Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients.

PURPOSE: The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144 Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70 Gy in 82 patients and 74 Gy in 170 patients. bNED rates (Phoenix definition) were assessed. RESULTS: The median follow-up was 46 months (range 1-148 months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002)-84% for patients receiving 70 Gy and 91% for patients receiving 74 Gy, respectively. In the univariate analysis, patients receiving 70 Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74 Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70 Gy EBRT showed significantly worse bNED rates compared to BT patients. CONCLUSION: Low-risk prostate cancer patients receiving 74 Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70 Gy show significantly worse outcome.

[Practice guideline 'Prostate cancer: diagnosis and treatment']. / Richtlijn 'Prostaatcarcinoom: diagnostiek en behandeling'.

--A national, multidisciplinary practice guideline was developed concerning diagnosis and treatment of patients with prostate cancer. Because of the lack of sufficient scientific evidence at this moment no practice guideline on screening is included. --The diagnosis of prostate cancer is made by transrectal ultrasound-guided prostate biopsies. The Gleason score is used for histological grading. --In localized prostate cancer and comorbidity 'active surveillance' is advised if the life expectancy is < 10 years. In healthy patients radical prostatectomy, external and internal radiotherapy are equivalent treatment options. The final decision is made after the patient has received adequate counselling. --In locally advanced prostate cancer in a patient with a life expectancy > or = 10 years external beam radiotherapy is the preferred treatment whether or not in combination with hormonal therapy. --In locally recurring prostate cancer following radical prostatectomy and prostate-specific antigen (PSA) < 1.0 ng/ml salvage radiotherapy can be advised. Recurrence following external beam radiotherapy may be treated by salvage radical prostatectomy or brachytherapy in selected cases. --In metastatic prostate cancer androgen deprivation therapy is advised, i.e. surgical castration, luteinizing hormone-releasing hormone (LH-RH) analogues, or parenteral estrogens. --In hormone resistant prostate cancer palliative treatment of painful metastases is advised, e.g. painkillers, local radiotherapy, or radionuclides. The role of docetaxel-based chemotherapy should be discussed. --During follow-up PSA is determined; digital rectal examination and imaging are performed whenever indicated.

Sequential versus concurrent chemo-radiotherapy in inoperable stage III non-small cell lung cancer.

AIM: To define the best sequence of radiotherapy and chemotherapy for inoperable stage III non-small cell lung (NSCL) tumours. MATERIALS AND METHODS: A systematic review was performed on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCL cancer stage III. The mean median survival time (MST) and mean overall survival (OS) percentages were derived for radiotherapy only, for sequential and for concurrent chemo-radiotherapy. RESULTS: The mean median survival duration +/- standard deviation for radiotherapy only was 10.4 +/- 1.8 months. For sequential chemo- and radiotherapy it was increased to 13.0 +/- 1.2 months. When radiotherapy in the sequential regimen was accompanied by chemotherapy, the mean median duration was 15.8 +/- 2.6 months. For concurrent radio-chemotherapy it was further increased to 16.4 +/- 2.7 months. The mean 2- and 3-year overall survivals for radiotherapy alone, sequential and concurrent radio-chemotherapy were 17.1 +/- 4.6 and 10, 23.8 +/- 6.3 and 18.5 +/- 7.0, and 32.5 +/- 8.7 and 25.7 +/- 6.3%, respectively. CONCLUSION: Concurrent chemo-radiotherapy demonstrated increased efficacy over sequential chemotherapy and radiotherapy and should be the treatment of choice. Further improvements may be obtained by optimising the conditions for concurrent chemo-radiotherapy.

Development of a tapping device: a new needle insertion method for prostate brachytherapy.

