ORIGINAL RESEARCH
A COMPARISON OF CONVENTIONAL EXTERNAL RADIOTHERAPY
TECHNIQUE AND CONFORMAL RADIOTHERAPY TECHNIQUE IN
TERMS OF ACUTE TOXICITY WITH REGARD TO HORMONAL
TREATMENT
İlknur Çetin, Ufuk Abacıoğlu, Meriç Şengöz
Department of Radiation Oncology, School of Medicine, Marmara University, Istanbul, Turkey
ABSTRACT
Objective: Comparing the application of conventional external radiotherapy technique (EBRT) and conformal radiotherapy technique (CRT) in terms of acute side effects with respect to hormonotherapy (HT) in the primary treatment of prostate cancer.
Materials and Methods: Seventy-five patients diagnosed with localized prostate cancer were treated with primary radiotherapy (RT) between March 1997 and July 2002, 47 with EBRT and 28 with CRT. 23 patients (31%) did not receive HT, 22 patients (29%) received concomitant HT (CHT) and 30 patients (40%) received neoadjuvant HT (NAHT). The patients were observed for at least 3 months and the acute toxicity was evaluated by EORTC/RTOG (European Organization for Research and Treatment of Cancer / Radiation Therapy Oncology Group) scale 1.
Results: There was no grade III-IV acute urinary and rectal toxicity. The percentage of grade I and II acute urinary toxicity was determined as 30% and 23%, respectively in the EBRT group. The ratios were 61% and 18%, respectively in the CRT group (p=0.025). Grade II urinary toxicities were 13% in patients who did not receive HT and who received NAHT, 41% in patients who received CHT (p=0.02). Grade II rectal toxicities were 30% for EBRT and 7% for CRT group (p=0.022).
Conclusion: CRT caused a decrease in grade II rectal and urinary toxicity. Grade II acute urinary toxicities were observed more frequently in the treatment of CHT than the NAHT.
Keywords: Acute toxicity,Cconventional-conformal radiotherapy, Prostate cancer
KONVANSİYONEL EKSTERNAL RADYOTERAPİ VE KONFORMAL
RADYOTERAPİ TEKNİKLERİNİN HORMONOTERAPİ DURUMUNA
GÖRE AKUT YAN ETKİLER AÇISINDAN KARŞILAŞTIRILMASI
ÖZET
Amaç : Prostat kanserinin primer tedavisinde konvansiyonel eksternal radyoterapi (EBRT) ile konformal radyoterapi teknik (CRT)uygulamaların hormonoterapi (HT) durumuna göre akut yan etkiler açısından karşılaştırılması amaçlanmıştır.
Gereç ve Yöntem : Mart 1997- Temmuz 2002 tarihleri arasında lokalize prostat kanseri tanısı konmuş ve primer radyoterapi uygulanmış 75 hastanın EBRT uygulanan 47 ve CRT uygulanan 28 hasta idi. Tüm hastalar için medyan yaş 72 (55-85), medyan radyoterapi dozu 70 Gray (Gy) (63-76 Gy) olarak tespit edilmiştir. Hastaların 23’u (%31) hormonoterapi almamış , 22’si (%29) eş zamanlı hormonoterapi almış ve 30’u (%40) neoadjuvan hormonoterapi almıştı. Hastaların en az 3 aylık takibi mevcut olup, görülen akut yan etkiler EORTC/RTOG (European Organisation for Research and Treatment of Cancer / Radiation Therapy Oncology Group) skalası kullanılarak değerlendirilmiştir 1 .
Bulgular: Grade I ve II akut üriner yan etkiler; konvansiyonel radyoterapi grubunda %30 ve %23 iken, konformal radyoterapi grubunda %61 ve %18 oranında gözlenmiştir (p=0.025). Grade II üriner yan etkiler; HT almayanda ve neoadjuvan hormonoterapi alanlarda %13 eş zamanlı hormonoterapi alan hastalarda %41 oranında saptanmıştır (p=0.02). Grade II rektal yan etkiler; konvansiyonel radyoterapi grubunda %30, konformal radyoterapi grubunda %7 oranında tespit edilmiştir (p=0.022).
Sonuç : Konformal radyoterapi uygulaması ile grade II akut rektal ve üriner yan etkilerin azaldığı tespit edilmiştir. Eşzamanlı hormonoterapi kullanımı ile grade II akut üriner yan etki neoadjuvan kullanıma göre daha sık gözlenmiştir.
