Japanese Journal of Clinical Oncology 31:541-547 (2001)
© 2001 Foundation for Promotion of Cancer Research
Toxicity and Health-related Quality of Life During and After High Dose Rate Brachytherapy Followed by External Beam Radiotherapy for Prostate Cancer
1Department of Urology, 2Department of Radiology and 3Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Background: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol.
Methods: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12–18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life.
Results: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes.
Conclusions: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Afterloading brachytherapy is the sole modality of interstitial radiotherapy currently available in Japan for treating prostate cancer. This technique has several advantages over permanent seed implantation, including absence of radiation protection and safety issues for the patient and his immediate family. Exposure of the treating personnel is also significantly reduced. Furthermore, dosimetry can be based on images with the needles in situ, making it easy to optimize the dose.
Utilizing the linear-quadratic equation, the 
/ß ratio has been used to calculate putative biological equivalent doses in interstitial radiotherapy. It has recently been suggested that the /ß ratio for prostate cancer is much lower than that for other common tumors, in the range 1.2–2.5 (1–3). This implies an increased sensitivity of the tumor to large doses per fraction, such as that delivered with high dose rate (HDR) brachytherapy. Whether this hypofractionation regimen will truly result in improved clinical and biochemical control with acceptable toxicity rates remains to be seen.
This paper reports a prospective investigation, in consecutive patients who underwent combined HDR brachytherapy and external beam radiation therapy, of toxicity over a 12–18-month period following initiation of treatment and of its impact on health-related quality of life. To our knowledge, this is the first such study in Japan.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Patients’ Characteristics
From June 1999 through January 2001, 58 patients, aged 49–82 years (mean 69.8, median 69.5 years), were treated for prostate cancer with HDR brachytherapy followed by 30 Gy external beam radiation therapy. Clinical characteristics at presentation are summarized in Table 1. Clinical stage at the time of diagnosis was determined in accordance with the 1992 unified tumor node metastasis (TNM) system (4). For the five patients who were already under endocrine therapy at the time of referral, clinical stage in the original reports by the local urologist was utilized.
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All histology slides were examined and reviewed by a single pathologist (S.K.) and tumor grade was assigned based on the Gleason grading system. Prostate-specific antigen (PSA) levels at diagnosis were measured at various laboratories using various techniques. These include Dainapack AxSYM PSA assay (Dinabot, Tokyo), Delfia PSA assay (Pharmacia and Upjohn, Tokyo) and Lumipulse PSA assay (Fujirebio, Tokyo). Results of these assays were not inter-converted, since they are considered virtually identical.
Patients were considered candidates for combination radiotherapy if they presented with clinically organ-confined or locally advanced prostate cancer but without distant metastasis (T1N0M0–T3N0M0). Prior to June 2000, patients in the high-risk group (PSA >20.0 ng/ml, biopsy Gleason score 
8, T2c) might, at the discretion of the local urologist or attending physician, be given 3 months of neoadjuvant endocrine therapy prior to irradiation; nine patients were in this group. The 15 high-risk patients since that date were prospectively enrolled into a study of 6 months’ neoadjuvant endocrine therapy followed by 3 years of adjuvant endocrine therapy following radiation therapy (5). Combined androgen blockade was used in 13 patients and luteinizing hormone-releasing hormone agonist alone in 12 patients.
Two patients who fell outside the usual entry criteria were treated. One with T4N0M0 at presentation was given radiation therapy after complete suppression of PSA by prolonged (15 months) endocrine therapy. Another was found by computed tomography (CT) scanning immediately before the scheduled treatment to have a metastasis in the obturator lymph node and was therefore reclassified as T3cN1M0, but nevertheless elected to undergo radiotherapy.
All patients were seen once every month for the first 3 months after completion of radiation therapy, quarterly for the first year and semiannually thereafter. Each follow-up visit required history, physical examination, serum PSA and recovery of self-administered questionnaires. The recommendations of the consensus panel of the American Society for Therapeutic Radiology and Oncology were followed for assessing biochemical failure (6). Bone scanning was repeated every year and ultrasound-guided biopsy of the prostate was recommended at 24 months. The mean follow-up period for the 58 patients was 10.0 months after completion of radiation therapy (range 1.0–20.0, median 11.0 months). That for 25 patients under endocrine manipulation was 14.9 months from the initiation of androgen ablation (range 7.0–23.5, median 13.0 months).
