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Keywords:

  • quality of life;
  • IMRT;
  • prostate;
  • fiducial gold markers

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

OBJECTIVE

To evaluate the change in quality of life (QoL) 3 years after high-dose intensity-modulated radiotherapy (IMRT) using gold fiducial marker-based position verification in patients with locally advanced prostate cancer.

PATIENTS AND METHODS

Between October 2003 and November 2004, 95 patients with locally advanced prostate cancer were treated with 76 Gy IMRT with gold-fiducial marker-based position verification. Before treatment (baseline) and 1, 6 and 36 months after RT the QoL was measured using the RAND-36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30(+3)) and the prostate tumour-specific module (EORTC QLQ-PR25). Changes in QoL with time of ≥10 points were considered clinically relevant.

RESULTS

After 3 years there was a statistically significant improvement in QoL for emotional role restriction and functioning, change in health, mental health and insomnia, compared with baseline. Emotional role restriction increased by >10 points and was therefore clinically relevant, while all other differences were of <10 points. There was a statistically significant deterioration of QoL after 3 years in physical and cognitive functioning, bowel symptoms/function and sexual activity. Only the sexual activity QoL score changed by 12 points and was therefore the only meaningful deterioration in QoL at 3 years after treatment.

CONCLUSION

IMRT and accurate position verification provide the possibility to deliver a high irradiation dose to the prostate without clinically relevant deterioration in long-term QoL, except for a persistent decrease in sexual activity score.


Abbreviations
QoL

quality of life

(IM)RT

(intensity modulated) radiotherapy

EORTC

European Organization for Research and Treatment of Cancer

PTV

planning target volume

PR25

prostate cancer module

ADT

androgen-deprivation therapy.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

External beam radiotherapy is one of the treatment options for localized and locally advanced prostate cancer. Several randomized trials showed an improvement in biochemical relapse-free survival rate with an increase in irradiation dose [1–3]. Further increases in dose are expected to lead to further improvement [4]. Especially patients with an unfavourable prognosis might benefit from an increased radiation dose [1]. By increasing the radiation dose, the risk of genitourinary and gastrointestinal toxicity also increases [5]. To evaluate treatment, not only toxicity but also the impact on quality of life (QoL) is important [6].

Intensity-modulated radiotherapy (IMRT) can be used to increase the dose to the prostate while the dose to the organs at risk remains acceptable, because this technique provides better coverage of the target and sparing of the organs at risk. Furthermore, daily verification of the position of the prostate, using fiducial gold markers, improves the precision of the treatment, and therefore the organs at risk might receive less radiation dose [7]. The theoretical advantages of IMRT dose distributions and the reduction of the positioning errors with fiducial markers has been established. However, not many clinical results of IMRT in combination with accurate position verification have been published [8].

Previously, we reported that improved technical possibilities prevented a deterioration in QoL when the radiation dose was increased. Patients treated with 76 Gy IMRT with accurate position verification even had clinically relevant improvements in QoL over a period of 6 months, compared with a group treated with 70 Gy conformal RT [9]. Yoshimura et al.[10] described comparable QoL outcomes between IMRT and conformal RT. However, concerns have been raised about the short-term follow-up of both studies, because late bladder and rectal toxicity can develop several years after completing RT [11]. Late rectal toxicity usually occurs within 3 years of completing RT and bladder toxicity even continues to develop thereafter. Only one study reported the QoL scorest at 3 years after IMRT, but this involved only six patients [12]. A few studies described the QoL scores 2 years after IMRT [13–15].

Good-quality QoL research has to meet certain conditions; not only are large groups of patients important, but it is also important to measure the patients’ perception of their health and ability to function in life, because physician assessment of treatment-induced complaints differs from morbidity reported by patients [16]. Other conditions for good-quality QoL research include validated QoL questionnaires including an organ-specific module, and a longitudinal study design including baseline scores, which is essential in this older patient group [17].

