Ryoong-Jin Oh

High-dose-rate brachytherapy as monotherapy for localized prostate cancer: A retrospective analysis with special focus on tolerance and chronic toxicity

PURPOSE To examine retrospectively fractionated high-dose-rate brachytherapy as monotherapy for localized prostate cancer with special focus on tolerance and toxicity, especially chronic toxicity. MATERIALS AND METHODS Between May 1995 and October 2001, 43 patients with localized prostate cancer were treated with high-dose-rate brachytherapy without external beam irradiation at Osaka University Hospital. The stage was T1, T2, T3, and T4 in 8, 14, 18, and 3 patients, respectively. The adenocarcinoma was well, moderately, or poorly differentiated in 12, 16, and 15 patients, respectively. The median initial prostate-specific antigen level was 19.3 ng/mL (range 3.8-233.0). Thirty-eight patients also received hormonal therapy. Metallic needles were implanted transperineally under real-time ultrasound guidance, followed by a dose optimization program. Patients were irradiated twice daily at intervals of >6 h. A total dose of 54 Gy in nine fractions within 5 days (48 Gy in eight fractions within 5 days for the first 7 cases) was administered in one implant session. The median follow-up was 24 months (range 1-76). RESULTS Radiation Therapy Oncology Group acute toxicity of Grade 4, 2, and 1 occurred in 1 (2%), 12 (28%), and 8 (19%) patients, respectively. Five patients had late toxicity: one with rectal ulcer (Grade 2) and four with rectal bleeding (Grade 1). The volume receiving 100% of the prescribed dose showed significant correlations with the incidence of acute and chronic toxicities (p = 0.005 and p = 0.014, respectively). The 3-year actuarial overall survival, local control, and biochemical no evidence of disease rate was 94%, 100%, and 55%, respectively. The crude biochemical control rate for low, intermediate, and high-risk patients was 100% (5 of 5), 80% (8 of 10), and 61% (17 of 28), respectively. CONCLUSIONS High-dose-rate brachytherapy as monotherapy was found to be feasible and well tolerated. It showed a low chronic toxicity rate without any event of Radiation Therapy Oncology Group of Grade 3 or greater.

New Approach for Treatment of Vertebral Metastases Using Intensity-Modulated Radiotherapy*

AbstractPurpose:To perform aggressive radiotherapy for vertebral metastases. Using very steep dose gradients from intensity-modulated radiotherapy (IMRT), a protocol based on the concept of partial volume dose to the spinal cord was evaluated.Patients and Methods:50 patients with vertebral metastases were treated using IMRT. In previously unirradiated cases, where a prescribed dose of 80 Gy (BED10) was delivered, the constraint to the spinal cord should be less than 100 Gy (BED2). For previously irradiated cases, on the other hand, the dose is the same as in the previously unirradiated case; however, constraints for the spinal cord are a cumulative BED2 of less than 150 Gy, BED2 of less than 100 Gy in each instance, and a treatment gap of more than 6 months. There were 6 patients considered for a partial volume dose to the spinal cord. They all received higher BED2, ranging from 51–157 Gy of D1cc.Results:Among the 24 patients who survived longer than 1 year, there was 1 case of transient radiation myelitis. There were no other cases of spinal cord sequelae.Conclusion:Based on the present results, we recommend a BED2 of 100 Gy or less at D1cc as a constraint for the spinal cord in previously unirradiated cases, and a cumulative BED2 of 150 Gy or less at D1cc in previously irradiated cases, when the interval was not shorter than 6 months and the BED2 for each session was 100 Gy or less. The prescribed BED10 of 80 Gy could be safely delivered to the vertebral lesions.ZusammenfassungHintergrund und Ziel:Aggressive Strahlentherapie bei vertebralen Metastasen. Unter Einsatz sehr steiler Dosisgradienten intensitätsmodulierter Strahlentherapie (IMRT) Evaluierung eines Therapieprotokolls basierend auf dem Konzept der partiellen Volumendosierung am Rückenmark.Patienten und Methodik:Wir behandelten mit IMRT 50 Patienten mit Wirbelsäulenmetastasen. In Fällen ohne vorangegangene Strahlentherapie, bei denen eine verordnete Dosis von 80 Gy BED10 appliziert wurde, sollte die Belastung des Rückenmarks weniger als 100 Gy BED2 betragen. In Fällen mit vorheriger Strahlentherapie wurde die gleiche Dosis appliziert, wobei allerdings die Belastung des Rückenmarks kumulativ unter 150 Gy BED2 und in der Einzelapplikation bei weniger als 100 Gy BED2 lag, außerdem die Behandlungspause mehr als 6 Monate betrug. Für die partielle Volumendosierung am Rückenmark kamen 6 Patienten in Frage. Alle erhielten die höhere BED2 von mehr als 51 Gy bis zu 157 Gy D1cc.Ergebnisse:Unter 24 Patienten, die länger als ein Jahr überlebten, gab es einen Fall vorübergehender Strahlenmyelitis. Es wurden keine weiteren Fälle von Bestrahlungsfolgen am Rückenmark beobachtet.Schlussfolgerung:Auf Basis der vorliegenden Ergebnissen würden wir eine BED2 von 100 Gy oder weniger bei D1cc am Rückenmark in Fällen ohne vorangegangene Strahlentherapie empfehlen und in Fällen mit vorheriger Strahlentherapie eine kumulative BED2 von 150 Gy oder weniger bei D1cc, wenn das Behandlungsintervall nicht kürzer als 6 Monate war und die Dosis der Einzelapplikation bei einer BED2 von 100 Gy oder weniger lag. Die verordnete Dosis einer BED10 von 80 Gy bei Wirbelsäulenläsionen ließ sich sicher applizieren.

