Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion.

AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method. RESULTS: A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD≤3 cm, prostate displacement will be ≤5 mm and that for a MRD≤3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively. CONCLUSIONS: We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

The utility of multimodality imaging with CT and MRI in defining rectal tumour volumes for radiotherapy treatment planning: a pilot study.

AIMS: This study compares the volumetric and spatial relationships of gross tumour volume (GTV) derived from CT (CT-GTV) and GTV derived from MRI (MR-GTV) to determine the utility of multi-modality imaging for radiotherapy treatment planning in rectal cancer. METHODS AND MATERIALS: Fifteen patients with T3 rectal cancer were accrued over 18 months. The male : female ratio was 2:1. The average age was 60.3 years (range 38-79). All patients underwent a diagnostic MRI and CT and MRI simulation. Data sets were co-registered. A site specialised diagnostic radiologist contoured all volumes in consultation with a radiation oncologist. CT-GTV was contoured while blinded to MR data sets. MR-GTV was contoured independently 2-4 weeks later whilst blinded to its respective CT-GTV data. Tumour volumes were analysed for three anatomical subregions (sigmoid, rectal and anal). Reference points on tumour volumes were used for spatial comparison and analysis. RESULTS: The mean CT-GTV/MR-GTV ratio was 1.2 (range 0.5-2.9). The tumour volume ratios for the rectal subregion were well correlated. CT-GTV provided adequate spatial coverage of tumour in reference to MR-GTV with the average mean discrepancy of 0.12 (range -0.08-0.38) or a maximum discrepancy of <0.4 cm (1.54 standard deviation). CT-GTV coverage was inadequate for tumours with MRI evidence of anal and sigmoid invasion. CONCLUSIONS: Conventional simulation CT imaging provided a reasonable estimate of the GTV. Multi-modality imaging with staging MRI can assist target volume definition where there is involvement of the sigmoid and anorectal region and avoid geographic misses. The role of a simulation MRI may aid in this process but remains investigational.

Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.

PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. CONCLUSION: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma.

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively.