N. Imano

Combined Ventilation and Perfusion Imaging Correlates With the Dosimetric Parameters of Radiation Pneumonitis in Radiation Therapy Planning for Lung Cancer

PURPOSE The purpose of this study was to prospectively investigate clinical correlations between dosimetric parameters associated with radiation pneumonitis (RP) and functional lung imaging. METHODS AND MATERIALS Functional lung imaging was performed using four-dimensional computed tomography (4D-CT) for ventilation imaging, single-photon emission computed tomography (SPECT) for perfusion imaging, or both (V/Q-matched region). Using 4D-CT, ventilation imaging was derived from a low attenuation area according to CT numbers below different thresholds (vent-860 and -910). Perfusion imaging at the 10th, 30th, 50th, and 70th percentile perfusion levels (F10-F70) were defined as the top 10%, 30%, 50%, and 70% hyperperfused normal lung, respectively. All imaging data were incorporated into a 3D planning system to evaluate correlations between RP dosimetric parameters (where fV20 is the percentage of functional lung volume irradiated with >20 Gy, or fMLD, the mean dose administered to functional lung) and the percentage of functional lung volume. Radiation pneumonitis was evaluated using Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as a P value of <.05. RESULTS Sixty patients who underwent curative radiation therapy were enrolled (48 patients for non-small cell lung cancer, and 12 patients for small cell lung cancer). Grades 1, 2, and ≥3 RP were observed in 16, 44, and 6 patients, respectively. Significant correlations were observed between the percentage of functional lung volume and fV20 (r=0.4475 in vent-860 and 0.3508 in F30) or fMLD (r=0.4701 in vent-860 and 0.3128 in F30) in patients with grade ≥2 RP. F30∩vent-860 results exhibited stronger correlations with fV20 and fMLD in patients with grade ≥2 (r=0.5509 in fV20 and 0.5320 in fMLD) and grade ≥3 RP (r=0.8770 in fV20 and 0.8518 in fMLD). CONCLUSIONS RP dosimetric parameters correlated significantly with functional lung imaging.

Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy

Abstract The purpose of this study was to evaluate the efficacy and safety of volumetric modulated arc therapy (VMAT) after extrapleural pneumonectomy (EPP) in patients with malignant pleural mesothelioma (MPM). A total of 15 patients who received VMAT after EPP were enrolled. All patients were males, and the median age was 67 years (Stage IB in two, II in six, and III in seven patients). The clinical target volume (CTV) included the entire preoperative ipsilateral hemithorax and involved nodal stations. The CTV was generally expanded by 10–15 mm beyond the planning target volume (PTV). The dose prescription was designed to cover 95% of the PTV with 54 Gy in 30 fractions. The median follow-up period was 11 months. Treatment-related toxicities were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) ver. 4. One-year local control, disease-free survival, and overall survival rates were 55.7% [95% confidence interval (CI): 25.6–85.8%], 29.3% (95% CI: 5.3–53.3%), and 43.1% (95% CI: 17.1–69.0%), respectively. According to the histological analysis, the one-year LC rate was significantly worse in patients with non-epithelial type (biphasic and sarcomatoid types) than in patients with epithelial type [epithelial type: 83.3% (95% CI, 53.5–100%), non-epithelial type: 0% (95% CI, 0%), P = 0.0011]. Grade 3 pneumonitis after VMAT was observed in three patients (20.0%); however, no patients died of pulmonary toxicity. VMAT appears to be relatively safe for patients with MPM after EPP because of the low pulmonary dose.

Comparison of Stereotactic Body Radiation Therapy Combined With or Without Transcatheter Arterial Chemoembolization for Patients With Small Hepatocellular Carcinoma Ineligible for Resection or Ablation Therapies

Introduction: To compare the efficacy and safety of stereotactic body radiation therapy with or without transcatheter arterial chemoembolization for patients with small hepatocellular carcinoma who were ineligible for resection or ablation therapies. Methods: A total of 150 patients with 185 hepatocellular carcinoma (≤3 nodules, Child-Turcotte-Pugh class A or B, and no vascular or extrahepatic metastases) were treated with stereotactic body radiation therapy. In principle, transcatheter arterial chemoembolization was combined before stereotactic body radiation therapy (combination group), but some patients were treated with stereotactic body radiation therapy alone. The prescribed dose of stereotactic body radiation therapy was 48 Gy in 4 fractions at the isocenter and 40 Gy in 4 or 5 fractions at the dose covering 95% of the planning target volume. The overall survival, progression-free survival, local progression free survival, and complication rates were retrospectively compared between the groups. Local progression was defined as irradiated tumor growth in dynamic computed tomography follow-up. Tumor responses were assessed according to the Modified Response Evaluation Criteria in Solid Tumors. Treatment-related toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. Results: Twenty-eight and 122 patients were enrolled in the stereotactic body radiation therapy alone and combination groups, respectively. The median follow-up periods were 16 and 29 months, respectively. The 2-year overall, progression-free, and local progression-free survival times in stereotactic body radiation therapy alone and combination groups were 78.6% and 80.3% (P = .6583), 49.0% and 42.9% (P = .188), and 71.4% and 80.8% (P = .9661), respectively. The incidence of ≥grade 3 toxicities was 17.9% in stereotactic body radiation therapy alone group and 18.9% in combination group (P = .903). Conclusions: Stereotactic body radiation therapy alone may be a good treatment option for patients with small hepatocellular carcinoma who were ineligible for resection or ablation therapies.

