Takero Hirata

Histopathological effects of preoperative chemoradiotherapy for pancreatic cancer: An analysis for the impact of radiation and gemcitabine doses

BACKGROUND AND PURPOSE Histopathological findings of patients who underwent resection for pancreatic adenocarcinoma (PC) after preoperative chemoradiotherapy (CRT) reportedly showed beneficial effects. The purpose of our study was to evaluate the correlation between histopathological effects (HE) of preoperative CRT and treatment parameters [radiation and gemcitabine (GEM) doses]. MATERIAL AND METHODS HE of CRT were assessed on 158 primary lesions of 157 patients with PC who underwent pancreatic resection after preoperative CRT with GEM between January 2006 and December 2011. The radiation dose delivered to the primary tumor site and surrounding regional nodal areas was 50 Gy until September 2009 followed by the dose escalation of a 10 Gy boost added for delivery with the field-in-field technique to the roots of the celiac and superior mesenteric arteries. Intravenous administration of GEM (1000 /m(2)) was initiated concurrently on days 1, 8, and 15, every 4 weeks and generally repeated for 3 cycles. HE of CRT on the primary tumor were categorized based on the number of tumor cells destroyed. RESULTS The median overall survival time was 74.5 months and 3-year and 5-year survival rates were 64.3% and 54.5%, respectively. Dose-volume parameters of radiation such as D33 with a cut-off value of 51.6 Gy were correlated significantly with HE (p=.0230). Lesions having received GEM>7625 mg/m(2) before surgical resection more frequently showed positive HE (p=.0002). Multivariate logistic regression analysis demonstrated that both D33 and cumulative GEM dose were significant predictors of definite HE (p=.0110 and <.0001, respectively). CONCLUSIONS Our retrospective analysis showed that dose intensity of radiation and GEM is significantly related to HE of preoperative CRT for PC.

Efficacy and Safety of Endoscopic Resection Followed by Chemoradiotherapy for Superficial Esophageal Squamous Cell Carcinoma: A Retrospective Study.

OBJECTIVES: The reported 1‐ and 3‐year overall survival rates after esophagectomy for stage I superficial esophageal squamous cell carcinoma (SESCC) are 95–97% and 86%, and those after definitive chemoradiotherapy (CRT) are 98% and 89%, respectively. This study was performed to elucidate the efficacy and safety of another treatment option for SESCC: endoscopic resection (ER) followed by CRT. METHODS: We retrospectively reviewed the overall survival, recurrence, and grade ≥3 adverse events of consecutive patients who refused esophagectomy and underwent ER followed by CRT for SESCC from 1 January 2006 to 31 December 2012. RESULTS: In total, 66 patients with SESCC underwent ER followed by CRT during the study period, and complete follow‐up data were available for all patients. The median age was 67 (range, 45–82) years, and the median observation period was 51 (range, 7–103) months. Local and metastatic recurrences occurred in 2 (3%) and 6 (9%) patients, respectively, and 17 (26%) patients died. The 1‐, 3‐, and 5‐year overall survival rates were 98%, 87%, and 75%, respectively. One of the 23 patients with mucosal cancer and 5 of 43 with submucosal cancer developed metastatic recurrences (P=0.65). Five of the 61 patients with negative vertical resection margin and 1 of 5 with positive vertical resection margin developed metastatic recurrences (P=0.39). None of the 30 patients without lymphovascular involvement developed metastatic recurrences; however, 6 of 36 patients with lymphovascular involvement developed metastatic recurrences (P=0.0098). Grade ≥3 adverse events occurred in 21 (32%) patients and all adverse events were associated with CRT, hematological adverse events in 13 (20%), and non‐hematological adverse events in 9 (14%). CONCLUSIONS: ER followed by CRT provides survival comparable with that of esophagectomy or definitive CRT and has a low local recurrence rate. A particularly favorable outcome is expected for cancers without lymphovascular involvement.

