International Journal of
Radiation Oncology biology
physics
www.redjournal.org
COMMENTARY
Better Radiation Therapy for Cervix Cancer Would Save Lives Gillian M. Thomas, BSc, MD, FRCPC, FRCR (Hon), FRCOG Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada Received Mar 3, 2014. Accepted for publication Mar 15, 2014.
Millions of dollars are spent every year by funding agencies and pharmaceutical companies in studying different treatment interventions to improve outcomes for patients with cervical cancer. Often the improvements sought and reported after large expense yield statistically significant results but trivial or nonexistent clinical improvements in terms of lives saved (1). The report in this issue of International Journal of Radiation Oncology, Biology, Physics by Eifel et al (2) is yet another sobering statement about the continuing nationwide lack of adherence to quality indicators in delivery of optimized standard concurrent chemoradiation treatment for advanced cervical cancer (3, 4). While this Quality Research in Radiation Oncology (QRRO) study, like the previous reports, is a process study not an outcomes study, several justifiable inferences can be made about the predictable negative impact on survival that is associated with the observed inferior delivery of curative treatment particularly in small facilities treating few patients (3-5). A similar conclusion in head and neck cancer was made in a study of radiation therapy with concurrent cisplatin plus tirapazamine. Radiation therapy plans were reviewed in real time. Approximately 25% of cases had noncompliant plans, and half of those had major deficits that led to markedly inferior survival and local control (20% difference from those with acceptable plans) (6). Although a concerted effort in many laboratories is ongoing to identify molecular prognostic and predictive markers in advanced cervical cancer, several critical evidence-based clinical treatment factors (quality indicators [QI]) are already identified whose application leads to
higher local control and survival rates, including (1) adequate radiation tumor dose and volume (3-5); (2) limitation of overall treatment time to less than approximately 56 days (5); (3) use of brachytherapy (2); and (4) administration of concurrent chemotherapy (usually platinum based) with radiation (7). This QRRO study surveyed 45 academic and small and large nonacademic facilities and actual on-site data from 261 randomly selected records were extracted and examined (2). The data were extrapolated to estimate nationwide results to capture the quality of treatment in the United States for 2005 to 2007. No data are provided as to possible reasons why centers did not participate in the survey. Several worrying facts in this survey have emerged again:
Reprint requests to: Dr Gillian M. Thomas, BSc, MD, FRCPC, FRCR (Hon), FRCOG, Sunnybrook Odette Cancer Centre, Radiation Oncology,
2075 Bayview Ave, Toronto, ON, Canada M4N 3M5. Tel: (416) 4806165; E-mail: [email protected]
Int J Radiation Oncol Biol Phys, Vol. 89, No. 2, pp. 257e259, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.03.021
1. Two-thirds of patients were treated in facilities with less than 3 patients per year. 2. Overall treatment time (when measured against a liberal benchmark of 10 weeks) was more protracted in “small/ medium” nonacademic centers (30%) and large nonacademic centers (34%) than in academic centers (13%). For the more satisfactory stringent standard of 60 days, 25%, 50%, and 51% in academic, large nonacademic and small/medium nonacademic centers respectively exceed this limit. 3. Concurrent chemotherapy was not given in one-quarter of patients treated in small/medium nonacademic facilities compared with 13% in large facilities. Only
258
Thomas
International Journal of Radiation Oncology Biology Physics
approximately one-half of women >60 years of age received chemotherapy.
cervical cancer declines with improved screening and uptake of human papilloma virus vaccines.
4. Thirteen percent of patients had no brachytherapy (almost double that observed in the 1996 to 1999 survey).
2. Can continuing medical education programs assist in ensuring continuing practical expertise, particularly for those treating only occasional patients?
5. Nonacademic centers large and small had significantly higher proportions of patients with stages III and IV disease than academic centers (42% and 30% vs 20%, respectively). Markedly advanced bulky pelvic disease is more difficult to define and irradiate adequately, especially if intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) are being used where experience is minimal and patient numbers are small.
3. Can professional societies such as American Society for Radiation Oncology (ASTRO) advise and influence members to refer patients with rare diseases such as cervical cancer to larger academic institutions where standards of care, as reflected in this study, are better?
