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Retrospective analysis of results of p(65)+Be neutron therapy for treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Leuve. Part II: Side effects and their influence on quality of life measured with QLQ-C30 of EORTC*1
Abstract
Between 1978 and 1998, 533 prostate adenocarcinoma patients were treated with mixed photon-neutron radiotherapy. We report on a retrospective series of patients for whom the side effects of the treatment and their impact on quality of life were assessed by a mailed questionnaire.Methods and materialsThe European Organization for Research and Treatment of Cancer quality-of-life core questionnaire and a prostate-specific questionnaire were used. Between 1990 and 1996, 308 consecutive patients were treated. Two protocols were used: pelvic fields (50 Gy equivalent photons, 2 Gy/fraction) followed by a prostate boost (66 Gy) or prostate alone. The neutron/photon ratio varied. The questionnaire was mailed to 262 patients presumed to be alive.ResultsOf the 262 patients, 230 replied. Of the 230 patients, 73% had no trouble doing strenuous activities and 4% had trouble with taking a short walk. The overall physical condition and quality-of-life questions received a mean score of 5.2 and 5.3 on a 7-point scale, respectively. Twenty-two percent had bowel movements at least four times daily, and 6% did so six times or more. Retaining stool was a problem in 26%, and only 38% reported full continence; 17% urinated four times or more nightly. Urinary incontinence was scored as “quite a bit” or “very much” in 11% and 5%, respectively. Hematuria and dysuria (pain) were reported by 7% and 16%, respectively, mainly as moderate. Only 28% reported easy erections, but 75% judged the sexual change acceptable. A greater neutron/photon ratio was significantly associated with more bowel problems (p = 0.003).Conclusion
Mixed photon-neutron therapy for prostate cancer was associated with significant patient-reported side effects. Their significant effect on patients' quality of life is described.
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To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum).
Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour.
Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral.
151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum).
Randomisation to neutron treatment was stopped in February 1990.
Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity.
In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups.
The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.
To assess health-related quality of life (HRQOL) in men treated for clinically localized prostate cancer.
A cross-sectional analysis of HRQOL after treatment with radical prostatectomy, pelvic irradiation, or observation alone for clinically localized prostatic adenocarcinoma, and in age-matched comparison patients.
A large managed care population in California.
A total of 528 men, including 214 treated for clinically localized prostate cancer (41 with evidence of metastatic disease were excluded from this analysis) and 273 age-matched, ZIP code-matched comparison patients without prostate cancer. Cancer patients were analyzed in three treatment groups: radical prostatectomy (n = 98), primary pelvic irradiation (n = 56), and observation alone (n = 60).
General HRQOL was measured with the RAND 36-Item Health Survey 1.0. Cancer-specific HRQOL was measured with the CAncer Rehabilitation Evaluation System-Short Form and the Functional Assessment of Cancer Therapy-General form. Disease-targeted quality of life was measured with a new instrument assessing function and bother in three organ systems: sexual, urinary, and bowel.
No differences among treatment groups were seen in comparisons of general HRQOL: Significant differences among treatment groups were seen in both function and bother in the prostate-targeted measures of sexual, urinary, and bowel domains. When cancer patients were compared with men of similar age without prostate cancer, differences were seen in the sexual, urinary, and bowel function and bother but not in general HRQOL measures. Although cancer-free men were found not to have full potency or continence, prostate cancer patients treated with surgery or radiation reported significantly worse sexual, urinary, and bowel function than men without cancer. Men who had undergone nerve-sparing prostatectomy did not differ from those who had undergone standard prostatectomy, but the power to detect a difference was low.
Although no differences were seen in general HRQOL, three disease-targeted domains were found to differ significantly among the treatment groups and comparison patients. Even after controlling for the sexual and urinary dysfunction experienced by older men without cancer, those receiving therapeutic interventions for their prostate cancer were found to have poorer disease-targeted HRQOL: We conclude that in addition to general HRQOL, disease-targeted measures must be used to assess outcomes of care in men treated for localized prostate cancer.
In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials.
We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included.
The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity.
The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe.
These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.
Purpose:
We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer.
Materials and methods:
Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months.
Results:
At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity.
Conclusions:
Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.
Purpose:
The impact of radical prostatectomy and external beam radiotherapy on the quality of life of patients was compared.
Materials and methods:
A total of 136 patients underwent radical prostatectomy and 60 underwent external beam radiotherapy for clinically localized prostate cancer. Patients were asked to complete a questionnaire containing The Functional Living Index: Cancer, the Profile of Moods States, and a series of questions evaluating bladder, bowel and sexual function.
Results:
The radical prostatectomy group had worse sexual function and urinary incontinence, while the external beam radiotherapy group had worse bowel function. Of the patients 90% from both groups stated that they would undergo the treatment again.
Conclusions:
Radical prostatectomy and external beam radiotherapy have comparable impact upon quality of life.
External beam pelvic irradiation in men is frequently complicated by erectile dysfunction. We tested the erectile function in 23 patients (mean age, 65 years) who received radiation therapy for prostate cancer. Fifteen patients experienced changes in erectile potency following radiotherapy. Neurological, endocrine, and vascular testing revealed abnormalities in 0, 5, and 15 of these patients, respectively. In two, arteriography revealed bilateral occlusive disease in the distal internal pudendal and penile arteries overlying the pelvic radiation field. A significant difference with cigarette smoking was found among the 15 patients whose erectile capacity decreased and the four patients whose capacity remained unchanged. Vasculogenic impotence is the most consistent organic erectile abnormality in RAI.
(JAMA 1984;251:903-910)
To report the 5-year outcomes of dose escalation with 3D conformal treatment (3DCRT) of prostate cancer.
Two hundred thirty-two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92 with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow-up was 60 months, and any patient free of clinical or biochemical evidence of disease was termed bNED. Biochemical failure was defined as prostate-specific antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml. Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the latter (FC-LENT). All patients were treated with a four-field technique with a 1 cm clinical target volume (CTV) to planning target volume (PTV) margin to the prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same. Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative incidence methods and compared using the log rank and Gray's test statistic, respectively. Cox regression models were used to establish prognostic factors predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates were utilized by dose group to estimate logit response models for bNED and late morbidity.
