Junichi Fukada

DOSE DISTRIBUTION ANALYSIS OF AXILLARY LYMPH NODES FOR THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY WITH A FIELD-IN-FIELD TECHNIQUE FOR BREAST CANCER

PURPOSE We previously reported that most of axillary regions could be irradiated by the modified tangential irradiation technique (MTIT). The purpose of this study was to determine whether the three-dimensional conformal radiotherapy (3D-CRT) with a field-in-field technique improves dosimetry for the breast and axillary nodes. METHODS AND MATERIALS Fifty patients with left-sided breast cancer were enrolled. With MTIT, we planned the radiation field to be wider in the cranial direction than the standard tangential fields to include the axillary regions. With 3D-CRT, a field-in-field technique was used to spare the heart and contralateral breast to the extent possible by applying the multileaf collimator manually. Dose-volume histograms were compared for the breast, axillary region, heart, lung, and other normal tissues. RESULTS There were no significant differences in the percent volume of the breast receiving >90% of the prescribed dose (V90) between MTIT and 3D-CRT. The mean V90 of the level I to III axillary regions were increased from 93.7%, 48.2%, and 41.3% with MTIT to 97.6%, 85.8%, and 82.8% with 3D-CRT. 3D-CRT significantly reduced the volume of the heart receiving >30 Gy (mean, 7.6 vs. 15.9 mL), the percent volume of the bilateral lung receiving >20 Gy (7.4% vs. 8.9%), and the volume of other normal tissues receiving >107% of the prescribed dose (0.1 vs. 2.9 mL). CONCLUSION The use of 3D-CRT with a field-in-field technique improves axillary node coverage, while decreasing doses to the heart, lungs, and the other normal tissues, compared with MTIT.

The value of drip infusion cholangiography using multidetector-row helical CT in patients with choledocholithiasis

The purposes of this study were to investigate the feasibility of drip infusion cholangiography computed tomography (CTCh) for choledocholithiasis and to compare the detection of the stone on CTCh with that of MR cholangiopancreatography (MRCP). CTCh examinations were performed after infusion of intravenous biliary contrast material (iotroxic acid meglumine, 100 ml) for patients with suspected biliary diseases and were reconstructed to maximum intensity projection (MIP) and multiplanar reformation (MPR). Of 432 patients who underwent CTCh, we identified 15 who underwent surgery or cholangioscopic removal for choledocholithiasis and 32 patients who underwent cholecystectomy due to cholecystolithiasis. Their MRCP images were compared with the CTCh images. The sensitivity and specificity of CTCh for detecting choledochal stones were 87% and 96% whereas those of MRCP were 80% and 88%. The sensitivity and specificity of CTCh for detecting gallstones were 78% and 100% whereas those of MRCP were 94% and 88%. CTCh allowed high sensitivity and specificity for detecting choledochal stones but diminished the detection for cholecystolithiasis compared with MRCP.

Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

PURPOSE We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. METHODS AND MATERIALS We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. RESULTS The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. CONCLUSIONS Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.

Weekly Low-Dose Docetaxel–Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

PURPOSE To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. METHODS AND MATERIALS Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m(2)]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. RESULTS The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade > or =3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. CONCLUSIONS Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04-

BackgroundIn patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin.MethodsPatients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1–15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m2, the second dose (level 2) was 20 mg/m2, and the third dose (level 3) was 25 mg/m2. Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1–29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned.ResultsNine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m2) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m2) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response.ConclusionsIn this phase I trial, RD of cisplatin was identified as 20 mg/m2. Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach.Trial registrationUMIN000008941

Detection of Esophageal Fiducial Marker Displacement During Radiation Therapy With a 2-dimensional On-board Imager: Analysis of Internal Margin for Esophageal Cancer

PURPOSE To quantify the interfraction displacement of esophageal fiducial markers for primary esophageal cancer radiation therapy. METHODS AND MATERIALS Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic clipping as fiducial metal markers. Displacement of the markers between the digitally reconstructed radiographs and on-board kilovoltage images during radiation therapy was analyzed according to direction and esophageal site. RESULTS Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29 distal), underwent 367 2D matching sessions during radiation therapy. The mean (SD) absolute marker displacement was 0.26 (0.30) cm in the right-left (RL), 0.50 (0.39) cm in the superior-inferior (SI), and 0.24 (0.21) cm in the anterior-posterior (AP) direction. Displacement was significantly larger in the SI than in the RL and AP directions (P<.0001). In the SI direction, mean absolute displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm, 0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement was significantly larger than those of the middle and proximal esophagus (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in the RL and AP directions. In the SI direction, the margin was 1.25 cm for the proximal and middle esophagus and 1.75 cm for the distal esophagus. CONCLUSIONS The magnitude of interfraction displacement of esophageal clips was larger in the SI direction, particularly in the distal esophagus, but substantial displacement was observed in other directions and at other esophageal sites. It is practical to take estimated movements into account with internal margins, even if vertebrae-based 2D matching is performed.

