High-dose-rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix

Inl. J. Radiation Oncology Bml. Phys.. Vol. 19. pp. 791-796 0360.3016/90 $3.00 + .Xl Printed in the U.S.A. All rights reserved. Copyright 0 1990 Pergamon Press plc

??Special Feature

HIGH-DOSE-RATE VERSUS LOW-DOSE-RATE INTRACAVITARY BRACHYTHERAPY FOR CARCINOMA OF THE CERVIX

KAREN K. Fu, M.D. AND THEODORE L. PHILLIPS, M.D.

Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA 94 143

High-dose-rate (HDR) remote afterloading intracavitary hrachytherapy has been widely used in the treatment of carcinoma of the cervix in Europe and Asia since the 1960’s. Recently, there has been an increase of interest in the use of this technique in North America. Most of the non-randomized studies suggest similar survival, local control, and complication rates using fractionated high-dose-rate remote afterloading intracavitary brachytherapy combined with external beam irradiation compared to historical or concurrent low-dose-rate (LDR) controls. However, the techniques as well as the dose fractionation schedules used in different institutions are variable. The optima1 technique and dose fractionation scheme has yet to be established through systematic clinical trials.

High-dose-rate, Low-dose-rate, Brachytherapy, Cervix, Cancer.

INTRODUCTION

In clinical brachytherapy, a wide range of dose rates have been used. According to ICRU report 38 on dose and volume specification for reporting intracavitary therapy in gynecology (1 l), dose rates in the range of 0.4-2.0 Gy/ hr are referred to as low dose rates and dose rates in the range of 2- 12 Gy/hr are referred to as medium dose rates. Dose rates greater than 12 Gy/hr are high dose rates.

Traditionally, low-dose-rate (LDR) intracavitary brachytherapy has been used in the treatment of cervical cancer worldwide. Although high-dose-rate (HDR) intracavitary brachytherapy using a remote afterloading technique was introduced by Henschke et al. at the Memorial Hospital in New York in the early 1960’s (9), low-dose- rate (LDR) intracavitary brachytherapy has been the standard treatment in this country. However, remote afterloading HDR techniques have been widely used in Eu- rope and Asia since the late 1960’s ( 18, 27).

Recently, there has been increased interest in HDR remote afterloading intracavitary brachytherapy for carcinoma of the cervix in the United States. The advantages of the HDR remote afterloading technique are obvious. With this technique, radiation exposure of medical per- sonnel is eliminated. Patient immobilization time is short. Therefore, complications resulting from prolonged bed rest such as pulmonary emboli are eliminated, general anesthesia is avoided, and patient discomfort is decreased.

The use of external applicator fixation devices allows more constant and reproducible geometry of source positioning. Treatment planning and dosimetry are more exact and optimization is possible. Furthermore, treatment can be performed on an outpatient basis and health care costs are reduced.

The technique and dose fractionation schedules currently used in different institutions are variable, and many people remain skeptical about the efficacy and potential complications associated with the increased dose rate. There is much radiobiological data to suggest that LDR optimizes the therapeutic ratio. In this review of results published in the English literature, an attempt was made to compare the results of HDR versus LDR intracavitary brachytherapy for carcinoma of the cervix.

METHODS AND MATERIALS

Randomized studies Thus far there have been two randomized trials com-

paring HDR versus LDR intracavitary brachytherapy for carcinoma of the cervix (7,2 1). The trial from Japan was reported by Shigematsu et al. (2 1). The dose fractionation schedule, 5-year survival, rectal and bladder complication rates are included in Tables 1, 2, 4 and 5. Although patients with Stage IIB or III disease treated with the HDR technique had a higher 1 -year local control rate (90% with

Presented at the 30th annual meeting of the American Society of Therapeutic Radiology and Oncology, 9-14 October 1988, New Orleans, LA.

Reprint requests to: Karen K. Fu, M.D., Department of Ra-

diation Oncology, Box 0226, University of California, San Francisco, CA 94 143.

