Iori Sumida

Monotherapeutic High-Dose-Rate Brachytherapy for Prostate Cancer: Five-Year Results of an Extreme Hypofractionation Regimen With 54 Gy in Nine Fractions

PURPOSE To evaluate an extreme hypofractionation regimen with 54 Gy in nine fractions provided by high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer by reporting 5-year clinical results. METHODS AND MATERIALS Between 1996 and 2005, 112 patients with localized prostate cancer were treated with HDR brachytherapy without external beam radiotherapy. Of the 112 patients, 15 were considered low risk, 29 intermediate risk, and 68 as high risk. The prescribed dose was uniformly 54 Gy in nine fractions within 5 days. Of the 112 patients, 94 also received hormonal therapy. The median follow-up time was 5.4 years. RESULTS All the patients safely completed the treatment regimen. The 5-year prostate-specific antigen (PSA) failure-free, local control, disease-free survival, and overall survival rate was 83%, 97%, 87%, and 96%, respectively. The 5-year PSA failure-free rate for low-, intermediate-, and high-risk patients was 85% (95% confidence interval, 66-100%), 93% (95% confidence interval, 83-100%), and 79% (95% confidence interval, 69-89%), respectively. The significant prognostic factors for PSA failure were the initial PSA level (p = .029) and younger age (p = .019). The maximal toxicities observed were Grade 3 using the Common Terminology Criteria for Adverse Events, version 3.0, for both acute and late toxicity (6 and 3 patients had acute and late Grade 3 toxicity, respectively). Late Grade 2 toxicity was observed in 13 patients. CONCLUSION Monotherapeutic HDR brachytherapy with an extreme hypofractionation regimen of 54 Gy in nine fractions associated with hormonal therapy was feasible, and its toxicity was acceptable. The interim tumor control rate at a median 5.4 years was promising, even for patients with locally advanced disease. This dose-fractionation scheme might be referred to by other terms, such as stereotactic body radiotherapy. Studies with longer follow-up periods and from multiple institutions are needed to confirm the efficacy of this novel approach.

CORRELATION BETWEEN DOSIMETRIC PARAMETERS AND LATE RECTAL AND URINARY TOXICITIES IN PATIENTS TREATED WITH HIGH-DOSE-RATE BRACHYTHERAPY USED AS MONOTHERAPY FOR PROSTATE CANCER

PURPOSE To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. METHODS AND MATERIALS The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. RESULTS The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >or= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >or= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. CONCLUSION Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

Gemstone spectral imaging: Determination of CT to ED conversion curves for radiotherapy treatment planning

The monochromatic images acquired by Gemstone spectral imaging (GSI) mode on the GE CT750 HD theoretically determines the computed tomography (CT) number more accurately than that of conventional scanner. Using the former, the CT number is calculated from (synthesized) monoenergetic X‐ray data. We reasoned that the monochromatic image might be applied to radiotherapy treatment planning (RTP) to calculate dose distribution more accurately. Our goal here was to provide CT to electron density (ED) conversion curves with monochromatic images for RTP. Therefore, we assessed the reproducibility of CT numbers, an important factor on quality assurance, over short and long time periods for different substances at varying energy. CT number difference between measured and theoretical value was investigated. The scanner provided sufficient reproducibility of CT numbers for dose calculation over short and long time periods. The CT numbers of monochromatic images produced by this scanner had reasonable values for dose calculation. The CT to ED conversion curve becomes linear with respect to the relationship between CT numbers and EDs as the energy increases. We conclude that monochromatic imaging from a fast switching system can be applied for the dose calculation, keeping Hounsfield units (HU) stability. PACS numbers: 87.55.‐x, 87.55.ne, 87.57.N‐, 87.59.bd

High-dose-rate interstitial brachytherapy for previously untreated cervical carcinoma

PURPOSE The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution. METHODS AND MATERIALS Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30Gy/15 fractions was followed by HDR-ISBT of 30Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20Gy/10 fractions was delivered with a midline block. The median followup period was 55 months. RESULTS The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3. CONCLUSIONS A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT.

