Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative assessment with diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient.

OBJECTIVE: To evaluate diffusion-weighted magnetic resonance (DW-MR) imaging for detection of metastases in lymph nodes by using quantitative analysis. METHODS: Seventy patients with non-small cell lung cancer were examined with DW and short inversion time inversion recovery (STIR) turbo-spin-echo MR imaging. Apparent diffusion coefficient of each lung cancer and lymph node was calculated from DW-MR images. Difference of the apparent diffusion coefficient in a lung cancer and a lymph node was calculated (D1). From STIR turbo-spin-echo MR images, ratios of signal intensity in a lymph node to that in a 0.9% saline phantom was calculated (lymph node-saline ratio [LSR1]). For quantitative analysis, the threshold value for a positive test was determined on a per node basis and tested for ability to enable a correct diagnosis on a per patient basis. Results of quantitative analyses of DW- and STIR-MR images were compared on a per patient basis with McNemar testing. RESULTS: Mean D1 in the lymph node group with metastases was lower than that in the group without metastases (P < 0.001). When an D1 of 0.24 x 10(-3) mm2/s was used as the positive test threshold, sensitivity, specificity, and accuracy were 69.2%, 100%, and 94.0%, respectively, on a per patient basis. There was no significant difference (P > 0.05) between quantitative analyses of DW-MR images and STIR-MR images. CONCLUSIONS: Quantitative analysis of DW-MR images enables differentiation of lymph nodes with metastasis from those without.

Outcome of MR-guided percutaneous cryoablation for hepatocellular carcinoma.

PURPOSE: To assess the mid-term results of MR-guided percutaneous cryoablation for small hepatocellular carcinoma (HCC). METHODS: Using an argon-based cryoablation system, MR-guided percutaneous cryoablation was performed. The number of tumors was three or fewer. The maximum diameter of tumors was less than 5 cm when solitary and no more than 3 cm when multiple. The Kaplan-Meier method was used to calculate the survival of patients. RESULTS: Among 15 patients, 16 tumors were treated. The maximum tumor diameter ranged from 1.2 to 4.5 cm, with a mean of 2.5 +/- 0.8 cm (mean +/- standard deviation). The volume of iceballs measured on MR-images was greater than that of the tumors in all cases. The follow-up period ranged from 10 to 52 months, with a mean of 36.6 +/- 12.1 months. One-year and 3-year overall survival were 93.8 and 79.3%, respectively. The complete ablation rate was 80.8% at 3 years. Immediate complications were pneumothorax, hemothorax, and pleural effusion. An ablation zone was not absorbed and content exuded from a scar of the probe tract 4 months after cryoablation in one patient. CONCLUSION: MR-guided percutaneous cryoablation appears to be a feasible modality and potentially good option for the treatment of small HCC.

Intercepting radiotherapy using a real-time tumor-tracking radiotherapy system for highly selected patients with hepatocellular carcinoma unresectable with other modalities.

PURPOSE: To assess the clinical outcome of intercepting radiotherapy, in which radiotherapy is delivered only when a tumor in motion enters a target area, using a real-time tumor-tracking radiotherapy (RTRT) system for patients with hepatocellular carcinoma who were untreatable with other modalities because the tumors were adjacent to crucial organs or located too deep beneath the skin surface. METHODS AND MATERIALS: Eighteen tumors, with a mean diameter of 36 mm, were studied in 15 patients. All tumors were treated on a hypofractionated schedule with a tight margin for setup and organ motion using a 2.0-mm fiducial marker in the liver and the RTRT system. The most commonly used dose of radiotherapy was 48 Gy in 8 fractions. Sixteen lesions were treated with a BED(10) of 60 Gy or more (median, 76.8 Gy). RESULTS: With a mean follow-up period of 20 months (range, 3-57 months), the overall survival rate was 39% at 2 years after RTRT. The 2-year local control rate was 83% for initial RTRT but was 92% after allowance for reirradiation using RTRT, with a Grade 3 transient gastric ulcer in 1 patient and Grade 3 transient increases of aspartate amino transaminase in 2 patients. CONCLUSIONS: Intercepting radiotherapy using RTRT provided effective focal high doses to liver tumors. Because the fiducial markers for RTRT need not be implanted into the tumor itself, RTRT can be applied to hepatocellular carcinoma in patients who are not candidates for other surgical or nonsurgical treatments.

Factors related to diagnostic sensitivity using an ultrathin bronchoscope under CT guidance.