In this prospective and longitudinal study we measured long-term QoL, using a prostate-specific module, of patients treated with IMRT of 76 Gy, using fiducial marker-based position verification. For this patient group we previously reported good QoL results at 1 and 6 months after RT, and in the present study we investigated the change in QoL between the measurement before RT (baseline) and 3 years afterward.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Between October 2003 and November 2004, 116 patients with mainly locally advanced prostate cancer were treated with IMRT. The prostate was delineated on CT and a margin of 8 mm was applied to the prostate and seminal vesicles to create a planning target volume (PTV). Patients received IMRT with a five-beam ‘step-and-shoot’ technique and 10-MV photons. A mean dose of 76 Gy in 35 fractions of 2.17 Gy was prescribed to the PTV and 95% of the prescribed dose (= 72 Gy) was prescribed to 99% of the PTV. The dose in the part of the PTV overlapping the rectum and bladder was limited so that ≤5% of the rectum and 10% of the bladder would receive a dose of ≥72 Gy [18,19]. For position verification, three fiducial gold markers were transrectally implanted inside the prostate, using antibiotic prophylaxis. During treatment the fiducial gold markers were visualized using portal images of the first fields of all five beam directions, using the iView-GT amorphous silicon flat-panel detector (Elekta Ltd, Crawley, UK). The position of the fiducial gold markers can be easily and reliable detected, allowing for fast and accurate determination of the position of the prostate. Daily imaging of the fiducial markers was used for off-line position verification, using an adapted ‘shrinking action level’ protocol [19].

General health-related QoL was measured using the RAND-36 generic health survey [20], cancer-specific QoL using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30(+3)) [21], and the prostate tumour-specific QoL using the EORTC prostate cancer module (QLQ-PR25) [22]. All questionnaires are well validated and widely used in oncology trials [23].

Scales and items of these questionnaires range in score from 0 to 100. For RAND-36 and for the ‘global’ QoL and functional scales of the EORTC questionnaires, a high score represents a high level of QoL and better functioning. For the symptom/problem items of the EORTC questionnaires, higher scores represent a higher level of symptoms and consequently a worse QoL. A change of 10% (or in general, 0.5 sd) of the scale breadth is perceptible to patients as a meaningful change, and a change in QoL of ≥10 points is therefore considered clinically relevant [17].

The first questionnaire was presented to the patient before treatment at the department of radiation oncology; at 1, 6 and 36 months after completing the treatment the measurements were repeated. For all patients treated between 2001 and 2004 at our department with 76 Gy IMRT and fiducial marker-based position verification, the pretreatment, acute and late toxicity was scored [24]. Ninety-five patients were included in the study, because 15 were lost to follow-up and six died within the 3 years of follow-up. All questionnaires had a high response rate, except for questions about sexual activity.

Because the data were normally distributed a paired sample t-test was used to examine differences in QoL scores between the time points (baseline vs 3 years). The QoL changes between baseline, 1 and 6 months were analysed previously [9]. Test results with a P ≤ 0.01 were considered statistically significant, to account for multiple comparisons. Cronbach’s coefficient α was calculated to determine internal consistency and reliability of the questionnaires.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

The characteristics of the 95 patients included in the study are shown in Table 1; most had locally advanced prostate cancer (tumour stage T3). At the time of the study entry, no national guidelines for hormonal treatment were available, and therefore, only 36 patients received adjuvant androgen-deprivation therapy (ADT), which was divided into short-term (≈6 months) and long-term hormonal treatment (≤36 months). All patients had a WHO performance score of ≤2.

Table 1.  The characteristics of the 95 patients
CharacteristicMean (range) or n (%)
Age at baseline, years68 (46–79)
PSA level, ng/mL 
 ≤1029 (31)
 10–2036 (38)
 >2030 (32)
Gleason score 
 2–648 (51)
 728 (30)
 8–1019 (20)
Tumour stage 
 T1 9 (10)
 T2 4 (4)
 T382 (86)
 T4 0
Hormonal treatment 
 None59 (62)
 Short-term (≈6 months)26 (27)
 Long-term (≤36 months)10 (11)
TURP before radiotherapy 
 Yes 8 (8)
 No87 (92)

During RT four patients developed grade 3 genitourinary toxicity, consisting of urinary frequency/urgency, urinary retention, haematuria and dysuria. One of these patients already had grade 3 complaints of urinary frequency before RT. There was no acute grade ≥3 gastrointestinal toxicity. Furthermore, one patient developed a UTI during RT that required i.v. antibiotic (grade 3).

