The American Brachytherapy Society Survey of Brachytherapy Practice for Carcinoma of the Cervix in the United States

Gynecologic Oncology 73, 111–118 (1999) Article ID gyno.1998.5334, available online at http://www.idealibrary.com on

The American Brachytherapy Society Survey of Brachytherapy Practice for Carcinoma of the Cervix in the United States 1 Subir Nag, M.D.,* ,2 Colin Orton, Ph.D.,† Donn Young, Ph.D.,* and Beth Erickson, M.D.‡ For the American Brachytherapy Society *The Ohio State University, Columbus, Ohio 43210; †Wayne State University, Detroit, Michigan; and ‡Medical College of Wisconsin, Milwaukee, Wisconsin Received August 14, 1998

Key Words: radiation therapy; brachytherapy; cervical cancer; practice patterns.

Purpose. The purpose of this study was to survey the brachytherapy practice for cervical cancer in the United States. Methods. The Clinical Research Committee of the American Brachytherapy Society (ABS) performed a retrospective survey of individual physicians of the ABS and American Society of Therapeutic Radiologists and Oncologists regarding the details of the brachytherapy techniques they personally used in the treatment of cervical cancer patients for the year 1995. The replies (some of which may have been an estimate only) were tabulated. The scope of this survey did not allow us to verify the data by chart audits. Results. A total of about 3500 questionnaires were mailed out; 521 responses were received. Of these responders, 206 (40%) did not perform any brachytherapy for carcinoma of the cervix in 1995. Of the other 315 responders reporting a total of 4892 patients treated in 1995, 88% used low dose rate (LDR) while 24% used high dose rate (HDR). There was a wide variation in the doses used. For LDR treatments, the median total external beam radiation therapy (EBRT) dose was 45 and 50 Gy and the LDR dose was 42 and 45 Gy for early and advanced cancers, respectively. For HDR treatments, the median EBRT dose was 48 and 50 Gy and the median HDR dose was 29 and 30 Gy for early and advanced cancers, respectively. The median dose per fraction was 6 Gy for a median of five fractions. Interstitial brachytherapy was used as a component of the treatment in 6% of the patients by 21% of responders. Very few responders treated with pulsed or medium dose rates. Conclusion. This retrospective survey showed the current brachytherapy practice pattern in the treatment of cervical cancer in the United States and can serve as a basis for future prospective national brachytherapy data registry. There was wide variation in the practice pattern, emphasizing the urgent need for consensus on these issues. © 1999 Academic Press

INTRODUCTION A previous survey of brachytherapy practice in the United States undertaken by the clinical research committee of the American Brachytherapy Society (ABS) revealed that the most common site treated with brachytherapy was the cervix [15], but the survey did not attempt to define practice patterns for the treatment of cervical carcinoma. The 1973 and 1978 Patterns of Care studies established the importance of the use of intracavitary radiation in the treatment of cervical cancer with respect to infield pelvic control for stage I, II, and III disease [10], but did not delve into the details of brachytherapy methodology. Although there have been reports on the brachytherapy treatment of cancer of the cervix from a few large institutions [3, 5, 18, 19], there are little data on the brachytherapy techniques employed across the United States. Data on the brachytherapy methods employed are essential prerequisites for establishing consensus guidelines in brachytherapy which is one of the goals of the ABS. Hence, the Clinical Research Committee of the ABS conducted a survey of the radiation treatment of carcinoma of the cervix in the United States in 1995 with an emphasis on brachytherapy techniques used. METHODS

1 Presented in part at the Annual Meetings of the American Brachytherapy Society, June 1–3, 1998, Albuquerque, NM; Gynecology Oncology Group, July 17–19, 1998, Toronto, Canada; and Radiation Therapy Oncology Group, July 24 –26, 1998, Washington, DC. 2 To whom correspondence and reprint requests should be addressed at Arthur G. James Cancer Hospital, The Ohio State University, 300 W. 10th Avenue, Columbus, OH 43210. Fax: 614-293-4044. E-mail: [email protected].

