To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution.
A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure.
Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years.
Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.
The therapeutic use of x-rays began almost immediately after their discovery by Röntgen, and within a few years two Swedish physicians could report the first successful treatment of human skin cancer by radiotherapy. Almost from the start it was clear that the biological effect of ionizing radiation depended critically on the exact distribution of the dose in time. The present paper reviews the historical development of dose-time concepts in radiotherapy as seen from a Nordic perspective. Among the topics reviewed are the discussion of single versus fractionated doses, Strandqvist's thesis and the development of power-law biological dose formulas, the effect of dose per fraction and of overall treatment time. It is only within the last 10-15 years that biologically and clinically important dissociation between the radiobiology of early- and late-responding human normal tissues has been appreciated. Biological developments have led to the proposal of altered fractionation schedules, hyperfractionation and accelerated fractionation, that are currently undergoing clinical trial.
The accuracy of central axis dose calculation was evaluated for 48 photon beams from 28 linear accelerators at nine centres in Finland. In addition, inter-accelerator consistency of beam data was evaluated for Varian Clinac 600 CDs and 2100 CDs, and averaged data sets were generated for output factors (OFs) and percentage depth doses (PDDs). The averaged data sets obtained were used to identify potential dosimetry reasons for local errors.
Agreement between measured and calculated doses was determined at isocentre at 10 cm depth in water for nine different sized open square and rectangular fields. Averaged OFs were determined for nominal energies of 4, 6, 10, 15 and 18 MV both at d(max) and at a 10-cm depth. In order to develop a function for the OF data, OFs for square fields were parameterised through empirical model fitting. The feasibility of a simple equivalent square collimator formula was also evaluated for the presentation of OFs for rectangular fields. Averaged PDDs were determined at a 10-cm depth.
The difference between measured and calculated doses exceeded +/-3%, +/-2% and +/-1% for 3, 6 and 35 of the investigated 48 beams, respectively. The differences were due to errors observed in both OFs and depth dose data. When the agreement between dose calculation and measurement was within +/-1%, inter-accelerator differences in OFs were within +/-1.0% at both the depth of dose maximum and at 10 cm for Clinac 600 CDs and also for 2100 CDs. Differences in PDDs were within +/-1.2%.
The importance of quality control for beam data was demonstrated by showing significant errors in measured data. For Clinac 600 and 2100 CDs, the quality control can be accurately performed by comparing local data to averaged reference data. Robust averaged data sets were obtained for 6, 15 and 18 MV beams of Clinac 2100 CDs.
In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae.
Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.
As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P=.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity.
Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.
Adjuvant chemotherapy is increasingly being given to patients with early breast cancer. Long-term follow-up studies suggest a higher frequency of secondary tumours, especially leukaemias, among women receiving such cytotoxic drugs. We studied the frequency of new primary malignancies in 1113 patients with early breast cancer who had been included in a randomised trial to compare chemotherapy as an adjunct to primary surgery with adjuvant locoregional radiotherapy. The estimated rate of new primary malignancies at ten years was significantly lower (p less than 0.0003) in the chemotherapy group (1%) than in the radiotherapy group (6%). The corresponding rate among 1986 patients treated with surgery alone was 5%. Our findings suggest that adjuvant chemotherapy in early breast cancer may protect against the development of new primary tumours in the first ten years of follow-up.
Comment In: Lancet. 1991 Oct 5;338(8771):885-61681236
We investigated the occurrence of thyroid and parathyroid disorders in 100 women (age 66-70 years) irradiated for cervical spondylosis on average 25 years previously and in 100 control women of similar age. Hyperparathyroidism (HPT), proven by operation, was diagnosed in one patient of each group, and three additional cases were diagnosed biochemically among irradiated women. The difference in incidence is not significant. Nor was there any significant difference in incidence of thyroid disorders. No thyroid carcinoma was found in either group. Even if there is a moderate increase of HPT after neck irradiation in middle-aged women the risk is not so great as to warrant organised follow-up.
The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of +/-2%-3%. These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron concentration of 15 microg g(-1) in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy(w) at the different facilities range between 7.6 and 13.2 Gy(w) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy(w) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.
The new technology of combined treatment for patients with ovarian carcinoma of III-IV stages and its relapse is presented. The essentially new component is systemic radiotherapy in nontumoricidal doses. It is used with both traditional surgical and chemotherapeutic components. Systemic radiotherapy is carried out in a form of subtotal body irradiation in two dose-time options with total dose of 1 Gy and 9 Gy. The choice of radiation option is carried out taking into account the initial somatic resource of patients estimated by the condition of lymphopoiesis. The use of systemic radiotherapy in combined treatment of advanced ovarian carcinoma allowed to achieve the significant increase of 3-, 5-year survival in patients as compared to traditional chemo-surgical method. Indirect mechanism of nontumoricidal systemic radiotherapy is to be considered as a vital way for tumor control.