PSA <10 ng/ml: No dose response was demonstrated using estimated bNED rates or by analysis of PSA nadir vs. dose. PSA 10-19.9 ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model showed 5-year bNED rates of 35% at 70 Gy and 75% at 76 Gy (p = 0.0049) and illustrated the relative ineffectiveness of conventional dose treatment. PSA 20+ ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model indicated a 5-year bNED rate of 10% at 70 Gy and 32% at 76 Gy (p = 0.10). Morbidity: Dose response was demonstrated for FC-LENT grade 2 and grade 3,4 GI morbidity and for LENT grade 2 GU sequelae. RTOG grade 3,4 GI morbidity at 5 years was <1%. Factors associated with bNED, cause-specific survival, and metastasis were studied using Cox multivariate analysis. Pretreatment PSA (p = 0.0001), Gleason score 7-10 (p = 0.0001), and dose (p = 0.017) were significantly predictive of bNED. For each 1 Gy increase in dose, the hazard of bNED failure decreased by 8%. Palpation stage was associated with cause-specific survival (p = 0.002) and distant metastasis (p = 0.0004). Gleason score was also predictive of distant metastasis (p = 0.02).
A dose response was observed for patients with pretreatment PSA >10 ng/ml based on 5-year bNED results. No dose response was observed for patients with pretreatment PSA < 10 ng/ml. Dose response was observed for FC-LENT grade 2 and grade 3,4 GI sequelae and for LENT grade 2 GU sequelae. Optimization of treatment was made possible by the results in this report. The improvement in 5-year bNED rates for patients with PSA levels > 10 ng/ml strongly suggests that clinical trials employing radiation should investigate the use of 3DCRT and prostate doses of 76-80 Gy.
BACKGROUND
Treatment of localized prostate carcinoma is often accompanied by disturbances in sexual function. The patient's own opinion and experience with these problems can be of great importance for his quality of life. In men older than 50 years, disturbances in sexual function are common. Treatment such as radiotherapy (RT), which can induce sexual dysfunction, should be evaluated in relation to the problems in an age-matched population without prostate carcinoma.METHODS
Sexual function was evaluated with a self-assessment questionnaire using linear-analogue scales. The questionnaire was sent to 199 patients with prostate carcinoma, median age 71 years (range, 51–86 years), who had received pelvic RT with curative intent and to 200 age-matched men in northern Sweden. Mean follow-up time after RT was 48 months (range, 24–56 months).RESULTSThe response rate was high: 141 (71%) and 181 (91%) in the control and patient groups, respectively. Field reduction and treatment pause during RT was not associated with decreased problems in the patient groups. A failure to achieve erection was indicated in 12% of the control subjects, 56% of the patients who had received (RT only) and 87% of the RT + castration (RT + A) patients. In general, patients < 70 years treated with RT + A indicated more sexual problems than the RT only patients < 70 years. There was a strong negative correlation between age and sexual problems in the RT + A < 70 years group. However, in patients < 70 years, sexual activity after RT only, was not significantly different from the age-matched control population.CONCLUSIONS
Patients with prostate carcinoma treated with RT only indicated higher levels of sexual dysfunction than age-matched controls. This was most obvious in patients younger than 70 years, although their sexual activity was comparable to age-matched controls. The addition of castration to RT tended to increase sexual problems, especially in patients < 70 years. In men between 70 and 74 years, the maintenance of sexual function seems to be very susceptible to disturbances. For patients older than 74 years, decreased sexual function was not perceived as such a significant problem, despite abolished desire and erection. Cancer 1996;78:1066-78.
Of the estimated 317,000 men in the United States diagnosed with prostate carcinoma in 1996, 57% will have localized disease, and their 5-year relative survival rate will be 98%. Limited information exists on patient-reported quality of life (QOL) and the incidence and severity of treatment-related side effects. The purpose of this study was to identify and compare patients' self-reported QOL and treatment side effects 1-5 years after radical prostatectomy or radiotherapy. Data collection for this cross-sectional study included a mailed, self-administered survey with three parts: a demographic survey, the Functional Assessment of Cancer Therapy-General (FACT-G), and a newly developed Prostate Cancer Treatment Outcome Questionnaire (PCTO-Q). The FACT-G measured the effect of prostate carcinoma on overall QOL in the two treatment groups. The PCTO-Q assessed the patients' perceptions of the incidence and severity of specific changes in bowel, urinary, and sexual functions. The test-retest reliability of the PCTO-Q in a pilot study was 91.2%. Two hundred seventy-four eligible men completed the questionnaires; 132 (48%) reported having undergone prostatectomy and 142 (52%) reported having undergone radiotherapy. After age adjustment, the radiotherapy group reported more bowel dysfunction (P = 0.001), whereas the prostatectomy group reported more urinary problems (P = 0.03) and more sexual dysfunction (P = 0.001). Scores for the FACT-G were similar in the two treatment groups. Men undergoing treatment for clinically localized prostate carcinoma continue to experience difficulty long after treatment. In this study, the prostatectomy group fared worse in regard to sexual and urinary functions, whereas the radiotherapy group experienced more bowel dysfunction. Survivor-reported QOL and treatment outcomes can assist physicians in counseling patients in the selection of the preferred course of treatment. Cancer 1997; 79:1977-86.
BACKGROUND
Treatment of localized prostate carcinoma (LPC) using radiotherapy (RT) can induce disturbances in a patient's quality of life (QOL) and urinary and intestinal function. Late symptoms and QOL were evaluated in a randomized trial between RT and deferred treatment (DT).METHODS
Quality of life was evaluated with European Organization for Research and Treatment of Cancer's QLQ-C30 (+3) formula. Urinary and intestinal problems were evaluated with a validated symptom specific self-assessment questionnaire, QUFW94. The questionnaires were sent to 108 randomized patients with LPC and to an age-matched control group (n = 68). Mean age was 72 years. Mean total dose was 65 grays (Gy; 62.3–70 Gy). The median follow-up time from randomization was 40.6 months for the RT group and 30.4 months for the DT group.RESULTSSocial functioning was the only QOL scale in which a significant difference was found between the two patient groups and compared with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of daily activities in response to intestinal problems caused this decrease in QOL in the RT group. A significant increase of intestinal problems was observed in the RT versus DT groups regarding mucus, stool leakage, intestinal blood, and planning of daily activity in response to intestinal problems.CONCLUSIONS
The RT patients showed increased levels of minor intestinal side effects compared with the DT patients and the controls, but the RT patients reported no decreased QOL except for decreased social functioning. This could be because this group developed coping skills or because of a low magnitude of side effects to influence the QOL. Cancer 2001;92:3111–9. © 2001 American Cancer Society.
