A pilot study on interobserver variability in organ-at-risk contours in magnetic resonance imaging-guided online adaptive radiotherapy for pancreatic cancer.

Purpose: Differences in the contours created during magnetic resonance imaging-guided online adaptive radiotherapy (MRgOART) affect dose distribution. This study evaluated the interobserver error in delineating the organs at risk (OARs) in patients with pancreatic cancer treated with MRgOART. Moreover, we explored the effectiveness of drugs that could suppress peristalsis in restraining intra-fractional motion by evaluating OAR visualization in multiple patients. Methods: This study enrolled three patients who underwent MRgOART for pancreatic cancer. The study cohort was classified into three conditions based on the MRI sequence and butylscopolamine administration (Buscopan): 1, T2 imaging without butylscopolamine administration; 2, T2 imaging with butylscopolamine administration; and 3, multi-contrast imaging with butylscopolamine administration. Four blinded observers visualized the OARs (stomach, duodenum, small intestine, and large intestine) on MR images acquired during the initial and final MRgOART sessions. The contour was delineated on a slice area of ±2 cm surrounding the planning target volume. The dice similarity coefficient (DSC) was used to evaluate the contour. Moreover, the OARs were visualized on both MR images acquired before and after the contour delineation process during MRgOART to evaluate whether peristalsis could be suppressed. The DSC was calculated for each OAR. Results: Interobserver errors in the OARs (stomach, duodenum, small intestine, large intestine) for the three conditions were 0.636, 0.418, 0.676, and 0.806; 0.725, 0.635, 0.762, and 0.821; and 0.841, 0.677, 0.762, and 0.807, respectively. The DSC was higher in all conditions with butylscopolamine administration compared with those without it, except for the stomach in condition 2, as observed in the last session of MR image. The DSCs for OARs (stomach, duodenum, small intestine, large intestine) extracted before and after contouring were 0.86, 0.78, 0.88, and 0.87; 0.97, 0.94, 0.90, and 0.94; and 0.94, 0.86, 0.89, and 0.91 for conditions 1, 2, and 3, respectively. Conclusion: Butylscopolamine effectively reduced interobserver error and intra-fractional motion during the MRgOART treatment.

Comparison of CT-based and MRI-based high-risk clinical target volumes in image guided-brachytherapy for cervical cancer, referencing recommendations from the Japanese Radiation Oncology Study Group (JROSG) and consensus statement guidelines from the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC ESTRO).

PURPOSE: The Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG) published recommendations for contouring high-risk clinical target volumes (HR-CTV) on CT for 3-dimentional image-guided brachytherapy for cervical cancer. The purpose of this study was to compare HR-CTV delineated on CT, referencing recommendations from JROSG, with HR-CTV delineated on MRI, referencing consensus guidelines from the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC ESTRO). MATERIAL AND METHODS: Fourteen patients were evaluated. After the insertion of the CT/MR applicator into the patient, CT and MRI were performed. HR-CTVMR was delineated on MRI for clinical examination and HR-CTVCT was delineated on CT retrospectively referencing the MRI just before brachytherapy within a week. The volume and dosimetry of HR-CTV based on a 6 Gy dose of the Manchester system were evaluated. RESULTS: The median volumes of HR-CTVMR and HR-CTVCT were 24.4 ml (range, 13.6-50.4 ml) and 29.9 ml (range, 13.2-49.2 ml), respectively. Median D90 of HR-CTVMR and HR-CTVCT were 6.7 Gy (range, 5.8-10.1 Gy) and 6.8 Gy (range, 5.1-10.4 Gy), respectively. CONCLUSION: Somewhat difference could be seen between HR-CTVMR and HR-CTVCT.

Preliminary results of a new workflow for MRI/CT-based image-guided brachytherapy in cervical carcinoma.