Procedure of HDR Brachytherapy and External Beam Radiation Therapy
The complete details of the procedure have been described by others elsewhere (7). Briefly, patients in the operating room were placed in a lithotomy position under epidural anesthesia and the prostate volume was sonographically defined. Prostate volume was determined as prostate length x width x height x (
/6). Treatment was initiated using closed transperineal hollow needle placement under transrectal ultrasound guidance. Multiple 20–25 cm long, closed-end, 15G plastic hollow needles were inserted transperineally using a Syed-Neblett plastic template (Alpha-Omega Services, Bellflower, CA) (7). Usually 18 needles were implanted. The needle tips were left within the urinary bladder 1–2 cm above the sonographically defined base of the prostate. Metallic marker seeds were placed transperineally into the base and apex. Flexible cystoscopy was conducted to ensure that the urethra had not been penetrated by the implanted tubes.
Immediately following the implant, anterior/posterior and lateral pelvic radiographs were taken and a spiral CT scan was done. The contours of the planning target volume (PTV), defined as the whole prostate gland and the critical tissues were identified on all CT slices. Digitized representations were sent to the PLATO BPS planning workstation (Nucletron, Veenendaal, The Netherlands) for optimization. On the PTV surface, equidistant dose points were generated in order to calculate the mean dose value. The active dwell positions were ascertained, with careful attention to ensure that all of them lay within the PTV. 3D dose optimization could then produce a homogeneous dose distribution.
Reference points were generated at a distance of 0.5 cm from the dwell positions around the dorsal aspects of the prostatic gland. The reference dose was defined as the 100% value. The whole prostate and any tumor extension beyond the capsule were irradiated five times over 3 days using an HDR iridium-192 source with a nominal activity of 370 GBq (microSelectron-HDR, Veenendaal, The Netherlands). Each single dose was 4 Gy during the period June 1999 through August 2000 and was 5 Gy during the period September 2000 through January 2001. Although our software does not allow us to measure doses to specific areas precisely, the radiation doses to the urethra, neurovascular bundles and prostatic capsules are roughly estimated from the dosimetry information to be 8–9, 6.5–7 and 7 Gy per time with the current protocol, respectively.
Three days after the last HDR brachytherapy fraction, external beam radiation therapy (EBRT) was started (10 MV, MEVATRON, Siemens, Munich, Germany). A two-dimensional conventional technique was used until April 2000. Beginning in May 2000, a CT-based conformal 3D dose plan was created for each patient. The PTV was defined as the prostate gland plus the seminal vesicle with a surrounding margin of 0.5 cm. External beam irradiation was given using a fractionation of five times 3.0 Gy per week, specified at the isocenter, for 2 weeks. Thus, the total EBRT dose was 30.0 Gy.
Evaluation of Health-related Quality of Life Related to Toxicities
Physician assessment and grading of treatment-related toxicity that lasted for 1 month or longer following completion of radiation therapy was carried out at the time of occurrence by one of us (S.E.) using the Radiation Therapy Oncology Group (RTOG) morbidity criteria (8). Late complications were defined as those that occurred 3 or more months after the end of treatment. Acute toxicity occurred during treatment.
Four separate questionnaires were used to acquire demographic data and general and prostate disease-targeted measures of quality of life. General health-related quality of life was measured sequentially prior to and following radiation therapy using the Japanese version of the RAND 36-Item Health Survey (SF-36, version 1.2), a self-administered 36-item questionnaire that includes eight multi-item scales (9). These scales comprise four physical domains (physical function, role limitations due to physical health problems, bodily pain and general health perceptions) and four mental domains (emotional well-being, role limitations due to emotional problems, energy fatigue and social function). Part of the Japanese version of the EORTC questionnaire was also used to assess quality of life issues in these patients (10,11), including domains of disease-related conditions [seven items, Nos 9–12, 15–17 in the original questionnaire (11)] and global sexual function [three items, Nos 24–26 in the original questionnaire (11)]. Five additional queries (shown in Fig. 1) were added to ask about gastrointestinal and genitourinary conditions. Answers to these questions were categorized by the same format. Each area is composed of the sum of several weighted items, giving scores of 28, 12 and 20, respectively. The higher the score, the higher is the level of symptomatology or problems.
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Patient mood during the first 7 days from the beginning of HDR brachytherapy was assessed using the Japanese language validated face scale (12,13). This is a brief, pictorial scale of mood, which uses a sequence of six faces; scores range from 0 to 5, with higher scores representing a higher level of symptomatology or problems. Only the highest score of the day was recorded for the purpose of analysis. International Prostate Symptom Score (IPSS) and QOL score were also assessed at the same time, giving total scores of 35 and 6, respectively (14). Again, higher scores represent a higher level of symptomatology or problems. Data are presented as the mean (± standard deviation) scores for all patients completing surveys at each time point. Hence the values represent longitudinal time trends in the groups and not in any individual.
