Clinical trial: Efficacy of a low or modified fat diet for the prevention of gastrointestinal toxicity in patients receiving radiotherapy treatment for pelvic malignancies.

BACKGROUND: Inflammatory responses to pelvic radiotherapy can result in severe changes to normal gastrointestinal function with potentially severe long-term effects. Reduced or modified fat diets may confer benefit. METHODS: This randomised controlled trial recruited patients with gynaecological, urological or lower gastrointestinal malignancy due to receive radical radiotherapy. Patients were randomised to a low fat (20% total energy from long chain triglycerides), modified fat (20% from long chain triglycerides and 20% from medium chain triglycerides) or normal fat diet (40% total energy from long chain triglycerides). The primary outcome was a difference in change in Inflammatory Bowel Disease Questionnaire--Bowel (IBDQ-B) score, from the start to end of radiotherapy. RESULTS: A total of 117 patients with pelvic tumours (48% urological; 32% gastrointestinal; 20% gynaecological), with mean (SD) age: 65 (11.0) years, male:female ratio: 79:38, were randomised. The mean (SE) fall in paired IBDQ-B score was -7.3 (0.9) points, indicating a worsening toxicity. Differences between groups were not significant: P = 0.914 (low versus modified fat), P = 0.793 (low versus normal fat) and P = 0.890 (modified versus normal fat). The difference in fat intake between low and normal fat groups was 29.5 g [1109 kJ (265 kcal)] amounting to 11% (of total energy intake) compared to the planned 20% differential. Full compliance with fat prescription was only 9% in the normal fat group compared to 93% in the low fat group. CONCLUSIONS: A low or modified fat diet during pelvic radiotherapy did not improve gastrointestinal symptom scores compared to a normal fat intake. An inadequate differential in fat intake between the groups may have confounded the results.

A comparison of treatment planning techniques used in two randomised UK external beam radiotherapy trials for localised prostate cancer.

AIMS: To compare the radiotherapy planning techniques from two multicentre randomised external beam radiotherapy trials in the UK of conformal radiotherapy vs intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Sixteen sequential patients with histologically confirmed localised prostate cancer treated in the conventional or hypofractionated IMRT trial (CHHiP) were planned using both the CHHiP and Medical Research Council RT-01 planning protocols to 74 Gy in 37 daily fractions. The CHHiP plan used a single phase simple forward planned three-field IMRT plan for easy multicentre adoption. The RT-01 plan used two phases: three-field conformal radiotherapy plan to 64 Gy followed by a six-field boost of 10 Gy. After coverage of the planning target volumes according to the respective trial protocols, the dose to the rectum and bladder was assessed for the two planning techniques. RESULTS: There was acceptable planning target volume coverage by both the CHHiP and RT-01 plans. All CHHiP plans produced lower mean irradiated rectal volumes at all measured dose levels compared with the RT-01 plans, particularly for irradiated rectal volumes at 50 and 70 Gy (P<0.05). In the cases when a CHHiP plan failed to meet its own trial dose constraints, the volumes of irradiated rectum were less than if an RT-01 planning technique had been used. The CHHiP plans gave lower mean irradiated bladder volumes at both 50 and 60 Gy, but higher volumes at 74 Gy. These differences in irradiated bladder volumes were significant at the 60 and 74 Gy dose levels (P<0.05) in favour of the CHHiP and RT-01 plans, respectively. CONCLUSION: The forward planned CHHiP IMRT planning solution gives more favourable rectal sparing than the RT-01 plan. This is important to limit any potential increase in late rectal toxicity for prostate cancer patients treated with high-dose conventional or hypofractionated schedules.

Evaluating inter-fractional changes in volume and position during bladder radiotherapy and the effect of volume limitation as a method of reducing the internal margin of the planning target volume.

AIMS: To quantify the inter-fractional variation in bladder volume and position during a course of bladder radiotherapy, and to assess the feasibility of reducing the planning target volume (PTV) internal margin using an empty bladder protocol. MATERIALS AND METHODS: Weekly computed tomography scans were taken immediately after micturition on 15 patients undergoing radical radiotherapy for bladder cancer. Bladder volume and positional variation were compared by co-registration of the serial computed tomography scans with the initial planning scan and a single 'full' scan at the onset of treatment for each patient. A PTV was generated on the initial planning scan using both our departmental standard of 1.5cm and a reduced 1cm isotropic internal margin around the target (whole bladder) and the relative proportion of the bladder breaching the PTV using both margins compared. RESULTS: The mean post void residual volume from the planning scan was 112cm(3) (standard deviation 42cm(3)). The mean weekly variation in bladder volume relative to the planning volume was 0-12% (standard deviation 20-34%) with no observable trends over time. No statistically significant differences were seen in the proportion of bladder breaching the 1.5 and 1cm internal margin (P=0.18). Regression analysis showed that it is possible to ensure complete coverage of the bladder with a 1cm margin, providing the volume did not exceed over 50% of the initial planning scan volume. CONCLUSION: Using an empty bladder protocol and where on-line imaging is available it is feasible to reduce the internal margin of the PTV from 1.5 to 1cm, providing the volumes do not exceed >50% of the planning scan volume.

Adjuvant chemoradiotherapy for gastric carcinoma: dosimetric implications of conventional gastric bed irradiation and toxicity.

AIMS: Recently, a survival advantage has been shown using adjuvant chemoradiotherapy after complete resection of gastric cancer. If survival advantages are to be maintained, treatment-related complications must be minimised. In this study, we explored the dosimetric implications and toxicity of conventional large field gastric bed irradiation. MATERIALS AND METHODS: Between 2000 and 2002, 16 patients received adjuvant 5-fluorouracil (5-FU) chemoradiotherapy after complete resection of gastric cancer. Radiotherapy was simulator planned using anterior-posterior parallel opposed fields to 45 Gy in 25 daily fractions over 5 weeks. RESULTS: Thirteen patients (81%) completed radiotherapy and eight patients (50%) completed chemotherapy as planned. Toxicity was the main factor for discontinuation. Substantial dose inhomogeneities were shown using retrospective computed tomography recreation of dose-volume histograms (DVHs) of the organs at risk. CONCLUSIONS: Although the delivery of chemoradiotherapy using conventional two-dimensional simulator planning is a feasible technique, significant under-appreciation of dose inhomogeneity exists. Conformal computed tomography planning is vital to document doses received by organs at risk, especially the spinal cord and kidneys, which may receive high doses, and prospectively correlate these with acute and long-term toxicity in order to redefine organ at risk tolerances in the setting of chemoradiation.

An assessment of clinically optimal gold marker length and diameter for pelvic radiotherapy verification using an amorphous silicon flat panel electronic portal imaging device.

Verification of target organ position is essential for the accurate delivery of conformal radiotherapy. Megavoltage electronic portal imaging with flat panel amorphous silicon detectors delivers high quality images that can be used for verification of bony landmark position. Gold markers implanted into the target organ can be visualized and used as a surrogate of actual organ position. On-line compensation for marker displacement, by adjusting patient position, can reduce geometric errors associated with radiation delivery. This study assesses the optimal marker length and diameter to be used with an amorphous silicon (a-Si) flat panel detector and electronic portal images (EPIs), prior to implementation of a clinical programme of gold marker insertion in prostate cancer patients. Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated in a group of patients undergoing pelvic radiotherapy using an 8 MV Elekta SL20 linear accelerator. Markers were placed on the skin entry and exit sites of the treatment beam and EPIs in both lateral and anterior pelvic views were acquired. Three observers independently assessed visibility success and failure using a subjective scoring system. Markers less than 5 mm in length or 0.9 mm in diameter were poorly visualized (<70% visualization success in lateral EPIs). The marker measuring 0.9 mm x 5 mm appears to be clinically optimal in pelvic radiotherapy patients (80% visualization success in lateral EPIs) and will be used for actual organ implantation.

Radiotherapeutic techniques for prostate cancer, dose escalation and brachytherapy.