Anahtar Kelimeler: Akut yan etkiler, Konvansiyonel, Konformal radyoterapi, Prostat kanseri Corresponding author: İlknur Çetin, M.D
Department of Radiation Oncology, School of Medicine, Marmara University Hospital, Tophanelioğlu Caddesi 13/15, 34660 Altunizade, İstanbul
E-mail: ilknurcet@hotmail.com
Radiation has been used in the curative treatment of prostate cancer for approximately a hundred-years. With the technical improvements in medicine, localized prostate cancer is now being treated with EBRT. Such patients are usually old and have comorbidities, so they have to be treated
effectively with the least side effects 1. The
radiation dose given in order to provide local tumor control remains insufficient with the EBRT
technique used today 2. Toxicities increase when
the treatment dose increases. Thus, 3-dimensional treatment planning and CRT has been widely accepted in the treatment of prostate cancer. The aim is to control the tumor by giving high doses while protecting the surrounding normal tissues as
much as possible 3-7. Retrospective and
prospective studies indicate that CRT has fewer side effects compared to standard technique with
the same dose 8-11. In addition, despite an increase
in the RT dose, tolerable side effects were reported in some studies, regarding the conformal
treatment technique 12-14.
In this study, in the Marmara University Hospital Radiation Oncology Department, the urinary - rectal side effects observed during and after treatment with EBRT and CRT were compared with regard to the HT situation.
METHODS
Seventy-five patients with localized prostate cancer treated in the Marmara University Hospital Radiation Oncology Department between March 1997 and July 2002 were classified according to 1997 AJCC classification with thin injection biopsy, Gleason score and/or BT accompanied with rectal examination, and transrectal ultrasonography (TRUSG) were taken before the
treatment 15. Metastatic disease was eliminated by
routine biochemical examination, whole body bone scintigraphy, and radiological examinations when required.
Fourty-seven patients (62.6%) were treated with EBRT, whereas 28 patients (37.3%) were treated with CRT. Median age of patients was 72 (55-85), median T phase was T2, median initial PSA (Prostate-Specific Antigen) was 8ng/ml, median RT dose was 70 Gy. 23 patients did not receive HT, 22 patients were treated with CHT and 30 patients were treated with NAHT.
Patient characteristics and treatment methods together with distribution and significance of two technical treatments are shown in Table I.
linear accelerator and 18 MV X-Ray. Immobilization in the supine position was ensured in the simulator for all patients. Axial BT images with 0.5 cm thickness were taken with empty rectum and full bladder in the same position. 10 mlt contrast were introduced to the urethra in order to visualize the urethra and the apex of the prostate. BT images were transferred to the treatment planning system by the 'Dicom Network' System.
Using the conventional technique, PTV1 was defined as small pelvis or prostate with seminal vesicular and PTV2 was defined as the prostate region. Standard lead blocks were used in the areas. Patients were treated with the four-field box technique (except for 3 patients with AP-PA fields and 2 patients with 3 fields- AP and two lateral opposing fields) to a dose range of 40-50 Gy. A boost was given with the four-field box technique to a total dose of 63-74 Gy.
In the CRT group, patients were treated with the four field box technique (except one patient treated with the 5 field technique) up to 40-50 Gy and then boosted to a total of 66-76 Gy RT with custom blocking to all fields. Median RT dose was 70 Gy (63-76 Gy), 1.8-2 Gy/fraction/day, 5 fractions per week. Maximal Androgen Blockade (MAD) (anti-androgen and LHRH analogue) was started concomitant with RT or before (1-17 months) in the patients. Duration of MAD was determined according to the risk group of the patient. Acute side effects (during or 3 months after primary RT) were evaluated by using the EORTC/RTOG scale (Annex).
The relation between two different treatment techniques and patient characteristics, the relation between acute urinary and rectal side effects with patient characteristics and treatment techniques were evaluated by using Chi-square test or Fisher's Exact Test in one variable analysis. Relative ratio (odds ratio-OR) and results were given in 95% confidence interval. The results were accepted at the level of significance p≤0.05. Statistical analysis was performed by the use of the SPSS 10.0 package program.
RESULTS
The distribution of urinary and rectal side effects observed regarding two different treatment techniques is shown in Table I.
