Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. RESULTS: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. CONCLUSION: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.

Prognostic Value of the Volumetric Parameters of Dual-Time-Point 18F-FDG PET/CT in Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy.

OBJECTIVE. The purpose of this study is to assess the effectiveness of the volumetric parameters of dual-time-point imaging (DTPI) with 18F-FDG PET (DTPI FDG PET) in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS. The records of consecutive patients who received definitive RT for NSCLC from April 2010 to April 2017 were retrospectively reviewed. Pretreatment DTPI FDG PET images were routinely obtained as part of the PET/CT examination. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor (SUVmax-T, MTV-T, and TLG-T, respectively) and those of the primary tumor and lymph nodes (N) combined (SUVmax-TN, MTV-TN, and TLG-TN, respectively) were used as variables, and the percentage change in these parameters (change in SUVmax [ΔSUVmax], change in MTV [ΔMTV], and change in TLG [ΔTLG]) on DTPI FDG PET were analyzed. RESULTS. Of the 118 patients identified and reviewed, 59 met the study eligibility criteria. After a median follow-up of 23.3 months, the 3-year local control rate (LCR) and disease-specific survival rates were 53.5% and 45.0%, respectively. On multivariate analysis, significant predictors of LCR were TLG-T and change in TLG-TN (ΔTLG-TN), and significant predictors of disease-specific survival were adjuvant chemotherapy, treatment response, TLG-T, and change in TLG-T (ΔTLG-T). Low percentage changes in ΔTLG (< 41.0% for ΔTLG-T and < 32.0% for ΔTLG-TN) correlated with poor LCR and disease-specific survival. SUVmax and MTV were not significant predictors of both LCR and disease-specific survival. CONCLUSION. TLG and ΔTLG were significant prognostic factors in patients with NSCLC treated with definitive RT. In particular, a relatively low ΔTLG resulted in poor outcomes in terms of LCR and disease-specific survival.

Dosimetric Comparison of Irregular Surface Compensator and Field-in-Field for Whole Breast Radiotherapy.

PURPOSE: The purpose of the present study was to evaluate the dosimetric benefits of the irregular surface compensator (ISC) technique for whole breast radiotherapy compared with the field-in-field (FIF) technique. MATERIALS AND METHODS: Radiotherapy was planned using both techniques in 50 breast cancer patients (25 left sided and 25 right sided). The Eclipse treatment planning system (Varian Medical Systems) was used for dose calculations. For the FIF technique, subfields were added to the main fields to reduce hot and cold regions; for the ISC technique, the fluence editor application was used to extend the optimal fluence. Planning target volume dose, dose homogeneity index (DHI), maximum dose, ipsilateral lung, and heart doses for the left breast irradiation and monitor unit (MU) counts required for treatment were compared between the two techniques. RESULTS: Compared with the FIF technique, the ISC technique significantly decreased DHI values and volumes receiving >105% of the prescription dose, and increased volumes receiving >95% of the dose and MU count (P < 0.01 for all comparisons). For the heart and ipsilateral lung, the FIF technique significantly reduced volumes receiving >5 Gy compared with the ISC technique (P < 0.01); however, volumes receiving >10, 20, and 30 Gy and the values of a mean dose did not differ significantly between the techniques (P > 0.05). CONCLUSIONS: The ISC technique is preferred over the FIF technique.

Investigation of optimal display size for viewing T1-weighted MR images of the brain using a digital contrast-detail phantom.

We clarified the relationship between the display size of MRI images and observer performance using a digital contrast-detail (d-CD) phantom. The d-CD phantom was developed using Microsoft Visual Basic 2010 Express. It had a 512 × 512 matrix in size and a total of 100 holes, whose diameter increased stepwise from 4 to 40 pixels with a 4-pixel interval in the vertical direction; the contrast varied stepwise in the horizontal direction. The digital driving level (DDL) of the back-ground, the width of the DDL, and the contrast were adjustable. These parameters were determined on the basis of the actual T1-weighted magnetic resonance (MR) images of the brain. In this study, the DDL, width, and contrast were set to 85, 20, and 1, respectively. The observer performance study was performed for three different display sizes (30 cm × 30 cm as the enlarged size, 16 cm × 16 cm as the original size, and 10 cm × 10 cm as the reduced size) using a 2-megapixel color liquid crystal display monitor, and it was analyzed using Friedman and Wilcoxon statistical tests. The observer performances for the original display (p < 0.01) and the reduced display sizes (p < 0.01) were superior to that observed for the enlarged size, whereas there was no significant difference between the original display and reduced display sizes (p = 0.31). Evaluation with the digital phantom simulating MR imaging also revealed that the original and reduced display sizes were superior to the enlarged display size in observer performance. The d-CD phantom enables a short-term evaluation of observer performance and is useful in analyzing relation-ship between display size and observer performance.