A three-page questionnaire asking the details of radiation techniques used in the treatment of carcinoma of the cervix was prepared by the members of the Clinical Research Committee of the ABS (members of the Committee are listed in the Acknowledgments) and mailed to all the individual physicians (a total of about 3500) listed in the ABS and American Society of Therapeutic Radiologists and Oncologists directories. The survey asked if the individual physician (rather than their institution) treated any patients of carcinoma of the cervix

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TABLE 1 Summary of Questions in the Survey Specific data required for Early a

Advanced b

x x x x x x x x x

x x x x x

x x x x x

x x x x

x x x x

x x x x

LDR

HDR

Number of patients treated (total, LDR, HDR, PDR, MDR, interstitial) Applicators used Radioisotopes used Remote afterloading unit used Treatment planning system used

x x x x

x x

Do you record the maximum dose to the bladder What is the maximum dose (as % of point A dose) Do you record the maximum dose to the rectum What is the maximum dose (as % of point A dose)

x x x x

x x x x

Are the bladder and rectal dose determined by In vivo measurements Calculated using reconstructed radiographs Calculated using CT Calculated using ICRU reference points Average total external beam dose (including parametrial boost) Midline block used Added after what dose Interval between start of external beam and first brachytherapy Average overall treatment time

x x x x x x x x x x x x

Number of brachytherapy applications/fractions Average interval between brachytherapy fractions Total brachytherapy dose to point A Average HDR dose per fraction

x x

Note. LDR, low dose rate; HDR, high dose rate; PDR, pulsed dose rate; MDR, medium dose rate. a Stages IB/IIA. b Stages IIB/III.

by brachytherapy in 1995. If they did, they were asked for the number of patients treated, isotopes, doses, fractionation, teletherapy component, and other details of techniques used with low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (see Table 1 for summary of questions asked). The responses were scanned into a computer and analyzed, and the results were tabulated. It must be recognized that this was a retrospective survey and not a prospective survey; as such it is subject to inherent biases of the responders. The data are based on the reply of the responders some of whom may have given actual data from patient charts while others may have given an estimate. The scope of this survey did not allow us to verify the data by chart audits. RESULTS A total of 521 responses were received. Of these responders, 206 (40%) did not perform any brachytherapy for carcinoma of the cervix in 1995. Hence, the data of the other 315 responders

reporting a total of 4892 patients treated in 1995 were analyzed. The median number of patients treated per physician was 6, with 25% of radiation oncologists treating fewer than 4 cervical carcinoma patients with brachytherapy in 1995 and 25% treating 15 or more. The median number of LDR patients treated per responder was 5, with 25% of the radiation oncologists treating fewer than 4 and another 25% treating 11 or more patients. The median number of HDR patients treated per responder was 4, with 25% of the radiation oncologists treating less than 3, and 25%, 10 or more such patients. The number of patients treated with various brachytherapy techniques is shown in Table 2. For LDR, the radioisotopes used were 137Cs (97%), 192Ir (17%), 226Ra (3%), and 198Au (,1%). About 89% of the LDR responders determined the rectal dose; 91% determined the bladder dose. The bladder and rectal doses were determined by calculation using reconstructed radiographs (78%), in vivo measurements (8%), or CT scans (4%). A total of 45% of those

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TABLE 2 Summary of Patients Treated by Various Brachytherapy Techniques

TABLE 4 Number of Applications Used for LDR

Treatment technique

Number of responders

Number of patients treated

Median of patient/responder (range)

LDR HDR Interstitial PDR MDR Total

277 (88%) 75 (24%) (21%) 5 (2%) 2 (1%) 315 (100%)

3585 (73%) 762 (16%) 295 (6%) 154 (3%) 67 (1%) 4892 (100%)

5 (1–250) 4 (1–120) 3 (1–50) N/A (8–60) N/A (2–65) 6 (1–250)

Note. LDR, low dose rate; HDR, high dose rate; PDR, pulsed dose rate; MDR, medium dose rate.