BACKGROUND: We investigated factors related to the diagnostic sensitivity of CT-guided transbronchial biopsy (TBB) using an ultrathin bronchoscope and virtual bronchoscopy (VB) navigation for small peripheral pulmonary lesions. METHOD: We have performed this procedure on 83 patients with 85 small peripheral pulmonary lesions (< 20 mm in diameter). We analyzed the relationship between the diagnostic sensitivity and the location of the lesions, the bronchial generation to which an ultrathin bronchoscope was inserted, and the lesion-bronchial and lesion-pulmonary arterial relationships on high-resolution CT. RESULTS: Fifty-six of the 85 lesions (66%) were diagnosed following CT-guided TBB using an ultrathin bronchoscope with VB navigation. The lesions located in the left superior segment of the lower lobe (S6) had a significantly low diagnostic sensitivity compared to other locations (p < 0.01). When an ultrathin bronchoscope could be inserted to the fifth or greater bronchial generation, the yield was above the average diagnostic sensitivity of 66%. Moreover, not only the patients with the presence of a bronchus leading directly to a lesion (CT-bronchus sign), but also the patients with the presence of a pulmonary artery leading to a lesion (CT-artery sign), had high diagnostic sensitivity (p < 0.01). Multivariate analysis revealed that the location of lesion was an independent predictor of diagnostic sensitivity (p < 0.05). CONCLUSIONS: The location of the lesion, the bronchial generation to which an ultrathin bronchoscope was inserted, and the presence of a bronchus as well as a pulmonary artery leading to the lesion were valuable for predicting successful CT-guided TBB using an ultrathin bronchoscope with VB navigation.

Uncertainty in treatment of head-and-neck tumors by use of intraoral mouthpiece and embedded fiducials.

PURPOSE: To reduce setup error and intrafractional movement in head-and-neck treatment, a real-time tumor tracking radiotherapy (RTRT) system was used with the aid of gold markers implanted in a mouthpiece. METHODS AND MATERIALS: Three 2-mm gold markers were implanted into a mouthpiece that had been custom made for each patient before the treatment planning process. Setup errors in the conventional immobilization system using the shell (manual setup) and in the RTRT system (RTRT setup) were compared. Eight patients with pharyngeal tumors were enrolled. RESULTS: The systematic setup errors were 1.8, 1.6, and 1.1 mm in the manual setup and 0.2, 0.3, and 0.3 mm in the RTRT setup in right-left, craniocaudal, and AP directions, respectively. Statistically significant differences were observed with respect to the variances in setup error (p <0.001). The systematic and random intrafractional errors were maintained within the ranges of 0.2-0.6 mm and 1.0-2.0 mm, respectively. The rotational systematic and random intrafractional errors were estimated to be 2.2-3.2 degrees and 1.5-1.6 degrees , respectively. CONCLUSIONS: The setup error and planning target volume margin can be significantly reduced using an RTRT system with a mouthpiece and three gold markers.

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.

Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors.

PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-beta)-secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-beta-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-beta-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the last follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas.

Comparison of imaging modalities for the accurate delineation of arteriovenous malformation, with reference to stereotactic radiosurgery.

PURPOSE: To investigate the discrepancy between the arteriovenous malformations seen on magnetic resonance angiography (MRA) and on stereotactic digital subtracted angiography (DSA). METHODS AND MATERIALS: The target volume on stereotactic DSA (V(DSA)) and the target volume on MRA (V(MRA)) were separately delineated in 28 intracranial arteriovenous malformations. The coordinates of the center and the outer edges of V(DSA) and V(MRA) were calculated and used for the analyses. RESULTS: The standard deviations (mean value) of the displacement of centers of V(MRA) from V(DSA) were 2.67 mm (-1.82 mm) in the left-right direction, 3.23 mm (-0.08 mm) in the anterior-posterior direction, and 2.16 mm (0.91 mm) in the craniocaudal direction. V(MRA) covered less than 80% of V(DSA) in any dimensions in 9 cases (32%), although no significant difference was seen in the target volume between each method, with a mean value of 11.9 cc for V(DSA) and 12.3 cc for V(MRA) (p = 0.948). CONCLUSION: The shift of centers between each modality is not negligible. Considering no significant difference between V(DSA) and V(MRA), but inadequate coverage of the V(DSA) by V(MRA), it is reasonable to consider that the target on MRA might include the feeding artery and draining vein and possibly miss a portion of the nidus.

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.

Real-time monitoring of a digestive tract marker to reduce adverse effects of moving organs at risk (OAR) in radiotherapy for thoracic and abdominal tumors.

PURPOSE: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin. METHODS AND MATERIALS: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker. RESULTS: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm. CONCLUSION: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system.