6. Fifteen percent of patients had part of their treatment, for example, external beam radiation, brachytherapy, and chemotherapy delivered at different facilities. The quality and timeliness of communication between providers with respect to treatment detail is unknown. These data raise major concerns about the consequently negative impact of lack of adherence to treatment QIs on local control and survival outcomes nation wide for patients with cervical cancer. A similar situation exists for patients with ovarian cancer and high-risk endometrial cancers. If care is not provided by experienced experts, outcomes are worse (8). In many countries this has been the stimulus for centralizing care for specific patients in “centers of excellence” with high volume and specialized settings (8). How can the observed deficits in “quality” radiation be overcome? What are the root causes related to the facility, expertise, training, and experience that need to be addressed and might be correctable? Are any improvements possible within the context of the diversity of treatment settings? Treating only the occasional patient is probably too few to maintain site-specific expertise and up-to-date knowledge. With current advances in the technical aspects of radiation both in external beam delivery and image guided brachytherapy, quality is even more problematic. While acknowledging that some adverse treatment factors identified in this survey may be patient related (eg, delays in completion or failure to complete treatment), other factors are related to the radiation oncologist or facility. Several controversial questions arise with respect to potential methods of improving the quality of treatment nationally. 1. Are residency training programs stringent enough with sufficient exposure and practice in treating cervical cancer patients to develop expertise (9)? The median number of “intracavity” brachytherapy procedures for residents in training in 2010 to 2011 was only 36. This probably included simple vault brachytherapy as well as cervical brachytherapy. Gaining sufficient brachytherapy training is even more problematic as the incidence of
4. Can state or nationwide acceptable methods be developed to audit radiation practice and outcomes and benchmark to improve quality? ASTRO and the Radiation Oncology Institute are collaborating on a National Radiation Oncology Registry pilot project to collect patient data to compare “effectiveness, outcome, utilization, safety and cost” to provide QI tools for individual oncologists (10). In Belgium, relevant quality indicators for the management of endometrial cancer have already been identified and implemented (11). Perhaps even more controversial are “pay for performance” initiatives. Financial incentives have been shown to influence behavior of health care professionals to improve quality of care (12). 5. Should stringent requirements for recertification of expertise and knowledge in radiation oncology be implemented specifically for treating each cancer? Although some patients have received suboptimal treatment as documented here, others received none. Trimble et al (13), using SEER data, reported that 9% of women in the United States received no treatment for their invasive cervical cancer and that 16% of women over 65 years of age with cancers requiring radiation (stages IIB to IVA) had no treatment (13). While the practice of radiation oncology is constantly evolving with more technically complicated conformal treatments such as IMRTand IGBTand research is directed toward identifying and testing “biologic agents,” radiation oncologists treating cervical cancer, as a minimum, need to adhere to the simple, defined strategies of optimized care: sufficient radiation dose and volume, limited overall treatment time, use of brachytherapy, and delivery of concurrent chemotherapy. The implementation of these QIs will save more lives than the small gains currently being achieved through expensive biological and technical research strategies unavailable to the majority of cervical cancer patients in the world.
References 1. Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734-743.
Volume 89 Number 2 2014 2. Eifel PJ, Khalid N, Erickson B, et al. Patterns of radiation therapy practice for patients treated for intact cervical cancer in 2005-2007: A quality research in radiation oncology study. Int J Radiat Oncol Biol Phys 2014;89:249-256. 3. Lanciano RM, Won M, Coia LR, et al. Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: A final report of the 1973 and 1978 patterns of care studies. Int J Radiat Oncol Biol Phys 1991;20:667-676. 4. Eifel PJ, Moughan J, Erickson B, et al. Patterns of radiotherapy practice for patients with carcinoma of the uterine cervix: A patterns of care study. Int J Radiat Oncol Biol Phys 2004;60:1144-1153. 5. Han K, Milosevic M, Fyles A, et al. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;87:111-119. 6. Peters LJ, O’Sullivan B, Giralt J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: Results from TROG 02.02. J Clin Oncol 2010;28: 2996-3001. 7. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and meta-analysis of
259
8.
9.
10.
11.
12.
13.
individual patient data from 18 randomized trials. J Clin Oncol 2008;26:5802-5812. Vernooij F, Heintz AP, Coebergh JW, et al. Specialized and highvolume care leads to better outcomes of ovarian cancer treatment in the Netherlands. Gynecol Oncol 2009;112:455-461. Compton JJ, Gaspar LE, Shrieve DC, et al. Resident-reported brachytherapy experience in ACGME-accredited radiation oncology training programs. Brachytherapy 2013;12:622-627. Palta JR, Efstathiou JA, Bekelman JE, et al. Developing a national radiation oncology registry: From acorns to oaks. Pract Radiat Oncol 2012;2:10-17. Werbrouck J, Bouche G, de Jonge E, et al. Evaluation of the quality of the management of cancer of the corpus uteridselection of relevant quality indicators and implementation in Belgium. Gynecol Oncol 2013;131:512-519. Kirschner K, Braspenning J, Akkermans RP, et al. Assessment of a pay-for-performance program in primary care designed by target users. Fam Pract 2013;30:161-171. Trimble EL, Harlan LC, Clegg LX. Untreated cervical cancer in the United States. Gynecol Oncol 2005;96:271-277.
