vulvar cancers were distinguished from anal margin cancers as much by the door through which patients entered the hospital as by the location of the primary lesion. Encouraged by these developments, clinicians began to explore ways of reducing the morbidity of the treatments that had been standard for decades (radical vulvectomy and total inguinal lymphadenectomy) through the use of less radical surgical approaches and broader use of radiation therapy. Unfortunately, there were also some major setbacks during these early years. Nearly all of these resulted from clinicians' overconfidence in their understanding of the anatomy of the region and particularly in their understanding of the regional drainage of the vulva. Early attempts to reduce the side effects of treatment in patients with clinically node negative groins by lessening the radicality of lymph node dissection 3 or by replacing groin dissection with groin irradiation 4 resulted in unacceptable rates of recurrence in the groin. Early trials of limited dissections in women with early vulvar cancers probably failed not because a full dissection of the deep inguinal nodes was necessary but because surgeons had underestimated the importance of the medial inguinofemoral nodes as sentinels for lymph node involvement. 5 An early Gynecologic Oncology Group (GOG) randomized trial that questioned whether radical groin dissection could be replaced with groin irradiation in women who had clinically node negative groins (GOG 88) failed for a similar reason. The trial had accrued only 50 patients of a planned 400 when the investigators noted an alarming rate of groin recurrence in the radiation therapy arm. The trial was terminated early, and many clinicians abandoned the use of prophylactic irradiation in this
1879-8500/$ – see front matter © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.04.006
280
P.J. Eifel
setting. However, publication of the trial results was swiftly followed by articles criticizing the radiation therapy technique used. In one of these articles, Koh et al 6 pointed out that the prescription point (3-cm depth) did not adequately encompass the inguinal nodes. Unlike the earlier Homesley et al trial, 1 which employed anterior-posteriorposterior-anterior photon fields, GOG 88 specified treatment using appositional fields of combined photons and 9- to 12MeV electrons. This approach undoubtedly resulted in serious underdosage of critical lymph nodes, particularly in the medial femoral region—nodes that routinely fall beyond the range of 12-MeV electrons. The story of GOG 88 begs the question: How could such an error be made, particularly in a multi-institutional trial that involved so many experienced clinicians? More importantly, could we be making similar errors today as we find ourselves in the midst of a new era of rapid technologic expansion? I believe the answer to the first question suggests an affirmative answer to the second and yields important lessons for the modern era of inverse planning and intensity modulated radiation therapy (IMRT). In the early 1980s, before publication of the Homesley trial in vulvar cancer and the chemoradiation trials in anal cancer, the only major indication for groin irradiation was in patients with lymphoma. The dose prescribed at that time (40-44 Gy) was undoubtedly higher than necessary, and the “superficial” beams used to spare the underlying femoral heads were kilovoltage X-rays (which had a relatively gradual fall-off in dose) rather than electrons. Although a prescription point of 3 cm was traditional and the femoral nodes undoubtedly received less than the prescribed dose, the treatment was probably still adequate to sterilize microscopic nodal involvement with lymphoma. Then, in the late 1980s, electron beams began to be widely available. Clinicians were thrilled with the ability to “conform” treatment more tightly to superficial target volumes and began to replace orthovoltage beams with electrons when treating relatively superficial targets in the groin, neck, and elsewhere. At the time, the quality of abdominal computed tomography (CT) was still poor, and CT-based planning was rare. Clinicians who had been taught for decades to prescribe treatment at 3-cm depth continued to do so, perhaps never realizing that 3 cm had originally been intended as a reference point, not a target volume. An error in perception that had been relatively unimportant when lymphomas were being treated with kilovoltage beams was disastrous when carcinomas (which really required the prescribed dose) were treated with 9- to 12-MeV electron beams (which contributed a negligible dose beyond 3-4 cm). What had for decades served fairly well as a surrogate for the actual target volume proved to be wholly inadequate in a new era with new technology and new applications. During the past decade, the rapidly expanding use of inverse planning and IMRT has required clinicians to review their understanding of anatomy and locoregional patterns of tumor progression. Thousands of radiation oncologists,
Practical Radiation Oncology: October-December 2012
trained to use standard treatment fields and boney landmarks as surrogates for primary and regional target volumes, must now understand precisely which tissues within those traditional fields were really important. In the late 1980s, we were making this kind of transition only for a few relatively superficial tumor sites amenable to electron treatment. Today, we are in the midst of a technology revolution that requires us to completely rethink our understanding of every facet of radiation treatment. The potential for tissue sparing is clear. However, at the same time, the complexity and potential for error are substantial. In the early 1990s, erroneous interpretations of the regional target volume for vulvar cancer led to unnecessary recurrences and deaths. In this issue of Practical Radiation Oncology, Kim et al 7 demonstrate how poorly informed target volume designation could again lead to critical errors and unnecessary recurrences. I completely agree with the authors' argument that the groin needs to be contoured with an understanding of the vascular tissue compartment and not with a fixed radial margin around the major vessels. The regional drainage of the vulva terminates not only in nodes immediately adjacent to the femoral and saphenous vessels but also in nodes that lie along less prominent tributaries of the major vessels that are not easily appreciated on CT and do not lie within a fixed radial margin around the major vessels. However, I disagree with the authors' suggestion that, in this respect, the inguinofemoral target volume is different from pelvic or other regional target volumes. The habit radiation oncologists have developed of using a fixed margin around major vessels as a surrogate for a regional target volume implies that only vessels that are easily appreciated on tomographic imaging are associated with potential sites of regional metastasis. This approach is just as dangerous as was the use of a 3-cm reference depth for groin irradiation in 1990. For example, I have seen cervical cancer patients treated with conformal or IMRT fields that entirely excluded primary drainage sites in the internal iliac or presacral nodes, presumably because the treating physician only contoured around vessels that were easily appreciated on CT. The lesson to be learned from GOG-88 and the work of Kim et al 7 is that we should be very suspicious of any simple surrogates for regional target volumes. Optimal use of modern treatment (whether image-based 3-dimensional conformal radiation therapy or IMRT) requires careful study, humility, a willingness to learn from our failures, and many more studies of the sort published in this issue of Practical Radiation Oncology.
References 1. Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol. 1986;68:733-740.
Practical Radiation Oncology: October-December 2012 2. Cummings BJ, Keane TJ, O'Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys. 1991;21:1115-1125. 3. Stehman FB, Bundy BN, Dvoretsky PM, Creasman WT. Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstet Gynecol. 1992;79:490-497. 4. Stehman FB, Bundy BN, Thomas G, et al. Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic
Regional treatment of vulvar cancer
281
Oncology Group study. Int J Radiat Oncol Biol Phys. 1992;24: 389-396. 5. Levenback C, Morris M, Burke TW, Gershenson DM, Wolf JK, Wharton JT. Groin dissection practices among gynecologic oncologists treating early vulvar cancer. Gynecol Oncol. 1996;62:73-77. 6. Koh WJ, Chiu M, Stelzer KJ, et al. Femoral vessel depth and the implications for groin node radiation. Int J Radiat Oncol Biol Phys. 1993;27:969-974. 7. Kim CH, Olson AC, Kim H, Beriwal S. Contouring inguinal and femoral nodes; how much margin is needed around the vessels? Practical Radiat Oncol. 2012;2:274-278.