There is evidence to confirm a dose-response relationship in prostate cancer. The relative benefit is dependent on the clinical prognostic risk factors (T stage, Gleason score and presenting prostate-specific antigen [PSA]) being more favourable for intermediate-risk patients. Refinement of prognostic groups and clinical threshold parameters is ongoing. Escalation of dose in prostate radiotherapy using conventional techniques is limited by rectal tolerance. Substantial advances have been made in radiotherapy practice, such as the development of conformal radiotherapy (CFRT) and intensity-modulated radiotherapy (IMRT). Randomised data support the value of CFRT in reducing rectal toxicity. IMRT can permit higher-dose escalation while still respecting known rectal tolerance thresholds. Brachytherapy is a recognised alternative for low-risk prostate cancer subgroups. New radiotherapeutic strategies for prostate cancer include pelvic nodal irradiation, exploiting the presumed low alpha/beta ratio in prostate cancer for hypofractionation and combining external beam with high-dose-rate brachytherapy boosts. New image-guided methodologies will enhance the therapeutic ratio of any radiotherapy technique or dose escalation programme by enabling more reliable and accurate treatment delivery for improved patient outcomes.

Optimization of coplanar six-field techniques for conformal radiotherapy of the prostate.

PURPOSE: To determine the optimal coplanar treatment technique for six-field conformal radiotherapy of prostate only (PO) or prostate plus seminal vesicles (PSV). METHODS AND MATERIALS: A series of 6-MV six-field coplanar treatment plans were created for PO and PSV volumes in 10 patients prescribed to both 64 and 74 Gy. All plans consisted of laterally-symmetric anterior oblique, lateral, and posterior oblique fields. The posterior oblique fields were varied through 20-45 degrees relative to the lateral fields, and for each of these angles, the anterior oblique fields were varied through 25-65 degrees relative to lateral. The plans were compared by means of rectal volumes irradiated to 80% or more of the prescribed dose (V80); normal tissue complication probability (NTCP) for rectum, bladder, and femoral heads; and tumor control probability (TCP). Femoral head tolerance was designated as 52 Gy to no more than 10% volume. RESULTS: For the PO group, anterior oblique fields at 50 degrees from lateral and posterior oblique fields at 25 degrees from lateral produced the lowest V80, together with femoral head doses which were appropriate for most patients (V80 = 24.4+/-5.3% [1 SD]). Compared to a commonly-used six-field (reference) plan with both anterior and posterior oblique fields at 35 degrees from lateral (V80 = 26.3+/-5.9%), this represented an improvement (p = 0.001). For the PSV group, the optimal anterior and posterior oblique fields were at 65 degrees and 30 degrees from lateral, respectively (V80 = 47.5+/-6.3%). Relative to the reference plan (V80 = 49.4+/-5.6%), this was a marginal improvement (p = 0.07). CONCLUSION: The optimized six-field plans provide increased rectal sparing at both standard and escalated doses. Moreover, the gain in TCP resulting from dose escalation can be achieved with a smaller increase in rectal NTCP using the optimized six-field plans.

Comparison of 2D and 3D algorithms for adding a margin to the gross tumor volume in the conformal radiotherapy planning of prostate cancer.

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 10 patients with localized prostate cancer; prostate gland only (PO) and prostate with seminal vesicles (PSV). A predetermined margin of 10 mm was applied to these two groups (PO and PSV) using both 2D and 3D margin-growing algorithms. The 2D algorithm added a transaxial margin to each GTV slice, whereas the 3D algorithm added a volumetric margin all around the GTV. The true planning target volume (PTV) was defined as the region delineated by the 3D algorithm. The adequacy of geometric coverage of the GTV by the two algorithms was examined in a series of transaxial planes throughout the target volume. RESULTS: The 2D margin-growing 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-margin algorithm. For the PO group, the mean transaxial difference between the 2D and 3D algorithm was 3.8 mm inferiorly (range 0-20), 1.8 mm centrally (range 0-9), and 4.4 mm superiorly (range 0-22). Considering all of these regions, the mean discrepancy anteriorly was 5.1 mm (range 0-22), posteriorly 2.2 (range 0-20), right border 2.8 mm (range 0-14), and left border 3.1 mm (range 0-12). For the PSV group, the mean discrepancy in the inferior region was 3.8 mm (range 0-20), central region of the prostate was 1.8 mm ( range 0-9), the junction region of the prostate and the seminal vesicles was 5.5 mm (range 0-30), and the superior region of the seminal vesicles was 4.2 mm (range 0-55). When the different borders were considered in the PSV group, the mean discrepancies for the anterior, posterior, right, and left borders were 6.4 mm (range 0-55), 2.5 mm (range 0-20), 2.6 mm (range 0-14), and 3.9 mm (range 0-45), respectively. Underestimation of the required margin with the 2D algorithm occurred when the transaxial definition of the GTV shifted in position significantly between successive adjacent slices, resulting in transaxial discrepancies of up to 22 mm and 55 mm, respectively, for the PO and PSV groups. In the superior regions, the 2D algorithm was inadequate, often providing a margin of less than 3 mm compared to the 10 mm margin delineated by the 3D algorithm. CONCLUSION: This study illustrates that target margins added by a laminar method in the transaxial plane are inadequate for covering a 3D tumor volume so that a margin-growing algorithm which fully takes into account the 3D shape of the GTV should be used. If a 2D-margin method is utilized, an appreciation of spatial margins in 3D is required.

