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Background: Chemoradiation (RT-CT) is standard treatment for locally advanced cervical cancer (LACC). This study tried to establish if radiotherapy combined with hyperthermia (RT-HT) should be preferred in bulky and/or FIGO-stage ⩾III., Methods: In this open-label, multicenter randomized trial, patients with LACC were randomly assigned by a computer-generated, biased coin minimization technique to RT-CT or RT-HT. Central randomization was done with stratification by FIGO-stage, tumour diameter and nodal status. Primary endpoint was event free survival (EFS). Secondary endpoints were pelvic recurrence free survival (PRFS), overall survival (OS) and treatment related toxicity. Analysis was done by intention to treat., Results: The trial was closed prematurely (87 of 376 planned patients enrolled: 43 RT-CT; 44 RT-HT). Median follow-up time was 7.1 years. The cumulative incidence of an event was 33% in the RT-CT group and 35% in the RT-HT group. The corresponding hazard rate (HR) for EFS was 1.15 (CI: 0.56-2.36, p=0.7). Also the hazards for PRFS (0.94; CI 0.36-2.44) and OS (1.04; CI 0.48-2.23) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity (6 RT-CT and 5 RT-HT patients)., Conclusion: After 25% of intended accrual, data suggest comparable outcome for RT-CT and RT-HT., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

A single dose of irradiation to the lumpectomy cavity alone after breast-conserving surgery in breast cancer patients has been available in the Netherlands since 2011. This new treatment modality is used in the Haaglanden Medical Centre in The Hague and in the Catharina Hospital in Eindhoven. The goal of intraoperative radiation therapy is to limit the patient burden caused by whole breast irradiation, while maintaining excellent local tumour control. The technique is used only in patients with a low probability of recurrent disease in the breast. Approximately 150 patients receive intraoperative radiation therapy each year In the Netherlands, an estimated 4,000 breast cancer patients were eligible in 2013 for this new treatment technique or another method of partial breast irradiation. In both hospitals the results are closely monitored. Only 15 of the first 200 patients experienced a side effect within a period of 3 months after intraoperative radiation therapy. These side effects were successfully treated either with antibiotics or with surgery.

Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series., Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses., Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors., Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up., Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT+HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity., Results: At the 12-year follow-up, local control remained better in the RT+HT group (37% vs. 56%; p=0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT+HT; p=0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups., Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity., Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters., Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, "intermittent bleeding," and "incontinence pads" (p < or = 0.01). For "stools > or =6/day" all three were strong predictors. No significant associations were found for "severe bleeding" and "use of steroids." The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints., Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

Purpose: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity., Methods and Materials: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifying factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used., Results: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence., Conclusions: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.

Purpose: To determine whether a dose of 78 Gy improves outcome compared with a conventional dose of 68 Gy for prostate cancer patients treated with three-dimensional conformal radiotherapy., Patients and Methods: Between June 1997 and February 2003, stage T1b-4 prostate cancer patients were enrolled onto a multicenter randomized trial comparing 68 Gy with 78 Gy. Patients were stratified by institution, age, (neo)adjuvant hormonal therapy (HT), and treatment group. Four treatment groups (with specific radiation volumes) were defined based on the probability of seminal vesicle involvement. The primary end point was freedom from failure (FFF). Failure was defined as clinical failure or biochemical failure, according to the American Society of Therapeutic Radiation Oncology definition. Other end points were freedom from clinical failure (FFCF), overall survival (OS), and toxicity., Results: Median follow-up time was 51 months. Of the 669 enrolled patients, 664 were included in the analysis. HT was prescribed for 143 patients. FFF was significantly better in the 78-Gy arm compared with the 68-Gy arm (5-year FFF rate, 64% v 54%, respectively), with an adjusted hazard ratio of 0.74 (P = .02). No significant differences in FFCF or OS were seen between the treatment arms. There was no difference in late genitourinary toxicity of Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer grade 2 or more and a slightly higher nonsignificant incidence of late gastrointestinal toxicity of grade 2 or more., Conclusion: This multicenter randomized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy.