Within 3 years after RT two patients developed grade 3 genitourinary toxicity and one developed severe radiation proctitis requiring several argon-plasma coagulations (grade 3).

Table 2 shows the mean (sd) of all QoL items before treatment (baseline), and 1, 6 and 36 months after treatment. Two-related samples tests between the QoL scores at baseline and after 3 years resulted in statistically significant differences between these time points for several QoL items. Figure 1 shows the course in QoL of the QoL items with a significant difference after 3 years, vs baseline scores. The RAND-36 questionnaire at 3 years showed a better QoL for ‘emotional role restriction’, ‘mental health’ and ‘change in health’, and worse ‘physical functioning’ than the baseline measurement. Only ‘emotional role restriction’ showed a change in QoL over time of >10 points and was therefore considered as the only clinically meaningful change in QoL for this questionnaire (Fig. 1A). The three statistically significant changes in QoL over time for the EORTC QLQ-C30 items were <10 points and therefore not clinically relevant (Fig. 1B). Figure 1C shows worse QoL for ‘bowel symptoms/function’ and ‘sexual activity’. ‘Sexual activity’ showed a clinically relevant decrease of 12 points after 3 years; this QoL item was worse at 1 month after treatment and that persisted after 6 months and 3 years.

Table 2.  The mean (sd) scores for scales and single items of each questionnaire
ItemBaseline1 month6 months3 yearsP for difference, baseline vs 3 years
  1. ns, not significant. *Statistically significant and clinically relevant change in score between baseline and 3 years of ≥10 points. P < 0.01 is considered significant. †Sexual activity scores were available for only 32 patients.

No. of patients95858595 
RAND-36
Physical functioning87 (14)85 (17)86 (16)83 (19) 0.007
Social functioning83 (18)85 (18)90 (16)88 (18)ns
Physical role restriction80 (35)71 (40)84 (30)83 (32)ns
Emotional role restriction79 (35)87 (30)92 (25)90 (24) 0.01*
Mental health77 (15)78 (13)81 (14)82 (15) 0.001
Vitality70 (20)68 (19)71 (19)71 (22)ns
Pain89 (17)86 (18)92 (15)90 (19)ns
General health68 (16)67 (16)70 (18)66 (19)ns
Change in health44 (13)53 (24)63 (24)52 (16) 0.002
EORTC QLQ-C30(+3)
Physical functioning89 (13)88 (13)89 (14)87 (16)ns
Role functioning88 (18)86 (20)90 (18)88 (22)ns
Emotional functioning80 (15)88 (16)89 (16)88 (16)<0.001
Cognitive functioning91 (14)87 (18)87 (18)85 (18)<0.001
Social functioning90 (14)92 (14)95 (12)93 (17)ns
Global health/QoL79 (14)79 (12)82 (13)80 (15)ns
Fatigue19 (19)23 (21)18 (18)21 (20)ns
Nausea and vomiting 2 (8) 2 (7) 1 (5) 1 (6)ns
Pain11 (18)12 (20) 8 (16)13 (21)ns
Dyspnoea 8 (18)11 (21)13 (21)13 (21)ns
Insomnia21 (25)24 (25)15 (24)14 (22) 0.01
Appetite loss 5 (13) 2 (8) 2 (7) 3 (9)ns
Constipation 3 (11) 5 (14) 6 (17) 6 (14)ns
Diarrhoea 5 (16)13 (21)11 (22) 8 (18)ns
Financial difficulties 3 (11) 4 (10) 2 (7) 2 (9)ns
EORTC QLQ-PR25
Urinary symptoms/problems17 (13)21 (18)15 (14)16 (13)ns
Bowel symptoms/function 5 (7) 8 (11) 8 (11) 8 (12) 0.004
Treatment-related symptoms 8 (12)13 (13)11 (12)10 (10)ns
Sexual functioning23 (21)24 (20)24 (21)26 (21)ns
Sexual activity68 (24)57 (28)54 (22)56 (26) 0.01*
image

Figure 1. Changes in QoL for the RAND-36 (A), the EORTC core QLQ-C30 (B), and the EORTC-QLQ-PR25 (C) QoL items, with a significant difference between baseline and 3 years. Error bars represent the 95% CI. In the RAND-36, a higher score reflects better health. In EORTC QLQ-C30(+3) and QLQ-PR25, a higher score reflects a high level of symptoms or functioning or QoL.