Accepted for publication 30 May 1990.

791

792 I. J. Radiation Oncology 0 Biology 0 Physics September 1990, Volume 19, Number 3

Table 1. HDR brachytherapy for carcinoma of the cervix: dose fractionation schedule

1 st author (country) Dose/Fx at pt. A(GY)

No. of Fxs. No. Fx/wk

External beam

Dose(Gy) Timing

Glaser (6) (Germany) 6-7 5-6 1 40-50 A Vahrson (26) (Germany) 6-14* 3-7 0.5-l 45-46 C Cikaric (5) (Yugoslavia) 9-10 4 1 35-46 C Akine (1) (Japan) 3-5 5-6 2-3 29-67 B Himmelman (10) 8.5+ 5 1 40-50 A Kuplers ( 14, 15) (Netherlands) 8.5 2 2 46 B Sato (20) (Japan) 6.1 5 1 50-60 B Shigematsu (2 1) (Japan) 8-10 3 1 40 C Taina (22) (Finland) 7.5-10 3-5 1 50 A Aral (4) (Japan) 3-7 4-13 l-3 45-65 C

A = After; B = Before; C = Concurrent with brachytherapy. * Dose-maximum on the A-line (or A-plane) 2 cm lateral from the central axis of the applicator. + Dose at the surface of the target volume.

HDR vs 77% with LDR), the rectal complication rate was also higher in this group than in the LDR group. The 5- year survival was 55% for both groups.

Another trial from India was recently presented by Gupta et al. at the 5th International Selectron Users’ Meeting in the Hague (7). This trial included patients with Stages IB, IIA, IIB and III disease. The local control rate was similar for both the HDR and LDR groups (80% vs 85%). However, the stage distribution in each group, the survival, and complication rates were not reported.

Non-randomized studies There are at least 10 non-randomized studies (3-6, 10,

14, 15, 19, 20, 22, 23, 26) in which the results of HDR

were compared to historical or concurrent LDR controls in the same institution. All of these studies have a relatively large number of patients with reasonably long follow-up. As shown in Table I, the dose fractionation schedules used are variable. Most studies used point A as a reference point, although it should be noted that the definition of point A may differ from center to center. The dose per fraction at point A varied from 3-10 Gy, the number of fractions varied from 2- 13, and the number of fractions per week varied from 1-3. However, most centers used a schedule of 7-8 Gy per fraction per week for 3-6 fractions. The external beam dose was variable and depended on the stage of disease. In most centers, the external beam irradiation was carried out concurrently with or after in-

Table 2. HDR vs LDR brachytherapy for carcinoma of the cervix: survival

1 st author (year)

Glaser (6) ( 1988) Vahrson (26) ( 1988)

Cikaric (5) (1988)

Akine (1) (1988)

Kuplers ( 15) ( 1984)

Sato (20) ( 1984)

Shigematsu (21) (1983) Taina (22) (198 1) Rotte (19) (1980)

Aral(4) ( 1980)

Stage

I-III I II III II III IIB IIIB I II III II III IIB & III I & II I II I II III IV

No. of patients HDR/LDR

4931288 241206 371213 291138 85166 521120 20183 371212 21132 5417 1 36142 31140 44185

143/106 40130 42128 59/121 8613 1

1731125 2121253

46180

5 yr survival (%)

HDR LDR

59* 33* (p = .OOl) 71 74 76 53 (p< .05) 62 24 (p < .OOl) 54 70 37 43 60 56 54 38 76 80 74 68 36 48 55 55 57 49 55 55 90+ 73+ 83 89 75 76 83 87 71 75 51 49 24 16

* Relapse-free survival. + 3 year survival.