Statistical Analysis
A Wilcoxon signed rank test was performed to assess differences between scores at each time point; p values <0.05 were considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Physician-assessed Toxicities
Treatment-related toxicities are listed in Table 2 according to the types of radiation and applied doses. Some degree of rectal bleeding (a few drops to a handful) was noted at least once in 13 patients (22%) at a median of 11 months (range, 5–19 months). Eleven of these were scored as having grade 1–2 toxicity. Two patients underwent laser cauterization once (grade 3). The remaining patients were followed conservatively and the rectal bleeding subsided spontaneously. All these events were seen in our earlier phase of experience with conventional external beam radiation therapy. Diarrhea was more common during the first month after irradiation. Acute retention and aggravation of lower urinary tract symptoms were noted in 10 patients (17%). One patient developed neurogenic disorders of the rectum and urinary bladder together with peripheral neuropathy of the lower extremities noted during the second day of the HDR. Chronic retention and fecal incontinence followed by severe constipation lasted for almost 12 months, but symptoms gradually resolved thereafter. Although the etiology is unknown, this event was classified as RTOG grade 3. However, there were no obvious changes with time in either genitourinary or gastrointestinal RTOG scores (Table 3).
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Patient-assessed Morbidities
Patient mood as judged by face scales improved significantly immediately after the removal of HDR needles at day 3 (p = 0.01, Table 4). Univariate analysis of time trends revealed that during the first month patients had a statistically significant decrease in five SF-36 domains, including role limitations due to physical health problems, bodily pain, role limitations due to emotional problems, energy fatigue and social function (Table 5). Most returned to normal by 3 months and all recovered by 12 months. The number of patients at 18 months was too small to allow statistical analysis. All selected domains in the Japanese version of the EORTC questionnaire, except for sexual function, showed the same trend (Table 6). Irradiation had no effect on items in the sexual function domain as a whole. Patients not undergoing neoadjuvant endocrine therapy had slightly better sexual function prior to irradiation than did those who had such therapy (median scores 8.0 versus 10.0, p = 0.01). This difference, however, did not persist following irradiation (p > 0.05, data not shown). Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of radiation therapy and recovered to baseline levels at all later times (Table 7, p < 0.05).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Brachytherapy is a technique for the delivery of a high radiation dose to a well-defined volume with high precision and with dose to the surrounding organs decreasing rapidly with distance. The distribution of the radiation dose is relatively inhomogeneous, however. On the other hand, in external beam radiation therapy inherent errors of repeated treatment set-ups compromise the dose to the clinical target volume and may increase damage to normal tissues. A combination of these two modalities may therefore maximize the advantages and minimize the disadvantages of each. The optimal distribution of the total radiation dose between brachytherapy and external beam irradiation is unknown, however.
There have been several investigations of combined treatment using different regimens (15–20). The total biological effect of the combined treatment is usually difficult to determine. A linear quadratic model is often used in an attempt to estimate the corresponding dose if the whole treatment had been given with a fractionation scheme with 2.0 Gy five times a week. It has recently been suggested that the /ß value for prostate cancer is much lower than those for other common tumors, in the range 1.2–2.5 (1–3). In theory, according to the linear quadratic model, this implies an increased sensitivity of the tumor to large doses per fraction. Recognizing the uncertainties in our current understanding of the /ß value for prostate cancer, however, toxicity rates and clinical and biochemical outcomes should be evaluated to validate each treatment protocol. Using the linear quadratic model and an assumed /ß value of 1.5 Gy for prostate cancer, the total dose in this study reached a value of 102.9 Gy. Assuming the /ß value of 3.0 Gy, the total dose for the rectum would be 76 Gy.