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A subanalysis showed that there were no significant differences in QoL for ‘sexual activity’ between patients with and without ADT at baseline, with a mean (sd) QoL score of 54 (25) vs 72 (22) at baseline and at 3 years after RT of 54 (32) vs 56 (25). However, patients with no ADT had decreased ‘sexual activity’ scores between baseline and 3 years (P = 0.004), while patients with ADT had no deterioration in ‘sexual activity’ after 3 years compared with baseline. Unfortunately ‘sexual activity’ scores were only available for seven patients with ADT and 25 without.

We also compared the change in QoL for patients with and with no increase in toxicity between baseline and 3 years after RT. There were no clinically relevant and significant differences in the change in QoL for patients with an increase in gastrointestinal and genitourinary complaints compared with those with a decrease or no change in toxicity.

For sufficient internal consistency, a Cronbach’s α coefficient of ≥0.70 is required. Reliability analysis gave a Cronbach’s α of ≥0.70 for all scales, except ‘nausea’ (0.31–0.73) and ‘cognitive’ and ‘social functioning’ (0.52–0.84) in the EORTC QLQ-C30(+3), and ‘bowel function’ (0.33–0.64), ‘treatment-related symptoms/problems’ (0.50–0.64) and ‘sexual activity’ (0.58–0.77) in the QLQ-PR25.

The present study, including 95 patients, was well powered to detect QoL differences of 10 points. In 95% of the scales the sd was 14–19 (Table 2). The power to detect a difference of 10 points between baseline and 3 years as statistically significant with 95 patients and a two-sided α of 0.01 is 100% (when using a sd of 14) and 99.7% (when using a sd of 19).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

To our knowledge, this is the first study to evaluate the change in QoL for a large group of patients 3 years after 76 Gy IMRT using gold-fiducial marker-based position verification. Previously we reported that, compared with 70-Gy conformal RT, there was no deterioration in QoL after 6 months. In the present study there was no meaningful deterioration of QoL 3 years after completing RT from the QoL before RT, except for the QoL item ‘sexual activity’. Better planning of the target volumes and sparing of the organs at risk using IMRT and adequate position verification might have resulted in little radiation damage and consequently no clinically relevant effect of the side-effects on QoL.

The previous evaluation of the short-term QoL changes after 76 Gy IMRT [9] showed a significant and meaningful increase in ‘emotional role restriction’ after 6 months. This increase in QoL score remained after 3 years, with a difference of 11 points from baseline. A decreasing fear of recurrence and death, and having a long time to adapt to the situation, might be involved in the persistent increase of this QoL item.

The short-term analysis also showed that after 6 months there was an increase in ‘change in health’ score [9]. The increase in QoL for ‘change in health’ between baseline and 3 years was significant (P = 0.002), but not clinically relevant (<10 points). However, the change in QoL between 6 months and 3 years was significant, with a clinically relevant decrease of 11 points. The improvement in ‘change in health’ after 6 months was attributed to the ‘response shift’ mechanism (referring to a changed internal standard on which patients base their perception, due to a life-threatening disease [25]). The worsening of ‘change in health’ thereafter might be due to ageing, as Aaronson et al.[26] reported lower QoL scores for older respondents (>70 years) than younger respondents in The Netherlands.

QoL for ‘sexual activity’ had already decreased by 1 month after RT. The persistent deterioration in QoL might be due to late radiation effects and has been reported previously [13,27,28], but also the patients’ age and comorbities might have influenced sexual activity [29]. Previous reports suggest an arteriogenic pathology as the main cause for erectile dysfunction after RT [30]. The Dutch translation of the EORTC QLQ-PR25 requests patients to complete the questions about sexual activity only when they were sexually active in the last 4 weeks. For that reason the sexual activity scores were available for only 32 patients, which could have led to under- or overestimated QoL scores.

Sanda et al.[15] reported long-lasting symptoms involving sexuality due to androgen suppression of limited duration. In the present study patients treated with ADT had no deterioration in ‘sexual activity’ between baseline and 3 years, but they seemed to have worse ‘sexual activity’ scores before RT. At 3 years after RT there was no difference in ‘sexual activity’ between patients with and without ADT. This might be due to the few patients treated with ADT in our study. However, Yoshimura et al.[10] even reported an improvement in sexual function during the follow-up, probably resulting from reduced sexual function before the start of RT, as a result of neoadjuvant hormone therapy.