HDR vs LDR for cervical cancer 0 K. K. Fu AND T. L. PHILLIPS 193

Table 3. HDR vs LDR intracavitary brachytherapy for carcinoma of the cervix ( 1979- 198 1)

(FIG0 annual report, 1987) (2)

Stage

I II

III IV

No. pts. HDR/LDR

1601422 3581796 386/588 66150

5 year survival (W)

HDR LDR

76.9 71.6 58.1 54.4 38.1 38.4 15.2 10.0

tracavitary brachytherapy. In three centers (1, 14, 20) it was given before intracavitary brachytherapy. In three series, 50% or more of the patients had surgery before (6) or after radiotherapy (10, 22). In this review, only the results in patients treated with radiotherapy alone are included.

Table 2 shows the 5-year survival of patients who re- ceived HDR and LDR brachytherapy combined with external beam irradiation for carcinoma of the cervix by stage. Stage for stage, 5-year survival of patients treated with the HDR technique was comparable to the historical or concurrent non-randomized LDR controls treated in the same institution. Two studies from Germany (6, 26) showed a significantly better survival for the HDR group. In the series by Glaser (6), the difference in relapse-free survival (RFS) was seen primarily in patients with Stage Ill disease. In the series by Vahrson and Romer (26), the difference in survival was significant for Stage II (p < .05)

and Ill (p < .OOl) but not for Stage I disease. In the 1986 FIG0 (International Federation of Gynecology and Ob- stetrics) annual report on the results of treatment of gynecological cancer from around the world similar 5-year survival rates were also reported for HDR and LDR intracavitary brachytherapy of carcinoma of the cervix (Ta- ble 3) (2).

Local control rates were available in two studies (I, 15). In the series by Akine et al. ( I), the local control rate was 7 1% in the HDR group and 83% in the LDR group for Stage IIB disease and 64% and 6 l%, respectively, for Stage IIIB disease. In the series by Kupiers et al. (15), the local control rate was 90% versus 88% for Stage I, 85% versus 89% for Stage II, and 70% versus 62% for Stage Ill disease. Thus, stage for stage, the local control rate with the HDR technique appears to be equally as good as the LDR technique.

Table 4 illustrates the rectal complication rates. Note that the scoring system for the complications was not clearly stated in all reports. Nonetheless, for individual institutions, the complication rates are comparable between the HDR and the LDR techniques. However, in the series by Cikaric (5), the rectal complication rate was significantly higher in the LDR group.

Table 5 shows the bladder complication rates. They are lower than rectal complication rates. Here again, except for the series by Cikaric (5) showing a higher complication rate with the LDR technique, there was no significant difference between the two techniques in most institutions.

In addition to these studies in which both HDR and

Table 4. HDR vs LDR brachytherapy for carcinoma of the cervix: rectal complications

1st author

Vahrson (26) Cikaric (5) Akine ( 1)

Kupiers ( 14) Sat0 (20) Shigematsu (2 1) Rotte ( 19)

* Rectal bleeding.

No. of patients HDR/LDR

1471835 140/187 841372

111/145 871147

1431106 1121237

Complication rate (%)

HDR LDR

3.0 (late, sev.) 2.0 (late, sev.) 7.1 16.6

24.0 (mod.) 36.0 (mod) 2.4 (sev.) 4.0 (sev.) 7.0 (grade 3) 6.6 (grade 3)

14.9 13.6 36.0* 25.0*

2.6 10.5

(P < .Ol)

Table 5. HDR vs LDR brachytherapy for carcinoma of the cervix: bladder complications

1st author No. of patients

HDR/LDR


HDR LDR

Vahrson (26) 1471835 3.0 (late, sev.) 2.0 (late, sev.) Cikaric (5) 140/187 5.0 9.6 (P < .01) Akine (1) 841372 1.2 (mod.) 11 (mod.)

