Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields.

PURPOSE: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. PATIENTS AND METHODS: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG≤1) group and the Grade 2-5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. RESULTS: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. CONCLUSION: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

Strategy of radiation therapy for bone metastases and MSCC in breast cancer patients.

Bone metastasis is a common event in advanced cancers such as prostate, breast, lung, and renal cancers. Radiation therapy has been widely used for bone metastasis. However, it remains a challenging therapy because no radiation therapeutic guidelines, including radiation dose, radiation field, and fractionation, for patients with bone metastasis have been established. Many randomized controlled trials for bone metastasis have been carried out. They showed no significant difference in pain relief with a short course of radiation therapy such as 8 Gy/1 Fr and 20 Gy/5 Fr or with a long course of radiation therapy such as 30 Gy/10 Fr, 37.5 Gy/15 Fr, and 40 Gy/20 Fr. Toxicity rates with short and long courses were also the same. Recurrence rate at 2 years, however, was significantly higher in patients irradiated with a short course than in patients irradiated with a long course. Those trials also showed that response rate is affected by patient's age, performance state, tumor type, pathological state, number of metastatic tumors, and span from diagnosis of cancer to development of metastatic tumor. Breast cancer has a better prognosis than most other cancers. Recently, there have been significant advances in cancer therapy techniques and improvement in clinical results. Bone metastasis can cause extreme pain and motor deficits. Quality of life for patients with bone metastasis is drastically worsened. Patients with bad prognosis should be treated with radiation therapy when analgesia is the main aim of treatment. Survival of patients with oligometastasis or predominantly bone metastasis is expected to be better than that of patients with visceral metastasis. For patients with vertebral or weight-bearing long bone metastasis, long-course therapy is recommended. Many patients who are expected to have a good prognosis should be treated with a long course of radiation.

Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: can SBRT be comparable to surgery?

PURPOSE: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non-small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. PATIENTS AND METHODS: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n=65; T2N0M0, n=22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively. RESULTS: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. CONCLUSION: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage I NSCLC. The survival rate for SBRT is potentially comparable to that for surgery.

Cesium implant for tongue carcinoma with a thickness of 1.5 cm or more: cases successfully treated with a Modified Manchester System.

PURPOSE: Deciding on treatment carcinoma of the tongue when the tumor has a thickness of 1.5 cm or more is difficult. Surgery often requires wide resection and re-construction, leading to considerable functional impairment. A cesium implant is an attractive option, but according to the Manchester System, a two plane implant is needed. MATERIALS AND METHODS: According to the textbook, a tumor is sandwiched between the needles, which are implanted at the edge of the tumor. This may cause an unnecessarily high dose to the outer surface of the tongue, which sometimes leads to a persistent ulcer. To avoid this complication, we invented a modified implantation method, and applied the method to five consecutive patients. RESULTS: With a minimum follow-up of 2 years, all primary tumors in 5 consecutive patients have been controlled. No complications occurred in soft tissue of the tongue or in the mandible. CONCLUSION: Our modified Manchester System was feasible and effective for tumors that has a thickness of 1.5 cm or more.

Three-dimensional intrafractional motion of breast during tangential breast irradiation monitored with high-sampling frequency using a real-time tumor-tracking radiotherapy system.

PURPOSE: To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. METHODS AND MATERIALS: A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. RESULTS: The mean +/- standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95% CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95% CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. CONCLUSION: Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution.

Steep dose-response relationship for stage I non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy.

PURPOSE: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. METHODS AND MATERIALS: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from +/-2 to 3 mm. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. RESULTS: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. CONCLUSION: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy.

Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study.

INTRODUCTION: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. METHODS: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57-180 Gy) based on alpha/beta = 10. RESULTS: During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p < 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p < 0.05). CONCLUSIONS: Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.

Contrast-enhanced FLAIR imaging in combination with pre- and postcontrast magnetization transfer T1-weighted imaging: usefulness in the evaluation of brain metastases.

PURPOSE: To assess whether the use of postcontrast fluid-attenuated inversion recovery (FLAIR) imaging in combination with pre- and postcontrast magnetization transfer (MT) T1-weighted imaging (T1WI) can increase diagnostic confidence in the evaluation of brain metastases. MATERIALS AND METHODS: Brain MR images from 41 patients with suspected brain metastases were reviewed. Two radiologists viewed pre- and postcontrast MT-T1W images for the presence of metastatic tumors and rated the possible enhanced lesions using a five-point confidence scale (session 1). The postcontrast FLAIR images were then viewed together with pre- and postcontrast MT-T1W images, and the presence of metastasis was rated again (session 2). RESULTS: A total of 240 possible enhanced lesions were detected in session 1. Judging by follow-up MR examinations, 196 were considered to be nonmetastatic findings and 44 were determined to be metastasis. In session 2 the confidence rating for nonmetastasis increased significantly in the subset of nonmetastatic findings (P < 0.001), and the confidence rating for metastasis increased significantly in the subset of metastases (P < 0.05). CONCLUSION: The addition of postcontrast FLAIR imaging to pre- and postcontrast MT-T1WI improves diagnostic confidence in evaluation of brain metastases.