In the present study the increase in gastrointestinal and genitourinary toxicity did not significantly affect the change in QoL. This could be because the incidence of severe toxicity was very low, but the absence of a correlation between QoL and toxicity was reported previously [16,31]. The increase in toxicity might be too small to be detected by the QoL questionnaires, but another explanation might be that patients had time to adapt to the RT-induced complaints and developed coping skills [25].

After a follow-up of 6 months there were no differences in QoL scores between IMRT and conformal RT, or improved QoL scores in patients treated with IMRT [9,10]. At ≈2 years after RT, Kupelian et al.[14] reported no differences in QoL between a dose of 70 Gy in 2.5 Gy fractions using IMRT and conformal RT. However, a less solid cross-sectional design was used and only 24 patients were included. In accordance with our findings, Namiki et al.[13] reported, for 12 patients at 2 years after monotherapy with 76 Gy IMRT, no significant difference in QoL from the baseline level. Recently Sanda et al.[15] reported worse bowel and sexual QoL scores 2 years after external beam RT (either IMRT or conformal RT) than baseline scores. Unfortunately no technical specifications and treatment dose were described. Only Junius et al.[12] measured the long-term QoL after IMRT; at 3 years after treatment with 66 Gy in 2.64 fractions there were no clinically relevant QoL changes for six patients, except an increase in emotional and decrease in cognitive functioning, which was also seen in the present patients.

We used a high RT dose of 76 Gy because it is expected to lead to high biochemical control rates [1–3]. In the present study we conclude that our treatment is well tolerated and causes no significant clinical deterioration in QoL, but a longer follow-up is required to determine the biochemical or clinical failure in our patient group.

