Arendjan Wijnmaalen

Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose

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.

Acute morbidity reduction using 3DCRT for prostate carcinoma : A randomized study

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.

Reirradiation combined with hyperthermia in recurrent breast cancer results in a worthwhile local palliation

SummaryBoth experimental and clinical research have shown that hyperthermia (HT) gives valuable additional effects when applied in combination with radiotherapy (RT). The purpose of this study was evaluation of results in patients with recurrent breast cancer, treated at the Daniel den Hoed Cancer Center (DHCC) with reirradiation (re-RT; eight fractions of 4 Gy twice weekly) combined with HT. All 134 patients for whom such treatment was planned were included in the analysis. The complete response rate in 119 patients with macroscopic tumour was 71%. Including the 15 patients with microscopic disease, the local control rate was 73%. The median duration of local control was 32 months, and toxicity was acceptable. The complete response (CR) rate was higher, and the toxicity was less with the later developed 433-MHz HT technique compared with the 2450-MHz technique used initially. With this relatively well-tolerated treatment, palliation by local tumour control of a worthwhile duration is achieved in the majority of patients. The technique used for hyperthermia appeared to influence the achieved results. The value of HT in addition to this re-RT schedule has been confirmed by a prospective randomized trial in a similar patient group. In The Netherlands, this combined treatment is offered as standard to patients with breast cancer recurring in previously irradiated areas.

Angiosarcoma of the breast following lumpectomy, axillary lymph node dissection, and radiotherapy for primary breast cancer: Three case reports and a review of the literature

INTRODUCTION One of the risks of therapeutic irradiation is the development of secondary malignant tumors. In this paper three cases are reported of angiosarcoma of the breast following breast-conserving surgery and irradiation for primary breast cancer, and the literature is reviewed. METHODS AND MATERIALS Until now, 13 other cases of postirradiation angiosarcoma of the breast have been reported. The mean interval between treatment of primary breast cancer and the development of angiosarcoma in these 16 patients is 76 months. The clinical aspect is typical with multiple bluish or purple nodules of the skin, purple discolorations, erythematous maculas or areas, sometimes combined with ulceration, edema, or a palpable mass. Mammography does not necessarily raise suspicion and the interpretation of fine-needle aspiration or biopsy may be difficult. RESULTS In all patients mastectomy was performed, Follow-up data are available for 12 cases. Two patients died of extensive local recurrences and one of distant metastases. CONCLUSION Angiosarcoma of the previously irradiated breast is an extremely rare tumor and diagnosis may be difficult. The number of patients with long-term follow-up after breast-conserving therapy is growing fast. Therefore, the authors advise to pay special attention to uncommon skin changes of the treated breast, since clinical suspicion is the main clue to the diagnosis of postirradiation angiosarcoma. The primary therapy is (simple) mastectomy if wide tumor-free margins can be achieved. There is no indication for standard adjuvant chemotherapy or irradiation.

Postoperative Radiation Therapy for Rectal Cancer An Interim Analysis of a Prospective, Randomized Multicenter Trial in The Netherlands

The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

Treatment outcome, body image, and sexual functioning after orchiectomy and radiotherapy for Stage I–II testicular seminoma

PURPOSE Orchiectomy followed by infradiaphragmatic irradiation is the standard treatment for Stage I-II testicular seminoma in The Netherlands. Because body image and sexual functioning can be affected by treatment, a retrospective study was carried out to assess treatment outcome, body image, and changes in sexuality after orchiectomy and radiotherapy. METHODS AND MATERIALS The medical charts of 166 patients with Stage I-II testicular seminoma were reviewed. A questionnaire on body image and current sexual functioning regarding the frequency and quality of erections, sexual activity, significance of sex, and changes in sexuality was sent to 157 patients (at a mean of 51 months after treatment). RESULTS Seventy-eight percent (n = 123, mean age 42 years) completed the questionnaire. During irradiation, almost half of patients experienced nausea and 19% nausea and vomiting. Only 3 patients had disease relapse. After treatment, about 20% reported less interest and pleasure in sex and less sexual activity. Interest in sex, erectile difficulties, and satisfaction with sexual life did not differ from age-matched healthy controls. At the time of the survey, 17% of patients had erectile difficulties, a figure that was significantly higher than before treatment, but which correlated also with age. Twenty percent expressed concerns about fertility, and 52% found their body had changed after treatment. Cancer treatment had negatively influenced sexual life in 32% of the patients. CONCLUSIONS Orchiectomy with radiotherapy is an effective and well-tolerated treatment for Stage I-II testicular seminoma. Treatment-induced changes in body image and concerns about fertility were detected, but the sexual problems encountered did not seem to differ from those of healthy controls, although baseline data are lacking.

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

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.

Low-dose radiotherapy in 179 patients with Peyronie's disease: treatment outcome and current sexual functioning.

PURPOSE To analyse retrospectively treatment outcome in patients irradiated for Peyronies disease. METHODS AND MATERIALS The records of 179 patients, median age 52 years, that received radiotherapy (RT) between 1982 and 1997 were reviewed. 78% presented with painful erections and 89% with penile deformity. The symptoms were present for a median duration of 6 months (range, 1-72 months). The RT schedule consisted of 13.5 Gy (9 x 1.5 Gy, 3 fractions per week) using orthovoltage X-rays in 123 patients or 12 Gy (6 x 2 Gy, daily fractions) using electrons in 56 patients. A questionnaire regarding current sexual functioning was mailed to 130 patients whose addresses could be traced; 106 (82%) responded. RESULTS At mean follow-up period of 3 months, 83% reported that pain was diminished or had disappeared after RT. Twenty-three percent of patients reported a decrease in penile deformity. Following RT, surgical correction of penile curvature was performed in 29% of patients. No RT-related complications occurred except transient dysuria in 1 patient. Questionnaire data: 72% of patients were currently sexually active, 48% had erectile dysfunction, and 49% expressed dissatisfaction with their current sexual functioning. CONCLUSION Low-dose external RT (12-13.5 Gy) results in relief of pain in the majority of patients with Peyronies disease. Improvement in penile deformity was observed, avoiding surgery in a number of patients. No significant RT-associated morbidity was encountered. It is disappointing that almost 50% of patients complain of sexual functioning, but this is presumably not related to radiotherapy.

Factors influencing the prognosis in bladder cancer

In the categories T1, T2 and T3NxM0 bladder cancer, diameter not exceeding 5 cm, the treatment in the Rotterdam Radio-Therapy Institute consists of interstitial irradiation with needles containing radioactive material. The results of treatment and the role of additional external irradiation are discussed. Category T3NxM0 tumors diameter exceeding 5 cm are treated by external irradiation followed by cystectomy; the results are presented here. Factors influencing prognosis appeared to be degree of differentiation, number of transurethral resections (TURs) prior to definitive treatment, intravenous pyelography (IVP), vascular invasion, T category after preoperative irradiation, and postsurgical histopathologically-assessed T category (pT).

Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

PURPOSE To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). METHODS AND MATERIALS Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-free survival. The endpoints were constructed according to the Kaplan-Meier method. RESULTS The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. CONCLUSIONS A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.