Evaluation of potential internal target volume of liver tumors using cine-MRI

PURPOSE Four-dimensional computed tomography (4DCT) is widely used for evaluating moving tumors, including lung and liver cancers. For patients with unstable respiration, however, the 4DCT may not visualize tumor motion properly. High-speed magnetic resonance imaging (MRI) sequences (cine-MRI) permit direct visualization of respiratory motion of liver tumors without considering radiation dose exposure to patients. Here, the authors demonstrated a technique for evaluating internal target volume (ITV) with consideration of respiratory variation using cine-MRI. METHODS The authors retrospectively evaluated six patients who received stereotactic body radiotherapy (SBRT) to hepatocellular carcinoma. Before acquiring planning CT, sagittal and coronal cine-MRI images were acquired for 30 s with a frame rate of 2 frames/s. The patient immobilization was conducted under the same condition as SBRT. Planning CT images were then acquired within 15 min from cine-MRI image acquisitions, followed by a 4DCT scan. To calculate tumor motion, the motion vectors between two continuous frames of cine-MRI images were calculated for each frame using the pyramidal Lucas-Kanade method. The target contour was delineated on one frame, and each vertex of the contour was shifted and copied onto the following frame using neighboring motion vectors. 3D trajectory data were generated with the centroid of the contours on sagittal and coronal images. To evaluate the accuracy of the tracking method, the motion of clearly visible blood vessel was analyzed with the motion tracking and manual detection techniques. The target volume delineated on the 50% (end-exhale) phase of 4DCT was translated with the trajectory data, and the distribution of the occupancy probability of target volume was calculated as potential ITV (ITV Potential). The concordance between ITV Potential and ITV estimated with 4DCT (ITV 4DCT) was evaluated using the Dices similarity coefficient (DSC). RESULTS The distance between blood vessel positions determined with motion tracking and manual detection was analyzed. The mean and SD of the distance were less than 0.80 and 0.52 mm, respectively. The maximum ranges of tumor motion on cine-MRI were 2.4 ± 1.4 mm (range, 1.0-5.0 mm), 4.4 ± 3.3 mm (range, 0.8-9.4 mm), and 14.7 ± 5.9 mm (range, 7.4-23.4 mm) in lateral, anterior-posterior, and superior-inferior directions, respectively. The ranges in the superior-inferior direction were larger than those estimated with 4DCT images for all patients. The volume of ITV Potential was 160.3% ± 13.5% (range, 142.0%-179.2%) of the ITV 4DCT. The maximum DSC values were observed when the cutoff value of 24.7% ± 4.0% (range, 20%-29%) was applied. CONCLUSIONS The authors demonstrated a novel method of calculating 3D motion and ITV Potential of liver cancer using orthogonal cine-MRI. Their method achieved accurate calculation of the respiratory motion of moving structures. Individual evaluation of the ITV Potential will aid in improving respiration management and treatment planning.