Radiation Oncology biology
physics
www.redjournal.org
COMMENTARY
Better Radiation Therapy for Cervix Cancer Would Save Lives Gillian M. Thomas, BSc, MD, FRCPC, FRCR (Hon), FRCOG Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada Received Mar 3, 2014. Accepted for publication Mar 15, 2014.
Millions of dollars are spent every year by funding agencies and pharmaceutical companies in studying different treatment interventions to improve outcomes for patients with cervical cancer. Often the improvements sought and reported after large expense yield statistically significant results but trivial or nonexistent clinical improvements in terms of lives saved (1). The report in this issue of International Journal of Radiation Oncology, Biology, Physics by Eifel et al (2) is yet another sobering statement about the continuing nationwide lack of adherence to quality indicators in delivery of optimized standard concurrent chemoradiation treatment for advanced cervical cancer (3, 4). While this Quality Research in Radiation Oncology (QRRO) study, like the previous reports, is a process study not an outcomes study, several justifiable inferences can be made about the predictable negative impact on survival that is associated with the observed inferior delivery of curative treatment particularly in small facilities treating few patients (3-5). A similar conclusion in head and neck cancer was made in a study of radiation therapy with concurrent cisplatin plus tirapazamine. Radiation therapy plans were reviewed in real time. Approximately 25% of cases had noncompliant plans, and half of those had major deficits that led to markedly inferior survival and local control (20% difference from those with acceptable plans) (6). Although a concerted effort in many laboratories is ongoing to identify molecular prognostic and predictive markers in advanced cervical cancer, several critical evidence-based clinical treatment factors (quality indicators [QI]) are already identified whose application leads to
higher local control and survival rates, including (1) adequate radiation tumor dose and volume (3-5); (2) limitation of overall treatment time to less than approximately 56 days (5); (3) use of brachytherapy (2); and (4) administration of concurrent chemotherapy (usually platinum based) with radiation (7). This QRRO study surveyed 45 academic and small and large nonacademic facilities and actual on-site data from 261 randomly selected records were extracted and examined (2). The data were extrapolated to estimate nationwide results to capture the quality of treatment in the United States for 2005 to 2007. No data are provided as to possible reasons why centers did not participate in the survey. Several worrying facts in this survey have emerged again:
Reprint requests to: Dr Gillian M. Thomas, BSc, MD, FRCPC, FRCR (Hon), FRCOG, Sunnybrook Odette Cancer Centre, Radiation Oncology,
2075 Bayview Ave, Toronto, ON, Canada M4N 3M5. Tel: (416) 4806165; E-mail: [email protected]
Int J Radiation Oncol Biol Phys, Vol. 89, No. 2, pp. 257e259, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.03.021
1. Two-thirds of patients were treated in facilities with less than 3 patients per year. 2. Overall treatment time (when measured against a liberal benchmark of 10 weeks) was more protracted in “small/ medium” nonacademic centers (30%) and large nonacademic centers (34%) than in academic centers (13%). For the more satisfactory stringent standard of 60 days, 25%, 50%, and 51% in academic, large nonacademic and small/medium nonacademic centers respectively exceed this limit. 3. Concurrent chemotherapy was not given in one-quarter of patients treated in small/medium nonacademic facilities compared with 13% in large facilities. Only
258
Thomas
International Journal of Radiation Oncology Biology Physics
approximately one-half of women >60 years of age received chemotherapy.
cervical cancer declines with improved screening and uptake of human papilloma virus vaccines.
4. Thirteen percent of patients had no brachytherapy (almost double that observed in the 1996 to 1999 survey).
2. Can continuing medical education programs assist in ensuring continuing practical expertise, particularly for those treating only occasional patients?
5. Nonacademic centers large and small had significantly higher proportions of patients with stages III and IV disease than academic centers (42% and 30% vs 20%, respectively). Markedly advanced bulky pelvic disease is more difficult to define and irradiate adequately, especially if intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) are being used where experience is minimal and patient numbers are small.
3. Can professional societies such as American Society for Radiation Oncology (ASTRO) advise and influence members to refer patients with rare diseases such as cervical cancer to larger academic institutions where standards of care, as reflected in this study, are better?