A Phase I study of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation for Stage III non-small cell lung cancer: WJTOG 3305.

PURPOSE: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. METHODS AND MATERIALS: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m(2)) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m(2)). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade ≥4 esophagitis and neutropenic fever and Grade ≥3 other nonhematologic toxicities, was monitored for 90 days. RESULTS: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. CONCLUSIONS: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

Effectiveness of the single-shot dual-energy subtraction technique for portal images.

The aim of the present study was to evaluate the clinical efficacy of the single-shot dual-energy subtraction technique for obtaining portal images. We prepared two storage phosphor plates for this study. A 1 mm thick tungsten sheet was placed between the two storage phosphor plates. A single use of the double-exposure technique provides two portal images simultaneously (i.e., a standard image and a low-contrast image), using the same patient position and with no additional radiation delivered to the patient. A bone-enhanced image is created by image subtraction between these two images. For evaluation of clinical efficacy, three treatment sites--the brain, lung, and pelvis--were imaged. Ten sets of images were obtained for each site, and five landmarks were selected for each treatment site. The visibility of each landmark and the ease of overall verification for the selected treatment sites were assessed separately for the standard and bone-enhanced images. Four observers consisting of one radiation oncologist and three radiation therapists participated in the present study. For most of the landmarks studied, the bone-enhanced images were significantly superior to the standard images. Regarding the ease of overall verification, the bone-enhanced images were significantly superior to the standard images at all sites. The p-values of mean rating for the brain, lung, and pelvis were 0.002, 0.012, and 0.003, respectively. The bone-enhanced images obtained using our technique increased the image quality in terms of bone visibility, and are considered useful for routine clinical practice.

Patient setup verification procedure for a portal image in a computed radiography system with a high-resolution liquid-crystal display monitor.

In our conventional visual inspection for setup verification, we have routinely used a console monitor of a CR system and a monitor of a treatment-planning system (i.e., the separate-monitor method) in order to avoid the need for CR portal-film generation. However, the separate-monitor method provided insufficient precision in detecting setup errors. We devised a setup verification procedure that uses a high-resolution liquid-crystal display monitor (i.e., the single-monitor method). Our objective in the present study was to evaluate the precision of the single-monitor method. These two methods were compared in terms of the precision of visual inspection. The single-monitor method was significantly superior to the separate-monitor method in sensitivity and in the magnitude of the discrepancy that could not be detected. The single-monitor method provides higher precision in visual inspection than does the separate-monitor method, and is a useful verification procedure.

Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron emission scan mimicking lung cancer recurrence.

We present the case of a 57-year-old woman with pulmonary suture abscess. She had undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and right breast-conserving surgery for invasive ductal carcinoma 5 months previously, followed by irradiation plus endocrine therapy. Chest radiography and computed tomography revealed an irregular mass (3.5 cm in diameter) between the residual S1 segment and the middle lobe, neighboring the staple line of the segmentectomy. 18F-fluorodeoxyglucose uptake into the mass increased, seen by positron emission scans. Therefore, we could not rule out the possibility of local recurrence of lung cancer and resected it. Pathologically and microbiologically, the mass was a suture abscess arising around the nylon suture of the previous segmentectomy. This lesion was the result of a foreign-body reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the segmentectomy and breast-conserving surgery may also have contributed to this condition.

Three cases of the nodular pulmonary amyloidosis with a longterm observation.