RECTAL DOSE AND SOURCE STRENGTH OF THE HIGH-DOSE-RATE IRIDIUM-192 BOTH AFFECT LATE RECTAL BLEEDING AFTER INTRACAVITARY RADIATION THERAPY FOR UTERINE CERVICAL CARCINOMA

PURPOSE The purpose of this study was to reconfirm our previous findings that the rectal dose and source strength both affect late rectal bleeding after high-dose-rate intracavitary brachytherapy (HDR-ICBT), by using a rectal dose calculated in accordance with the definitions of the International Commission on Radiation Units and Measurements Report 38 (ICRU(RP)) or of dose-volume histogram (DVH) parameters by the Groupe Européen de Curietherapie of the European Society for Therapeutic Radiology and Oncology. METHODS AND MATERIALS Sixty-two patients who underwent HDR-ICBT and were followed up for 1 year or more were studied. The rectal dose for ICBT was calculated by using the ICRP(RP) based on orthogonal radiographs or the DVH parameters based on computed tomography (CT). The total dose was calculated as the biologically equivalent dose expressed in 2-Gy fractions (EQD(2)). The relationship between averaged source strength or the EQD(2) and late rectal bleeding was then analyzed. RESULTS When patients were divided into four groups according to rectal EQD(2) (>or= or or= or <2.4 cGy.m(2).h(-1)), the group with both a high EQD(2) and a high source strength showed a significantly greater probability of rectal bleeding for ICRU(RP), D(2cc), and D(1cc). The patients with a median rectal dose above the threshold level did not show a greater frequency of rectal bleeding unless the source strength exceeded 2.4 cGy.m(2).h(-1). CONCLUSIONS Our results obtained with data based on ICRU(RP) and CT-based DVH parameters indicate that rectal dose and source strength both affect rectal bleeding after HDR-ICBT.

Estimation of the total rectal dose of radical external beam and intracavitary radiotherapy for uterine cervical cancer using the deformable image registration method

We adapted the deformable image registration (DIR) technique to accurately calculate the cumulative intracavitary brachytherapy (ICBT) and external beam radiotherapy (EBRT) rectal dose for treating uterine cervical cancer. A total of 14 patients with primary cervical cancer radically treated with ICRT and EBRT were analysed using the Velocity AITM software. Computed tomography (CT) images were registered, and EBRT and ICBT dose distributions were determined. Cumulative D2cm3, D1cm3 and D0.1cm3 were calculated by simple addition of fractional values or by DIR. The accuracy of DIR was evaluated by means of a virtual phantom mimicking the rectum. The dice similarity coefficient (DSC) was calculated to evaluate rectal contour concordance between CT images before and after DIR. Virtual phantom analysis revealed that the average difference between the DIR-based phantom Dmean and the simple phantom Dmean was 1.9 ± 2.5 Gy (EQD2), and the DIR method included an uncertainty of ∼8.0%. The mean DSC between reference CT and CT was significantly improved after DIR (EBRT: 0.43 vs 0.85, P < 0.005; ICBT: 0.60 vs 0.87, P < 0.005). The average simple rectal D2cm3, D1cm3 and D0.1cm3 values were 77.6, 81.6 and 91.1 Gy (EQD2), respectively; the DIR-based values were 76.2, 79.5 and 87.6 Gy, respectively. The simple addition values were overestimated, on average, by 3.1, 3.7 and 5.5 Gy, respectively, relative to the DIR-based values. In conclusion, the difference between the simple rectal dose–volume histogram (DVH) parameter addition and DIR-based cumulative rectal doses increased with decreasing DVH parameters.

Three-dimensional dose prediction based on two-dimensional verification measurements for IMRT.

Dose verifications for intensity‐modulated radiation therapy (IMRT) are generally performed once before treatment. A 39‐fraction treatment course for prostate cancer delivers a dose prescription of 78 Gy in eight weeks. Any changes in multileaf collimator leaf position over the treatment course may affect the dosimetry. To evaluate the magnitude of deviations from the predicted dose over an entire treatment course with MLC leaf calibrations performed every two weeks, we tracked weekly changes in relative dose error distributions measured with two‐dimensional (2D) beam‐by‐beam analysis. We compared the dosimetric results from 20 consecutive patient‐specific IMRT quality assurance (QA) tests using beam‐by‐beam analysis and a 2D diode detector array to the dose plans calculated by the treatment planning system (TPS). We added back the resulting relative dose error measured weekly into the original dose grid for each beam. To validate the prediction method, the predicted doses and dose distributions were compared to the measurements using an ionization chamber and film. The predicted doses were in good agreement, within 2% of the measured doses, and the predicted dose distributions also presented good agreement with the measured distributions. Dose verification results measured once as a pretreatment QA test were not completely stable, as results of weekly beam‐by‐beam analysis showed some variation. Because dosimetric errors throughout the treatment course were averaged, the overall dosimetric impact to patients was small. PACS numbers: 87.55.D‐, 87.55.dk, 87.55.km, 87.55.Qr