A general formula (α) of which a special case is the Kuder-Richardson coefficient of equivalence is shown to be the mean of
all split-half coefficients resulting from different splittings of a test. α is therefore an estimate of the correlation between
two random samples of items from a universe of items like those in the test. α is found to be an appropriate index of equivalence
and, except for very short tests, of the first-factor concentration in the test. Tests divisible into distinct subtests should
be so divided before using the formula. The index
[`(r)]ij\bar r_{ij}
, derived from α, is shown to be an index of inter-item homogeneity. Comparison is made to the Guttman and Loevinger approaches.
Parallel split coefficients are shown to be unnecessary for tests of common types. In designing tests, maximum interpretability
of scores is obtained by increasing the first-factor concentration in any separately-scored subtest and avoiding substantial
group-factor clusters within a subtest. Scalability is not a requisite.
Analysing quality of life (QOL) data may be complicated for several reasons, such as: repeated measures are obtained; data may be collected on ordered categorical responses; the instrument may have multidimensional scales, and complete data may not be available for all patients. In addition, it may be necessary to integrate QOL with length of life. The major undesirable effects of missing data, in QOL research, are the introduction of biases due to inadequate modes of analysis and the loss of efficiency due to reduced sample sizes. Currently, there is no standard method for handling missing data in QOL studies. In fact, there are very few references to methods of handling missing data in this context. The aim of this paper is to provide an overview of methods for analysing incomplete longitudinal QOL data which have either been presented in the QOL literature or in the missing data literature. These methods of analysis include complete case, available case, summary measures, imputation and likelihood-based approaches. We also discuss the issue of bias and the need for sensitivity analyses.
The patients' perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity.
Significant late intestinal and urinary morbidity from external beam irradiation for adenocarcinoma of the prostate has been a constant concern of both the urologist and the radiation oncologist. We analyzed two large Radiation Therapy Oncology Group trials (7506 and 7706) using primary irradiation in the treatment of local or locoregional adenocarcinoma of the prostate to assess morbidity via the Radiation Therapy Oncology Group scoring scheme (grade 1-5). One thousand twenty patients were treated in total with a minimum follow-up of 7 years in the surviving patients. There was a 3.3% incidence of intestinal complications defined as grade 3 toxicity or more with .6% of patients experiencing bowel obstruction or perforation. Urinary complications defined as grade 3 toxicity or more were found in 7.7% of patients with only 0.5% experiencing morbidity that would require a major surgical intervention such as laparotomy, cystectomy, or prolonged hospitalization. Intestinal and urinary complications were evaluated in reference to several parameters that might have an impact on their incidence (i.e., previous laparotomy, stage of disease, hypertension, positive lymph nodes, previous transurethral resection, total dose, and energy of accelerator used). Only total dose (greater than 70 Gray) was found to have a significant impact on the incidence of the urinary complications. None of these factors had a significant impact on the incidence of intestinal complications. These data from two large multi-institutional trials represent a fair estimate of the actual incidence of major intestinal and urinary complications from external beam irradiation in the management of local and locoregional adenocarcinoma of the prostate. Since the incidence of these major complications remains very low, we believe that external beam irradiation remains an excellent alternative to radical prostatectomy in the management of these patients.
The epidemiological literature has been ambiguous concerning reliability estimates for continuous variables. Reproducibility and internal consistency have been presented as different aspects of reliability, the former being estimated with some form of intraclass correlation coefficient, the latter with Cronbach's alpha. Based on demonstrations available in the literature this paper recalls that both estimates are based on the same measurement model and on the same definition of reliability. It also highlights the conditions under which they are equivalent and provides practical suggestions concerning the estimation of reliability, based on design considerations.
Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series.
A retrospective analysis of the incidence of radiation proctitis was performed in 154 patients with carcinoma of the prostate treated with external radiotherapy assisted by CT-scan planning from 1983 to 1985. An attempt was made to assess a dose-response relationship for proctitis. Multivariate Cox regression analysis showed that previous bowel disease or surgery, anterior rectal dose, and average rectal dose contributed to a higher risk of proctitis. The anterior rectal dose was the most important indicator. No statistically significant correlation was found for the posterior rectal dose. The actuarial 2-year incidence of moderate or severe proctitis was 22% for anterior rectal doses less than 70 Gy and 20% for anterior rectal doses between 70 and 75 Gy, but increased to 60% when the dose was more than 75 Gy. A dose effect relation was evident, with a sharp dose-response gradient around 75 Gy at the anterior rectal wall.
A research program was performed at Louvain-la-Neuve to systematically determine the RBE of fast neutrons for the growth inhibition in Vicia faba bean roots and for the regeneration of the intestinal crypts in mice. The following neutron beams were compared p(75) + Be, p(65) + Be, p(45) + Be, p(34) + Be, d(20) + Be, and d(50) + Be. The RBE-variation as a function of neutron energy is larger for the Vicia faba system than for the regeneration of the intestinal crypt cells. This can be related to the inherent differency of the biological systems, but also to the different dose ranges involved (0.33 to 0.56 Gy and 7.66 to 8.56 Gy, respectively). In the high energy range explored, defined by the reactions p(75) + Be to p(34) + Be RBE varies only between 0.92 and 1.28 for Vicia faba and 0.96 and 1.12 for crypt cells normalized to the p(65) + Be beam. By contrast the RBE at lower energy beams (d(20) + Be and d(14.5) + Be) reaches values between 1.5 and 1.6 Finally fractionation has shown to be likely more important at the high energy beams.
Over 900 patients have been treated with radiation therapy in the 30-year Stanford prostate study. Overall survival, i.e., scoring death due to all causes, was 45%, 35%, 33%, 20%, and 10% for Stanford stages T0, T1, T2, T3, and T4 (nominal stages A, B1, B2, C) at 15 years; lymph node status was unknown. Disease-specific survival at 15 years was 85%, 64%, 45%, 33%, and 15%, respectively, for the same patients. In 141 patients with restricted nodular disease (lymph node status unknown) equal to or less than one-half of one lobe involved (stage B1), the 15-year overall survival was 50% and identical to the expected survival of an age-matched cohort of males. Potency was preserved in 86% of the patients at 15 months posttreatment, and 50% of the patients maintained erectile potency for 7 years posttherapy. Other sequelae and complications are analyzed. The incidence of second neoplasms did not exceed expectations for an age-matched population.
Between June 1977 and April 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized study investigating fast neutron radiation therapy in the treatment of patients with locally advanced (Stage C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation therapy or fast neutron irradiation used in a mixed-beam treatment schedule (neutron/photon). A total of 91 analyzable patients were entered in the study; 78 of them were treated without major protocol deviations. The two treatment groups were balanced in regard to all major prognostic variables. Actuarial curves for "overall" survival, "determinantal" survival and local/regional control are presented both for the entire group of 91 patients and the 78 patients treated within protocol guidelines. The overall local/regional tumor recurrence rate is 7% for the mixed-beam treated group of patients and is 22% for the photon (X ray) treated group of patients. The difference is statistically significant at the p = 0.05 level. For the entire group of 91 evaluable patients, the 5-year "overall" survival rate is 62% for the mixed-beam-treated group and 35% for the photon-treated group. This difference is also statistically significant (p less than 0.05). However, this statistical significance is lost when the smaller number of patients treated strictly within protocol guidelines is considered. The significance is regained (p less than 0.02) when one looks at "determinantal" survival, which uses active cancer at time of death as the failure endpoint. This study demonstrates that a regional treatment modality, in this case mixed-beam irradiation, can influence both local/regional tumor control and survival in patients with locally-advanced adenocarcinoma of the prostate gland.
The variable energy cyclotron of the Catholic University of Louvain is used to produce intense neutron beams for neutron therapy purposes. As a first step, neutrons were produced by bombarding a Be target with 50 MeV deuterons; at present they are produced by 65 MeV protons. This paper describes the improvements to the target system. A new (17 mm) Be target together with the old (10 mm) Be target are inserted in a movable support which allows the production of neutrons either by 65 MeV protons or by 50 MeV deuterons. Both targets can be removed for proton beam therapy. The dosimetric characteristics of the p(65)+Be and d(50)+Be neutron beams are compared: dose rate, gamma-contribution, depth dose and room activation.
To assess institutional and patient compliance with quality of life (QL) instruments in RTOG clinical trials. To assess feasibility of using the Functional Assessment Cancer Therapy (FACT), Sexual Adjustment Questionnaire (SAQ), and Changes in Urinary Function (CUF) QL instruments in a prostate clinical trial and to compare patient self-report of symptoms to medical professional ratings of the same symptoms using the RTOG acute toxicity rating scales.
Three self-assessment QL instruments, the FACT, the SAQ, and CUF, were to be administered to patients on a Phase II locally advanced prostate trial at specified time points. Specific instructions for both data managers and for patients on when, how, and why to fill out the questionnaires were included.
Sixty-seven percent (24 out of 36) of patients accrued to RTOG 90-20 completed both the initial FACT and SAQ. Eighty-five percent completed FACT at end of RT and 73% at 3 months. Eighty-one percent completed SAQ at end of treatment, while 69% completed this form at 3 months. Compliance drops off thereafter. Seventy-five percent of patients who had their symptom of dysuria rated by a medical professional as 0 on the RTOG toxicity rating scale self-reported the same. Only 56% of patient self-reports on FACT regarding diarrhea were in agreement with the medical professional's RTOG rating of 0 toxicity. The measures were determined to be in moderate agreement when the patient evaluated a symptom as a 1 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG toxicity rating scale. There was moderate agreement in 13% of patients with dysuria and 31% of patients with diarrhea. Low agreement occurred when the patient evaluated a symptom as a 2 or 3 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG scale. Low agreement occurred in 13% of both patients reporting dysuria and diarrhea. Differences between how medical professionals and patients were able to rate erectile function make direct comparisons difficult, but the trend towards significant discrepancies is still noteworthy.
Quality of life assessments are necessary and attainable in RTOG clinical trials. Compliance rates for both institutional and patient participation were acceptable at initial and 3 month follow-up. Reasons for noncompliance were predominantly institution related and not patient related. Strategies to address both institution and patient compliance have been developed and implemented within the RTOG. Serious disagreement between patient self-reports of symptoms on the FACT QL scale and medical professional ratings on the RTOG acute toxicity rating scales of the same symptoms was 13% at 3 months follow-up. This warrants continued use of QL self-assessments in clinical trials.
In this article we present the results of mixed-beam, photon/neutron radiation therapy in 45 patients with locally advanced, bulky, or postoperative recurrent prostate cancer treated at the University of Chicago between 1978 and 1991. Survival, disease-free survival, local control, and long-term complications are analyzed in detail.
Between 1978 and 1991, 45 patients with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the treatment was delivered with neutron irradiation at either the University of Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy equivalent. This was followed by a boost to the prostate for an additional 20 photon Gy equivalent.
The median follow-up for patients in this series is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients have died from prostate cancer and 7 from other medical illness. Twenty-seven patients are alive, and 12 of these patients have recurrent and or metastatic disease. The local control rate was 89% (40 out of 45). Histologic material was available on 18 patients following treatment (i.e., prostate biopsy in 16 patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%). Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the patients treated with mixed-beam radiation therapy and were related to dose and beam quality. Factors related to survival, disease-free survival, local control, and complications are analyzed.
The survival and local control results of mixed-beam radiation therapy at the University of Chicago appear to be superior to those series using photon radiation in patients with locally advanced prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to studies using dose escalation or implant techniques as a method to increase local control and survival at institutions with this capability. However, appropriate plans with high-energy neutrons are necessary to minimize complications.
The aim of this study was to assess to what extent patients treated with radiation therapy for prostate cancer experience change in sexual functioning and to what extent this effects quality of life.
Information was provided by 53 men treated with radiation therapy for localized prostate cancer. Assessment was made with the "Radiumhemmets Scale of Sexual Functioning," which measures sexual desire, erectile capacity, orgasm, and to what extent a decrease in any of these aspects of sexual functioning affects quality of life. Function before treatment was assessed retrospectively.