Longterm observation with chest radiograph and computed tomography (CT) scan was performed for pulmonary amyloidosis. There are few reports of primary pulmonary amyloidosis with a longterm observation. We encountered three cases of nodular pulmonary amyloidosis observed by intermittent chest radiograph or CT for 5 years or more. The patients were a 54-year-old man, and 67- and 68-year old women. For diagnosis, transbronchial biopsy and percutaneous lung biopsy were performed. Amyloid nodules grew slowly and two cases showed findings of cavity and calcification.

Non-small cell lung cancer: radiation therapy for locoregional recurrence after complete resection.

BACKGROUND: We investigated patterns of failure after radical radiation therapy in relation to the radiation field in patients with postsurgical locoregional recurrence of non-small cell lung cancer. METHODS: Between 1992 and 2002, 31 patients with locoregional recurrence were treated with radiation therapy. At the time of radiation therapy, the sites of recurrence were the bronchial stump, the regional lymph nodes, the chest wall, and both the regional lymph nodes and the chest wall in 7, 20, 3, and 1 patient, respectively. The prescribed dose was 60 Gy in 30 fractions over 6 weeks in all patients. RESULTS: The response rate was 87%. The overall 1-year, 2-year, and 4-year Kaplan-Meier survival rates were 61%, 30%, and 15%, respectively, and the median survival time was 14 months. Locoregional relapse with or without distant metastasis occurred in 15 patients (in-field, 7; marginal, 7; out-field, 1), and distant metastasis alone occurred in 7 patients. The sites of marginal relapse were the upper margin in two patients, the ipsilateral margin in one patient, the contralateral margin in one patient, and the lower margin in three patients, respectively (in one patient, the data for marginal relapse overlapped). In all patients with relapse on the lower margin, the mediastinal lymph nodes were dissected at the initial surgery. CONCLUSION: Postoperative recurrent non-small cell lung cancer showed distinctive features: the response rate was high, and the incidence of marginal relapse was also high, as in small cell lung cancer. The incidence of lower marginal relapse was high, in contrast to that in surgery-naive patients.

Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy.

BACKGROUND: We evaluated the efficacy and toxicity of reirradiation for patients with loco-regional relapse of non-small-cell lung cancer after radiation therapy. METHODS: Between 1992 and 2002, 19 patients with loco-regional relapse underwent reirradiation. The median interval between the initial irradiation and reirradiation was 16 months, with a range of 5 to 60 months. The prescribed dose of reirradiation was 50 Gy in 25 fractions over 5 weeks for 18 patients and 60 Gy in 30 fractions over 6 weeks for 1 patient. RESULTS: Five patients could not receive the prescribed dose of reirradiation. The response rate was 43% among the 14 patients who received the prescribed dose of reirradiation. The overall 1-year and 2-year Kaplan-Meier survival rates were 26% and 11%, respectively, and the median survival time was 7.1 months. The median survival times associated with intervals between the initial irradiation and reirradiation of less than 12 months, 12-18 months, and more than 18 months were 2.1, 7.1, and 11.5 months, respectively. There were significant differences in survival between patients with an interval of less than 12 months and those with an interval of 12-18 months, and between those with an interval of less than 12 months and those with an interval of more than 18 months (generalized Wilcoxon method; P < 0.05 for both). Grade 3 radiation pneumonitis and grade 2 radiation esophagitis occurred in 1 and 3 patients, respectively. CONCLUSION: Reirradiation is considered to contribute to salvage in selected patients with relapsed non-small-cell lung cancer. Patients with a long interval after the initial irradiation are good candidates for reirradiation. On the other hand, patients with Eastern Cooperative Oncology Group (ECOG) performance status 3 were not good candidates.

Close radiographic landmarks for spinal cord localization in treatment of thoracic malignancy.