Assessment with cone-beam computed tomography of intrafractional motion and interfractional position changes of resectable and borderline resectable pancreatic tumours with implanted fiducial marker

OBJECTIVE The volume of targets to which a high radiation dose can be delivered is limited for pancreatic radiotherapy. We assessed changes in movements of pancreatic tumours between simulation and treatment and determined compensatory margins. METHODS For 23 patients, differences in implanted fiducial marker motion magnitude (MMM) and mean marker position (MMP) between four-dimensional CT and cone-beam CT were measured. Subsequently, residual uncertainty was simulated after no action level (NAL) and extended no action level (eNAL) protocols were adopted. RESULTS With no correction, respective 95th percentile of MMM were 4.5 mm, 6.2 mm and 16.0 mm and systematic (random) errors of MMP were 2.8 mm (3.3 mm), 3.2 mm (2.0 mm) and 5.9 mm (4.0 mm) in the left-right (L-R), anteroposterior (A-P) and superoinferior (S-I) directions, so that large margins were required (L-R, 10.5 mm; A-P, 11.7 mm; and S-I, 24.8 mm). NAL reduced systematic errors of MMP, but resultant margins remained large (L-R, 8.0 mm; A-P, 9.6 mm; and S-I, 18.1 mm). eNAL compensated for time trends and obtained minimal margins (L-R, 6.7 mm; A-P, 6.7 mm; and S-I, 15.2 mm). CONCLUSION Motion magnitude and position of pancreatic tumours during simulation are frequently not representative of that during treatment. eNAL compensated for systematic interfractional position change and would be a practical approach for improving targeting accuracy. Advances in knowledge: Considerably large margins, especially in the S-I direction, were required to compensate for intrafractional motion and interfractional position changes of the pancreatic tumour. An application of eNAL was an effective strategy to diminish these margins.

Clinical implementation of contrast-enhanced four-dimensional dual-energy computed tomography for target delineation of pancreatic cancer

BACKGROUND AND PURPOSE The accurate delineation of pancreatic tumor with respiratory motion is challenging. This study demonstrates the application of contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT) for tumor delineation and assesses the objective and subjective image quality. MATERIAL AND METHODS Twelve patients underwent CE-4D-DECT, and quantitative spectral analysis was performed on the resulting virtual monochromatic images (VMI) to determine the optimal VMI (O-VMI) with the highest contrast-to-noise ratio (CNR). The objective value of the CNR between pancreatic parenchyma and tumor, and the subjective measurement with five-point scale were compared between O-VMI, standard VMI (S-VMI, 77 keV) and single energy CT (SECT, 120 kVp). RESULTS The CNR was the highest in the VMI at 60 keV, and the corresponding CNR in the O-VMI (3.4) was significantly higher (p < 0.05) than that in the S-VMI (2.4) and the SECT (2.7). The overall mean subjective measurements among 4 radiation oncologists were higher for the O-VMI over the S-VMI and SECT with respect to overall image quality (4.0, 3.3 and 3.7, respectively), tumor enhancement (3.4, 2.6 and 3.2, respectively), and vessel delineation (4.2, 3.6 and 4.2, respectively). CONCLUSIONS The O-VMI derived from the CE-4D-DECT demonstrated its superiority over the S-VMI and SECT in depicting pancreatic tumor.

Radiation Dose Escalation in Accelerated Hyperfractionated Radiotherapy for Stage III Non-small-cell Lung Cancer

Aim: To identify clinical benefits of dose escalation in accelerated hyperfractionated radiotherapy (AH-RT) for stage III non-small-cell lung cancer (NSCLC) using propensity score-matched (PSM) analysis. Materials and Methods: Our study retrospectively examined 294 patients undergoing definitive radiotherapy [131 patients, conventional once-daily radiotherapy (OD-RT); and 163, AH-RT] who were followed-up for a median of 40.4 months. The impact of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) was investigated. Results: Pre-PSM, the median OS, PFS, and LRC durations were 23.1 vs. 39.9 (p=0.03), 8.9 vs. 13.5 (p<0.01), and 12.9 vs. 50.3 (p<0.01) months in the OD-RT and AH-RT groups, respectively. After-PSM (two matched groups of 144 patients), AH-RT was associated with better LRC [adjusted hazard ratio (aHR)=0.59, 95% confidence interval (CI)=0.33-0.99, p=0.04] and marginally better PFS (aHR=0.65, 95% CI=0.41-1.03; p=0.06), but not OS (aHR=0.75, 95% CI=0.46-1.24; p=0.26). Conclusion: After PSM analysis, dose escalation using AH-RT improved LRC and PFS in patients with locally advanced NSCLC. AH-RT can be a promising option for patients with advanced NSCLC.