[en] Purpose: To evaluate the adequacy of tumor volume coverage using a three dimensional (3D) margin growing algorithm compared to a two dimensional (2D) margin growing algorithm in the conformal radiotherapy planning of prostate cancer. Methods and Materials: Two gross tumor volumes (GTV) were segmented in each of ten patients with localized prostate cancer: prostate gland only (PO) and prostate with seminal vesicles (PSV). A margin of 10 mm was applied to these two groups (PO and PSV) using both the 2D and 3D margin growing algorithms. The true planning target volume (PTV) was defined as the region delineated by the 3D algorithm. Adequacy of geometric coverage of the GTV with the two algorithms was examined throughout the target volume. Discrepancies between the two margin methods were measured in the transaxial plane. Results: The 2D algorithm underestimated the PTV by 17% (range 12-20) in the PO group and by 20% (range 13-28) for the PSV group when compared to the 3D algorithm. For both the PO and PSV groups, the inferior coverage of the PTV was consistently underestimated by the 2D margin algorithm when compared to the 3D margins with a mean radial distance of 4.8 mm (range 0-10). In the central region of the prostate gland, the anterior, posterior, and lateral PTV borders were underestimated with the 2D margin in both the PO and PSV groups by a mean of 3.6 mm (range 0-9), 2.1 mm (range 0-8), and 1.8 (range 0-9) respectively. The PTV coverage of the PO group superiorly was radially underestimated by 4.5mm (range 0-14) when comparing the 2D margins to the 3D margins. For the PSV group, the junction region between the prostate and the seminal vesicles was underestimated by the 2D margin by a mean transaxial distance of 18.1 mm in the anterior PTV border (range 4-30), 7.2 mm posteriorly (range 0-20), and 3.7 mm laterally (range 0-14). The superior region of the seminal vesicles in the PSV group was also consistently underestimated with a radial discrepancy of 3.3 mm (range 0-12). The maximum underestimation using the 2D algorithm occurred when the target volume angulated sharply to 90 deg. within successive adjacent slices resulting in transaxial plane differences of up to 20 and 55 mm respectively for the PO and PSV groups when compared to coverage by the 3D margin. This was most evident in the junction region of the PSV group. In this region, the 2D algorithm was inadequate, often not providing any margin (range 0-3 mm) in both the sagittal and coronal planes to the GTV compared to the 10 mm margin delineated with the 3D algorithm. Conclusion: This study illustrates the problem of assuming margins delineated in the transaxial plane are adequate to cover a 3D target volume. An appreciation of spatial margins in 3D is required if 2D margin growing algorithms are used. If 2D margin methods are utilised, beams eye view evaluations are required in sagittal and coronal planes to ensure adequate margin and coverage of the target volume

[en] Purpose: To evaluate the extent of tumor down-staging in patients with locally advanced rectal cancer, treated with preoperative chemoradiotherapy. Materials and Methods: Preoperative chemoradiotherapy was given to 116 patients, using a regime that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m²/day). The pretreatment stage distribution, by endorectal ultrasound (u), were uT2 N0 in 2%, uT3 NX in 5%, uT3 NO in 42%, uT3 N1 in 42%, uT4 N0 in 2% and uT4 NX in 4% of cases. In 3% of cases, endorectal ultrasound was not performed. Surgery was performed in all patients, approximately 6 weeks following completion of chemoradiation therapy. Results: The final posttreatment pathological tumor stages were complete response in 28%, Tis-2 NO in 26%, T2 N1 in 5%, T3 N0 in 20%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Downstaging occurred in 61% of cases; the preoperative stage was unchanged in 35% and was more advanced in 4% at surgery. In the cases that were downstaged, 44% decreased in T stage by one level. Of the 56% that had pathological downstaging of more than one level, 45% had a complete pathological response to preoperative chemoradiotherapy. Factors predictive of tumor downstaging included performance status, uT and N staging [p pound 0.05], tumor mobility [p pound 0.02], and circumference of the bowel wall involved by tumor [p pound 0.03]. Conclusion: Downstaging of tumor is pathologically confirmed in approximately two-thirds of patients receiving preoperative chemoradiotherapy, allowing sphincter preservation surgery in patients with locally advanced rectal cancer. TNM staging remains important in assessing patients most likely to benefit from preoperative therapy