Characteristics of patients who developed radiation pneumonitis requiring steroid therapy after stereotactic irradiation for lung tumors.

BACKGROUND: To find possible risk factors for symptomatic radiation pneumonitis (RP) after stereotactic irradiation (STI) for peripheral non-small cell lung cancer (NSCLC), pre-treatment pulmonary function test and dose volume statistics in patients who developed RP requiring steroid intake were retrospectively compared with statistics of those who did not develop RP. MATERIALS AND METHODS: From 1996 to 2002, 156 patients with Stage I NSCLC received STI at 5 hospitals in Japan. Of those patients, 12 were medicated with steroids for RP after treatment (RP group). For comparison, 31 patients were randomly selected from the remaining 144 patients who received STI but did not receive steroids (control group). RESULTS: There were no statistical differences in age, sex, tumor size, performance status, forced expiratory volume in 1 sec (FEV1.0%), or percent vital capacity (%VC) between patients medicated with steroids for RP and those who did not have RP and received no steroids. V20 (%) was 7 to 18% (median 8%) in patients medicated with steroids for RP and 2 to 16% (median 7%) in those who did not have RP. No difference was observed in V20, the biologically effectively dose (BED) at the periphery of the planning target volume, or the dose per fraction between the two groups. CONCLUSIONS: Pre-treatment pulmonary function test (%VC, FEV1.0%), and dose volume statistics V20, total dose, BED, dose per fraction, peripheral dose) were not predictive of RP requiring steroid intake after STI for stage I NSCLC.

Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy.

BACKGROUND: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. METHODS AND MATERIALS: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. RESULTS: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. CONCLUSION: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology.

The effect of tumor location and respiratory function on tumor movement estimated by real-time tracking radiotherapy (RTRT) system.

PURPOSE: The effects of tumor location and pulmonary function on the motion of fiducial markers near lung tumors were evaluated to deduce simple guidelines for determining the internal margin in radiotherapy without fiducial markers. METHODS AND MATERIALS: Pooled data collected by a real-time tumor-tracking radiotherapy system on 42 markers in 39 patients were analyzed. The pulmonary functions of all patients were assessed before radiotherapy. Using chest X-ray film, the position of the marker was expressed relative to the geometry of the unilateral lung. Posterior location meant the area of the posterior half of the lung in a lateral chest X-ray film, and caudal location meant the caudal half of the chest X-ray film; these categories were determined by measuring the distance between the marker and anatomic landmarks, including the apex, costophrenic angle, midline of spinal canal, lateral, anterior, and posterior boundary of the lung. RESULTS: Before the radiotherapy, 18 patients had obstructive respiratory dysfunction (ratio of forced expiratory volume in 1 s to forced vital capacity [FEV1.0/FVC] <70), 5 patients had constrictive dysfunction (percent vital capacity [%VC] <80), and 3 had mixed dysfunction. Means of FEV1.0/FVC and %VC were 97.0% and 66.5%, respectively. Median tumor movements in the x (left-right), y (anteroposterior), and z (craniocaudal) directions were 1.1 mm, 2.3 mm, and 5.4 mm, respectively. There was no significant correlation between respiratory function and magnitude of marker movement in any direction. Median marker movement in the z direction was 2.6 mm for the cranial location and 11.8 mm for the caudal location, respectively (p < 0.001). Median movement in the z direction was 11.8 mm for posterior location and 3.4 mm for anterior location, respectively (p < 0.01). CONCLUSIONS: Simple measurement of the relative location on plain chest X-ray film was related, but respiratory function test was not related, to the craniocaudal amplitude of the motion of the fiducial marker near lung tumors.

Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy.

PURPOSE: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. METHODS AND MATERIALS: Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 set-ups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). RESULTS: In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within +/-2 mm in 95% and +/-1 mm in 80% during treatment. The variation in the distances between the implanted markers was >2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. CONCLUSION: The fixation of markers into the bronchial tree was useful for the setup for peripheral lung cancer and had an accuracy of +/-2 mm during the 1-2-week treatment period. The relationship between the markers and tumor can change significantly after 2 weeks, suggesting that adaptive four-dimensional RT is required.