Ten patients (17%) noted temporary aggravation of their lower urinary tract obstructive symptoms. In this study, various degrees of rectal bleeding due to radiation proctitis were experienced in 13 patients (22%) at a median of 11 months. Two of these patients needed hospitalization to undergo laser cauterization of the rectal mucosa. Rectal bleeding subsided spontaneously in the others. Proctologic complications following conventional external radiation for prostate cancer have been reported to range from 6.6 to 14% (21). Most studies using a combination of HDR brachytherapy and external beam radiation found the incidence of grade 2 or greater proctitis to be less frequent (1.9–11.4%) (15–20). Treatment plans exposing more than 40% of the anterior rectum to more than 75 Gy with conventional fractionation have been associated with an increase in the incidence of rectal bleeding (21). This accounts in part for the higher incidence of rectal bleeding in this study. No patient has developed rectal bleeding since the introduction of conformal external beam irradiation in May 2000 (p < 0.01). However, it is too early to confirm the safety of this modality owing to the short follow-up.
The average time to complication has been reported as 12.8 months for gastrointestinal toxicity and 32.9 months for genitourinary toxicity after conformal or conventional radiation treatment (22). Schultheiss et al. in their preliminary experience using 3D-CRT reported that acute gastrointestinal and genitourinary complications were found to correlate with development of the corresponding late complication (23). Longer follow-up is needed to determine the true incidence of late toxicity for our treatment regimens.
We examined changes in health-related quality of life longitudinally following radiation therapy using separate self-administered questionnaires. Our patients had a statistically significant decrease in five SF-36 domains during the first month of treatment. All recovered to the baseline level by 12 months. The sexual function domain as a whole did not show significant changes after irradiation. No differences in scores following radiation therapy were evident between those with and without endocrine therapy. Helgason et al. reported that 77% of patients noted a decrease in the quality of their erections within two years of radiation therapy for prostate cancer (24). Only 50% of patients who were potent prior to therapy were potent following treatment. Most of our patients had reduced sexual function prior to therapy, precluding such detailed analysis. The preservation of sexual function scores after irradiation in this study is probably better accounted for by this finding rather than reflecting the less toxic nature of the treatment itself. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment and recovered to baseline levels at all later times.
Physician-assessed RTOG scores failed to detect these changes and thus appeared relatively insensitive. Such contradictory findings in assessing physical conditions by patients and physicians have been reported previously (25,26).
Our study is limited owing to the small number of patients and relatively short follow-up. The decrease in health-related quality of life and patient-assessed morbidity appeared substantial immediately after irradiation, but most measures returned to baseline shortly thereafter. The high incidence of rectal bleeding is alarming and needs longer follow-up. The interested patient may easily become frustrated as he struggles with the available literature and information during the process of deciding on treatment for his localized prostate cancer. Patients always need to be involved in the therapeutic decision, which should consider not only expected survival rate but also quality of life. Further study is essential.
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Acknowledgments |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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We thank Dr W. A. Thomasson for expert editorial assistance. This work was supported in part by grants from the Ministry of Health and Welfare of Japan (7–42) and the Foundation for Promotion of Cancer Research in Japan
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FOOTNOTES |
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+ For reprints and all correspondence: Shin Egawa, Department of Urology, Kitasato University School of Medicine, 1–15–1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. E-mail s-egpro@sa2.so-net.ne.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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1 Brenner DJ, Hall EJ. Fractionation and protraction of radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 1999;43:1095–101.[Web of Science][Medline]
2 Algan O, Stobbe CC, Helt AM, Hanks GE, Chapman JD. Radiation in activation of human prostate cancer cells: the role for apoptosis. Radiat Res 1996;146:267–75.[Web of Science][Medline]
3 Leith JT. In vitro sensitivity of the LNCaP prostatic tumor cell line. Prostate 1994;24:119–24.[Web of Science][Medline]
4 International Union Against Cancer. TNM Atlas, 3rd ed, 2nd revision. New York: Springer 1992;241–50.
5 Egawa S, Suyama K, Arai Y, Tsukayama C, Matsumoto K, Kuwao S, et al. Treatment outcome by risk group after radical prostatectomy in Japanese men. Int J Urol 2001;8:295–300.[Web of Science][Medline]
6 American Society for Therapeutic Radiology and Oncology Consensus Panel. Consensus statement: guidelines for PSA following radiation therapy. Int J Radiat Oncol Biol Phys 1997;37:1035–41.[Web of Science][Medline]
7 Syed AMN, Puthawala A, Austin P, Cherlow J, Perley J, Tansey L, et al. Temporary iridium-192 implant in the management of carcinoma of the prostate. Cancer 1992;69:2515–24.[Web of Science][Medline]
8 Slater JD, Rossi CJ Jr, Yonemoto LT, Reyes-Molyneux NJ, Bush DA, Antoine JE, et al. Conformal proton therapy for early-stage prostate cancer. Urology 1999;53:978–84.[Web of Science][Medline]
9 Fukuhara S, Bito S, Green J, Hsiao A, Kurokawa K. Translation, adaptation and validation of the SF-36 Health Survey for use in Japan. J Clin Epidemiol 1998;51:1037–44.[Web of Science][Medline]
10 Isaka S, Shimazaki J, Akaza H, Usami M, Kotake T, Kanetake H, et al. Assessment of the quality of life of prostate cancer patients. Nippon Hinyokika Gakkai Zasshi 1993;84:1611–7 (in Japanese).[Medline]
11 Fossa SD, Aaronson NK, Newling D, van Cangh PJ, Denis L, Kurth K-H, et al. Quality of life and treatment of hormone resistant metastatic prostatic cancer. Eur J Cancer 1990;26:1133–6.