0 (scv.) 0.5 (sev.) Kupiers ( 14) Ill/145 3.5 (grade 3) 3.3 (grade 3) Sat0 (20) 871147 9.2 7.5 Shigematsu (2 1) 143/106 2.0 7.0 Rotte ( 19) 1121237 0.8 2.5


Table 6. HDR brachytherapy for carcinoma of the cervix: dose fractionation schedule

1 st author (country)

Joslin (UK) (13) Mizoe (Japan) (16) Ilic (Yugoslavia) ( 12) Teshima (Japan) (24) Utley (USA) (25) Newman (UK) ( 17)

Dose/Fx at No. of Pt. A(GY) Fxs.

8.5 2-5 5.0 6-7

9-10.5 4 7.5 3-6

5-6.6 6-10 7-8.5 2-5

No. Fx/wk

I 2 1 1 2 1

External beam

Dose(Gy) Timing

24-45 C, B 40-50 B

27 C 14-40 C 20-50 C 22-63 C

B = Before; C = Concurrent with brachytherapy.

LDR results from the same institution were presented, there were six other large series (12, 13, 16, 24,25) on the results of HDR remote afterloading intracavitary brachytherapy for carcinoma of the cervix. Table 6 shows the dose fractionation schedules used in these studies. The dose per fraction at point A ranged from 5- 10.5 Gy, and the number of fractions per week ranged from l-2. Ex- ternal beam dose depended on the stage. In most centers, brachytherapy was carried out concurrently with external beam irradiation. The 5-year survival according to stage is shown in Table 7. These results are comparable to the results of radiotherapy for carcinoma of the cervix from around the world in the 1987 FIG0 annual report (2). Local-regional control rates are available from two of the studies ( 13, 17). In the series by Joslin (13) the local control rate was 93.7% for Stage I, 66.5% for Stage II, and 39.6% for Stage III disease. In the series by Newman et al. (17), it was 91% for Stage I, 78% for Stage IB, 76% for Stage IIA, 57% for Stage IIB, 17% for Stage IIIA, and 52%

Table 7. HDR brachytherapy for CA. of the cervix: survival

1 st author (year) Stage No. of 5 yr. survival

patients (%)

Joslin (13) (1988)

Mizoe ( 16) ( 1988)

Ilic ( 12) ( 1988)

Teshlma (24) ( 1987)

Utley (25) ( 1984)

Newman (17) (1983)

I 95 94 II 170 62 III 106 37 I 17 71 II 68 66 III 212 39 I 232 93 II 462 73 III 430 54 IV 34 18 IA 8 100 IB 22 86 IIA 22 67 IIB 53 72 III 85 41 IV 10 20 I 29 89 II 50 58 III 43 33 I 92 81 IIA 53 74 IIB 50 40 III 92 27

for Stage IIIB disease. The rectal complication rate varied from 1.4- 10% for major or severe and 0.7-24% for minor to moderate complications (Table 8). The bladder complication rate was low and varied from 0.3-4.0% (Table 9). These local control rates and complication rates are comparable to those in the patterns of care survey reported by Hanks et al. (8).

Dose fractionation versus local control and complications

One of the major concerns in the application of the high dose rate intracavitary brachytherapy technique is the potential risk of increased complication associated with high dose rate. Available clinical data suggest that in addition to total dose, the most important factor in late complication is the dose/fraction and the number of fractions. The major site of complication is the rectum whereas the bladder complication rate is relatively low.

The relationship between dose and fractionation for high and low dose rate intracavitary irradiation of Stage I and II carcinoma of the cervix was examined by Arai and colleagues (3, 4) in Japan and is shown in Figure 1. The dose was specified at point A. The dose rate was 200- 300 cGy/min ( 120- 180 Gy/hr) for HDR and 1- 1.5 cGy/ min (0.6-0.9 Gy/hr) for LDR irradiation. The overall time was 28.9 f 6 to 36.6 + 4.9 days for HDR and 24.8 t- 7.4 to 44.8 + 10.2 days for LDR in most cases. Concurrent external beam irradiation with 45-50 Gy in 5 weeks was given to the parametria with a central shield. For bulky Stage II disease, 23-30 Gy was given to the whole pelvis

Table 8. HDR brachytherapy for CA. of the cervix: rectal complications

1st author

Joslin (13) Mizoe ( 16) Teshima (24) Utley (25)

Newman ( 17)

No. of patients

371 206 200 127

291


2.7 (late) 14.6 (grade l-3) 7.0 (mod.-sev.)