Approach to dose definition to the gross tumor volume for lung cancer with respiratory tumor motion

The purpose of this study was to validate the dose prescription defined to the gross tumor volume (GTV) 3D and 4D dose distributions of stereotactic radiotherapy for lung cancer. Treatment plans for 94 patients were generated based on computed tomography (CT) under free breathing. A uniform margin of 8 mm was added to the internal target volume (ITV) to generate the planning target volume (PTV). A leaf margin of 2 mm was added to the PTV. The prescription dose was defined such that 99% of the GTV should receive 100% of the dose using the Monte Carlo calculation (iPlan RT DoseTM) for 6-MV photon beams. The 3D dose distribution was determined using CT under free breathing. The 4D dose distribution plan was recalculated to investigate the effect of tumor motion using the same monitor units as those used for the 3D dose distribution plan. D99 (99% of the GTV) in the 4D plan was defined as the average D99 in each of the four breathing phases (0%, 25%, 50% and 75%). The dose difference between maximum and minimum at D99 of the GTV in 4D calculations was 0.6 ± 1.0% (range 0.2–4.6%). The average D99 of the GTV from 4D calculations in most patients was almost 100% (99.8 ± 1.0%). No significant difference was found in dose to the GTV between 3D and 4D dose calculations (P = 0.67). This study supports the clinical acceptability of treatment planning based on the dose prescription defined to the GTV.

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.

Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging

The purpose of the present study was to investigate the threshold dose for focal liver damage after stereotactic body radiation therapy (SBRT) in cirrhotic and normal livers using magnetic resonance imaging (MRI). A total of 64 patients who underwent SBRT for liver tumors, including 54 cirrhotic patients with hepatocellular carcinoma (HCC) and 10 non-cirrhotic patients with liver metastases, were analyzed. MRI was performed 3-6 months after SBRT, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1-weighted sequences. All MRI datasets were merged with 3D dosimetry data. All dose distributions were corrected to the biologically effective dose using the linear-quadratic model with an assumed α/β ratio of 2 Gy. The development of liver dysfunction was validly correlated with isodose distribution. The median biologically effective dose (BED2) that provoked liver dysfunction was 57.3 (30.0-227.9) and 114.0 (70.4-244.9) Gy in cirrhotic and normal livers, respectively (P = 0.0002). The BED2 associated with a >5% risk of liver dysfunction was 38.5 in cirrhotic livers and 70.4 Gy in normal livers. The threshold BED2 for liver dysfunction was not significantly different between Child-Pugh A and B patients (P = 0.0719). Moreover, the fractionation schedule was not significantly correlated with threshold BED2 for liver dysfunction in the cirrhotic liver (P = 0.1019). In the cirrhotic liver, fractionation regimen and Child-Pugh classification did not significantly influence the threshold BED2 for focal liver damage after SBRT. We suggest that the threshold BED2 for liver dysfunction after SBRT is 40 and 70 Gy in the cirrhotic and normal liver, respectively.

High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: Results of a retrospective analysis

PurposeHigh-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively.Materials and MethodsBetween May 1995 and April 2002, 35 patients with prostate cancer [Stage≥T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level≥20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23–117 months).ResultsThe 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated.ConclusionHDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.

Prospective study of HDR (192Ir) versus MDR (137Cs) intracavitary brachytherapy for carcinoma of the uterine cervix