6. Fifteen percent of patients had part of their treatment, for example, external beam radiation, brachytherapy, and chemotherapy delivered at different facilities. The quality and timeliness of communication between providers with respect to treatment detail is unknown. These data raise major concerns about the consequently negative impact of lack of adherence to treatment QIs on local control and survival outcomes nation wide for patients with cervical cancer. A similar situation exists for patients with ovarian cancer and high-risk endometrial cancers. If care is not provided by experienced experts, outcomes are worse (8). In many countries this has been the stimulus for centralizing care for specific patients in “centers of excellence” with high volume and specialized settings (8). How can the observed deficits in “quality” radiation be overcome? What are the root causes related to the facility, expertise, training, and experience that need to be addressed and might be correctable? Are any improvements possible within the context of the diversity of treatment settings? Treating only the occasional patient is probably too few to maintain site-specific expertise and up-to-date knowledge. With current advances in the technical aspects of radiation both in external beam delivery and image guided brachytherapy, quality is even more problematic. While acknowledging that some adverse treatment factors identified in this survey may be patient related (eg, delays in completion or failure to complete treatment), other factors are related to the radiation oncologist or facility. Several controversial questions arise with respect to potential methods of improving the quality of treatment nationally. 1. Are residency training programs stringent enough with sufficient exposure and practice in treating cervical cancer patients to develop expertise (9)? The median number of “intracavity” brachytherapy procedures for residents in training in 2010 to 2011 was only 36. This probably included simple vault brachytherapy as well as cervical brachytherapy. Gaining sufficient brachytherapy training is even more problematic as the incidence of
4. Can state or nationwide acceptable methods be developed to audit radiation practice and outcomes and benchmark to improve quality? ASTRO and the Radiation Oncology Institute are collaborating on a National Radiation Oncology Registry pilot project to collect patient data to compare “effectiveness, outcome, utilization, safety and cost” to provide QI tools for individual oncologists (10). In Belgium, relevant quality indicators for the management of endometrial cancer have already been identified and implemented (11). Perhaps even more controversial are “pay for performance” initiatives. Financial incentives have been shown to influence behavior of health care professionals to improve quality of care (12). 5. Should stringent requirements for recertification of expertise and knowledge in radiation oncology be implemented specifically for treating each cancer? Although some patients have received suboptimal treatment as documented here, others received none. Trimble et al (13), using SEER data, reported that 9% of women in the United States received no treatment for their invasive cervical cancer and that 16% of women over 65 years of age with cancers requiring radiation (stages IIB to IVA) had no treatment (13). While the practice of radiation oncology is constantly evolving with more technically complicated conformal treatments such as IMRTand IGBTand research is directed toward identifying and testing “biologic agents,” radiation oncologists treating cervical cancer, as a minimum, need to adhere to the simple, defined strategies of optimized care: sufficient radiation dose and volume, limited overall treatment time, use of brachytherapy, and delivery of concurrent chemotherapy. The implementation of these QIs will save more lives than the small gains currently being achieved through expensive biological and technical research strategies unavailable to the majority of cervical cancer patients in the world.
References 1. Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734-743.
Volume 89 Number 2 2014 2. Eifel PJ, Khalid N, Erickson B, et al. Patterns of radiation therapy practice for patients treated for intact cervical cancer in 2005-2007: A quality research in radiation oncology study. Int J Radiat Oncol Biol Phys 2014;89:249-256. 3. Lanciano RM, Won M, Coia LR, et al. Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: A final report of the 1973 and 1978 patterns of care studies. Int J Radiat Oncol Biol Phys 1991;20:667-676. 4. Eifel PJ, Moughan J, Erickson B, et al. Patterns of radiotherapy practice for patients with carcinoma of the uterine cervix: A patterns of care study. Int J Radiat Oncol Biol Phys 2004;60:1144-1153. 5. Han K, Milosevic M, Fyles A, et al. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;87:111-119. 6. Peters LJ, O’Sullivan B, Giralt J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: Results from TROG 02.02. J Clin Oncol 2010;28: 2996-3001. 7. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and meta-analysis of
259
8.
9.
10.
11.
12.
13.
individual patient data from 18 randomized trials. J Clin Oncol 2008;26:5802-5812. Vernooij F, Heintz AP, Coebergh JW, et al. Specialized and highvolume care leads to better outcomes of ovarian cancer treatment in the Netherlands. Gynecol Oncol 2009;112:455-461. Compton JJ, Gaspar LE, Shrieve DC, et al. Resident-reported brachytherapy experience in ACGME-accredited radiation oncology training programs. Brachytherapy 2013;12:622-627. Palta JR, Efstathiou JA, Bekelman JE, et al. Developing a national radiation oncology registry: From acorns to oaks. Pract Radiat Oncol 2012;2:10-17. Werbrouck J, Bouche G, de Jonge E, et al. Evaluation of the quality of the management of cancer of the corpus uteridselection of relevant quality indicators and implementation in Belgium. Gynecol Oncol 2013;131:512-519. Kirschner K, Braspenning J, Akkermans RP, et al. Assessment of a pay-for-performance program in primary care designed by target users. Fam Pract 2013;30:161-171. Trimble EL, Harlan LC, Clegg LX. Untreated cervical cancer in the United States. Gynecol Oncol 2005;96:271-277.