Correlations between dose-surface histograms and the incidence of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer.

BACKGROUND AND PURPOSE: In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS: Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS: Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION: The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors.

PURPOSE: Intensity-modulated radiotherapy (IMRT) offers the potential to more closely conform dose distributions to the target, and spare organs at risk (OAR). Its clinical value is still being defined. The present study aims to compare IMRT with stereotactically guided conformal radiotherapy (SCRT) for patients with medium size convex-shaped brain tumors. METHODS AND MATERIALS: Five patients planned with SCRT were replanned with the IMRT-tomotherapy method using the Peacock system (Nomos Corporation). The planning target volume (PTV) and relevant OAR were assessed, and compared relative to SCRT plans using dose statistics, dose-volume histograms (DVH), and the Radiation Therapy Oncology Group (RTOG) stereotactic radiosurgery criteria. RESULTS: The median and mean PTV were 78 cm3 and 85 cm3 respectively (range 62-119 cm3). The differences in PTV doses for the whole group (Peacock-SCRT +/-1 SD) were 2%+/-1.8 (minimum PTV), and 0.1%+/-1.9 (maximum PTV). The PTV homogeneity achieved by Peacock was 12.1%+/-1.7 compared to 13.9%+/-1.3 with SCRT. Using RTOG guidelines, Peacock plans provided acceptable PTV coverage for all 5/5 plans compared to minor coverage deviations in 4/5 SCRT plans; acceptable homogeneity index for both plans (Peacock = 1.1 vs. SCRT = 1.2); and comparable conformity index (1.4 each). As a consequence of the transaxial method of arc delivery, the optic nerves received mean and maximum doses that were 11.1 to 11.6%, and 10.3 to 15.2% higher respectively with Peacock plan. The maximum optic lens, and brainstem dose were 3.1 to 4.8% higher, and 0.6% lower respectively with Peacock plan. However, all doses remained below the tolerance threshold (5 Gy for lens, and 50 Gy for optic nerves) and were clinically acceptable. CONCLUSIONS: The Peacock method provided improved PTV coverage, albeit small, in this group of convex tumors. Although the OAR doses were higher using the Peacock plans, all doses remained within the clinically defined threshold and were clinically acceptable. Further improvements may be expected using other methods of IMRT planning that do not limit the treatment delivery to transaxial arcs. Each IMRT system needs to be individually assessed as the paradigm utilized may provide different outcomes.

Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation.

PURPOSE: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. MATERIALS AND METHODS: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. RESULTS: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. DISCUSSION: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.

A Comparison of clinical target volumes determined by CT and MRI for the radiotherapy planning of base of skull meningiomas.