Sexual desire diminished among 77% after treatment. The erection stiffness decreased in 77%. Before external radiation therapy, 66% had an erection usually sufficient for intercourse. Half of the men lost this ability after treatment. Of those retaining orgasm after treatment, 47% reported a decreased orgasmic pleasure and 91% a reduced ejaculation volume. Of all men, 50% reported that quality of life had decreased much or very much due to a decline in the erectile capacity following external radiation therapy.
The results of the present study indicate that external radiation therapy for prostate cancer is associated with a reduction in sexual desire, erectile capacity, and organism functions. In a majority of patients this reduces quality of life. Previously, we may have underestimated the importance an intact sexual function has for the quality of life in this patient category of elderly men.
Analysis of the dose-response function in normal tissues following pelvic irradiation for carcinoma of the prostate.
A homogeneous group of 136 patients with locally advanced carcinoma of the prostate were treated with the Fermilab high-energy neutron beam at three dose levels: 19, 20.4, and 21 Gy, using the same treatment plan and fractionation scheme for all patients.
Tumor control rates were about 83% at the three dose levels studied. However, the normal tissue complication rate (late sequelae) varied with dose: 0 out of 5 at 19 Gy, 5 out of 58 (8.6%) at 20.4 Gy, and 9 out of 73 (12.3%) at 21 Gy.
Neutron therapy to the pelvis reveals a steep dose-response function for late effects with a coefficient of variation of only 11%. This is lower than that usually observed with photons or with less uniform clinical data sets, and may be characteristic for well-planned high-LET radiotherapy.
To evaluate the effectiveness of variable multileaf collimation, three-dimensional treatment planning, and computer-controlled conformal radiation therapy of prostate cancer.
Two hundred and forty-five patients with locally advanced prostate cancer have completed treatment over a 9-year time span using a multileaf collimator and conformal treatment techniques on the University of Washington cyclotron. All patients had three-dimensional treatment planning with computed tomography scans in the treatment position, and had treatment fields individually shaped to the target volume with a continuously variable multileaf collimator. Treatment was delivered under computer control with network transfer of the multileaf collimator settings from the treatment planning computer to the cyclotron control system.
The multileaf collimator combined with three-dimensional treatment planning results in elegant dose distributions. These neuron dose distributions resulted in a reduced local/regional tumor failure rate with no increase in complications when compared to control treatment with photons in a randomized trial. Neutron treatment delivered at other institutions without conformal beam shaping resulted in the same improvement in local-regional tumor control rates, but was associated with a significantly higher normal tissue complication rate than seen with conformal neutron beam delivery techniques (grade 3 and 4 cumulative late normal tissue toxicity rates of 39% vs. 10%, p = 0.0007).
Conformal treatment of prostate cancer using a multileaf collimated neutron beam results in increased local/regional tumor control rates with low normal tissue toxicities. This experience is directly applicable to the conformal treatment of prostate cancer with photons.
To evaluate sequelae and estimate quality of life utilizing a survey instrument in 133 consecutive patients who have undergone definitive radiation therapy for localized prostate cancer.
All patients reported on have been followed for 14 to 60 months (median, 31 months) after radiation therapy and only patients with definitive prostate radiation therapy are included. Of the patients still alive at time of follow-up, 115 were mailed the questionnaire. Data regarding tumor grade and stage as well as treatment were extracted from patient files.
Of the 91% of patients who returned the questionnaire, 11% used a pad and 13% leaked more than a few drops of urine daily. Of all the respondents, 9% stated that incontinence was a problem, and 31% found urinary leaking significantly worsened after radiation therapy compared with before their diagnosis of prostate cancer. With respect to sexual function, 77% recalled being able to have full or partial erections prior to radiation therapy. At some time after radiation therapy, 22% of previously potent respondents were able to have a full erection and 41% were able to have a partial erection. Twenty-nine percent of all patients who were able to establish an erection prior to radiation therapy reported that impotence was a problem at the time of follow-up. Forty-nine percent of patients had abdominal pain, diarrhea, or abdominal cramping during or after radiation therapy and 31% of all patients still had some intestinal symptoms at the time of follow-up. Eighteen percent of all patients were significantly bothered by one or more of these bowel problems. Overall, 31% of all patients reported a persistent degree of physical discomfort that they believed was secondary to their prostate cancer or the effect of treatment. Eighty-one percent were satisfied with radiation therapy and 97% of the patients said they would have radiation therapy again if faced with the decision.
Utilizing a sensitive questionnaire on patients who had definitive radiation therapy for prostate cancer, we found the incidence of patients bothered by incontinence to be surprisingly frequent and higher than previously reported. The frequency of impotence is similar to previous studies. However, when our incontinence and impotence data were compared to Medicare patients who had undergone radical prostatectomy, the frequencies after radiation therapy were significantly lower. Despite the rates of sequelae, the patients were generally satisfied with the decision to undergo radiation therapy and with the medical treatment received.
Twenty-five randomised clinical trials have been completed which have investigated the value of fast neutron therapy. The results of these trials are reviewed in terms of the reported rates of local tumour control and late morbidity. The trials have included patients with cancers of the head and neck region, brain, lung, pancreas, cervix, bladder and rectum. None has demonstrated neutrons to be advantageous compared with photons. Two trials of locally advanced prostate cancer have given conflicting results. A trial of mixed schedule therapy has demonstrated improved local tumour control and survival. A trial of neutrons alone for similar stage disease has not shown any therapeutic advantages. It is still claimed that salivary gland tumours may be more effectively treated by neutrons but the clinical trial results are not definitive. Late morbidity after neutron therapy is a persistent cause for concern and often has been unacceptably high. There is no convincing evidence that fast neutrons are either as safe or as effective in cancer control as photon therapy.
To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate.
From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis.
With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment.
High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.
We reviewed retrospectively a series of 58 patients with deeply invasive bladder cancer treated with fast neutron therapy (p(65) + Be) in order to evaluate its tolerance and side effects. Patients were divided into three groups according to treatment technique. Patients of group A received whole pelvis irradiation up to 50 Gy photon equivalent followed by a boost to the bladder up to 57-66 Gy photon equivalent (40-56 days). Group B patients were treated by a split course regimen of 30 Gy photon equivalent on the whole pelvis at 3-4 weeks interval (66-108 days). Group C patients, not suitable for radical treatment, received only 40-54 Gy photon equivalent (26-70 days). The overall 5-year actuarial survival rate was 30% (SE 8%). As expected, T stage was a statistically significant prognostic factor. The overall local control rate reached 21% at 4 years. Acute and late side effects were minimal to moderate. These results suggest that high-energy neutron beam treatment is at least as effective as photon beam treatment for bladder carcinoma, without a higher incidence of major side effects.