In conclusion, 3 years after IMRT with 76 Gy using fiducial gold marker-based position verification, all QoL items, except ‘sexual activity’, had no significant and clinically relevant deterioration compared with the QoL scores before the start of RT. The QoL for ‘emotional role restriction’ improved after 6 months and remained high 3 years after RT. The satisfactory QoL results 3 years after treatment might be a consequence of the few side-effects after treatment with IMRT and accurate position verification. IMRT is especially suitable for avoiding organs at risk, e.g. rectum and bladder, while a high dose of radiation is delivered to the prostate. In combination with daily position verification using fiducial markers, the organs at risk might have received little irradiation, leading to fewer complaints during and after treatment.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES
  • 1
    Pollack A, Zagars GK, Starkschall G et al. Prostate cancer radiation dose–response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002; 53: 1097105
  • 2
    Peeters ST, Heemsbergen WD, Koper PC et al. Dose–response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006; 24: 19906
  • 3
    Zietman AL, DeSilvio ML, Slater JD et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 2005; 294: 12339
  • 4
    Eade TN, Hanlon AL, Horwitz EM, Buyyounouski MK, Hanks GE, Pollack A. What dose of external-beam radiation is high enough for prostate cancer? Int J Radiat Oncol Biol Phys 2007; 68: 6829
  • 5
    Cheung MR, Tucker SL, Dong L et al. Investigation of bladder dose and Volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2007; 67: 105965
  • 6
    Litwin MS, Fitzpatrick JM, Fossa SD, Newling DW. Defining an international research agenda for quality of life in men with prostate cancer. Prostate 1999; 41: 5867
  • 7
    Van Vulpen M, Van Der Heide UA, Van Moorselaar JR. How quality influences the clinical outcome of external beam radiotherapy for localized prostate cancer. BJU Int 2008; 101: 9447
  • 8
    Veldeman L, Madani I, Hulstaert F, De Meerleer G, Mareel M, De Neve W. Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies. Lancet Oncol 2008; 9: 36775
  • 9
    Lips I, Dehnad H, Kruger AB et al. Health-related quality of life in patients with locally advanced prostate cancer after 76 Gy intensity-modulated radiotherapy vs. 70 Gy conformal radiotherapy in a prospective and longitudinal study. Int J Radiat Oncol Biol Phys 2007; 69: 65661
  • 10
    Yoshimura K, Kamoto T, Nakamura E et al. Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy. Prostate Cancer Prostatic Dis 2007; 10: 28892
  • 11
    Gardner BG, Zietman AL, Shipley WU, Skowronski UE, McManus P. Late normal tissue sequelae in the second decade after high dose radiation therapy with combined photons and conformal protons for locally advanced prostate cancer. J Urol 2002; 167: 1236
  • 12
    Junius S, Haustermans K, Bussels B et al. Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study. Radiat Oncol 2007; 2: 29
  • 13
    Namiki S, Ishidoya S, Tochigi T et al. Health-related quality of life after intensity modulated radiation therapy for localized prostate cancer: comparison with conventional and conformal radiotherapy. Jpn J Clin Oncol 2006; 36: 22430
  • 14
    Kupelian PA, Reddy CA, Klein EA, Willoughby TR. Short-course intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life. Int J Radiat Oncol Biol Phys 2001; 51: 98893
  • 15
    Sanda MG, Dunn RL, Michalski J et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 2008; 358: 125061
  • 16
    Lilleby W, Fossa SD, Waehre HR, Olsen DR. Long-term morbidity and quality of life in patients with localized prostate cancer undergoing definitive radiotherapy or radical prostatectomy. Int J Radiat Oncol Biol Phys 1999; 43: 73543
  • 17
    Osoba D, Bezjak A, Brundage M, Zee B, Tu D, Pater J. Analysis and interpretation of health-related quality-of-life data from clinical trials: basic approach of The National Cancer Institute of Canada Clinical Trials Group. Eur J Cancer 2005; 41: 2807
  • 18
    Nederveen AJ, Van Der Heide UA, Hofman P, Welleweerd H, Lagendijk JJ. Partial boosting of prostate tumours. Radiother Oncol 2001; 61: 11726
  • 19
    Van Der Heide UA, Kotte AN, Dehnad H, Hofman P, Lagenijk JJ, Van Vulpen M. Analysis of fiducial marker-based position verification in the external beam radiotherapy of patients with prostate cancer. Radiother Oncol 2007; 82: 3845
  • 20
    Hornbrook MC, Goodman MJ. Assessing relative health plan risk with the RAND-36 health survey. Inquiry 1995; 32: 5674
  • 21
    Aaronson NK, Ahmedzai S, Bergman B et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 36576
  • 22
    Borghede G, Sullivan M. Measurement of quality of life in localized prostatic cancer patients treated with radiotherapy. Development of a prostate cancer-specific module supplementing the EORTC QLQ-C30. Qual Life Res 1996; 5: 21222
  • 23
    Henderson A, Laing RW, Langley SE. Quality of life following treatment for early prostate cancer: does low dose rate (LDR) brachytherapy offer a better outcome? A review. Eur Urol 2004; 45: 13441
  • 24
    Lips IM, Dehnad H, Van Gils CH, Boeken Kruger AE, Van Der Heide UA, Van Vulpen M. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients. Radiat Oncol 2008; 3: 15
  • 25
    Breetvelt IS, Van Dam FS. Underreporting by cancer patients: the case of response-shift. Soc Sci Med 1991; 32: 9817
  • 26
    Aaronson NK, Muller M, Cohen PD et al. Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol 1998; 51: 105568
  • 27
    Pinkawa M, Gagel B, Piroth MD et al. Erectile dysfunction after external beam radiotherapy for prostate cancer. Eur Urol 2008; Epub ahead of print
  • 28
    Little DJ, Kuban DA, Levy LB, Zagars GK, Pollack A. Quality-of-life questionnaire results 2 and 3 years after radiotherapy for prostate cancer in a randomized dose-escalation study. Urology 2003; 62: 70713
  • 29
    Lue TF. Erectile dysfunction. N Engl J Med 2000; 342: 180213
  • 30
    Incrocci L, Slob AK, Levendag PC. Sexual (dys) function after radiotherapy for prostate cancer: a review. Int J Radiat Oncol Biol Phys 2002; 52: 68193
  • 31
    Staff I, Salner A, Bohannon R, Panatieri P, Maljanian R. Disease-specific symptoms and general quality of life of patients with prostate carcinoma before and after primary three-dimensional conformal radiotherapy. Cancer 2003; 98: 233543