PURPOSE: To assess the utility of image registration and to compare the localization of clinical target volumes (CTV) using CT and MRI for patients with base of skull meningiomas undergoing radiotherapy. METHODS AND MATERIALS: Seven patients were imaged using CT and a T1-weighted MR volumetric sequence. Following image registration using a chamfer-matching algorithm, transaxial MR slices were reconstructed to match the planning CT slices. The accuracy of the image fusion was assessed in a preliminary study with matching accuracy better than 1.5 mm. The CTV in each patient was separately segmented by two independent observers for both CT and reconstructed MR image sets. Scalar and vector assessments were made of the difference in radial extent between the two outlines on each transaxial plane for all patients. A positive vector value corresponded to a greater extension of the tumor on MR compared to CT and vice versa. Scalar measurements compared the modulus of the differences between MR and CT, regardless of which volume was more extensive. Qualitative comparisons were also performed. RESULTS: Interobserver difference was small with a mean (+/- 1SD) volume difference of 1.5 +/- 1.5 cm(3) for CT and 0.5 +/- 1.0 cm(3) for MRI. The mean CT- and MR- CTVs were 17.6 +/-10.8 and 19.6 +/-14.2 cm(3) respectively. The mean overlap and composite volumes were 13.8 +/-10. 1 and 23.3 +/-14.8 cm(3) respectively. Average scalar differences in the left, right, anterior, and posterior directions were 6.0 +/- 7.0, 3.3 +/- 2.5, 4.9 +/- 3.9, and 4.5 +/- 5.0 mm respectively. The average vector differences were 3.3 +/- 8.5, -0.3 +/- 3.8, 1.1 +/- 5. 8, 1.5 +/- 6.4 mm (for left, right, anterior, and posterior directions respectively). Qualitatively, MR appeared to discern more tumor involvement in soft tissue regions adjacent to the skull base whereas CT appeared to provide larger target volumes within bony regions. CONCLUSIONS: MRI appeared to define CTVs that were larger but not inclusive of CT-defined CTVs. Although the average vector differences were small, the differences on individual borders could be large. In some instances, the CT or MR volumes were vastly different, each providing separate information. Therefore, the use of MRI and CT is complementary. Until accurate histological confirmation of disease extent is available, it is prudent to consider composite CT/MR volumes for the radiotherapy planning of base of skull meningiomas.

Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI.

PURPOSE: To evaluate the dynamic interrelationship between rectal distension and rectal movements, and to determine the effect of rectal movement on the position of the prostatic gland using cine magnetic resonance imaging (MRI). METHODS AND MATERIALS: Fifty-five patients with biopsy-proven or suspected prostate cancer were examined in the axial plane using repeated spoiled gradient-echo sequences every 10 seconds for 7 minutes. Twenty-four patients received bowel relaxants before imaging. Images were analyzed for the degree of rectal distension, for the incidence, magnitude, and number of rectal and prostate movements. RESULTS: Rectal movements were seen in 28 (51%) patients overall, in 10 (42%) of those receiving bowel relaxants and in 18 (58%) not receiving bowel relaxants. The incidence of rectal movements correlated with the degree of rectal distension (p = 0.0005), but the magnitude of rectal movements did not correlate with the degree of rectal distension. Eighty-six rectal movements resulting in 33 anterior-posterior (AP) prostate movements were seen. The magnitude of rectal movements correlated well with degree of prostate movements (p < 0.001). Prostate movements in the AP direction were seen in 16 (29%) patients, and in 9 (16%) patients the movement was greater than 5 mm. The median prostate AP displacement was anterior by 4.2 (-5 to +14 mm). CONCLUSIONS: Cine MRI is able to demonstrate near real time rectal and associated prostate movements. Rectal movements are related to rectal distension and result in significant displacements of the prostate gland over a time period similar to that used for daily fractionated radiotherapy treatments. Delivery of radiotherapy needs to take into account these organ movements.

Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.

PURPOSE: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. RESULTS: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4NI in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. > or = 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of > 1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41 % of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004). CONCLUSIONS: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy.

An evaluation of three-field coplanar plans for conformal radiotherapy of prostate cancer.

BACKGROUND AND PURPOSE: A series of coplanar three-field configurations for two different clinical treatment volumes, prostate only (PO) and prostate plus seminal vesicles (PSV) were studied to determine the optimal three-field plan arrangement for prostate radiotherapy. MATERIALS AND METHODS: A variety of conformal three-field 6 MV plans prescribed to both 64 and 74 Gy were created for PO and PSV volumes in each of ten patients. For description, the orientation of each sequential beam was named in a clockwise fashion. Plans included series with arrangements of 0 degrees, 60-150 degrees, 210-300 degrees; 0 degrees, 90 degrees, 225-255 degrees; 90 degrees, 210-240 degrees, 300-330 degrees and a four-field (4F) box plan for comparison. Six-hundred and eighty plans were compared using the rectal volume irradiated to greater than 50% (V(50)), 80% (V(80)), and 90% (V(90)) of the prescribed dose, normal tissue complications (NTCP) for rectum, bladder, and femoral heads (FH), and tumour control probabilities (TCP). FH tolerance was set at 52 Gy to 10% volume. RESULTS: In comparing the 34 different three-field configurations for each of the PO and PSV groups, the greatest rectal sparing was achieved by a three-field plan with gantry angles of 0 degrees, 90 degrees, 270 degrees (PO: rectal V(80)=22.8+/-5.5% (1S.D.), V(90)=18.4+/-5.7%, and PSV: rectal V(80)=41.9+/-5.8%, V(90)=35.5+/-5.9%). This also improved on the 4F-box plan (PO: rectal V(80)=26.0+/-5.8%, V(90)=21.4+/-5.2%, P<0.001; and PSV: rectal V(80)=47.3+/-5.5%, V(90)=41.6+/-5.1%, P<0.001). The worst rectal sparing was seen with the 0 degrees, 120 degrees, 240 degrees plan (PO: rectal V(80)=35.2+/-8.0%, V(90)=30.3+/-7.1%, P<0.001; and PSV: rectal V(80)=65.7+/-9.0%, V(90)=58.8+/-8.8%, P<0.001). In the PO group, the increase in predicted rectal NTCP with dose escalation from 64 to 74 Gy was 3.3% using the 0 degrees, 90 degrees, 270 degrees plan, 4.7% with the 4F-box plan, and 6.9% with the 0 degrees, 120 degrees, 240 degrees plan. In the PSV group, dose escalation increased the predicted rectal NTCP by 7.9, 10.1 and 15.7% for the 0 degrees, 90 degrees, 270 degrees plan, 4F-box plan, and 0 degrees, 120 degrees, 240 degrees plan, respectively. CONCLUSIONS: For both PO and PSV volumes, the three-field plan which afforded the greatest rectal sparing with acceptable bladder and femoral head doses was the 0 degrees, 90 degrees, 270 degrees plan. This plan also improved on the 4F-box. The increase in predicted rectal NTCP when escalating dose from 64 to 74 Gy was smaller using this plan compared to either the three-field 0 degrees, 120 degrees, 240 degrees plan or the 4F-box plan.

A comparison of coplanar four-field techniques for conformal radiotherapy of the prostate.

BACKGROUND AND PURPOSE: Conformal radiotherapy of the prostate is an increasingly common technique, but the optimal choice of beam configuration remains unclear. This study systematically compares a number of coplanar treatment plans for four-field irradiation of two different clinical treatment volumes: prostate only (PO) and the prostate plus seminal vesicles (PSV). MATERIALS AND METHODS: A variety of four-field coplanar treatment plans were created for PO and PSV volumes in each of ten patients. Plans included a four-field 'box' plan, a symmetric plan having bilateral anterior and posterior oblique fields, a plan with anterior oblique and lateral fields, a series of asymmetric plans, and a three-field plan having anterior and bilateral fields for comparison. Doses of 64 and 74 Gy were prescribed to the isocentre. Plans were compared using the volume of rectum irradiated to greater than 50% (V50), 80% (V80) and 90% (V90) of the prescribed dose. Tumour control probabilities (TCP) and normal tissue complication probabilities (NTCP) for the rectum, bladder and femoral heads were also evaluated. Femoral head dose was limited such that less than 10% of each femoral head received 70% of the prescribed dose. RESULTS: For the PO group, the optimal plan consisted of anterior oblique and lateral fields (Rectal V80 = 23.8+/-5.0% (1 SD)), while the box technique (V80 = 26.0+/-5.8%) was less advantageous in terms of rectal sparing (P = 0.001). Similar results were obtained for the PSV group (Rectal V80 = 43.9+/-5.0% and 47.3+/-5.5% for the two plan types, respectively, P = 0.001). The three-field plan was comparable to the optimal four-field plan but gave higher superficial body dose. With dose escalation from 64 to 74 Gy, the mean TCP for the optimal plan rose from 52.0+/-2.8% to 74.1+/-2.0%. Meanwhile, rectal NTCP for the optimal plan rose by 3.5% (PO) or 8.4% (PSV), compared to 4.7% (PO) or 10.1% (PSV) for the box plan. CONCLUSIONS: For PO volumes, a plan with gantry angles of 35 degrees, 90 degrees, 270 degrees and 325 degrees offers a high level of rectal sparing and acceptable dose to the femoral heads for all patients, while for PSV volumes, the corresponding plan has gantry angles of 20 degrees, 90 degrees , 270 degrees and 340 degrees. Using these plans, the gain in TCP resulting from dose escalation can be achieved with a smaller increase in anticipated rectal NTCP.

A comparison of multileaf collimator with conformal blocks for the boost phase of dose-escalated conformal prostate radiotherapy.

A multileaf collimator (MLC) is compared with conformal blocks for delivering the boost phase of dose-escalated conformal prostate radiotherapy. When using conformal blocks, the volume of rectum irradiated to 90% (V90) is lower (1.4+/-1.3%, 1 SD) for a three-field plan with gantry angles 0 degree, 90 degrees, 270 degrees than for a six-field plan with gantry angles 50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees (2.1 +/- 1.3%, P = 0.002). However, when using an MLC in which the leaves and wedge are oriented at right angles, V90 is higher (4.7 +/- 3.0%) for a three-field plan than for a six-field plan (2.7 +/- 1.6%, P=0.05). The larger increase in V90 for the three-field plan when changing from conformal blocks to MLC is mainly due to the limitation imposed upon the MLC orientation by the use of wedges.

Magnetic resonance imaging (MRI): considerations and applications in radiotherapy treatment planning.

The emerging utilisation of conformal radiotherapy (RT) planning requires sophisticated imaging modalities. Magnetic resonance imaging (MRI) has introduced several added imaging benefits that may confer an advantage over the use of computed tomography (CT) in RT planning such as improved soft tissue definition, unrestricted multiplannar and volumetric imaging as well as physiological and biochemical information with magnetic resonance (MR) angiography and spectroscopy. However, MRI has not yet seriously challenged CT for RT planning in most sites. The reasons for this include: (1) the poor imaging of bone and the lack of electron density information from MRI required for dosimetry calculations; (2) the presence of intrinsic system-related and object-induced MR image distortions; (3) the paucity of widely available computer software to accurately and reliably integrate and manipulate MR images within existing RT planning systems. In this review, the basic principals of MRI with its present potential and limitations for RT planning as well as possible solutions will be examined. Methods of MRI data acquisition and processing including image segmentation and registration to allow its application in RT planning will be discussed. Despite the difficulties listed, MRI has complemented CT-based RT planning and in some regions of the body especially the brain, it has been used alone with some success. Recent work with doped gel compounds allow the MRI mapping of dose distributions thus potentially providing a quality assurance tool and in a manner analogous to CT, the production of dose-response information in the form of dose volume histograms. However, despite the promise of MRI, much development research remains before its full potential and cost-effectiveness can be assessed.

A randomized study of the use of a customized immobilization system in the treatment of prostate cancer with conformal radiotherapy.

PURPOSE: To evaluate the impact of a customized immobilisation system on field placement accuracy, simulation and treatment delivery time, radiographer convenience and patient acceptability. PATIENTS AND METHODS: Thirty men receiving radical radiotherapy for prostate cancer were randomised using a cross over trial design to have radiotherapy planning and treatment given either in a conventional treatment position (CTP) or using an immobilisation system (IMS). The randomisation was to have either the CTP or IMS for the initial 3 weeks of radiotherapy after which patients were replanned and changed to the alternative treatment set-up. Treatment accuracy was measured using an electronic portal imaging device. Radiographers and patients completed weekly questionnaires. RESULTS: Median simulation time was 22.5 min (range 20-30 min) in the CTP and 25 min (range 15-40 min) for the IMS (P < 0.001). Median treatment time was 9 min for CTP (range 8-10 min), and 10 min (range 8.5-13.5 min) for IMS (P < 0.001). Median isocentre displacement for anterior fields was 1.7 mm from the simulated isocentre for the CTP compared to 2.0 mm for IMS (P = 0.07). For left lateral fields values were 1.8 and 1.8 mm (P = 0.98), and for right lateral fields 2.1 and 1.7 mm (P = 0.06), respectively. No clinically significant reduction in either systematic or random field placement errors was demonstrated. Radiographers reported that patients found the IMS more comfortable than CTP (P < 0.001), but when using the IMS, they noticed greater difficulty in patient positioning (P < 0.001), and alignment to skin tattoos (P < 0.001). CONCLUSIONS: Although IMS may have been more comfortable, treatment accuracy was not improved compared to the CTP in our department. In addition, treatment took longer and patient set-up was more difficult.

Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.