14-24 (mod.)* 3-10 (sev.)* 0.7 (minor) 1.4 (major)

* Complication rates: 1970-1972: severe lo%, moderate 24%; 1973-1975: severe 3%, moderate 20%; 1976-1979: severe 4%, moderate 14%.

HDR vs LDR for cervical cancer 0 K. K. Fu AND T. L. PHILLIPS 795

Table 9. HDR brachytherapy for CA. of the cervix: bladder complication

1st author

Joslin ( 13) Mizoe ( 16) Teshima (24) Newman (17)

No. of patients

371 206 200 291

Complication rate (W)

4.0 (late) 3.4 (mild) 3.0 (mod.-sev.) 4.0 (minor) 0.3 (major)

followed by 25-30 Gy with central shielding and reduced intracavitary irradiation. Two diagonal lines were drawn to represent what the authors felt to be the optimal con- ditions. From these data, they concluded that the optimal dose fractionation schedules for intracavitary irradiation were: (a) for HDR: 28 Gy + 3 Gy in 4-5 fractions, or 34 + 4 Gy in 8- 10 fractions or 40 -t 5 Gy in 12- 14 fractions at point A; (b) for LDR: 51 k 5 Gy in 3-4 fractions at point A. The dose at point A with the LDR technique appeared low compared to European and American prac- tice. Not all the cases treated were included in their graph (4).

DISCUSSION AND CONCLUSION

In conclusion, most of the non-randomized studies suggest similar survival, local-control, and complication rates using fractionated remote afterloading HDR intracavitary brachytherapy combined with external beam irradiation for carcinoma of the cervix compared to historical or concurrent LDR controls. However, in review- ing the results in the literature, several problems became apparent to us: (a) dose specification between different centers was not standardized, (b) dosimetry systems and methods were variable, (c) there were technical variations

100 90 F

a I

including the type of applicators, use of protective shields, treatment positions etc., (d) dose-volume information was unavailable in most reports, (e) external beam dose or treatment time as well as the time sequence of external beam irradiation and intracavitary radiotherapy were variable, (f) different methods of rectal and bladder dose measurements were used, (g) toxicity grading systems were not standardized, and (h) length of patient follow-up was variable. Thus, results between centers may not be inter- comparable. However, within the same institution, the results of the HDR and LDR techniques were not significantly different in most studies. Although in some studies, the number of patients treated with each technique was not always comparable. In a few centers a difference in survival, local-control or complication rate was noted (5, 6, 2 1, 22, 26). The difference may not be due to a difference in dose rate alone. In addition to dose rate, technical, geometrical, and anatomic factors may be important.

With HDR intracavitary brachytherapy, the complication rate increases with increase of dose/fraction and decrease of number of fractions. Currently, the dose fractionation schedules used in different centers are variable. The optimal time/dose/fractionation scheme and the technique for remote afterloading intracavitary brachytherapy for cervical cancer have yet to be established through systematic clinical trials. In addition, future clinical trials should establish the optimal integration of external beam irradiation and intracavitary brachytherapy for the treatment of different stages of cervical cancer. For the results from different centers to be comparable it is necessary that dose specification, dose reference points, dosimetry systems and methods, normal tissue toxicity grading, quality assurance procedures, and reporting systems be standardized. Optimization of treatment planning may be facilitated through the use of computer programs and the use of CT and MRI scans. The use of external

HIGH DOSE - RATE LOW DOSE - RATE .