Between June 1977 and April 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized trial investigating the use of fast neutron radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation or fast neutron radiation used in a mixed-beam (neutron/photon) treatment schedule. A total of 91 analyzable patients were entered into the study, and the two patient groups were balanced with respect to the major prognostic variables. Actuarial curves are presented for local/regional control and "overall" survival. Ten-year results for clinically assessed local control are 70% for the mixed-beam group versus 58% for the photon group (p = 0.03) and for survival are 46% for the mixed-beam group versus 29% for the photon group (p = 0.04). This study suggests that a regional method of treatment can influence both local tumor control and survival in patients with locally advanced adenocarcinoma of the prostate gland.
This study was designed to obtain representative estimates of the quality of life and probabilities of possible adverse effects among Medicare-age patients treated with external-beam radiation therapy for prostate cancer.
Patients treated for local or regional prostate cancer with high-energy external-beam radiation between 1989 and 1991 were sampled from a claims data base of the Surveillance, Epidemiology, and End Results (SEER) program from three regions. Patients were surveyed primarily by mail, with telephone follow-up evaluation of non-respondents. There were 621 respondents (83% response rate). The results were compared with data from a previously published national survey of Medicare-age men who had undergone radical prostatectomy.
Although they were older at the time of treatment, radiation patients were less likely than surgical patients to wear pads for wetness (7% v 32%) and had a lower rate of impotence (23% v 56% for men < 70 years), while they were more likely to report problems with bowel dysfunction (10% v 4%). Both groups reported generally positive feelings about their treatments. Radiation and surgical patients reported similar rates of additional subsequent treatment (24% v 26% at 3 years after primary treatment). However, radiation patients were less likely to say they were cancer-free, and they reported more worry about cancer than did surgical patients.
The health-related quality of life of radiation and surgical patients, on average, is similar, but the pattern of experience with adverse consequences of treatment differs by treatment.
To assess the impact of high dose three-dimensional conformal radiotherapy (3D CRT) for prostate cancer on the sexual function-related quality of life of patients and their partners.
Sixty of 124 consecutive patients (median age 72.3 years) treated with 3D CRT for localized prostate cancer were surveyed and reported being potent prior to treatment. The answers to survey questions assessing the impact of quality of life related to sexual function from these 60 patients and their partners forms the basis for this retrospective analysis.
Following 3D CRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Intercourse at least once per month was reduced from 71 to 40%, whereas intercourse less than once per year increased from 12 to 35%. Following treatment, 25% of patients reported that the change in sexual dysfunction negatively affected their relationship or resulted in poor self-esteem. This outcome was associated with impotence following treatment (p < 0.01). Patients who had partners and satisfactory sexual function appeared to be at a higher risk of having a negatively affected relationship or losing self-esteem if they become impotent (p < 0.05). Partners of patients who reported a negatively affected relationship or loss of self-esteem appear to be less likely to return the survey instrument used (p = 0.02).
More work is needed to evaluate the impact of radiotherapy and other treatments on the quality of life of patients and their partners to allow adequate informed consent to be given.
To assess the quality of life (QoL) of patients with localized prostate cancer (LPC) after treatment by radical radiotherapy (RR).
An "ad hoc' self-administered questionnaire was developed, which comprised a series of 41 items grouped into seven subscales reflecting the main QoL domains, and the questionnaire's psychometric properties were assessed. A consecutive series of 118 patients treated with RR for LPC from 1981 to 1994 were then selected for a retrospective study and asked to complete the questionnaire.
Ninety patients (76%) completed the questionnaire; because 20 of them were also treated with hormonal therapy, QoL was assessed only in the remaining 70 patients, to avoid confusion. The assessment of the psychometric properties showed that the questionnaire was valid and reliable (Cronbach's alpha coefficient > 0.8 for each subscale). The main side-effects of RR were urinary symptoms and sexual impairment, while physical, psychological and relational well-being were good. The degree of information available about the therapy and the disease seemed to play a major role in the patients' QoL adjustment after RR.
The study assessed a sample of patients with LPC treated with RR and showed that QoL was acceptable after RR. Prospective studies are needed to improve knowledge of the factors involved in the restoration of the QoL after therapy for LPC.
The multileaf collimator of the fast neutron therapy facility at Louvain-la-Neuve is described, as well as some of the physics experiments performed in order to evaluate the attenuation of neutron beams in different materials and thus optimize the composition of the collimator leaves. The multileaf collimator consists of two sets of 22 leaves each, which can be moved independently. They are made of iron and their thickness is 95 cm. Seven borated polyethylene disks are located in the distal part of the leaves in order to absorb more efficiently the low-energy component of the neutron spectrum. The width of the leaves is 1 cm at their distal part. The leaves can move 11 cm outwards and 6 cm inwards from their reference position, and field sizes up to 25.7 x 24.8 cm, as well as irregular field shapes, can be obtained. The inner part of the leaves and their two sides are always focused on the target. The complete multileaf collimator can rotate around the beam axis, from -90 degrees to +90 degrees from the reference position. The width of the penumbra (80-20% isodoses) is 0.64 cm and 1.17 cm at the depth of the maximum buildup and at 10 cm in depth respectively, for a 10 x 10 cm field size. The collimator is adequate for the energy of the p(65)+Be neutron beam of Louvain-la-Neuve and has been adapted to the fixed vertical beam. It has been designed following the original plans of Scanditronix, adjusted and fully assembled at the workshop of the Centre de Recherches du Cyclotron (CRC). Systematic measurements were performed in order to optimize the design and the composition of the leaves. In particular the attenuations of the actual beam and of monoenergetic neutron beams were measured in different materials such as iron and polyethylene. Above (upstream) the multileaf collimator, a fixed pre-collimator (iron thickness 50 cm; section 1 x 1 m) defines a conical aperture aligned on the largest opening of the leaves. It contains the two transmission chambers and a 2 cm thick polyethylene layer used for hardening the beam.
