A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial.

PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.

How effective is a virtual consultation process in facilitating multidisciplinary decision-making for malignant epidural spinal cord compression?

PURPOSE: The purpose of this study was to assess the accuracy of a virtual consultation (VC) process in determining treatment strategy for patients with malignant epidural spinal cord compression (MESCC). METHODS AND MATERIALS: A prospective clinical database was maintained for patients with MESCC. A virtual consultation process (involving exchange of key predetermined clinical information and diagnostic imaging) facilitated rapid decision-making between oncologists and spinal surgeons. Diagnostic imaging was reviewed retrospectively (by R.R.) for surgical opinions in all patients. The primary outcome was the accuracy of virtual consultation opinion in predicting the final treatment recommendation. RESULTS: After excluding 20 patients who were referred directly to the spinal surgeon, 125 patients were eligible for virtual consultation. Of the 46 patients who had a VC, surgery was recommended in 28 patients and actually given to 23. A retrospective review revealed that 5/79 patients who did not have a VC would have been considered surgical candidates. The overall accuracy of the virtual consultation process was estimated at 92%. CONCLUSION: The VC process for MESCC patients provides a reliable means of arriving at a multidisciplinary opinion while minimizing patient transfer. This can potentially shorten treatment decision time and enhance clinical outcomes.

A one-step cone-beam CT-enabled planning-to-treatment model for palliative radiotherapy-from development to implementation.

PURPOSE: To develop a cone-beam computed tomography (CT)-enabled one-step simulation-to-treatment process for the treatment of bone metastases. METHODS AND MATERIALS: A three-phase prospective study was conducted. Patients requiring palliative radiotherapy to the spine, mediastinum, or abdomen/pelvis suitable for treatment with simple beam geometry (≤2 beams) were accrued. Phase A established the accuracy of cone-beam CT images for the purpose of gross tumor target volume (GTV) definition. Phase B evaluated the feasibility of implementing the cone-beam CT-enabled planning process at the treatment unit. Phase C evaluated the online cone-beam CT-enabled process for the planning and treatment of patients requiring radiotherapy for bone metastases. RESULTS: Eighty-four patients participated in this study. Phase A (n = 9) established the adequacy of cone-beam CT images for target definition. Phase B (n = 45) established the quality of treatment plans to be adequate for clinical implementation for bone metastases. When the process was applied clinically in bone metastases (Phase C), the degree of overlap between planning computed tomography (PCT) and cone-beam CT for GTV and between PCT and cone-beam CT for treatment field was 82% ± 11% and 97% ± 4%, respectively. The oncologist's decision to accept the plan under a time-pressured environment remained of high quality, with the cone-beam CT-generated treatment plan delivering at least 90% of the prescribed dose to 100% ± 0% of the cone-beam CT planning target volume (PTV). With the assumption that the PCT PTV is the gold-standard target, the cone-beam CT-generated treatment plan delivered at least 90% and at least 95% of dose to 98% ± 2% and 97% ± 5% of the PCT PTV, respectively. The mean time for the online planning and treatment process was 32.7 ± 4.0 minutes. Patient satisfaction was high, with a trend for superior satisfaction with the cone-beam CT-enabled process. CONCLUSIONS: The cone-beam CT-enabled palliative treatment process is feasible and is ready for clinical implementation for the treatment of bone metastases using simple beam geometry, providing a streamlined one-step process toward palliative radiotherapy.

Quantifying interobserver variation in target definition in palliative radiotherapy.

PURPOSE: To describe the degree of interobserver and intraobserver variability in target and field definition when using three-dimensional (3D) volume- vs. two-dimensional (2D) field-based planning. METHODS AND MATERIALS: Standardized case scenario and diagnostic imaging for 9 palliative cases (3 bone metastases, 3 palliative lung cancer, and 3 abdominal pelvis soft-tissue disease) were presented to 5 study radiation oncologists. After a decision on what the intended anatomic target should be, observers created two sets of treatment fields, first using a 2D field-based and then a 3D volume-based planning approach. Percent overlap, under-coverage, and over-coverage were used to describe interobserver and intraobserver variations in target definition. RESULTS: The degree of interobserver variation for 2D and 3D planning was similar with a degree of overlap of 76% (range, 56%-85%) and 74% (range, 55%-88%), respectively. When comparing the treatment fields defined by the same observer using the two different planning methods, the mean degree of overlap was 78%; over-coverage, 22%; and under-coverage, 41%. There was statistically significantly more under-coverage when field-based planning was used for bone metastases (33%) vs. other anatomic sites (16%) (p = 0.02). In other words, 2D planning is more likely to result in geographic misses in bone metastases compared with other areas. CONCLUSIONS: In palliative radiotherapy clinically significant interobserver and intraobserver variation existed when using both field- and volume-based planning approaches. Strategies that would reduce this variability deserve further investigation.