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer., Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months., Results: Anal dosimetric variables were associated with RTOG/EORTC Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D(mean). Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus., Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

Purpose: To identify dosimetric variables predictive of acute gastrointestinal (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy (HT) is independently associated with acute GI and GU toxicity in prostate cancer patients treated with conformal radiotherapy (RT)., Methods and Materials: This analysis was performed on 336 patients participating in a multicenter (four hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume consisted of the prostate with or without the seminal vesicles, depending on the risk of seminal vesicle involvement. The margin from the clinical target volume to the planning target volume was 1 cm. For these patients, the treatment plan for a total dose of 68 Gy was used, because nearly all toxicity appeared before the onset of the 10-Gy boost. Acute toxicity (<120 days) was scored according to the Radiation Therapy Oncology Group criteria. The dosimetric parameters were obtained from the relative and absolute dose-volume/surface histograms derived from the rectal wall (rectal wall volume receiving > or =5-65 Gy) and the bladder surface (bladder surface receiving > or =5-65 Gy). Additionally, relative and absolute dose-length histograms of the rectum were created, and the lengths of rectum receiving more than a certain dose over the whole circumference (rectal length receiving > or =5-65 Gy) were computed. The clinical variables taken into account for GI toxicity were neoadjuvant HT, hospital, and dose-volume group; for GU toxicity, the variables pretreatment GU symptoms, neoadjuvant HT, and transurethral resection of the prostate were analyzed. The variable neoadjuvant HT was divided into three categories: no HT, short-term neoadjuvant HT (started < or =3 months before RT), and long-term neoadjuvant HT (started >3 months before RT)., Results: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients. Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT (50%). The volumes of the prostate and seminal vesicles were significantly smaller in both groups receiving neoadjuvant HT compared with those receiving no HT. In multivariate logistic regression analysis, including the two statistically significant clinical variables neoadjuvant HT and hospital, a volume effect was found for the relative, as well as absolute, rectal wall volumes exposed to intermediate and high doses. Of all the length parameters, the relative rectal length irradiated to doses of > or =5 Gy and > or =30 Gy and absolute lengths receiving > or =5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or worse was reported in 56% of cases. For patients with pretreatment GU symptoms, the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate analysis, containing the variables pretreatment symptoms and neoadjuvant HT, only the absolute dose-surface histogram parameters (absolute surface irradiated to > or =40, 45, and 65 Gy) were significantly associated with acute GU toxicity., Conclusion: A volume effect was found for acute GI toxicity for relative, as well as absolute, volumes. With regard to acute GU toxicity, an area effect was found, but only for absolute dose-surface histogram parameters. Neoadjuvant HT appeared to be an independent prognostic factor for acute toxicity, resulting in less acute GI toxicity, but more acute GU toxicity. The presence of pretreatment GU symptoms was the most important prognostic factor for GU symptoms during RT.

Purpose: In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented., Methods and Materials: The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death., Results: Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001)., Conclusions: In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse.

Purpose: To study the correlations between the dose distributions in the anorectal region and late GI symptoms in patients treated for localized prostate carcinoma., Methods and Materials: Data from a randomized study were analyzed. In this trial, patients were treated with either rectangular or conformal fields with a dose of 66 Gy. Data concerning GI symptoms were collected from questionnaires of 197 patients. The distributions of the anorectal region were projected on maps, and the dose parameters were calculated. The incidences of complaints were studied as a function of the dose-area parameters and clinical parameters, using a proportional hazard regression model. Finally, we tested a series of dose parameters originating from different parts of the anorectal region., Results: Analyzing the total region, only a statistically significant dose-area effect relation for bleeding was found (p < 0.01). Defining subareas, we found effect relations for bleeding, soiling, fecal incontinence, and mucus loss. For bleeding and mucus loss, the strongest correlation was found for the dose received by the upper 70-80% of the anorectal region (p < 0.01). For soiling and fecal incontinence, we found the strongest association with the dose to the lower 40-50% (p < 0.05)., Conclusion: We found evidence that complaints originate from specific regions of the irradiated lower GI tract. Bleeding and mucus loss are probably related to irradiation of the upper part of the rectum. Soiling and fecal incontinence are more likely related to the dose to the anal canal and the lower part of the rectum.

Purpose: To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy., Methods and Materials: Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA < or =4 ng/mL. Stratification was done for four dose-volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV-planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria., Results: The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity grade > or =2 was 23.2% for 68 Gy, and 26.5% for 78 Gy (p = 0.3). The 3-year risks of late RTOG/EORTC GU toxicity grade > or =2 were 28.5% and 30.2% for 68 Gy and 78 Gy, respectively (p = 0.3). Factors related to acute GI toxicity were HT (p < 0.001), a higher dose-volume group (p = 0.01), and pretreatment GI symptoms (p = 0.04). For acute GU toxicity, prognostic factors were: pretreatment GU symptoms (p < 0.001), HT (p = 0.003), and prior transurethral resection of the prostate (TURP) (p = 0.02). A history of abdominal surgery (p < 0.001) and pretreatment GI symptoms (p = 0.001) were associated with a higher incidence of late GI grade > or =2 toxicity, whereas HT (p < 0.001), pretreatment GU symptoms (p < 0.001), and prior TURP (p = 0.006) were prognostic factors for late GU grade > or =2., Conclusions: Raising the dose to the prostate from 68 Gy to 78 Gy resulted in higher incidences of acute and late GI and GU toxicity, but these differences were not significant, except for late rectal bleeding requiring treatment and late nocturia. Other factors than the studied dose levels appeared to be important in predicting toxicity after radiotherapy, especially previous surgical interventions (abdominal surgery or TURP), hormonal therapy, and the presence of pretreatment symptoms.

Background and Purpose: The late morbidity of a randomized study was analyzed after a follow up of 2 years. The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters. The correlation with acute toxicity and (pre-existing) bowel complaints was investigated., Patients and Methods: 266 T1-4N0M0 prostate cancer patients were randomized for conventional (open fields) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose (66 Gy) and gross target volume-planning target volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self-assessment questionnaire was used to obtain detailed information on morbidity., Results: At 2 years there is only a trend for less rectal toxicity (grade >/=1) in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10 versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A significant relation was found between late rectal toxicity (grade >/=1) and the volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity. The patient self-assessment questionnaire analysis revealed that patients are most bothered by compliance related symptoms like urgency, soiling and fecal loss. In a multivariate analysis, all other variables loose significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation frequency are accounted for. Late anal toxicity is low and related only to acute anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms. The incidence of grade 2 toxicity increases with a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of treatment., Conclusions: Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal, anal and bladder toxicity compared to conventional radiotherapy. There is a significant relationship between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal (and urological) symptoms at start have a major impact on late toxicity.

The purpose of this study is to evaluate anatomy based inverse planning as implemented in PLATO BPS 14.2 for planning of HDR prostate implants. Six patients were analysed. The dose distributions were optimized using geometric optimization followed by graphical optimization (GO), anatomy based inverse planning or standard inverse optimization (SIO), tuned inverse optimization (TIO) and tuned inverse optimization followed by graphical optimization (GOTIO). The mean target coverage was 93+/-4%, 53+/-11%, 74+/-8%, 90+/-3%, respectively, for GO, SIO, TIO and GOTIO. The conformal index COIN was 0.74+/-0.02, 0.43+/-0.15 and 0.77+/-0.07, respectively, for GO, SIO and GOTIO. Improved dose homogeneity was found when comparing GOTIO with GO.

Purpose: Stage IC, grade 3 endometrial cancer is regarded as a high-risk category. Stage IC, grade 3 patients were not eligible for the randomized Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial, but were registered and received postoperative radiotherapy., Patients and Methods: The PORTEC trial included 715 patients with stage IC, grade 1 or 2, and stage IB, grade 2 or 3 endometrial cancer. Patients were randomly assigned after surgery to receive pelvic radiotherapy (RT) or no further treatment. A total of 104 patients with stage IC, grade 3 endometrial cancer were registered, of whom 99 could be evaluated. Patterns of relapse and survival were compared with PORTEC patients receiving RT. Median follow-up was 83 months., Results: The actuarial 5-year rates of locoregional relapse were 1% to 3% for PORTEC patients who received RT, compared with 14% for stage IC, grade 3 patients. Five-year distant metastases rates were 3% to 8% for grade 1 and 2 tumors; 20% for stage IB, grade 3 tumors; and 31% for stage IC, grade 3 tumors. Overall survival rates were 83% to 85% for grades 1 and 2; 74% for stage IB, grade 3; and 58% for stage IC, grade 3 patients (P <.001). In multivariate analysis grade 3 was the most important adverse prognostic factor for relapse and death as a result of endometrial cancer (hazard ratios, 5.4 and 5.5; P <.0001)., Conclusion: Patients with stage IC, grade 3 endometrial carcinoma are at high risk of early distant spread and endometrial carcinoma-related death. Novel strategies for adjuvant therapy should be explored to improve survival for this patient group.