To use data from a prospective quality-of-life study to assess differences in disease-specific and general health-related quality-of-life changes after treatment with different external-beam irradiation techniques for prostate cancer.
Patients were divided into three groups based on their pretreatment field size and planning technique: whole pelvis, small field, or conformal. Measures of bowel, urinary, and sexual function and of global health-related quality-of-life parameters (from the Health Survey Short Form [SF-36] and the Profile of Mood States [POMS]) were obtained from self-report questionnaires completed before initiation of therapy and at 3 and 12 months after therapy.
Irritative gastrointestinal and genitourinary side effects were frequent 3 months after treatment, but were substantially improved at 12 months. Sexual dysfunction increased steadily over the study period. The POMS and the SF-36 did not demonstrate significant changes over time. Despite small patient numbers, we found trends in favor of conformal therapy across several symptom measures, including sexual function. In the fatigue, energy, and vigor subscales, patients who received whole-pelvis treatment fared significantly worse than those in the other two groups.
Prospective, detailed data from a feasibility study allowed us to assess the effect of technique on quality of life following external-beam irradiation. Although limited by the small planned sample size, these results suggest that smaller radiation fields limit treatment-related complications, including, unexpectedly, sexual dysfunction. However, confirmation in a larger study is necessary.
To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate.
Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or proctitis. Late Grade 3 GU morbidity was cystitis or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects > or = Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP).
Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI morbidities were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were significantly related to acute GI side effects. The parameters significantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivariate analysis. Acute GU side effects were highly correlated with late GU injury. The following were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (-), TURP before RT (-), presentation with urinary obstructive symptoms.
Both late GI and GU morbidity demonstrate a dose dependence, but only the volume dependence observed is a reduction in late Grade 2-4 GI morbidity by increasing the rectal shielding in the lateral fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence.
To evaluate the prevalence of urological morbidity in patients with prostate cancer and its influence on global quality of life (QL).
379 patients with prostate cancer completed several questionnaires (EORTC QLQ-C33, I-PSS, PAIS [sexuality]) and were grouped according to the type of treatment they had undergone: observation only (n = 57), androgen deprivation (n = 112), radiotherapy (n = 114) and radical prostatectomy (n = 96). A group of 86 urologists also completed the questionnaires, imagining that they had stable prostate cancer and had been undergoing androgen deprivation for at least 1 year. Their responses were compared with those from patients who had undergone androgen deprivation.
In all patient groups urinary symptoms were mostly mild to moderate but 12% of patients who had undergone radiotherapy and 11% of hormonally treated patients described severe symptoms. Severe urinary leakage occurred in 16% of patients who had undergone radical prostatectomy. 22% of all patients were impotent before treatment; after treatment sexual life was considerably disturbed in all patients except those who had undergone observation only. Fatigue was a general problem in all patients. In the logistic regression analysis fatigue and lower urinary tract symptoms (LUTS), but not disturbance of sexual life or urinary leakage, were correlated with global QL. In the doctor-patient comparison, doctors underestimated the disturbance of sexual life in patients who had undergone androgen deprivation therapy but overestimated the impairment of QL and psychological distress experienced by these patients.
LUTS and fatigue are independent predictive factors for global QL after initial treatment in patients with prostate cancer. Radiotherapy of the prostate leads to more significant morbidity than was generally anticipated by doctors. The disagreement between doctors' and patients' assessments of QL following treatment indicates the necessity for further systematic QL evaluation in these patients.
Of the estimated 317,000 men in the United States diagnosed with prostate carcinoma in 1996, 57% will have localized disease, and their 5-year relative survival rate will be 98%. Limited information exists on patient-reported quality of life (QOL) and the incidence and severity of treatment-related side effects. The purpose of this study was to identify and compare patients' self-reported QOL and treatment side effects 1-5 years after radical prostatectomy or radiotherapy.
Data collection for this cross-sectional study included a mailed, self-administered survey with three parts: a demographic survey, the Functional Assessment of Cancer Therapy-General (FACT-G), and a newly developed Prostate Cancer Treatment Outcome Questionnaire (PCTO-Q). The FACT-G measured the effect of prostate carcinoma on overall QOL in the two treatment groups. The PCTO-Q assessed the patients' perceptions of the incidence and severity of specific changes in bowel, urinary, and sexual functions. The test-retest reliability of the PCTO-Q in a pilot study was 91.2%.
Two hundred seventy-four eligible men completed the questionnaires; 132 (48%) reported having undergone prostatectomy and 142 (52%) reported having undergone radiotherapy. After age adjustment, the radiotherapy group reported more bowel dysfunction (P = 0.001), whereas the prostatectomy group reported more urinary problems (P = 0.03) and more sexual dysfunction (P = 0.001). Scores for the FACT-G were similar in the two treatment groups.
Men undergoing treatment for clinically localized prostate carcinoma continue to experience difficulty long after treatment. In this study, the prostatectomy group fared worse in regard to sexual and urinary functions, whereas the radiotherapy group experienced more bowel dysfunction. Survivor-reported QOL and treatment outcomes can assist physicians in counseling patients in the selection of the preferred course of treatment.
Although neutron irradiation for prostate cancer has been associated with significant morbidity, pilot data in patients with early stage disease suggested that conformal neutron and photon irradiation was well tolerated without severe complications. A self-assessment questionnaire was mailed to the first 83 patients treated with conformal neutron and photon irradiation to objectively evaluate the impact on quality of life of this regimen. In total, 75 patients (90%) returned the completed questionnaire. These patients had received either 9 neutron Gy (N Gy) plus 38 photon Gy (50 patients) or 10 N Gy plus 38 photon Gy (33 patients) for stage T1/T2 N0 M0 prostate cancer (Gleason score < or = 7). The irradiated volume included the prostate and seminal vesicles with a 1.5 cm margin. Neutrons were delivered as a boost to the prostate only with a non-axial four field beam arrangement. Approximately 50% of the dose to the prostate was from neutron irradiation. Follow-up ranged from 6 to 25 months (median 13 months). The questionnaire used was a validated quality of life instrument used previously in patients treated with surgery or radiation. Prior to irradiation, 29% of patients reported urinary symptoms and 11% had prostate surgery (TURP). At follow-up, 23% reported persistent urinary symptoms. Of these, 21% dripped a few drops of urine, 3% used pads but none leaked > 1 tablespoon/day. One patient underwent surgery to dilate a urethral stricture. Although 55% of patients had gastrointestinal symptoms during radiation therapy, only 26% had persistent symptoms at the time of questioning. These included minor rectal bleeding in 20% and significant hematochezia in 3%. Of the 85% of patients able to obtain full or partial erections prior to irradiation, 87% maintained their potency. Fifteen percent sought treatment for impotence. Overall, at last follow-up, 84% felt little or no physical discomfort, 91% were very satisfied with their treatment, and 97% would choose radiation therapy again. This patient self-assessment questionnaire confirmed that this regimen of conformal neutron and photon irradiation resulted in levels of chronic toxicity acceptable to the patient.