Comparison of genitourinary and gastrointestinal toxicity among four radiotherapy modalities for prostate cancer: Conventional radiotherapy, intensity-modulated radiotherapy, and permanent iodine-125 implantation with or without external beam radiotherapy

PURPOSE To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. MATERIALS AND METHODS This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI+EBRT). The effects of treatment- and patient-related factors on late grade ⩾ 2 (G2+) GU/GI toxicity risk were assessed. RESULTS The median follow-up was 43 months (range, 12-97 months). Compared to the PI+EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR] = 0.39; 95% CI, 0.20-0.77) and the IMRT (HR=0.45, 95% CI, 0.27-0.73). Compared to the PI+EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR = 2.38; 95% CI, 1.16-4.87). In PI-related groups, prostate equivalent dose in 2 Gy fractions was a significant predictor of G2+ GU toxicity (p = 0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity (p = 0.001). CONCLUSION The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

The reproducibility of a HeadFix relocatable fixation system: analysis using the stereotactic coordinates of bilateral incus and the top of the crista galli obtained from a serial CT scan

We analysed the repositioning accuracy of bite-plate fixations from serial QA-CT (quality-assurance CT) taken during the course of stereotactic radiotherapy. A total of 72 series of CT examinations from 15 consecutive patients, who underwent stereotactic radiotherapy for various intracranial tumours, were examined. Three or four CT scans were obtained for the purpose of QA for the right and left incus, as well as the crista galli. The stereotactic coordinates of the centres of the incus and the top of the crista galli were semi-automatically obtained for each QA-CT scan. Positional displacements for these anatomical reference points and the centre of the points were obtained. The mean displacements for these points in the 3D directions ranged from -0.10 to 0.08 mm (standard deviations: 0.44-0.94). The absolute positional displacement ranged from 0.93 to 1.09 mm (standard deviations: 0.52-0.88 mm). The rotations of the head were 0.49+/-0.36 degrees. Our 3D measurement technique using anatomical landmarks revealed excellent stability of the mouthpiece fixation system in terms of translational and rotational displacements. This technique can also be used as a QA method for other fixation devices.

Predicting pubic arch interference in prostate brachytherapy on transrectal ultrasonography-computed tomography fusion images

We investigated the usefulness of the fusion image created by transrectal ultrasonography (TRUS) and large-bore computed tomography (CT) for predicting pubic arch interference (PAI) during prostate seed brachytherapy. The TRUS volume study was performed in 21 patients, followed by large-bore computed tomography of patients in the lithotomy position. Then, we created TRUS-CT fusion images using a radiation planning treatment system. TRUS images in which the prostate outline was the largest were overlaid on CT images with the narrowest pubic arch. PAI was estimated in the right and left arch separately and classified to three grades: no PAI, PAI positive within 5 mm and PAI of >5 mm. If the estimated PAI was more than 5 mm on at least one side of the arch, we judged there to be a significant PAI. Brachytherapy was performed in 18 patients who were evaluated as not having significant PAI on TRUS. Intra-operative PAI was observed in one case, which was also detected with a fusion image. On the other hand, intra-operative PAI was not observed in one case that had been evaluated as having significant PAI with a fusion image. In the remaining three patients, TRUS suggested the presence of significant PAI, which was also confirmed by a fusion image. Intra-operative PAI could be predicted by TRUS-CT fusion imaging, even when it was undetectable by TRUS. Although improvement of the reproducibility of the patients’ position to avoid false-positive cases is warranted, TRUS-CT fusion imaging has the possibility that the uncertainty of TRUS can be supplemented.

Comparison of the repair of potentially lethal damage after low- and high-LET radiation exposure, assessed from the kinetics and fidelity of chromosome rejoining in normal human fibroblasts

Potentially lethal damage (PLD) and its repair (PLDR) were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining after X-ray or heavy-ion exposures. Cells were either held in the non-cycling G0 phase of the cell cycle for 12 h, or forced to proliferate immediately after irradiation. Fusion premature chromosome condensation (PCC) was combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. The culture condition had no impact on the rejoining kinetics of PCC breaks during the 12 h after X-ray or heavy-ion irradiation. However, 12 h after X-ray and silicon irradiation, cycling cells had more chromosome exchanges than non-cycling cells. After 6 Gy X-rays, the yield of exchanges in cycling cells was 2.8 times higher than that in non-cycling cells, and after 2 Gy of 55 keV/μm silicon ions the yield of exchanges in cycling cells was twice that of non-cycling cells. In contrast, after exposure to 2 Gy 200-keV/μm or 440-keV/μm iron ions the yield of exchanges was similar in non-cycling and cycling cells. Since the majority of repair in G0/G1 occurs via the non-homologous end joining process (NHEJ), increased PLDR in X-ray and silicon-ion irradiated cells may result from improved cell cycle-specific rejoining fidelity through the NHEJ pathway, which is not the case in high-LET iron-ion irradiated cells.