Purpose: To identify dose-volume parameters related to late rectal bleeding after radiotherapy for prostate cancer., Materials and Methods: Clinical complication data from a randomized trial were collected and linked to the individual dose-volume data. In this trial, patients with prostate cancer were treated with either conventional (with rectangular fields) or three-dimensional conformal radiotherapy to a dose of 66 Gy. Patient complaints, including rectal blood loss, were collected for 199 patients, using questionnaires. Absolute and relative dose-volume histograms (DVHs) of the rectal wall (with and without the anal region) were calculated with and without rectal filling. A proportional hazard regression (PHR) model was applied to estimate the probability of any rectal blood loss within 3 years, as a function of several DVH parameters. In a multivariable analysis, dose-volume parameters were tested together with patient- and treatment-related parameters (age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional and rectal bleeding during treatment)., Results: The estimated incidence of any and moderate/severe rectal bleeding at 3 years was 33% and 8%, respectively. Differences between the conventional and conformal technique were small and not significant. The analysis of relative DVHs of the rectal wall (with and without the anal region), showed significant (p < 0.01) relations between the irradiated volume and the probability of rectal blood loss within 3 years for dose levels between 25 Gy and 60 Gy. This relationship was shown in subgroups defined by dose-volume cutoff points as well as in the PHR model, in which a continuously rising risk was seen with increasing volumes. For absolute DVHs and DVHs of the rectum including filling, less or no significant results were observed. The most significant volume-effect relation (p = 0.002) was found at 60 Gy for the rectum wall excluding the anal region. The probability of rectal bleeding increased from 10% to 63% when the irradiated rectum volume at 60 Gy increased from 25% to 100%. Other factors. including age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional, rectal bleeding during treatment, rectum length. and whole rectum volume. did not have a significant effect in the multivariable analysis. When controlling for the volumes at 60 Gy, the volumes at lower dose levels (25-55 Gy) were no longer significant (p = 0.5)., Conclusions: For any rectal bleeding within 3 years, an overall incidence of 33% was observed for patients treated to 66 Gy. For this endpoint, a volume-effect relation was found for DVH parameters of the relative rectal wall volume. This relationship appeared to be most significant for the rectum without the anal region and for the higher dose levels (50-60 Gy).

Based on the good results of re-irradiation plus hyperthermia in breast cancer recurrences on the chest wall, it was decided to offer similar treatment to a patient with recurrent metastatic breast cancer in the orbital region. A female patient was diagnosed in 1997 with breast cancer stage T4N0M0. She was treated with six neo-adjuvant chemotherapy courses and mastectomy, followed by hormonal treatment. In December 1998, she was diagnosed with metastatic disease in the medial upper quadrant of the left orbit. This was excised, followed by 40 Gy radiotherapy. Nine months later, the tumour had recurred in the left orbit at the margin of the radiotherapy field. This again was treated with surgery, followed by 30 Gy radiotherapy. Two months thereafter, the eyelid tumour progressed and hormonal therapy was changed, without an effect on the eyelid tumour. Screening gave no evidence of tumour activity elsewhere. The patient preferred treatment with re-irradiation plus hyperthermia to a surgical approach. Eight fractions of 4 Gy were given in 4 weeks, combined with once weekly hyperthermia. One week after treatment, the tumour had regressed completely. The patient died 22 months following treatment. Until last follow-up, a few weeks before death, the patient mentioned a dry left eye for which she used eyedrops, an unchanged vision and no further difficulties. On examination, there was epilation of the eyelids, a slight conjunctival oedema, no subcutaneous fibrosis and no evidence of tumour regrowth. For this patient, a surgical approach would have resulted in loss of the left eye. Toxicity of re-irradiation plus hyperthermia might lead to either a loss of vision or a delayed loss of her left eye due to treatment-induced toxicity. The chosen local treatment resulted in a very good palliative effect, which lasted for the patient's remaining lifetime of 22 months.