12 Lorish CD, Maisiak R. The face scale: a brief, nonverbal method for assessing patient mood. Arthritis Rheum 1986;29:906–9.[Web of Science][Medline]
13 Japanese Urological Association, Japanese Society of Pathology. General Rules for Clinical and Pathological Studies on Prostate Cancer, 3rd ed. Tokyo: Kanehara 2001;8.
14 Homma Y, Kawabe K, Tsukamoto T, Yamaguchi O, Okada K, Aso Y, et al. Estimate criteria for diagnosis and severity in benign prostatic hyperplasia. Int J Urol 1996;3:261–6.[Medline]
15 Martin T, Hey-Koch S, Strassmann G, Kolotas C, Baltas D, Rogge B, et al. 3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Strahlenther Onkol 2000;176:361–7.[Web of Science][Medline]
16 Dinges S, Deger S, Koswig S, Boehmer D, Schnorr D, Wiegel T, et al. High-dose rate interstitial with external beam irradiation for localized prostate cancer – results of a prospective trial. Radiother Oncol 1998;48:197–202.[Web of Science][Medline]
17 Klein FA, Ali MM, Marks SE, Hackler RH. Bilateral pelvic lymphadenectomy, iridium-192 template and external beam therapy for localized prostatic carcinoma: complications and results. South Med J 1988;81:27–31.[Web of Science][Medline]
18 Borghede G, Hedelin H, Holmang S, Johansson KA, Sernbo G, Mercke C. Irradiation of localized prostatic carcinoma with a combination of high dose rate iridium-192 brachytherapy and external beam radiotherapy with three target definitions and dose levels inside the prostate gland. Radiother Oncol 1997;44:245–50.[Web of Science][Medline]
19 Hiratsuka J, Jo Y, Yoden E, Nagase N, Narihiro N, Kubota J, et al. High dose rate interstitial brachytherapy with external beam irradiation for localized prostate cancer: preliminary results. Nippon Hoshasen Shuyo Gakkaishi 2000;12:327–35.
20 Mate TP, Gottesman JE, Hatton J, Gribble M, Hollebeke LV. High dose-rate afterloading 192iridium prostate brachytherapy: feasibility report. Int J Radiat Oncol Biol Phys 1998;41:525–33.[Web of Science][Medline]
21 Benk VA, Adams JA, Shipley WU, Urie MM, McManus PL, Efird JT, et al. Late rectal bleeding following combined X-ray and proton high dose irradiation for patients with stages T3–4 prostate carcinoma. Int J Radiat Oncol Biol Phys 1993;26:551–7.[Web of Science][Medline]
22 Schultheiss TE, Hanks GE, Hunt MA, Lee WR. Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate. Int J Radiat Oncol Biol Phys 1995;32:643–9.[Web of Science][Medline]
23 Schultheiss TE, Lee WR, Hunt MA, Hanlon AL, Peter RS, Hanks GE. Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:3–11.[Web of Science][Medline]
24 Helgason AR, Fredrikson M, Adolfsson J, Steineck G. Decreased sexual capacity after external radiation therapy for prostate cancer impairs quality of life. Int J Radiat Oncol Biol Phys 1995;32:33–9.[Web of Science][Medline]
25 Joly F, Brune D, Couette J-E, Lesaunier F, Heron J-F, Peny J, et al. Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer. Ann Oncol 1998;9:751–7.
26 Fowler FJ Jr, Roman A, Barry MJ, Wasson J, Lu-Yao G, Wennberg JE. Patient-reported complications and follow-up treatment after radical prostatectomy. The national Medicare experience: 1988–1990 (updated June 1993). Urology 1993;42:622–9.[Web of Science][Medline]
Received May 31, 2001; accepted July 27, 2001.
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