who determined rectal/bladder doses reported that they used ICRU reference points for their calculations [8]. For HDR, the dosimetry was performed using the Nucletron planning system/ PLATO (72% of cases), Gamma-Med (7%), other commercial system (16%), in-house system (8%), or preplanned (10%). Eighty-three percent of the HDR responders determined the rectal dose; 81% determined the bladder dose. Table 3 gives a summary of the applicators used and the rectal and bladder doses by LDR and HDR responders. Table 4 gives a summary of the number of brachytherapy applications used for LDR. Table 5 gives a summary of the LDR and HDR doses used in treating early and advanced cervical cancers while Figs. 1– 8 give the frequency of distribution of the various doses used and the treatment durations to show the wide variation among responders. DISCUSSION Although there have been reports on the brachytherapy treatment of cancer of the cervix from a few large institutions [3, 5, 18, 19], there are little data on the brachytherapy techTABLE 3 Summary of LDR and HDR Responders

Number of responders Applicators used Fletcher Henschke Ring Other Maximum rectal dose a Maximum bladder dose a

LDR

HDR

277 (100%)

75 (100%)

259 (94%) 22 (8%) 0 40 (14%) 75% (15–95) 75% (6–100)

47 (64%) 5 (7%) 22 (30%) 21 (29%) 70% (15–100) 75% (15–100)

Note. LDR, low dose rate; HDR, high dose rate. a The rectal/bladder doses were an estimation of the highest doses at either ICRU reference points or at “hot spots.”

Number of applications

Early a

Advanced b

1 2 .2 1 and 2 2 and .2 Total

30 (11%) 198 (72%) 5 (2%) 32 (12%) — 277

36 (13%) 174 (63%) 4 (1%) 38 (14%) 4 (1%) 277

Note. LDR, low dose rate. a Stage IB or IIA carcinoma of cervix. b Stage IIB or IIIA/B carcinoma of cervix.

niques employed across the United States, since the Patterns of Care studies have concentrated on outcome data [10 –12] rather than brachytherapy methodology. Data on the brachytherapy methods employed are essential prerequisites for establishing consensus guidelines in brachytherapy that is one of the future goals of the ABS. This survey reveals that 40% of the radiation oncologists stated that they did not perform any brachytherapy for cervical carcinoma in 1995. This could be due to a combination of factors. Our previous survey revealed that 20% of the institutions (especially the smaller ones) did not perform any brachytherapy [15]. Some institutions (e.g., Veterans Administration Hospitals) may not treat gynecological patients. In many institutions (especially the larger ones), radiation oncologists tend to be specialized, and gynecological cancers are treated by designated individuals. This survey further reveals that each radiation oncologist who performs brachytherapy treats an average of only about six cervix cancer patients per year, with 25% of those surveyed treating less than four per year. Hence such treatments do not constitute a major portion of the practice of most radiation oncologists. It is well known that the outcome of brachytherapy is dependent, in part, on the skill and expertise of the brachytherapist. Hence, this case load may be too small to maintain the skills necessary to perform optimal brachytherapy insertions. These patients may need to be referred to physicians or major medical centers with established brachytherapy expertise. On comparing the treatment of early versus advanced disease for LDR, one notes that a higher external beam radiation therapy (EBRT) dose is used for treating the advanced disease but the LDR dose increases only minimally. Figure 4 shows that when using HDR, the EBRT dose distribution reveals that a higher dose is used in the treatment of advanced versus early disease; however, Table 5 shows that there is only a slight increase in the median EBRT dose (from 48 to 50 Gy). Figure 5 and Table 5 reveals that there is very little difference between the HDR doses used to treat early versus advanced disease. Replacement of LDR brachytherapy by HDR in the management of cancer of the cervix remains controversial [1, 2, 4,

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TABLE 5 Summary of LDR and HDR Treatment Doses and Times LDR

Median EBRT (Gy) Midline block placed after (Gy) Interval between (days) Start of EBRT and first brachytherapy LDR, first and second brachytherapy HDR, fractions Median dose per fraction (Gy) Median number of fractions Median brachytherapy dose to point A (Gy) Median overall treatment time (days)

HDR

Early

Advanced

Early

Advanced

45 (20–60) 40 (11–60)

50 (40–65) 45 (20–60)