Background and Purpose: To develop a method to project surface elements of a bent tubular organ, e.g. the rectum, in order to create a two-dimensional (2D) map and to use this method to quantify on a local scale shape and position variations of the rectum., Patients and Methods: For this study we used data of 19 patients, who each received a planning CT scan and 9-13 repeat CT scans that were considered representative for the radiotherapy course. We combined maps from multiple CT scans of the same patient to quantify local rectal wall displacements. To make a map we first computed a central axis through the rectum and divided it into segments of equal length assuming that the length of these segments was invariant under rectum shape and position changes. Next, we constructed for each segment a planar cross section through the rectum, which was oriented orthogonally to that segment. The amount of rectal wall tissue was assumed to be constant in all orthogonal cross sections throughout the entire rectum. We unfolded the cross-sected rectal wall at the dorsal side and projected either the associated dose or the coordinates onto the map., Results: The largest variation in the position of the rectal wall during the treatment course occurred at the upper anterior, left and right side (1 SD=5-7 mm). Near the anus the variation was <3 mm (1 SD) and at the posterior side of the rectum <4 mm (1 SD). The anterior-posterior (AP) and left-right displacements between the rectum in the planning CT scan and the mean rectum shape during the treatment were localized between 40 and 80% of the central axis. At the upper anterior, left, and right side the displacements were 5-8 mm (1 SD). These rectal wall displacements correlated with the rectum volume in the planning CT scan. At the upper anterior side the correlation coefficient between the AP displacements and the planning rectum volume was 0.85., Conclusions: We quantified variations in rectum shape and in dose in the rectal wall. The systematic error in rectal wall position was found to be larger than the random shape and position variations. We successfully developed a method to virtually unfold a rectum and to project the dose onto a 2D map. The spatial information of the dose distribution can be used in the analysis of rectum complications.

Objective: The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial., Methods: The PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment., Results: The analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group., Conclusion: Survival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvic relapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival.

Purpose: To develop a model that predicts possible rectum configurations that can occur during radiotherapy of prostate cancer on the basis of a planning CT scan and patient group data., Materials and Methods: We used a stochastic shape description model with a limited number of parameters (area, area difference, and curvature) on a slice-by-slice basis to simulate rectum motion. The probability distributions of the chosen parameters were obtained from a group of 9 reference patients, who each received 15-17 repeat CT scans. We used a Monte Carlo technique to generate different rectum configurations from the probability distributions. We verified the model by comparing dose-wall histograms (DWHs) of the originally delineated rectal contours and simulated rectums for a three-field treatment technique with a prescription dose of 78 Gy. The 15-17 sets of rectal contours of each patient are regarded as the golden standard and provide a good estimate of the actual dose received during the treatment. We determined the equivalent uniform dose (EUD) for a quantitative comparison between the actual dose, the dose predicted on the basis of the simulations, and the dose predicted on the basis of a single planning CT scan., Results: The simulated rectum configurations yield a better estimate of the actual dose in the rectal wall than the rectum in the planning CT scan alone. The differences between the EUD based on the planning CT scan and the actual EUD ranged between -1.1 Gy and 2.1 Gy, with respect to a mean actual EUD of 69.8 Gy. This range is smaller for the EUD based on the simulated rectums, namely -0.4 Gy to 0.6 Gy. Furthermore, the simulation generates a set of rectum configurations that provides an estimate of the variation in DWHs during the course of the treatment. This estimate can be used in addition to the DWH of the planning CT scan in the analysis of gastrointestinal toxicity., Conclusions: To simulate rectum shapes, we have developed a model that can be used in addition to the information available in the planning CT scan in the analysis of the received dose to the rectal wall during radiotherapy of prostate cancer.

Randomized trials have shown that results of radiotherapy in patients with cervical cancer can be improved by combining the treatment with either cisplatin based chemotherapy, or hyperthermia. The studies on both the combination of radiotherapy with chemotherapy, and the combination on radiotherapy with hyperthermia, leave several important questions unanswered. At present, no definite conclusions can be drawn with regard to which combination results in the best therapeutic ratio. Therefore, on both ethical and scientific grounds, the next logical step would be to compare the two types of combined treatment to each other, and each combination with a treatment including all three modalities, in a randomized fashion.

Purpose: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial., Methods and Materials: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French-Italian glossary., Results: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1-4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3-4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1-2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p = 0.001). The 4-field box technique was associated with a lower risk of late complications (p = 0.06)., Conclusion: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.

Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer., Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded., Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate., Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.

This article evaluates current sexual functioning in patients with prostate cancer who are awaiting treatment. One-hundred fifty-eight patients filled out a 15-item questionnaire regarding current sexual functioning. Median age was 67 years. Sixty percent reported to have spontaneous erections at least once a week, and 37% reported a good firmness. Thirty-five percent reported that during sexual activity they had no difficulty in getting erections, and 33% reported that they had no difficulty in maintaining an erection. After diagnosis, all patients reported a decrease in sexual interest, activity, and pleasure. Diagnosis of prostate cancer does have an impact on sexual functioning, therefore sexual counseling prior to treatment is advised.