Table I: Patient Characteristics EBRT (%) CRT (%) P Number of Patients 47 (62.6) 28 (37.2) Age < 70 ≥ 70 17 (36.1) 30 (63.8) 10 (35.7) 18 (64.2) 0.96 T stage T1 T2 T3 T4 12 (25.5) 25 (53.1) 9 (19.1) 1 (2.1) 4 (14.2) 22 (78.5) 2 (7.1) 0.19 Initial PSA (ng/ml) 0-10 10-20 > 20 unknown 18 (38.2) 11 (23.4) 13 (27.6) 5 (10.6) 6 (21.4) 9 (32.1) 13 (46.4) 0.17 Known Disease Hypertension Heart Disease Diabetes Haemorrhoid Pelvic Operation TUR-P Unknown 3 (6.3) - 4 (8.5) 15 (31.9) 2 (4.2) 2 (4.2) 14 (29.7) 6 (21.4) 4 (14.2) 2 (7.1) 13 (46.4) 3 (10.7) - - 0.09 Radiotherapy Dose 63-69 Gy 70 Gy 71-76 Gy 15 (%31.9) 22 (46.8) 10 (21.2) 5 (8.6) 20 (71.4) 3 (10.7) 0.11 Hormonotherapy NoneConcomitant Neoadjuvant 18 (38.2) 17 (36.1) 12 (25.5) 5 (17.9) 5 (17.9) 18 (64.3) 0.004
and rectal side effects in both groups. Grade II
urinary side effects were observed in 18% of
the patients after CRT, in 23% after EBRT
effects in patients who received CHT, NAHT and no HT was 41%, 13% and %13 respectively (p=0.02) (Fig. 2).
Fig. 1. Distribution of acute GUS toxicity according to treatment technique
Fig. 2. Distribution of acute GUS toxicity according to hormonal treatment
Grade II rectal side effects were observed in
30% of the patients after CRT and 7% after
EBRT (p=0.022) (Fig. 3).
No significant relationship was found
between urinary-rectal side effects observed
after treatment and characteristics related to
patients (age, diseases previously known,
operation undergone before) and
characteristics related to treatment (RT dose)
(p>0.05).
Fig. 3. Distribution of acuterectal toxicity according to treatment technique
DISCUSSION
Koper and his colleagues compared the technical applications of CRT and EBRT. They applied 66 Gy RT and found that CRT treatment caused less grade II acute rectal side effects (16%-8%,
p<0.0001) 10.
Tait and his colleagues investigated CRT and EBRT in terms of acute side effects in the treatment of primary prostate cancer. A questionnaire was given a week before, during and after the treatment. It was determined that the side effects increased during the treatment and
decreased after the treatment 16.
In the study of Pollack and his colleagues, 70 Gy with EBRT and 78 Gy with CRT were applied. Although RT dose was higher with CRT, no significant difference regarding acute side effects
was found 11,17.
Vijayakumar and his colleagues applied EBRT and CRT to patients with localized prostate cancer. According to the outcome of weekly gastrointestinal (GIS)-genitourinary (GUS) toxicities evaluation during RT for three groups, it was found that there was an increase in acute side effects until 4-5 weeks, after that there was a
decrease or they remained at the same level 18.
Soffen and his colleagues reported urinary and rectal side effects with a median dose of 68 Gy RT with two different techniques in 46 patients. Urinary side effects were observed in 80%-65% of the patients and rectal side effects were observed in 55%-42%. Acute side effects were
less in patients treated with CRT (p>0.05) 9.
Hanks and his colleagues found that the frequency of grade II side effects was 34% in CRT and 57% in EBRT (p<0.001). The frequency of grade II side effects in the patients over age 65 decreased in CRT (p<0.00001). With the use of CRT, grade II side effects were observed less in patients with early stage (T1-2) tumor (p<0.005). Conformal technique and treatment volume were found as independent significant indicators for grade II side
effects in multivariable analysis 8.
Nuyttens and his colleagues compared patients who had CRT≤72 Gy and CRT≥76 Gy with regard to acute and chronic complications. 10%-18% grade II acute rectal side effects and 33%-47% urinary side effects were observed. They determined that acute rectal side effects depend on dose, while acute and chronic urinary side effects
are independent from dose 19.
Odrazka and his colleagues applied 74 Gy CRT and found a significant relationship between GUS
side effects and TUR applied before RT 20.
Herold and his colleagues reported that diabetes increased grade II GIS side effects and especially
GUS late side effects 21.
While apoptotic activity is 2%, this ratio increases
up to 10% with androgen blockade 22. Tumor
oxidation increases in relation with volume decline and this leads to an increase in radiation effectiveness. Target volume in NAHT decreases
in relation with the decrease in tumor size 23. In
randomized studies, the addition of neoadjuvant androgen blockade caused an increase in survival,
were found to be independent prognostic factors in terms of acute side effects, yet no like effect of
HT was observed 26.
Sanguinetti and his colleagues stated that NAHT did not increase side effects, whereas adjuvant HT
increased rectal side effects 27.
In conclusion, no grade III-IV urinary and rectal acute side effects were observed in both of the techniques in this study. It was found that application of CRT technique causes a reduction in the frequency of grade II acute rectal and urinary side effects. There was an increase in grade II urinary side effects in patients treated with CHT.
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