BACKGROUND: On simulation radiographs of oblique fields, the spinal canal is estimated to be located on the deep surface of the tangential parts of the vertebral laminae within a width of the oblique diameter of the spinal canal. The aim of this study was to evaluate the accuracy of the estimated location of the spinal canal. MATERIALS AND METHODS: Beam's eye view digital simulation radiographs were produced using actual patient data from a computed tomography (CT) scanner. The spinal canal was projected onto the Beam's eye view image, and measurement of the distance between the tangential parts of the vertebral laminae and the anterior border of the spinal canal was performed. The oblique diameter on the axial CT image was compared to the measured distance. RESULTS: In all 10 patients, the tangential parts of the vertebral laminae were detectable on the Beam's eye view image. At all levels in all patients, the oblique diameter was slightly larger than or equal to the distance. With a gantry angle of 30 degrees the difference ranged from 0 to 2.5 mm (mean, 1.2 mm), from 0 to 1.0 mm (mean, 0.4 mm), and from 0 to 1.5 mm (mean, 0.4 mm) at levels T-1, T-4, and T-7, respectively. With a gantry angle of 45 degrees the difference ranged from 0 to 1.5 mm (mean, 0.8 mm), from 0 to 0.5 mm (mean, 0.3 mm), and from 0 to 1.0 mm (mean, 0.4 mm), respectively. CONCLUSION: The tangential parts of the vertebral laminae are useful landmarks, since the spinal canal location estimated using the tangential parts and measured oblique diameter of the spinal canal on the axial CT image is sufficiently accurate.

Monitoring of respiratory movement of the diaphragm for gated radiotherapy.

PURPOSE: In order to obtain a respiratory signal for gated radiotherapy, diaphragm movement was monitored. MATERIALS AND METHODS: To obtain the diaphragm signal, an image brightness stabilizer for fluoroscopy of an X-ray simulator was used. The image brightness stabilizer output electric current in response to image brightness, which changed with diaphragm movement. The electric current was recorded as the diaphragm signal and compared with the abdominal wall signal, which was obtained by monitoring the height of the abdominal wall using a laser displacement sensor. RESULTS: A regular diaphragm signal was obtained in all of nine patients. At 70% expiration of the abdominal wall signal, the diaphragm signal ranged from 35% to 70% expiration (median, 55%). At 30% inspiration of the abdominal wall signal, the diaphragm signal ranged from 10% to 30% inspiration (median, 20%). CONCLUSION: A regular diaphragm signal could be conveniently obtained utilizing an image brightness stabilizer. The diaphragm signal tended to be delayed in comparison with the abdominal wall signal.

Accelerated hyperfractionated irradiation with concomitant boost for stage II laryngeal cancer and locally advanced head and neck cancer.

OBJECTIVE: This study was conducted to evaluate the efficacy and feasibility of our accelerated hyperfractionation with concomitant boost for stage II laryngeal cancer and stages III-IVb locally advanced head and neck cancer. PATIENTS AND METHODS: From January 2000 to October 2001, eight patients with AJCC 1998 stage II laryngeal cancer and 11 patients with AJCC 1998 stages III-IVb locally advanced head and neck cancer underwent accelerated hyperfractionated radiation therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8 and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For stages III-IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with 1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients, 16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin. Acute toxicity based on RTOG criteria and tumor response at 1 month post-treatment were estimated as initial effects. RESULTS: The overall response rate was 100% in patients with stage II laryngeal cancer and 91% in patients with stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute effects was 47%. Eighteen patients (95%) completed radiation therapy without interruption related to acute side effects, while one had prolongation of the treatment for more than 1 week because of neutropenia. CONCLUSIONS: Our results demonstrated that accelerated hyperfractionation, mostly combined with concomitant chemotherapy, had a good overall response rate with acceptable toxicity in stage II laryngeal cancers and stages III-IVb head and neck tumors.

A single institutional subset analysis of the WJLCG study comparing concurrent and sequential chemoradiotherapy for stage III non-small-cell lung cancer.