Background: Postoperative radiotherapy for International Federation of Gynaecology and Obstetrics (FIGO) stage-1 endometrial carcinoma is a subject of controversy due to the low relapse rate and the lack of data from randomised trials. We did a multicentre prospective randomised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma., Methods: Patients with stage-1 endometrial carcinoma (grade 1 with deep [> or =50%] myometrial invasion, grade 2 with any invasion, or grade 3 with superficial [<50%] invasion) were enrolled. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, without lymphadenectomy, 715 patients from 19 radiation oncology centres were randomised to pelvic radiotherapy (46 Gy) or no further treatment. The primary study endpoints were locoregional recurrence and death, with treatment-related morbidity and survival after relapse as secondary endpoints., Findings: Analysis was done according to the intention-to-treat principle. Of the 715 patients, 714 could be evaluated. The median duration of follow-up was 52 months. 5-year actuarial locoregional recurrence rates were 4% in the radiotherapy group and 14% in the control group (p<0.001). Actuarial 5-year overall survival rates were similar in the two groups: 81% (radiotherapy) and 85% (controls), p=0.31. Endometrial-cancer-related death rates were 9% in the radiotherapy group and 6% in the control group (p=0.37). Treatment-related complications occurred in 25% of radiotherapy patients, and in 6% of the controls (p<0.0001). Two-thirds of the complications were grade 1. Grade 3-4 complications were seen in eight patients, of which seven were in the radiotherapy group (2%). 2-year survival after vaginal recurrence was 79%, in contrast to 21% after pelvic recurrence or distant metastases. Survival after relapse was significantly (p=0.02) better for patients in the control group. Multivariate analysis showed that for locoregional recurrence, radiotherapy and age below 60 years were significant favourable prognostic factors., Interpretation: Postoperative radiotherapy in stage-1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival. Radiotherapy increases treatment-related morbidity. Postoperative radiotherapy is not indicated in patients with stage-1 endometrial carcinoma below 60 years and patients with grade-2 tumours with superficial invasion.

Previous research has indicated that the appearance of large gas pockets in portal images of prostate cancer patients might imply internal prostate motion. This was verified with simulations based on multiple computed tomography (CT) data for 15 patients treated in supine position. Apart from the planning CT scan, three extra scans were made during treatment. The clinical target volume (CTV) and the rectum were outlined in all scans. Lateral portal images were simulated from the CT data and difference images were calculated for all possible combinations of CT scans per patient; each scan was used both as reference and repeat scan but gas pockets in the reference scan were removed. Gas pockets in a repeat CT scan then show up as black areas in a difference image. Due to gravity, they normally appear in the ventral part of the rectum. The distances between the ventral edge of a gas pocket in a difference image and the projection of the delineated ventral rectum wall in the reference scan were calculated. These distances were correlated with the "true" rectum wall shifts (determined from direct comparison of the rectum delineations in reference and repeat scan) and with CTV movements determined by three-dimensional chamfer matching. Gas pockets occurred in 23% of cases. Nevertheless, about 50% of rectum wall shifts larger than 5 mm could be detected because they were associated with gas pockets with a lateral diameter > 2 cm. When gas pockets were visible in the repeat scan, rectum wall shifts could be accurately detected by the ventral gas pocket edge in the difference images (r= 0.97). The shift of the rectum wall as detected from gas pockets also correlated significantly with the anterior-posterior shift of the center of mass of the CTV (r=0.88). In conclusion, the simulations showed that lateral pelvic images contain more information than the bony structures that are normally used for setup verification. If large gas pockets appear in those images, a quantitative estimate of the position of prostate and rectum wall can be obtained by determination of the ventral edge of the gas pocket.