PURPOSE: We propose a method of image-guided brachytherapy (IGBT) that combines MRI-based target volume delineation for the first fraction with CT datasets of subsequent fractions, using an automatic, applicator-based co-registration, and report our preliminary experience. MATERIALS AND METHODS: The MRI of the first fraction was used for the first brachytherapy planning. For each subsequent brachytherapy fraction, after the same applicator insertion, a new CT scan with the applicator in place was obtained. The MR image set was registered to the subsequent brachytherapy treatment planning CT using the applicator for rigid body registration. To demonstrate the registration quality, we used here the Dice index as a measurement of tandem delineation overlap between CT and MRI. RESULTS: The median Dice index was 0.879 (range 0.610-0.932), which indicated that the contours on CT and MRI fitted well. With this combination method, the median D90 of HR CTV and the calculated D2 cm3 of the bladder, rectum, and sigmoid in each fraction were 7.2 (4.0-10.4), 5.9 (2.3-7.7), 4.0 (1.9-6.7), and 3.8 (0.6-7.2) Gy, respectively. CONCLUSION: Our described method of MRI-guided IGBT offers a practical option for the benefits of target delineation.

Initial experience of radiotherapy plus cetuximab for Japanese head and neck cancer patients.

In Japan, cetuximab with concurrent bioradiotherapy (BRT) for squamous cell carcinoma of head and neck (SCCHN) was approved in December 2012. We herein report our initial experience of BRT, with special emphasis on acute toxicities of this combination therapy. Thirty-one non-metastatic SCCHN patients who underwent BRT using cetuximab between July 2013 and June 2014 were retrospectively evaluated. All patients received cetuximab with a loading dose of 400 mg/m(2) one week before the start of radiotherapy, followed by 250 mg/m(2) per week during radiotherapy. The median cycle of cetuximab was seven cycles and the median dose of radiotherapy was 70 Gy. Twenty-five patients (80.6%) accomplished planned radiotherapy and six cycles or more cetuximab administration. Six patients (19.4%) discontinued cetuximab. Grade 3 dermatitis, mucositis and infusion reaction occurred in 19.4%, 48.3% and 3.2%, respectively. One patient experienced Grade 3 gastrointestinal bleeding caused by diverticular hemorrhage during BRT. Grade 3 drug-induced pneumonitis occurred in two patients. The response rate was 74%, including 55% with a complete response. BRT using cetuximab for Japanese patients with SCCHN was feasible as an alternative for cisplatin-based concurrent chemoradiation, although longer follow-up is necessary to evaluate late toxicities.

New approach to relieving pain and distress during high-dose-rate intracavitary irradiation for cervical cancer.

BACKGROUND AND PURPOSE: To relieve the pain and distress experienced by women who undergo high-dose-rate intracavitary radiotherapy (HDR-ICRT) for cervical cancer and to improve the current status of gynecologic brachytherapy in Japan, a new intravenous anesthetic protocol involving the administration of a combination of propofol and ketamine was developed. The primary aim of this study is to investigate the efficacy and safety of this new anesthetic protocol during HDR-ICRT for cervical cancer. METHODS AND MATERIALS: All the patients who were diagnosed with cervical cancer between December 2008 and February 2011, treated with three-channel brachytherapy and subjected to the new sedation protocol, were evaluated. A visual analog scale (VAS) was used to assess the pain during brachytherapy, and we collected VAS score at the next HDR-ICRT. Toxicities were graded using the Common Toxicity Criteria, version 3. RESULTS: A total of 178 sessions of HDR-ICRT were delivered to 57 patients. The patients' median VAS pain score was 0 (range, 0-10). The most frequent side effect was Grade 1-2 nausea, which occurred in 33 sessions (34%). However, 13 of 14 patients received concurrent cisplatin chemotherapy. None of the patients experienced Grade 3 or 4 adverse events. CONCLUSIONS: We have demonstrated that our new intravenous anesthetic protocol produces appropriate effects and can be performed by radiation oncologists who were required to finish training in basic life support and the cooperative system of emergency according to in-house guideline.

Delayed renal dysfunction after total body irradiation in pediatric malignancies.

The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1-17 years old). The follow-up period ranged from 79-170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8-12 Gy delivered in 3-6 fractions over 2-3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right-left and left-right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.