To investigate whether Dose-Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer.
DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70-78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well.
The actuarial incidence at 2 years for GI complications > or =Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications > or =Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications > or =Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications > or =Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose > or = 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07).
These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose-volume thresholds.
To compare the quality-of-life (QOL) perceptions of men treated for prostate cancer with surgery to those of men treated for prostate cancer with radiation therapy.
A two-group descriptive study.
Midwestern community cancer center and teaching hospital.
The study group consisted of 121 men: 68 treated by radical prostatectomy and 53 treated with radiation therapy.
Mailed survey using the Quality of Life Index (QLI) Cancer Version and the University of California at Los Angeles Prostate Cancer Index.
QOL; level of urinary, bowel, and sexual function; impact of dysfunction on patients' lives.
No significant differences were found between the groups in QLI scores, but significant differences were found in urinary, bowel, and sexual function. Urinary function was superior in the radiation therapy group (p = 0.0002). Patients who had undergone surgery were more likely to leak urine every day (p < 0.001). Only 6% of patients who had undergone radiation therapy needed to use pads or diapers as compared to 32% of patients who had undergone surgery. Bowel function was better in the surgery group (p = 0.05). Both groups reported poor sexual function, although it was worse in the surgery group (p = 0.009).
The patients who were treated with surgery had significantly worse urinary and sexual function and better bowel function than those treated with radiation therapy. QOL scores were consistent with these findings, although they did not differ significantly between groups.
This information on the problems of survivors of prostate cancer after surgery and radiation therapy and the effects of therapy on QOL will assist nurses in providing patient education, emotional support, and rehabilitative interventions.
To investigate the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix.
Anorectal manometry was carried out on 24 patients (complication group) with late radiation proctitis. All of the manometric data from these patients were compared with those from 24 age-matched female volunteers (control group), in whom radiation treatment had not yet been performed.
Regardless of the severity of proctitis symptoms, 25% of patients demonstrated all their manometric data within the normal range, but 75% of patients exhibited one or more abnormal manometric parameters for sensory or motor functions. Six patients (25%) had an isolated sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction, and four patients (16.7%) had combined disturbances of both sensory and motor functions. The maximum tolerable volume, the minimal threshold volume, and the urgent volume in the complication group were significantly reduced compared with those in the control group. The mean squeeze pressure in the complication group was significantly reduced, whereas the mean resting pressure and anal sphincter length were unchanged.
Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction.
To evaluate late physical and psychosocial sequelae in patients treated with an association of external beam irradiation (EBI) and brachytherapy (BT) for localized prostate cancer.
Seventy-one patients free of disease, treated at the Centre François Baclesse from 1988 to 1992, were enrolled in a case-control study. Seventy-one healthy controls, matched on age and residence, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in January 1996. The French translation of the Nottingham Health Profile questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire were used to evaluate physical, role, emotional, cognitive and social functioning, global health status as well as energy and sleep disturbance. Specific problems related to prostate cancer were explored using the prostate specific module developed by the EORTC Genito-Urinary Tract Cancer Cooperative Group. Concordance between clinical complications reported by patients and those reported by physicians was also analyzed.
General health quality of life scale scores did not significantly differ between patients and controls, nor did general symptom scale scores. Furthermore, no more late psychosocial sequelae were reported by patients than by controls. No major digestive complications were observed among patients. However, statistical differences were observed concerning interest in sex (P = 0.016) and sexual activity (P < 0.001), urinary incontinence (P < 0.001) and cystitis (P = 0.01). Late subjective morbidity (dysuria, nocturia, urinary incontinence, pelvic pain) appraisal differed slightly between patients and physicians who generally underestimate its severity. While nocturia was reported more often by physicians than by patients (P = 0.0016), patients reported urinary incontinence and pelvic pain more often than physicians (P < 0.001 and P < 0.001, respectively).
The study demonstrates that survivors from localized prostate cancer treated with an association of BT and EBI have good global health status. Major problems that persist are sexual disorders, urinary incontinence and cystitis while digestive disorders were rare. This association could be an alternative to standard EBI in patients with localized prostate cancer. Whatever the treatment choice, patients should be involved in the therapeutic decision which should consider not only expected survival rate but also quality of life.
To evaluate urinary symptoms, potency, and quality of life in a group of patients with prostate cancer followed up with deferred treatment.
A self-administered questionnaire was mailed to patients with localized prostate cancer who were followed up with deferred treatment. Data regarding clinical stage, pathologic grade, and treatment after diagnosis were obtained from patient files.
A total of 71 consecutive patients (age 79 years or less) were included. Of the 52 patients (73%) who responded, 31% had undergone transurethral resection of the prostate, 8% underwent radiation therapy, and 44% underwent hormonal deprivation during the follow-up period. With respect to incontinence, 21% were using pads and 37% leaked urine daily; in 21% of the patients, urine dripping or leaking was a substantial problem. Before the diagnosis of their prostate cancer, 81% stated they were able to have an erection. At the time of the questionnaire, 77% stated that their ability to have erections was reduced and only 29% had had an erection after the prostate cancer was diagnosed. For 12%, impotence was a problem. With respect to quality of life, 52% of the patients rated their health as excellent or good and 61% would be happy to spend the rest of their life feeling the way they did at the time of the questionnaire. Eighty-five percent were satisfied with the treatment policy for their prostate cancer, and 96% would choose deferred treatment again if faced with the decision.
By use of a self-administered questionnaire, a high frequency of incontinence and impotence was found in a group of patients with prostate cancer followed up with deferred treatment. Despite these problems, more than half of the patients rated their health as good and would undergo expectant management again if faced with the decision.