Purpose: To minimize differences in the treatment planning procedure between two institutions within the context of a radiotherapy prostate cancer trial., Patients and Methods: Twenty-two patients with N0 M0 prostate cancer underwent a computed tomography (CT) scan for radiotherapy treatment planning. For all patients, the tumor and organs at risk were delineated, and a treatment plan was generated for a three-field technique giving a dose of 78 Gy to the target volume. Ten of the 22 cases were delineated and planned in the other institution as well. The delineated volumes and dose distributions were compared., Results: All treatments fulfilled the trial criteria. The mean volume ratio of the gross tumor volumes (GTVs) in both institutions was 1.01, while the mean volume ratio of the planning target volumes (PTVs) was 0.88. The three-dimensional (3D) PTV difference was 3 mm at the prostate apex and 6-8 mm at the seminal vesicles. This PTV difference was mainly caused by a difference in the method of 3D expansion, and disappeared when applying an improved algorithm in one institution. The treated volume (dose > or =95% of isocenter dose) reflects the size of the PTV and the conformity of the treatment technique. This volume was on average 66 cm3 smaller in institution A than in institution B; the effect of the PTV difference was 31 cm3 and the difference in technique accounted for 36 cm3. The mean delineated rectal volume including filling was 112 cm3 and 125 cm3 for institution A and B, respectively. This difference had a significant impact on the relative dose volume histogram (DVH) of the rectum., Conclusion: Differences in GTV delineation were small and comparable to earlier quantified differences between observers in one institution. Different expansion methods for generation of the PTV significantly influenced the amount of irradiated tissue. Strict definitions of target and normal structures are mandatory for reliable trial results.

Background and Purpose: To compare supine and prone treatment positions for prostate cancer patients with respect to internal prostate motion and the required treatment planning margins., Materials and Methods: Fifteen patients were treated in supine and fifteen in prone position. For each patient, a planning computed tomography (CT) scan was used for treatment planning. Three repeat CT scans were made in weeks 2, 4, and 6 of the radiotherapy treatment. Only for the planning CT scan, laxation was used to minimise the rectal content. For all patients, the clinical target volume (CTV) consisted of prostate and seminal vesicles. Variations in the position of the CTV relative to the bony anatomy in the four CT scans of each patient were assessed using 3D chamfer matching. The overall variations were separated into variations in the mean CTV position per patient (i.e. the systematic component) and the average 'day-to-day' variation (i.e. the random component). Required planning margins to account for the systematic and random variations in internal organ position and patient set-up were estimated retrospectively using coverage probability matrices., Results: The observed overall variation in the internal CTV position was larger for the patients treated in supine position. For the supine and prone treatment positions, the random components of the variation along the anterior-posterior axis (i.e. towards the rectum) were 2.4 and 1.5 mm (I standard deviation (1 SD)), respectively; the random rotations around the left-right axis were 3.0 and 2.9 degrees (1 SD). The systematic components of these motions (1 SD) were larger: 2.6 and 3.3 mm, and 3.7 and 5.6 degrees, respectively. The set-up variations were similar for both treatment positions. Despite the smaller overall variations in CTV position for the patients in prone position, the required planning margin is equal for both groups (about 1 cm except for 0.5 cm in lateral direction) due to the larger impact of the systematic variations. However, significant time trends cause a systematic ventral-superior shift of the CTV in supine position only., Conclusions: For internal prostate movement, it is important to distinguish systematic from random variations. Compared to patients in supine position, patients in prone position had smaller random but somewhat larger systematic variations in the most important coordinates of the internal CTV position. The estimated planning margins to account for the geometrical uncertainties were therefore similar for the two treatment positions.

Purpose: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used., Methods and Materials: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system., Results: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs., Conclusions: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.

In the Daniel den Hoed Cancer Centre in Rotterdam, the Netherlands, patients with recurrent breast cancer within a previously irradiated area, are treated by application of hyperthermia in addition to reirradiation. In this development, the following issues are important: (a) the choice of an effective and tolerable reirradiation schedule; (b) the establishment of the limitations of the hyperthermia techniques available; (c) the finding that additional hyperthermia has to be applied to the total tissue volume at risk for tumour recurrence; (d) the assessment of the value of additional hyperthermia by a randomised study. With the reirradiation schedule of 8 x 4 Gy and the hyperthermia application technique at present available, local control is achieved in 76% of the patients for a median duration of 32 months. The probability of local control is related to tumour size. The treatment is tolerated well, with acceptable toxicity. In patients with recurrent breast cancer in a previously irradiated area, combined reirradiation and hyperthermia is very effective, well tolerated and little toxic.