0

15 ' I I I I 1 I,, I 1 2 3 4 56 0 10 12 14 , I I I

2 3 4 5

NUMBER OF FRACTIONS

Fig. 1. Relationship between total dose, number of fractions and local control, failure, and complication for HDR and LDR intracavitary brachytherapy of Stage I and II carcinoma of the cervix (redrawn from Arai et ul., 1980) (4).


applicator fixation devices, rectal retractors, and protective optimal technique for the delivery of high dose rate remote shields may further minimize the complication rates. afterloading intracavitary brachytherapy for carcinoma Much clinical research effort is needed to establish the of the cervix.

REFERENCES

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

Akine, Y.; Arimoto, H.; Ogino, T.; Kajiura, Y.; Tsukiyama, I.; Egawa, S.; Yamada, T.; Tanemura, K.; Tsunematsu, R.; Ohmi, K.; Sonoda, T.; Kasamatsu, T. High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: Early experience with 84 patients. Int. J. Ra- diat. Oncol. Biol. Phys. 14893-898; 1988. Annual Report on the results of treatment in gynecological Cancer. In: Pettersson, F., ed. Twentieth volume statements of results obtained in patients treated in 1979- 198 1, inclu- sive 5-year survival up to 1986. Stockholm, Sweden: Inter- national Federation of Gynecology and Obstetrics; 1987 20: 52. Arai, T.; Morita, S.; Linuma, T.; Nakamura, Y.; Fukuhisa, K.; Kubo, H.; Onai, Y.; Tomaru, T.; Masubuchi, K.; Tsuya, A.; Kawahara, Y.; Tazaki, E. Radiation treatment of cervix cancer using high dose rate remote afterloading intracavitary irradiation: an analysis of the correlation between optimal dose range and fractionation. Japan. J. Cant. Clin. 25:605- 612; 1979. Arai, T.; Morita, S.; Kutsutani, Y.; Linuma, T.; Masubuchi, K.; Tsuya, A.; Onai, Y.; Ito, Y.; Tazaki, E. Relationship between total iso-effect dose and number of fractions for the treatment of uterine cervical carcinoma by high dose- rate intracavitary irradiation. In: Bates, T. D., Berry, R. J., eds. High dose rate afterloading in the treatment of cancer of the uterus. London: Br. J. Radiol. Special Report 17; 1980:89-92. Cikaric, S. Radiation therapy of cervical carcinoma using either HDR or LDR afterloading: comparison of 5-year results and complications. Strahlenther. Onkol. 82(Suppl.): 119-122; 1988. Glaser, F. H. Comparison of HDR afterloading with 19*Ir versus conventional radium therapy in cervix cancer: 5-year results and complications. Strahlenther. Onkol. 82(Suppl.): 106-l 13; 1988. Gupta, B. D.; Ayyagari, S.; Sharma, S. C.; Negi, P. S.; Patel, F. Carcinoma cervix: optimal time-dose-fractionation of HDR brachytherapy and comparison with conventional dose-rate brachytherapy. In: Mould, R. F., ed. Brachyther- apy. Leersum, The Netherlands: Nucleotron Trading BV; 1989:307-308. Hanks, G. E.; Herring, D. F.; Kramer, S. Patterns of care outcome studies. Cancer 51:959-967; 1983. Henschke, U. K.; Hiiaris, B. S.; Mahan, D. G. Remote afterloading with intracavitary applicators. Radiology 83:344- 345; 1964. Himmelmann, A.; Holmberg, E.; Oden, A.; Skogsberg, K. Intracavitary irradiation of carcinoma of the cervix stage IB and IIA: a clinical comparison between a remote high dose- rate afterloading system and a low dose-rate manual system. Acta Radiol. Oncol. 24:139-144; 1985. ICRU Report No. 38. Dose and volume specifications for reporting intracavitary therapy in gynecology. Bethesda, MD: International Commission on Radiation Units; 1985: 4-5. Ilic, S., Ristic, B. 5-year results with HDR afterloading cervix cancer: dependence on fractionation and dose. Strahlenther. Onkol. 82(Suppl.): 139- 146; 1988.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25

26.