Quantifying esophageal motion during free-breathing and breath-hold using fiducial markers in patients with early-stage esophageal cancer

Introduction Cardiac toxicity after definitive chemoradiotherapy for esophageal cancer is a critical issue. To reduce irradiation doses to organs at risk, individual internal margins need to be identified and minimized. The purpose of this study was to quantify esophageal motion using fiducial makers based on four-dimensional computed tomography, and to evaluate the inter-CBCT session marker displacement using breath-hold. Materials and methods Sixteen patients with early stage esophageal cancer, who received endoscopy-guided metallic marker placement for treatment planning, were included; there were 35 markers in total, with 9, 15, and 11 markers in the upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction regions, respectively. We defined fiducial marker motion as motion of the centroidal point of the markers. Respiratory esophageal motion during free-breathing was defined as the amplitude of individual marker motion between the consecutive breathing and end-expiration phases, derived from four-dimensional computed tomography. The inter-CBCT session marker displacement using breath-hold was defined as the amplitudes of marker motion between the first and each cone beam computed tomography image. Marker motion was analyzed in the three regions (upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction) and in three orthogonal directions (right-left; anterior-posterior; and superior-inferior). Results Respiratory esophageal motion during free-breathing resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior-posterior, and superior-inferior directions, of 1.7 (1.4) mm, 2.0 (1.5) mm, and 3.6 (4.1) mm, respectively, in the upper thoracic region, 0.8 (1.1) mm, 1.4 (1.2) mm, and 4.8 (3.6) mm, respectively, in the middle thoracic region, and 1.8 (0.8) mm, 1.9 (2.0) mm, and 8.0 (4.5) mm, respectively, in the lower thoracic/esophagogastric region. The inter-CBCT session marker displacement using breath-hold resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior–posterior, and superior-inferior directions, of 1.3 (1.0) mm, 1.1 (0.7) mm, and 3.3 (1.8) mm, respectively, in the upper thoracic region, 0.7 (0.7) mm, 1.1 (0.4) mm, and 3.4 (1.4) mm, respectively, in the middle thoracic region, and 2.0 (0.8) mm, 2.6 (2.2) mm, and 3.5 (1.8) mm, respectively, in the lower thoracic/esophagogastric region. Conclusions During free-breathing, esophageal motion in the superior-inferior direction in all sites was large, compared to the other directions, and amplitudes showed substantial inter-individual variability. The breath-hold technique is feasible for minimizing esophageal displacement during radiotherapy in patients with esophageal cancer.

Long-term results of neoadjuvant chemoradiotherapy using cisplatin and 5-fluorouracil followed by esophagectomy for resectable, locally advanced esophageal squamous cell carcinoma

Abstract This study retrospectively evaluated the long-term results of neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy for the patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC). Altogether, 49 patients treated from 2008 to 2012 were analyzed. Chemotherapy consisted of 5-fluorouracil and cisplatin. Radiotherapy was performed with a total dose of 40 Gy in 20 fractions for primary tumor, metastatic lymph nodes, and elective nodal area. Subsequently, transthoracic esophagectomy with extensive lymphadenectomy was performed. The median follow-up time for the survivors was 86 (range, 55–111) months. Pathological complete response from NCRT was observed in 17 (35%) patients. The 5-year overall survival and relapse-free survival rates were 56% [95% confidence interval (CI): 43–71%] and 55% (95% CI: 41–69%), respectively. The 5-year locoregional control rate was 84% (95% CI: 74–95%). Multivariate analyses revealed body mass index, N-factor, and %ΔSUVmax as significant factors for overall survival. Recurrences and within–irradiation field failure were observed in 16 (31%) and 4 (8%) patients, respectively. Toxicities of NCRT were generally mild. Postoperative Grade IIIb or worse complications were seen in 14% of patients, including one Grade V case (2%). The 5-year incidence rate of late complications of Grade 3 or worse was 22% (95% CI: 7–36%). The cumulative 5-year incidence rate of metachronous malignancies was 13% (95% CI: 1–26%). NCRT followed by esophagectomy for patients with resectable, locally advanced ESCC showed favorable locoregional control and overall survival, with acceptable postoperative complications. Long-term careful follow-up for late complications and metachronous malignancies is needed.

Evaluation of adverse events in atomic bomb survivors receiving curative-intent radiation therapy from 2005 to 2010

BACKGROUND AND PURPOSE To evaluate the safety of radiation therapy (RT) in atomic bomb (A-bomb) survivors (ABS), we evaluated the frequency of RT-associated adverse events (AEs) in ABS. MATERIALS AND METHODS We selected patients who underwent curative external-beam RT (EBRT) at Hiroshima University Hospital between January 2005 and December 2010 and were born before August 1946; the patients were divided into ABS and non-ABS groups, which groups received identical treatments without stratification. RESULTS We retrospectively reviewed the medical records of 220 ABS and 753 non-ABS patients. The median age was 72 years. The median observation durations were 41 and 37 months for the ABS and non-ABS groups, respectively. The ABS group had higher frequencies of women, breast cancer patients, and concurrent chemotherapy and had a lower incidence of only acute hematological AEs. However this tendency disappeared when breast cancer patients were excluded, and no significant differences were observed between the ABS and non-ABS groups regarding Grade ⩾ 3 other acute and late AEs. The overall cumulative incidence of Grade ⩾ 3 late AEs did not significantly differ between the ABS and non-ABS groups. CONCLUSIONS Notable increases in AEs were not observed during or after RT among ABS. This study clarified that stratification is not required when treating ABS with RT.