Purpose: To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients., Methods: For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient., Results: For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion)., Conclusions: The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

Purpose: To demonstrate the need for a fully three-dimensional (3D) computerized expansion of the gross tumour volume (GTV) or clinical target volume (CTV), as delineated by the radiation oncologist on CT slices, to obtain the proper planning target volume (PTV) for treatment planning according to the ICRU-50 recommendations., Materials and Methods: For 10 prostate cancer patients two PTVs have been determined by expansion of the GTV with a 1.5 cm margin, i.e. a 3D PTV and a multiple 2D PTV. The former was obtained by automatically adding the margin while accounting in 3D for GTV contour differences in neighbouring slices. The latter was generated by automatically adding the 1.5 cm margin to the GTV in each CT slice separately; the resulting PTV is a computer simulation of the PTV that a radiation oncologist would obtain with (the still common) manual contouring in CT slices. For each patient the two PTVs were compared to assess the deviations of the multiple 2D PTV from the 3D PTV. For both PTVs conformal plans were designed using a three-field technique with fixed block margins. For each patient dose-volume histograms and tumour control probabilities (TCPs) of the (correct) 3D PTV were calculated, both for the plan designed for this PTV and for the treatment plan based on the (deviating) 2D PTV., Results: Depending on the shape of the GTV, multiple 2D PTV generation could locally result in a 1 cm underestimation of the GTV-to-PTV margin. The deviations occurred predominantly in the cranio-caudal direction at locations where the GTV contour shape varies significantly from slice to slice. This could lead to serious underdosage and to a TCP decrease of up to 15%., Conclusions: A full 3D GTV-to-PTV expansion should be applied in conformal radiotherapy to avoid underdosage.

Purpose: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer., Methods and Materials: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates., Results: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient., Conclusions: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

Purpose: In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTV) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose., Methods and Materials: The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The application of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields., Results: Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for the setup and delivery of the boost fields is usually about 1 min., Conclusion: The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

A substantial number of patients need radiotherapy after surgery for pelvic malignancy. Approximately 15% of them will experience radiation enteritis. After omentoplasty, reduction of irradiated bowel volume may be obtained. We evaluated the pedicled omentoplasty during gynaecologic surgery as a technique to improve safe irradiation of the pelvic region.

Purpose: No adequate high dose rate brachytherapy technique exists to cover all known tumor volume by using one type of applicator in patients presenting with a cervix carcinoma extending to the vaginal wall and the parametria., Methods and Materials: We adapted the existing high dose rate applicator, existing of two ovoids and one intrauterine tube, to achieve adequate irradiation of the uterus, the parametria, and the vaginal wall in these patients. Using the optimization program of the Nucletron Planning System, isodose curves were obtained to apply a specified dose of 8.5 Gy at point A and at 5 mm depth of the vaginal wall by using a single applicator for both fractions., Results: Fractionated high dose rate brachytherapy can be given with both higher dosimetric accuracy and more adequate irradiation of the vaginal and the parametrial tumor component after adapting the existing high dose rate applicator for brachytherapy in cervical cancer.

The records of 15 women presenting with axillary nodal metastases from an occult primary consistent with breast carcinoma were reviewed. Nine patients underwent complete axillary clearance and in six the clinical mass only was excised. Radiotherapy to the axilla was given to eight patients. One woman underwent mastectomy at the time of axillary surgery but no tumour was found in the excised breast; in the remaining 14 patients the breast was left untreated. One premenopausal woman received adjuvant systemic chemotherapy and one postmenopausal patient was given tamoxifen. Three patients died from recurrent disease at 16, 50 and 56 months after treatment of the axillary mass; one is alive at 42 months with systemic recurrence. In two of these patients the tumour in the breast became apparent before other metastases. Eleven patients survived for a median of 92 (range 18-144) months without evidence of disease. The prognosis of this patient group is better than that generally reported for stage II breast carcinoma.

Twenty-six patients with a local and/or regional relapse of a previously surgically treated adenocarcinoma of the endometrium were referred to the Dr. Daniel den Hoed Cancer Center (DDHCC) in Rotterdam, The Netherlands between 1965 and 1985 for external radiotherapy (ERT) and/or brachytherapy (BT). The 5-year overall survival was 44%. Tumour volume seemed to be an important prognostic factor in locoregional control; 1 out of 17 patients with tumour sizes smaller than or equal to 4 cm relapsed locoregionally, while in 3 out of 9 patients with tumour sizes of more than 4 cm a locoregional recurrence developed. Another important finding is the impact of RT on treatment outcome: none of the 16 patients treated with a combination of ERT and BT failed locoregionally, while 4 out of 10 patients treated with either ERT or BT relapsed.

The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.