27.

Joslin, C. A. F. High-activity source afterloading in gyne- cologic cancer and its future prospects. Endocuriether. Hy- perther. Oncol. 5:69-82; 1989. Kuipers, T. Dosimetry and complication rate in the treatment of cervix carcinoma with external irradiation and brachytherapy. Strahlenther. Onkol. 82(Suppl.): 127- 13 1; 1980. Kuipers, T. High dose-rate intracavitary irradiation: results of treatment. In: Mould, R. F., ed. Brachytherapy. Leersum, The Netherlands; Nucleotron Trading BV; 1984: 169- 175. Mizoe, J.; Tsujii, T.; Kamada, T.; Arimoto, Y.; Matsuoka, H.; Shirato, H.; Tsuji, Irie, G. Five-year results and complications with HDR afterloading in cervix cancer using a linear arrangement of source. Strahlenther. Onkol. 82(Suppl.):ll4-126; 1988. Newman, H.; Jur, C. H. B. B.; James, K. W.; Smith, C. W. Treatment of cancer of the cervix with a high-dose-rate afterloading machine (the cathetron). Int. J. Radiat. Oncol. Biol. Phys. 9:93 l-937; 1983. O’Connel, D.; Howard, N.; Joslin, C. A. F.; Ramsey, N. W.; Liversage, W. E. A new remotely controlled unit for the treatment of uterine carcinoma. Lancet 2:570-57 1; 1965. Rotte, K. A randomized clinical trial comparing a high dose- rate with a conventional dose-rate technique. In: Bates, T. D., Berry, R. J., eds. High dose rate afterloading in the treatment of cancer of the uterus. Wurzburg, West Germany: Br. J. Radiol. Special Report; 17:75-79; 1980. Sato, S.; Yajima, A.; Suzuki, M. Therapeutic results using high-dose-rate intracavitary irradiation in cases of cervical cancer. Gynecol. Oncol. 19: 143- 147; 1984. Shigematsu, Y.; Nishiyama, K.; Masaki, N.; Inoue, T.; Mi- yata, Y.; Ikeda, H.; Ozeki, S.; Kawamura, Y.; Kurachi, K. Treatment of carcinoma of the uterine cervix by remotely controlled afterloading intracavitary radiotherapy with high- dose rate: a comparative study with a low-dose rate system. Int. J. Radiat. Oncol. Biol. Phys. 9:35 l-356; 1983. Taina, E.; Gronroos, M. A comparison of clinical results following high dose-rate intracavitary afterloading irradiation with C06’ (cathetron) and conventional radium therapy for St. I-II cervical carcinoma. Acta Obstet. Gynecol. Stand. Suppl. 103:31-38; 1981. Taina, E. Complications following high and low dose-rate intracavitary radiotherapy for St. I-II cervical carcinoma: a comparison of remotely afterloaded C06’ (Cathetron) and conventional radium therapy. Acta. Obstet. Gynecol. Scan. 103(Suppl.):39-49; 198 1. Teshima, T.; Chatani, M.; Hata, K.; Inoue, T. High-dose rate intracavitary therapy for carcinoma of the uterine cervix: I. General figures of survival and complication. Int. J. Radiat. Oncol. Biol. Phys. 13:1035-1041; 1987. Utley, J. F.; von Essen, C. F.; Horn, R. A.; Moeller, J. H. High-dose-rate afterloading brachytherapy in carcinoma of the uterine cervix. Int. J. Radiat. Oncol. Biol. Phys. l&2259- 2263; 1984. Vahrson, G.; Romer, G. 5-year results with HDR afterloading in cervix cancer: dependence on fractionation and dose. Strahlenther. Onkol. 82(Suppl.): 139- 146; 1988. Vahrson, H.; Glaser, F. H. History of HDR afterloading in brachytherapy. Strahlenther. Onkol. 82(Suppl.):2-6; 1988.

Documents

High-dose-rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix