Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2).

PURPOSE: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. METHODS: This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2­year overall survival (OS). Arm A was considered insufficiently active if 2­year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. RESULTS: Two-year OS was 71% in arm A (95% CI: 55-87%) vs. 53% in arm B (95% CI: 36-71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30-1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25-1.04) for progression, 0.43 (0.13-1.40) for locoregional failure, and 0.43 (0.17-1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). CONCLUSION: Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer.

PURPOSE: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. METHODS: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n = 43) or the same treatment with additional deep regional hyperthermia (n = 60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). RESULTS: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p = 0.09). Five-year rates for OS (88% versus 76%, p = 0.08), DFS (77% versus 73%, p = n.s.) and DMFS (75% versus 77%, p = n.s.) were not statistically different between the two groups. CONCLUSION: Radiochemotherapy combined with hyperthermia results in excellent long-term local control.

Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer.

BACKGROUND: As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. METHODS: Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. RESULTS: From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. CONCLUSIONS: This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003273.

[A special radiation shielding for the radiotherapy of a pregnant patient]. / Eine Spezialabschirmung für die Strahlentherapie von Schwangeren.

PURPOSE: Measurement of the radiation dose of different radiotherapy techniques with a phantom at the position of the uterus of a pregnant patient with and without a special radiation shielding. MATERIAL AND METHODS: A special radiation shielding for the radiation therapy of a pregnant patient was constructed in the shape of a tunnel over the abdomen from 1 cm thick lead to reduce scatter radiation to the uterus and the fetus therein. The reduction of the scatter radiation to the lower abdomen was measured for three typical cases (cerebrum with lateral opposed fields, 6-MV photons; tangential fields for mamma irradiation, 6 MV; and anteroposterior-posteroanterior [AP-PA] opposed fields of 15 MV for treatment of the mediastinum) at an anthropomorphic Alderson phantom with thermoluminescence dosimeters in different depths and with an ionization chamber positioned in an RW3 solid water phantom. In the case of lateral opposed fields, a movable lead wall was additionally positioned next to the accelerator's head to reduce the scatter radiation from this source. RESULTS: Depending on the geometry of the radiation fields and on the photon energy, a reduction of the dose to the lower abdomen averaged over the depths of 6, 9, and 12 cm from 16% (15 MV, mediastinum case) to 51% (6 MV, cerebrum with additional lead wall) was achieved. The absolute scattered dose with shielding in place for a 2-Gy fraction dose results to 3.85 mGy and 0.27 mGy, respectively. CONCLUSION: National and international recommendations on the radiation dose to a fetus of a pregnant patient state limits of 200 mSv (DGMP report no. 7) and 100 mGy (ICRP 84), below which an abortion should not be considered and above which an indication for termination of the pregnancy could be given, respectively. The dose to the fetus can be kept below these limits with the shielding described in this work. Therefore, a radiation therapy of a pregnant patient is possible when these special precautions to reduce the scatter radiation to the fetus are met.