The purpose of this study is to develop and test a tapping device for needle insertion for prostate brachytherapy. This device will tap the needle into the prostate with a certain, well-defined, amount of momentum, instead of the currently used method of pushing the needle. Because of the high needle insertion velocity, we expect prostate motion and deformation to be less compared to current methods. We measured the momentum that is applied when manually tapping the needle into the prostate and found a mean momentum of 0.50 +/- 0.07 N s. The tapping device is pneumatically driven and we found that the delivered momentum increased linearly with the applied air pressure. The efficacy of the tapping device was tested on a piece of beef, placed on a freely moving and rotating platform. A significant correlation was found between the applied pressure and the rotation and displacement of the beef. Displacements and rotations were minimal for the highest pressure (4 bar) and amounted to only 2 mm and 6 degrees, respectively. Higher air pressures will further reduce displacements and rotations.

Tumour control probability of stage III inoperable non-small cell lung tumours after sequential chemo-radiotherapy.

UNLABELLED: The aim of this study was to investigate the influence of the duration of waiting time between the end of induction chemotherapy and the start of radiotherapy on tumour control probability (TCP). PATIENTS AND METHODS: Twenty-three patients with inoperable stage III non-small cell lung cancer (NSCLC) received induction chemotherapy followed by radiotherapy. The mean waiting period between the end of induction chemotherapy and the start of radiotherapy was 80 days; in this period, the median tumour volume increased by a factor of about 6. The Poisson model for TCP and the linear-quadratic model were used to calculate changes in TCP in the waiting time. RESULTS: The 2-year survival of patients treated with curative intent was 8%, lower than the mean value of 26% derived from other studies. Assuming that radiotherapy started on the day of restaging or on the first day of radiotherapy (RT1), the calculated mean TCP at restaging was 13.3% and at RT1 was 0.5% for patients treated with curative intent. CONCLUSION: The calculated TCP decreased in the waiting period from 13.3 to less than 1%. Hence, the relatively long interval time between chemo- and radiotherapy had a deleterious effect on local control. We recommend the waiting time to be as short as possible.

Results of d + T fast neutron irradiation on advanced tumors of bladder and rectum.

From November, 1975 to November, 1981, around 400 patients were irradiated with 14 MeV d + T fast neutrons at the Antoni van Leeuwenhoek Hospital in Amsterdam. Special interest was focused on inoperable tumors of bladder and rectum. During the pilot phase of the study 47 patients were treated, mostly via two parallel opposed ports with dosages that ranged from 18 to more than 22 Gy. Although persistent local control was achieved in 23 patients (48%), 14 patients (29%) died of severe complications. By the introduction of a six field technique, the fatal complication rate could be reduced significantly. Since May 1978 patients were randomized in a three arm trial, using two dose levels on the neutron site. The preliminary results of a group of 91 patients show a similar survival in the three treatment arms with a somewhat better local control rate for high dose neutrons. An attempt was made to estimate RBE values for tumor control and normal tissue reactions by comparing the data for neutron irradiation with the data obtained with photons on a similar group of patients. From the values derived it must be concluded that the gain for neutron irradiation on these tumors in the pelvis will be negligible.

The Amsterdam fast neutron therapy project: a final report.

In the period from February 1975 through September 1981 a total of 435 patients received radiotherapy with the 14 MeV d + T neutron generator, hospital based in the Netherlands Cancer Institute (the Antoni van Leeuwenhoek Hospital). Preliminary data on clinical results were published during the past few years. In this paper a final report is given of the program. The results can be summarized as follows: The neutron generator fulfilled the criteria for clinical use, that is it was reliable and had the required minimal output of 10(12) neutrons s-1. However, the dose distribution was more comparable with a 250 kV X-ray machine than with a modern accelerator. A number of physical parameters of importance for clinical neutron dosimetry have been determined for our therapy unit. These data, as well as the results of dosimetry intercomparisons in which our institute participated, contributed in the drafting of a European protocol for clinical neutron dosimetry. Pilot studies were carried out on different tumor sites, including head and neck, brain, pelvis, soft tissue and pulmonary metastases. In many patients local tumor control was seen, however, often concomitant with severe complications, especially in deep seated tumors. Randomized clinical trials were carried out for head and neck tumors (in collaboration with some other European centers) and for inoperable bladder and rectal tumors. No significant difference was observed in local tumor control or late morbidity between photon and neutron irradiation for the head and neck tumors. Also the results for pelvic tumors failed to demonstrate an advantage for neutron therapy. In this study two neutron arms were used with different dose schedules. As could be expected a higher local control rate was noticed for the higher neutron dose group, but concomitant with a higher complication rate. From our experience we have to conclude that treatment with our fast neutron treatment facility did not result in a benefit over photon irradiation. It seemed that the differential effect between tumor and normal tissues is smaller with fast neutrons than with photons.

Evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging.

PURPOSE: The aim of this study is the evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twenty-one patients underwent radiography on the simulator and MRI within 3 days after implantation of the I-125 seeds. Isocentric radiographs were used for reconstruction of the seed distribution, after which registration with the seed-induced signal voids on MRI provided the seed positions in relation to the prostate. The prostate was contoured on the transversal magnetic resonance images, and dose-volume histograms were computed to evaluate the implants. The validity of the ellipsoidal prostate volume approximation, as applied in preimplant dose calculation, was assessed by comparison of ellipsoidal volumes given by prostate width, height, and length and prostate volumes obtained by a slice-by-slice contouring method, both on postimplant MRI. Prostate volume changes due to postimplant prostate swelling were assessed from radiographs taken at 3 days and 1 month after the implantation. RESULTS: The seeds were readily identified on T1-weighted spin-echo images and matched with the seed distribution reconstructed from the isocentric radiographs. The matching error, averaged over 21 patients, amounted to 1.8 +/- 0.4 mm (mean +/- standard deviation). The fractions of the prostate volumes receiving the prescribed matched peripheral dose (MPD) ranged from 32 to 71% (mean +/- standard deviation: 60 +/- 10%). Prostate volumes, obtained by the contouring method on postimplant MRI, were a factor 1.5 +/- 0.3 larger than the ellipsoidal volumes given by the prostate dimensions on postimplant MRI. Prostate volumes 3 days after the implantation were a factor 1.3 +/- 0.2 larger than the prostate volumes 1 month after the implantation. Registration of the reconstructed seed distribution and the MR images showed inaccuracies in seed placement, for example, two or more seeds clustering together or seeds outside the prostate. CONCLUSIONS: Registration of the reconstructed seed distribution and the MR images enabled evaluation of target coverage, which amounted to 60 +/- 10%. The discrepancy between prescribed dose and realized dose was caused by underestimation of the preimplant prostate volume due to the ellipsoidal approximation, postimplant prostate swelling at the time of evaluation, and inaccuracies in seed placement.

Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region.

PURPOSE: To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated. METHODS AND MATERIALS: One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%-40% to 90-100% in patients with a mean parotid dose of 35-45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%-100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD(50) (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve (m = 0.45 at 1 year postradiotherapy). CONCLUSIONS: This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).

Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters.

PURPOSE: To determine prospectively the cataract-free interval (latency time) after total body irradiation (TBI) and bone marrow transplantation (BMT) and to assess accurately the final severity of the cataract. METHODS AND MATERIALS: Ninety-three of the patients who received TBI as a part of their conditioning regimen for BMT between 1982 and 1995 were followed with respect to cataract formation. Included were only patients who had a follow-up period of at least 23 months. TBI was applied in one fraction of 8 Gy or two fractions of 5 or 6 Gy. Cataract-free period was assessed and in 56 patients, who could be followed until stabilization of the cataract had occurred, final severity of the cataract was determined using a classification system. With respect to final severity, two groups were analyzed: subclinical low-grade cataract and high-grade cataract. Cataract-free period and final severity were determined with respect to type of transplantation, TBI dose, and posttransplant variables such as graft versus host disease (GVHD) and steroid treatment. RESULTS: Cataract incidence of the analyzed patients was 89%. Median time to develop a cataract was 58 months for autologous transplanted patients. For allogeneic transplanted patients treated or not treated with steroids, median times were 33 and 46 months, respectively. Final severity was not significantly different for autologous or allogeneic patients. In allogeneic patients, however, final severity was significantly different for patients who had or had not been treated with steroids for GVHD: 93% versus 35% high-grade cataract, respectively. Final severity was also different for patients receiving 1 x 8 or 2 x 5 Gy TBI, from patients receiving 2 x 6 Gy as conditioning therapy: 33% versus 79% high-grade cataract, respectively. The group of patients receiving 2 x 6 Gy comprised, however, more patients with steroid treatment for GVHD. So the high percentage of high-grade cataract in the 2 x 6 Gy group might also have been caused to a significant extent by steroid treatment. The percentage of patients with high-grade cataract was lower in allogeneic transplanted patients without steroid treatment for GVHD than in autologous transplanted patients: 35% versus 48%. An explanation for this could be pretransplant therapy containing high-dose steroids. CONCLUSIONS: After high-dose-rate TBI in one or two fractions, steroids for GVHD influence latency time of a cataract and are of great importance for the severity the cataract finally attains. Although a cataract will develop in all patients, a clinically important high-grade cataract is relatively infrequent in patients not treated with steroids. Pretransplant therapy might also influence final severity of cataract.

Prognostic significance of cell proliferation markers and DNA-ploidy in head and neck tumors.

PURPOSE: The purpose of this study was to evaluate the prognostic significance of cell proliferation markers and DNA ploidy in patients with a squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: With flow cytometry, DNA index, G1PF-phase fraction (G1PF), S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd) labeling-index (LI), and potential doubling time (Tpot), were determined. T-stage and N-stage were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: After multivariate analysis, it appeared that the probability of locoregional recurrent disease was increased by (a) T4-stage, (b) high values of the ratio SPF to LI, (c) DNA tetraploidy. Prognostic significance G1PF for SPF, LI, and Tpot was not demonstrated. However, the treatment regimen was not uniform for the total group of 103 patients. In 45 patients treated with radiation as single treatment and in 49 patients treated with postoperative radiotherapy, prognostic significance for G1PF, SPF, LI, and Tpot could not be demonstrated either. Separate statistical analysis was not executed for nine patients, treated by surgery alone. CONCLUSIONS: Prognostic significance could not be demonstrated for Tpot, LI, SPF, and G1PF in our series. The ratio of SPF to LI was found to be a promising prognosticator and is regarded to be indicative for the size of the hypoxic fraction. Prognostic significance for DNA ploidy was confirmed.

Interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors.

PURPOSE: The purpose of this study was to evaluate the interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors. METHODS AND MATERIALS: DNA-index, S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd)-labeling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were determined by flow cytometry. T-stage and N-stage were assessed in accordance with the TNM classification system (UICC 1987). RESULTS: T1-2-, when compared with T3-4-stage tumors, had significantly higher LI values (independent from N-stage) resulting in lower Tpot values. No such relationship was found with respect to N-stage. N1-3 tumors, as opposed to NO tumors, appeared to be characterized by a significantly shorter Ts (and, hence, a shorter Tpot). Ts values appeared to vary considerably (range 1.9-6.2 h). For DNA-aneuploidy, as opposed to DNA-diploidy, a significantly higher geometric mean LI was noted. Locally advanced (T3-4) tumors, when compared with T1-2 tumors, were characterized by a significantly higher percentage of DNA-aneuploidy. CONCLUSIONS: The reported lack of prognostic relevance of cell proliferation markers to predict radiation treatment efficacy may relate to a decreased proliferative capacity (LI, Tpot) in locally advanced (T3-4) tumors, as found in our series. In laryngeal tumors, the predictive value of cell proliferation markers (LI, Tpot) should, therefore, be evaluated after stratification for T-stage. The existence of higher LI values in DNA-aneuploidy tumors was confirmed in our series, stressing the need for distinction of DNA-diploid tumor cells from DNA-diploid normal cells. The prognostic potential of DNA-index was confirmed.

Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms.

PURPOSE: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation with graded doses of X-rays. METHODS: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 mg/kg) was administered intraperitoneally, 1 hour prior to irradiation. Saliva samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irradiation. The parotid salivary flow rate (microl/min) was used as a parameter for the assessment of parotid gland function. RESULTS: Our data confirm that a single prophylactic treatment of pilocarpine can attenuate radiation-induced loss of gland function. Surprisingly, the effect of pilocarpine was not restricted to the irradiated gland only. Pilocarpine also enhanced the flow rate in the contralateral, nonirradiated gland. The latter effect was found for all doses above 10 Gy and became apparent around 7 days after the radiation treatment. The effectiveness of pilocarpine to attenuate function loss in the irradiated gland decreased with increasing dose and was lost after single doses of 30 Gy. CONCLUSIONS: Our data provide direct evidence that increasing the compensatory potential of the nondamaged gland, at least in part, underlies the "radioprotective effect" of pilocarpine in case of unilateral radiation. The ability of pilocarpine to ameliorate the early radiation-induced impairment of the parotid gland function in the irradiated gland may therefore be dependent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal.

I-125 implantation for localized prostate cancer: the Utrecht University experience.

BACKGROUND AND PURPOSE: I-125 seed implantation is one of the treatment modalities for localized prostate carcinoma. It has few side-effects compared with radical prostatectomy and beam irradiation. MATERIALS AND METHODS: At the University Medical Centre, Utrecht, 249 naive patients were treated by perineal implantation between December 1989 and December 1998. Mean age was 69 years (range 45-91 years). Stage and grade were: T(1), 121; T(2), 126; T(3), 2; well differentiated, 136; moderate, 100; undifferentiated, 15; not established, 8. Mean initial PSA level was 16.1 ng/ml (range <1.0-165). Mean prostate volume was 33 cm(3). Sixty-two patients had had previous surgical intervention for voiding problems. Treatment evolved from single seeds to RAPID Strand, and from a probe-mounted template to stepping unit and pre-planning. The introduction of RAPID Strand considerably increased the number of seeds (mean 41->65 seeds). Mean follow-up was 32.8 months, median 29.2 months (range 6-94 months). RESULTS: A total of 195 patients had no evidence of disease (18 died of intercurrent causes) and 54 had evidence of disease (13 died with prostate cancer). Toxicity was found in 22 patients. Urinary side-effects occurred in 18 patients, in nine cases after previous TURP. Four patients had intestinal problems, but only one had a rectal ulcer, which healed after hormonal therapy for local recurrence. CONCLUSIONS: Our findings indicate a correlation between the number of seeds implanted per cm(3) prostate volume and the final result. This is also reflected in a better volume coverage from MRI studies.

Feasibility of permanent implants for prostate cancer after previous radiotherapy in the true pelvis.

BACKGROUND AND PURPOSE: Permanent seed implantation was used in the management of primary and recurrent prostate cancer in patients who had been treated previously by radiotherapy of the true pelvis. MATERIAL AND METHODS: Between 1993 and 1998 a total of 21 patients received an I-125 implant after radiotherapy for bladder cancer (two patients), anal cancer (one patient), seminoma (two patients) and prostate cancer (16 patients). Two seminoma and 10 prostate cancer patients were treated after earlier definitive external beam radiation therapy (EBRT), while the bladder and anal cancer were initially treated with EBRT plus iridium implantation. Six prostate cancer patients were initially treated by brachytherapy alone. The interval between the two treatments was longer in patients with radiotherapy for other malignancies than prostate cancer. RESULTS: After EBRT no serious late toxicity was observed. However, 1/6 patients who had two seed implants experienced serious complications, resulting in a vesico-rectal fistula. CONCLUSIONS: The permanent seed implantation with I-125 is feasible after previous radiotherapy in the prostate area. Also a second implant is possible, but may result in severe complications, depending on the initial dose and interval between the two treatments.