PURPOSE: To supplement findings of the West Japan Lung Cancer Group (WJLCG) study, treatment outcomes in our institution were reviewed from the perspective of radiation oncology. MATERIALS AND METHODS: Chemotherapy consisted of cisplatin (80 mg/m2 on days 1 and 29), vindesine (3 mg/m2 on days 1, 8, 29, and 36), and mitomycin (8 mg/m2 on days 1 and 29). In the concurrent arm, radiation therapy began on day 2 with a dose of 56 Gy in 28 fractions over 6.8 weeks, with an interval of 10 days at 28 Gy. In the sequential arm, radiation therapy began on day 50 with a dose of 56 Gy in 28 fractions over 5.6 weeks, without an interval. RESULTS: Twenty-four patients in the concurrent arm and 25 patients in the sequential arm in our institution were eligible for the WJLCG study. In the concurrent arm, three patients could not receive the full dose of radiation therapy and 12 patients required interruption of radiation therapy for more than 4 days. The median survival time among per-protocol patients and in those with interruption or with incomplete radiation therapy was 28.9 months and 14.1 months, respectively (p = 0.02). In the sequential arm, one patient could not receive the full dose of radiation therapy and none of the patients required such interruption. Local relapse and distant metastases as the first site of relapse occurred in 12 (11 in-field, 1 marginal) and five patients, respectively, in the concurrent arm, and in eight (7 in-field, 1 marginal) and 11 patients, respectively, in the sequential arm. CONCLUSION: In the concurrent regimen, noncompletion or interruption of radiation therapy was frequent, and the prognosis of such patients was poor.

Use of FDG-microPET for detection of small nodules in a rabbit model of pulmonary metastatic cancer.

OBJECTIVE: The performance of microPET using 18F-FDG was evaluated in a rabbit model of hematogenous pulmonary metastatic cancer. METHODS: A total of 15 Japanese white rabbits and VX-2 carcinoma were used in this study. In the microPET study, tumor-bearing rabbits were administered intravenously 74 MBq of 18F-FDG, and 30 min later, the emission data were acquired for 60 min. The transmission scans were performed with a 68Ge/68Ga external point source. To augment the anatomical information, we performed multi-detector row computed tomography (MDCT) in the combination with MDCT and microPET on 10 rabbits. The other 5 rabbits were followed once a week for 5 weeks only by microPET. Tumor/muscle (T/M) ratios were used for quantitative evaluation in this study. RESULTS: Multiple pulmonary nodules were detected by MDCT and microPET starting 14 days after the tumor injection. The high-uptake lesions in the lung detected by microPET corresponded well to the tumors detected by MDCT. The smallest nodule detected by microPET was ca. 1.5 mm in diameter. Overall, 87 nodules were detected by MDCT and the ratios of lesions detected by microPET to those by MDCT were 35.3%, 77.5%, and 90% for tumors equal to or smaller than 2 mm, 2-4 mm, and 4-6 mm in diameter, respectively. The respective T/M ratios were 2.41 +/- 0.41, 2.93 +/- 0.55, and 3.34 +/- 0.71. The T/M ratio increased with tumor size, but it was similar in each tumor size category. In the 35-day follow-up protocol, it was possible to follow sequentially the same tumor by the microPET. CONCLUSIONS: By FDG-microPET, it is possible to evaluate tumors larger than 2 mm in diameter and to follow the growth of individual tumors. Our results also suggest that the rabbit model of VX-2 pulmonary metastasis is a stable experimental model for evaluation using FDG. Monitoring of the therapeutic effects of anticancer drugs and radiation therapy could be tried by using this model and microPET.

Inhomogeneity correction in radiotherapy for lung cancer in multicenter clinical trials.

PURPOSE: Dose distribution in patients in past multicenter clinical trials was reviewed from the perspective of clinicians to evaluate the quality of treatment and to improve the quality of future clinical trials. MATERIALS AND METHODS: Thirty patients with stage III lung cancer, who had undergone radical radiation therapy in multicenter clinical trials were retrospectively reviewed. A two-dimensional treatment planning system using Clarkson integration was used to calculate correction factors at the primary lesions and at the mediastinal lymph nodes. RESULTS: Correction factors at the primary lesions ranged from 1.00 to 1.12 (mean, 1.06) and from 1.02 to 1.14 (mean, 1.06) in the AP/PA fields and in the oblique fields, respectively. The lowest values of correction factors at the mediastinal lymph nodes on the axial plane including the primary lesions ranged from 0.93 to 1.04 (mean, 0.98) and from 0.97 to 1.10 (mean, 1.02) in the AP/PA fields and in the oblique fields, respectively. In 14 patients whose primary tumor was located in the upper lung field, the correction factors at the subcarinal lymph nodes ranged from 0.90 to 1.01 (mean, 0.96) in the AP/PA fields. CONCLUSION: Delivered doses lower than those prescribed at the mediastinal lymph nodes should be taken into consideration to improve the quality of multicenter clinical trials.