Treatment outcomes using CyberKnife for brain metastases from lung cancer

We investigated the clinical outcomes following treatment using stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for brain metastases from lung cancer. A total of 67 patients with 109 brain metastases from lung cancer treated using CyberKnife between 1998 and 2011 were retrospectively analyzed. SRS (median dose, 24 Gy) was used to treat 79 lesions, and 3-fraction SRT (median dose, 30 Gy) was used to treat 30 lesions. The median follow-up time was 9.4 months (range, 0.4–125 months). The 1-year local control rate was 83.3%, and the 1-year distant brain failure rate was 30.1%. The median survival time was 13.1 months, and the 1- and 3-year overall survival (OS) rates were 54.8% and 25.9%, respectively. On multivariate analysis, three factors were found to be statistically significant predictors of OS: (i) presence of uncontrolled primary disease [hazard ratio (HR) = 3.04; P = 0.002]; (ii) Brinkman index (BI) ≥ 1000 (HR = 2.75; P = 0.007); and (iii) pulmonary metastases (HR = 3.54; P = 0.009). Radionecrosis and worsening of neurocognitive function after radiosurgery were observed in 5 (7%) and 3 (4%) patients, respectively. Our results indicated that SRS/SRT for brain metastases from lung cancer was effective. Uncontrolled primary disease, high BI, and pulmonary metastases at treatment were significant risk factors for OS.

Megavoltage cone beam computed tomography dose and the necessity of reoptimization for imaging dose-integrated intensity-modulated radiotherapy for prostate cancer.

PURPOSE Megavoltage cone beam computed tomography (MV-CBCT) dose can be integrated with the patients prescription. Here, we investigated the effects of imaging dose and the necessity for additional optimization when using intensity-modulated radiotherapy (IMRT) to treat prostate cancer. METHODS AND MATERIALS An arc beam mimicking MV-CBCT was generated using XiO (version 4.50; Elekta, Stockholm, Sweden). The monitor units (MU) for dose calculation were determined by conforming the calculated dose to the dose measured using an ionization chamber. IMRT treatment plans of 22 patients with prostate cancer were retrospectively analyzed. Arc beams of 3, 5, 8, and 15 MU were added to the IMRT plans, and the dose covering 95% of the planning target volume (PTV) was normalized to the prescribed dose with (reoptimization) or without optimization (compensation). RESULTS PTV homogeneity and conformality changed negligibly with MV-CBCT integration. For critical organs, an imaging dose-dependent increase was observed for the mean rectal/bladder dose (D(mean)), and reoptimization effectively suppressed the D(mean) elevations. The bladder generalized equivalent uniform dose (gEUD) increased with imaging dose, and reoptimization suppressed the gEUD elevation when 5- to 15-MU CBCT were added, although rectal gEUD changed negligibly with any imaging dose. Whereas the dose elevation from the simple addition of the imaging dose uniformly increased rectal and bladder dose, the rectal D(mean) increase of compensation plans was due mainly to low-dose volumes. In contrast, bladder high-dose volumes were increased by integrating the CBCT dose, and reoptimization reduced them when 5- to 15-MU CBCT were added. CONCLUSION Reoptimization is clearly beneficial for reducing dose to critical organs, elevated by addition of high-MU CBCT, especially for the bladder. For low-MU CBCT aimed at bony structure visualization, compensation is sufficient.

Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer

PURPOSE This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. METHODS We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D95%, and D2% to planning target volume (PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity. RESULTS RP and CMO values for PTV D95%, PTV D2%, HI, and CN were significantly similar (p<0.05 for all). RP mean dose, V50Gy, and V70Gy to rectum were superior or comparable to CMO values; RP V75Gy and V78Gy were higher than in CMO plans (p<0.05). RP bladder dose-volume parameter values (except V78Gy) were lower than in CMO plans (p<0.05). MU values were RP: 730±55MU and CMO: 580±37MU (p<0.05); and MLC sequence complexity scores were RP: 0.25±0.02 and CMO: 0.35±0.03 (p<0.05). CONCLUSIONS RP plans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planners skill and knowledge.