Results of implantation for T1 and T2 bladder tumours.

In the period from January 1972 through December 1983 a total of 123 patients was treated for a bladder malignancy by preoperative external irradiation followed by interstitial therapy. Criteria for selection of patients are solitary lesion, tumour smaller than 5 cm in diameter, state T1 and T2. The majority of patients was in state T2 (89 patients). Persisting local control was achieved in 29 out of 34 T1 cases and in 69 out of 85 T2 cases. The actuarial 10 years survival was 72% for T1 and 34% for T2, with a total disease-free percentage at 10 years of 77% for T1 and 56% for T2. Although in many patients delayed wound healing was noticed, no serious late reactions were seen in skin, bladder or intestine. The causes of death are distant metastases in 13 patients and intercurrent diseases in another 21 patients.

What degree of accuracy is required and can be achieved in photon and neutron therapy?

In this paper an attempt is made to formulate criteria for the accuracy in the delivery of absorbed dose to a patient during photon or neutron therapy. These requirements are mainly based on the relative steepness of dose-effect curves for local tumour control and normal tissue damage. A review of these dose-effect curves after photon irradiation shows a great variety in steepness; the curves for normal tissue complications in general may be steeper than those for local tumour control. From these data a standard requirement for the combined uncertainty of type A (random) and type B (systematic), given as one relative standard deviation, in the absorbed dose delivery of 3.5% is proposed, even though it is known that in many cases larger values are acceptable and in a few special cases an even smaller value should be aimed at. From the available radiobiological and clinical data it can be concluded that no statistically significant difference can be observed in the relative steepness of dose-effect curves after photon or neutron irradiation. Similar limits will thus be requested in neutron therapy. The uncertainties in the various steps involved in the delivery of an absorbed dose to a point in a patient have been analysed for a treatment with two parallel-opposed beams. The results of this analysis showed that even for these simple treatment conditions, the required accuracy in the delivery of the absorbed dose cannot completely be obtained in photon therapy, and not nearly in neutron therapy. The uncertainties in physical, radiobiological and clinical approaches for weighting of the biological effectiveness of neutron radiation have been compared. The uncertainty in the RBE ratio will replace the type B uncertainty in the absorbed dose during patient treatment if the same dosimetry protocol is applied during biological and clinical procedures.

Preliminary results with iodine-125 seeds for permanent implantation in patients with localized prostatic cancer.

Since August 1981, a permanent implantation with iodine-125 seeds has been performed in 41 patients with localized prostatic cancer. The seeds are implanted through a suprapubic incision. This gives the opportunity also to perform a diagnostic dissection of the regional lymph nodes. In five patients, the nodes were positive. In 4 out of these 5 patients bone metastases became manifest within one year. Two patients died of disseminated tumor, the first also had a local recurrence. Two other patients died shortly after treatment because of heart failure, while a third patient also died of heart failure, 2 years after implantation. Out of 31 patients with a follow-up period of 6 months or longer, distant metastases were found in four, in 2 followed by a local recurrence in the prostate. We can conclude that the preliminary results of this technique are encouraging with only three local recurrences in 41 patients. The prognostic value of positive lymph nodes was once again established.

Fast neutrons in the treatment of head and neck cancers: the results of a multi-centre randomly controlled trial.

The results are presented of a multi-centre randomly controlled trial of fast neutron irradiation and mega-voltage X-rays in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck region. No significant difference was observed in local tumour control rates. Salvage surgery was performed in a similar number of patients in the two groups. Late morbidity was also similar in the two treatment groups. Patients in a subgroup with cancer of the larynx treated by photons had a significantly better survival than those in the neutron treated group.