[en] Purpose: To evaluate the pretreatment clinical and tumor factors that may predict for complete response in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: The clinical, radiological and pathological records were reviewed in 116 patients who received preoperative chemoradiotherapy using 45 Gy delivered in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m²/day). Factors including TNM staging, tumor size, mobility, location within the bowel lumen, distance from the anal verge, and histological grade were assessed. The pretreatment stage distribution determined by endorectal ultrasound were T2 N0 in 2%, T3 NO-1 in 89%, and T4 N0-1 in 6% of cases. Endorectal ultrasound was not performed in 3% of cases. All patients underwent surgery approximately 6 weeks following completion of chemoradiotherapy. Results: The final pathology revealed a complete response in 28% of cases, residual microscopic disease only in 26% and gross disease in 46%. The initial rectal ultrasound TNM stage in the complete response group was T2 N0 in 6%, T3 NX in 3%, T3 N0 in 47%, T3 N1 in 41%, and T4 N1 in 3%. T stage was predictive of a complete response (p≤ 0.05). All T2 lesions achieved a complete response compared to 28% of T3 and 14% of T4 tumors. Ultrasound evidence of adenopathy was not a factor in achieving a complete response. The clinical factors listed above, including tumor location and extent, were not significant in predicting for a complete response. Conclusion: The extent of tumor beyond the bowel wall is a significant predictor of a complete response to preoperative chemoradiotherapy. However, complete response can still be achieved in a significant proportion of patients with locally advanced lesions

[en] Purpose: To evaluate the value of pretreatment endorectal ultrasound in staging and predicting response to preoperative chemoradiation for rectal cancer. Materials and Methods: Endorectal ultrasound was performed in 116 patients prior to administration of preoperative chemoradiation for rectal cancer. Treatment consisted of 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m²/day). Determined by endorectal ultrasound, the pretreatment stage distribution, was uT2 N0 in 2%, uT3 NX in 5%, uT3 NO in 42%, uT3 N1 in 42%, uT4 N0 in 2% and uT4 NX in 4%. Endorectal ultrasound was not performed in 4% of cases. Surgery was performed approximately 6 weeks following completion of chemoradiation in all patients. Results: The posttreatment pathological tumor stages were Tis-2 NO in 26%, T2 N1 in 5%, T3 N0 in 20%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Overall 28% of patients achieved a complete response to preoperative chemoradiation. Downstaging occurred in 61% of patients after chemoradiation and stabilization of disease stage in 35%. Only 4% of our study population had disease that was more advanced, either due to underestimation of tumor extent by endorectal ultrasound or tumor progression under therapy, at the time of surgical resection. Preoperative endorectal ultrasound staging was predictive of overall response to therapy [p≤0.05], complete response [p≤0.05], and final pathological stage [p≤0.05]. Conclusion: Endorectal ultrasound reliably evaluated pretreatment extent of tumor and the findings were predictive of response to therapy

[en] The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients randomized to dog-let RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized tiral of field sizes (TE10). (Author)

[en] Purpose: Several studies have documented that patients with high risk prostate cancer benefit from androgen ablation (AA) in conjunction with radiotherapy, as compared to those treated with androgen ablation or radiotherapy alone. The hypothesis is that a supra-additive effect is manifested when the treatments are given concomitantly as opposed to sequentially. However, the supra-additivity of this approach is difficult to prove in clinical trials due to tumor heterogeneity and because it takes over 6 years to obtain meaningful data on survival differences. Moreover, under certain conditions androgen ablation might induce quiescence (a more radioresistant state), resulting in a sub-additive interaction. For these reasons, we investigated the effects of androgen ablation and radiation using the androgen sensitive R3327-G Dunning rat prostate model. Materials and Methods: The R3327-G tumor line was used in the 23rd-24th in vivo transplant generations. The tumors were grown in the flanks of 250-300g male Copenhagen rats and were used when they reached approximately 1 cc. The growth fraction was determined by continuously labelling the tumors in vivo with chlorodeoxyuridine (CldUrd) via Alzet minipumps implanted in the opposite flank and measuring the incorporated CldUrd and DNA by flow cytometry. Pulse labelling with iododeoxyuridine (IdUrd) to determine the cell kinetic parameters of labelling index (LI), length of S-phase (Ts), and potential doubling time (Tpot) was accomplished by intraperitoneal injection; these parameters were also calculated from flow cytometric data. Apoptotic index was quantified using an immunohistochemical deoxynucleotidyl transferase (TUNEL) assay on formalin-fixed paraffin-embedded tissue; 2000 cells (20 or more high powered fields) were counted per tumor. Results: Tumor volume measurements revealed that the doubling time (Td) increased from an average of 10 d in intact rats to 37 d in castrates. The pulse labelling of tumors with IdUrd at different times after castration revealed that the LI dropped from a pretreatment level of 9.8 ± 0.4% (±SE) to 1.6 ± 0.2% at 3 days. Measurements taken after 3 d post-castration were similar with LIs leveling off at 1-2%, indicating that a new cell kinetic equilibrium had been reached. Whereas the LI dropped significantly in response to androgen ablation, Ts changed minimally from 19.3 ± 0.6 hr to 22.6 ± 0.7 hr. The dramatic change in LI, and consequently Tpot, in response to androgen ablation occurred with minimal cell loss by apoptosis, which remained at ∼1% after castration. The drop in LI in the absence of a major change in Ts or apoptosis suggests that the principal effect of androgen ablation was to reduce the proportion of tumor cells in the cell cycle. In fact, the growth fraction under equilibrium conditions was 70 % in intact rats and <15% in castrates. These results suggest that irradiating the tumors at 3 d post-castration might be less effective because over 85% of the tumor cells are in a resting state at this point. To examine this further, we measured apoptosis levels after radiotherapy alone (7 Gy, single fraction, cobalt-60) compared to radiotherapy administered 3 d after castration. Peak apoptotic indices, seen at 6 hr following irradiation, were 2% with radiotherapy alone and 10% with the combination treatment. Hence the enhancement in apoptotic index was supra-additive when the combination was used. Conclusion: The loss of the apoptotic response to androgen ablation may be a fairly early occurrence in humans and this was reflected in the R3327-G tumor line. Although androgen ablation induced a tremendous shift of tumor cells into a quiescent state with very little apoptosis, the addition of radiation resulted in a 5-10 fold increase in apoptosis levels over radiation or androgen ablation alone. These findings document an enhancement in cell killing when androgen ablation and radiation treatments are combined in this prostate cancer model and suggest that this interaction contributes to the improved clinical out come of prostate cancer patients so treated