48 (36–60) 40 (20–45)

50 (45–65) 41 (20–50)

24 (0–70) 14 (5–28) — — — 42 (15–95) 52 (28–80)

30 (1–92) 14 (5–49) — — — 45 (10–95) 56 (30–90)

15 (3–56) — 7 (0.5–20) 6 (4–10) 5 (2–12) 29 (12–46) 50 (25–84)

25 (3–84) — 7 (0.5–14) 6 (4–9) 5 (1–8) 30 (15–40) 56 (25–103)

Note. EBRT, external beam radiation therapy; LDR, low dose rate; HDR, high dose rate.

13, 17, 21–23]. Although HDR has been used for treating cervical cancer in other countries since the 1960s, it had not been in routine use for treating cervical cancer in the United States until the 1980s [7]. The present study shows that about four times as many radiation oncologists currently (in 1995) treat cervical cancer with LDR techniques as with HDR (88 vs 24%). In terms of number of patients treated, 73% were by LDR and 16% were by HDR, a ratio of 4.5:1. Recently, there has been a trend toward increasing use of HDR in this country, due to its numerous potential advantages [7, 22, 23]. It will be interesting to see how the use of HDR vs LDR techniques will change over time. The data reported here show that the brachytherapy practice varies considerably in the United States. For example, eight responders (3%) reported that they used EBRT doses of 35 Gy or less (Fig. 4) for the treatment of early disease with HDR when the median dose is 48 Gy. The biological effectiveness of such a low dose to the pelvic nodes is of concern. The use of midline blocking varies even more. A

FIG. 1. Total EBRT dose (including parametrial boosts) in patients of early and advanced carcinoma of cervix treated by LDR.

total of 43% of responders reported that they did not use midline blocks. When they were used, the doses at which they were added varied considerably, from a low of 11 Gy to a high of 60 Gy (Table 5). The brachytherapy doses employed also varied widely (Table 5; Figs. 2 and 5). This wide variation could be explained in part by the variation in the pelvic EBRT doses and the various doses at which midline blocks were placed. For HDR, there was a wide variation in both the dose per fraction and the number of fractions employed. The average HDR dose per fraction was 6 Gy (range 4 –10 Gy), with most institutions using 5 fractions (range 4 –12 fractions). This is a lower dose per fraction than that reported in the Orton et al. survey [16], in which the average dose per fraction was about 7.5 Gy and may possibly indicate efforts to achieve lower late complications through the use of lower dose per fraction. The major difference between LDR and HDR is in the brachytherapy dose to point A. On average, the HDR dose to point A is about 68% of that prescribed with LDR. Also, the distribution of point A doses prescribed with HDR (Fig. 5) is considerably broader than that for LDR (Fig. 2); that is, there is less consensus as to the point A dose to use for HDR, probably due to the relative “newness” of the modality in this country. Other parameters such as EBRT dose, midline blocking, and overall treatment time are similar for both HDR and LDR. There are various methods of determining the rectal and bladder doses including in vivo dosimetry and calculations at various rather arbitrary points. The ICRU Report No. 38 attempted to bring some consensus by defining the point for calculating doses to the rectum and bladder [8]. It is interesting to note that fewer than half (45%) of those responders who determine rectal and bladder doses reported that they were

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FIG. 2. Brachytherapy dose to point A in patients of early and advanced carcinoma of cervix treated by LDR.

currently calculating doses at ICRU reference points. In the review of the 1978, 1983, and 1988 –1989 Patterns of Care studies by Montana, the use of intracavitary point calculations for the bladder and rectum was documented at 80 and 76% of the institutions surveyed [12]. The present survey shows that these percentages have increased to about 90% by 1995. The worldwide survey of HDR brachytherapy by Orton et al. [16] revealed a lower bladder and rectal dose given by HDR compared to that given by LDR techniques (63 vs 72% of the point A dose). These were the average of the “hot spot” doses as determined by calculation or measurement on patients. In the present survey, we did not request measured or calculated bladder or rectal doses but rather an estimation of the maximum doses to these tissues; the estimates provided were not markedly different for LDR (75%) or HDR (70 –75%). Although the doses reported were the goal, this survey does not reveal the actual doses achieved. The predominant LDR applicator used was the Fletcher