PURPOSE The aim of this study was to compare the results of high-dose rate (HDR) and medium-dose rate (MDR) intracavitary brachytherapy for carcinoma of the uterine cervix on the basis of a prospective study and to determine the dose rate conversion factor (DRCF) from low-dose rate (LDR) to MDR via HDR, because a DRCF of 0.54 from LDR to HDR has been widely accepted. MATERIALS AND METHODS Between August 1991 and July 1999, 104 patients were entered into this trial to compare results between HDR (n=54) and MDR (n=50). Three patients were excluded from this study, leaving 54 HDR patients and 47 MDR patients eligible. Method and dose of external beam radiotherapy were the same for both groups. For HDR intracavitary brachytherapy, point A dose was adjusted to 32 Gy/4 fractions for stages I and II, to 30 Gy/4 fractions for stage III, and to 22.5 Gy/3 fractions for stage IV. The corresponding values for MDR were 35.6 Gy/4 fractions, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. The average dose rate at point A was 30 Gy/hour (9.0-65.2) for HDR and 1.7 Gy/hour (1.3-2.2) for MDR. We assumed a DRCF of 0.9 from MDR to HDR. RESULTS The 3-year cause-specific survival rates for HDR were 85%, 83%, 75%, and 0% for stages I, II, III, and IV, respectively. The corresponding figures for MDR were 100%, 82%, 58%, and 40%. Six of the HDR patients (11%) and 2 of the MDR patients (4%) developed Kottmeiers grade 2 or 3 late complications. A DRCF of 0.6 from LDR to MDR could be derived from a DRCF of 0.9 from MDR to HDR and one of 0.54 from LDR to HDR. CONCLUSIONS There were no statistically significant differences in cause-specific survival and incidence of late complications between HDR and MDR. A DRCF of 0.6 from LDR to MDR could be determined. However, because the results of this trial were preliminary, a further study is needed.

Reirradiation of paraaortic lymph node metastasis by brachytherapy with hyaluronate injection via paravertebral approach: With DVH comparison to IMRT

UNLABELLED PURPOSE/INTRODUCTION: To safely irradiate retroperitoneal targets as paraaortic lymph node by separating abdominal at-risk organs from the target during irradiation, we created a percutaneous paravertebral approach of high-dose-rate brachytherapy with hyaluronate gel injection (HGI). We report a case treated with this technique. METHODS AND MATERIALS We encountered a patient with symptomatic regrowth of paraaortic lymph node metastasis from prostatic cancer. He had previously received 58.4Gy of radiotherapy to the same region 12 months prior. Brachytherapy needles and a HGI needle were deployed via the paravertebral approach under local anesthesia at our outpatient clinic. RESULTS A single dose of 22.5Gy (equivalent to 60.94Gy in 2Gy per fraction schedule calculated at α/β=10) was delivered to the target, with preservation of the surrounding small intestine by HGI with D(2cc) (minimum dose to the most irradiated volume of 2mL) of 5.05Gy. Therapeutic ratio was 3.64 times higher for this brachytherapy plan compared with an intensity-modulated radiation therapy plan. At followup at 1 year after brachytherapy, the symptoms had disappeared, tumor size had reduced with no fluorodeoxyglucose accumulation, and prostate-specific antigen level had decreased. CONCLUSION We consider that high-dose-rate brachytherapy with the HGI procedure offers effective treatment even in this type of reirradiation situation.

Differences in rates of radiation-induced true and false rib fractures after stereotactic body radiation therapy for Stage I primary lung cancer

Abstract The purpose of this study was to analyze the dosimetry and investigate the clinical outcomes of radiation-induced rib fractures (RIRFs) after stereotactic body radiotherapy (SBRT). A total of 126 patients with Stage I primary lung cancer treated with SBRT, who had undergone follow-up computed tomography (CT) at least 12 months after SBRT and who had no previous overlapping radiation exposure were included in the study. We used the Mantel–Haenszel method and multiple logistic regression analysis to compare risk factors. We analyzed D(0.5 cm3) (minimum absolute dose received by a 0.5-cm3 volume) and identified each rib that received a biologically effective dose (BED) (BED3, using the linear–quadratic (LQ) formulation assuming an α/β = 3) of at least 50 Gy. Of the 126 patients, 46 (37%) suffered a total of 77 RIRFs. The median interval from SBRT to RIRF detection was 15 months (range, 3–56 months). The 3-year cumulative probabilities were 45% (95% CI, 34–56%) and 3% (95% CI, 0–6%), for Grades 1 and 2 RIRFs, respectively. Multivariate analysis showed that tumor location was a statistically significant risk factor for the development of Grade 1 RIRFs. Of the 77 RIRFs, 71 (92%) developed in the true ribs (ribs 1–7), and the remaining six developed in the false ribs (ribs 8–12). The BED3 associated with 10% and 50% probabilities of RIRF were 55 and 210 Gy to the true ribs and 240 and 260 Gy to the false ribs. We conclude that RIRFs develop more frequently in true ribs than in false ribs.