[en] Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible. Copyright (1999) Blackwell Science Pty Ltd

[en] Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, Iymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated. Copyright (1998) Blackwell Science Pty Ltd

[en] A treatment-planning case study has been performed on a patient with a medium-sized, convex brain tumour. The study involved the application of advanced treatment-plan optimization techniques to improve on the dose distribution of the 'standard plan' used to treat the patient. The standard plan was created according to conventional protocol at the Royal Marsden NHS Trust, and consisted of a three-field (one open and two wedged) non-coplanar arrangement, with field shaping to the beam's-eye view of the planning target volume (PTV). Three optimized treatment plans were created corresponding to (i) the optimization of the beam weights and wedge angles of the standard plan, (ii) the optimization of the beam orientations, beam weights and wedge angles of the standard plan, and (iii) a full fluence tomotherapy optimization of 1 cm wide (at isocentre), 270 deg. arcs. (i) and (ii) were created on the VOXELPLAN research 3D treatment-planning system, using in-house developed optimization algorithms, and (iii) was created on the PEACOCK tomotherapy planning system. The downhill-simplex optimization algorithm is used, in conjunction with 'threshold-dose' cost-function terms enabling the algorithm to optimize specific regions of the dose-volume histogram (DVH) curve. The 'beam-cost plot' tool is presented as a visual aid to the selection of beneficial beam directions. The methods and pitfalls in the transfer of plans and patient data between the two planning systems are discussed. Each optimization approach was evaluated, relative to the standard plan, on the basis of DVH and dose statistics in the PTV and organs at risk (OARs). All three optimization approaches were able to improve on the dose distribution of the standard plan. The magnitude of the improvement was greater for the optimized beam-orientation and tomotherapy plans (up to 15% and 30% for the maximum and mean OAR doses). A smaller improvement was observed in the beam-weight and wedge-angle optimized plan (up to 5% and 10% in the maximum and mean OAR doses). In the tomotherapy plan, difficulty was encountered achieving an acceptable homogeneity of dose in the PTV. This was improved by treating the gross tumour volume (GTV) and (PTV-GTV) regions as separate targets in the inverse planning, with the latter region prescribed a slightly higher dose to reduce edge under-dosing. In conclusion, for the medium-sized convex tumour studied, the tomotherapy dose distribution showed a significant improvement on the standard plan, but no significant improvement over a conventional three-field plan where the beam orientations, beam weights and wedge angles had been optimized. (author)

[en] Image distortion is an important consideration in the use of magnetic resonance (MR) images for radiotherapy planning. The distortion is a consequence of system distortion (arising from main magnetic field inhomogeneity and nonlinearities in the applied magnetic field gradients) and of effects arising from the object/patient being imaged. A two-stage protocol has been developed to correct both system- and object-induced distortion in pelvic images which incorporates measures to maintain the quality, accuracy and consistency of the imaging and correction procedures. The first stage of the correction procedure is described here and involves the removal of system distortion. Object- (patient-) induced effects will be described in a subsequent work. Images are acquired with the patient lying on a flat rigid bed, which reproduces treatment conditions. A frame of marker tubes surrounding the patient and attached to the bed provides quality assurance data in each image. System distortions in the three orthogonal planes are mapped using a separate phantom, which fits closely within the quality control frame. Software has been written which automates the measurement and checking of the many marker positions which the test objects generate and which ensures that patient data are acquired using a consistent imaging protocol. Results are presented which show that the scanner and the phantoms used in measuring distortion give highly reproducible results with mean changes of the order of 0.1 mm between repeated measurements of marker positions in the same imaging session. Effective correction for in-plane components of system distortion is demonstrated. (author)