applicator (94%); only 8% used the Henschke. Though the modified Fletcher applicator was used most frequently for HDR techniques (64%), a substantial number of practitioners use the ring and tandem applicator (30%) and various other applicators (29%). Current data on the ring applicator use indicate favorable results in comparison to those seen with other HDR and LDR series [7]. There is increasing interest in the impact of treatment duration on both local control and survival in cervical carcinoma [20]. As expected, the average interval between the start of EBRT and first brachytherapy insertion was shorter in patients treated for early disease than for advanced disease, presumably because of such factors as patency of the cervical os and the larger tumor diameter requiring extra EBRT dose. There was a shorter interval between the start of EBRT and first brachytherapy for HDR vs LDR to allow the delivery of the larger number of intracavitary insertions required for HDR. There

FIG. 3. Total treatment time (days) for patients of early and advanced carcinoma of cervix treated by LDR.

FIG. 4. Total EBRT dose (including parametrial boosts) in patients of early and advanced carcinoma of cervix treated by HDR.

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FIG. 5. Brachytherapy dose to point A in patients of early and advanced carcinoma of cervix treated by HDR.

was a remarkable consistency in the median overall treatment duration (varying only from 50 to 56 days) among the various groups of patients (early, advanced, LDR, and HDR), although there was a large spread (from a low of 25 days to a high of 103 days). On analysis of the other brachytherapy modalities, the survey revealed, not unexpectedly, that pulsed dose rate and medium dose rate is rarely used in the United States. It is interesting to note that while 21% of those responders who treated by brachytherapy have used interstitial brachytherapy as a component of treatment, only 6% of patients were treated with this modality. This survey did not ask what the specific

indications were for the use of interstitial brachytherapy on this small fraction of patients. In general, the following are the indications for the use of interstitial brachytherapy in cervical cancer patients [6, 14]: (1) bulky parametrial extension; (2) extensive paravaginal or distal vaginal involvement; (3) narrow vagina or poor geometry not accommodating an ovoid (colpostat) application; (4) loss of endocervical canal not allowing a tandem placement; and (5) prior radiation therapy to the implanted area. It must be recognized that there are some limitations of this study. As a retrospective (rather than a prospective) survey, it is subject to inherent biases of the responders. The data are

FIG. 6. The number of HDR fractions used in patients of early and advanced carcinoma of cervix treated by HDR.

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FIG. 7. Brachytherapy dose per fraction to point A in patients of early and advanced carcinoma of cervix treated by HDR.

based on the reply of the responders some of whom may have given actual data from patient charts while others may have given an estimate; the scope of this survey did not allow us to verify the data by chart audits. This survey included 521 responses whereas there are about 3000 radiation oncologists in this country; thus, it may not accurately reflect the brachytherapy practice of the entire radiation oncology community. It should be noted that this survey did not intend to define optimal patterns of care or seek outcome data for cervical cancer. However, in spite of these limitations, it is an attempt at defining the brachytherapy practice for cervical cancer in this country and can serve as a basis for future prospective national brachytherapy data registry. The large variation in the brachytherapy practice patterns in the United States that it reveals emphasizes the urgent need for consensus on these issues which can only be provided by multi-institutional, controlled clinical trials.

ACKNOWLEDGMENTS The questionnaire for this survey was developed by the Clinical Research Committee of the American Brachytherapy Society (ABS). The members of the gynecology subcommittee were Drs. Andre Abitbol, Beth Erickson, James Fontanesi, Basil Hilaris, Alvaro Martinez, Subir Nag, Dattatreyudu Nori, Arthur Porter, Burton Speiser, and Judith Stitt. The authors thank all the radiation oncologists who cooperated by replying to the questionnaire; Ms. Suzanne Bohn of the ABS, who coordinated this study; Mr. William Bodley, B.A., who compiled the data; and Mr. David Carpenter who edited the manuscript. This study was funded by the American Brachytherapy Society.

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