Koji Konishi

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.

Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer.

OBJECTIVE To investigate the value of endoscopic biopsy in predicting the clinicopathological response and survival in patients with esophageal cancers who received chemoradiotherapy (CRT) alone or CRT followed by surgery. BACKGROUND Endoscopic biopsy examination after CRT for esophageal cancer has been used to confirm the presence of residual tumor before surgery, but there is little or no information on the clinical significance of the results of endoscopic biopsy in neoadjuvant or definitive CRT. METHODS We studied 189 patients who underwent endoscopic biopsy after induction CRT (40 Gy) for esophageal cancer, consisting of 123 patients who received neoadjuvant CRT (40 Gy) followed by surgery and 66 patients who underwent definitive CRT (mostly more than 60 Gy). The correlations between the results of endoscopic biopsy and clinicopathological factors, including response to CRT and survival, were examined. RESULTS For neoadjuvant CRT, endoscopic biopsy findings correlated significantly with pathological tumor regression and lymph node involvement,although the majority of cases with negative biopsy (64%) displayed residual tumor cells in the surgical specimen. The 5-year survival rate was significantly higher in patients with negative biopsy (48.3%) than in those with positive biopsy (21.8%, P = 0.006). For definitive CRT, patients with negative biopsy at the time of 40 Gy showed clinical complete response to CRT (P = 0.002)and had significantly better 3-year survival (57.0%) than those with positive biopsy (22.5%, P = 0.0008). CONCLUSIONS The results of endoscopic biopsy examination after induction CRT can predict the response to CRT and prognosis of patients who receive CRT with and without surgery.

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.

Histopathological effects of preoperative chemoradiotherapy for pancreatic cancer: An analysis for the impact of radiation and gemcitabine doses

BACKGROUND AND PURPOSE Histopathological findings of patients who underwent resection for pancreatic adenocarcinoma (PC) after preoperative chemoradiotherapy (CRT) reportedly showed beneficial effects. The purpose of our study was to evaluate the correlation between histopathological effects (HE) of preoperative CRT and treatment parameters [radiation and gemcitabine (GEM) doses]. MATERIAL AND METHODS HE of CRT were assessed on 158 primary lesions of 157 patients with PC who underwent pancreatic resection after preoperative CRT with GEM between January 2006 and December 2011. The radiation dose delivered to the primary tumor site and surrounding regional nodal areas was 50 Gy until September 2009 followed by the dose escalation of a 10 Gy boost added for delivery with the field-in-field technique to the roots of the celiac and superior mesenteric arteries. Intravenous administration of GEM (1000 /m(2)) was initiated concurrently on days 1, 8, and 15, every 4 weeks and generally repeated for 3 cycles. HE of CRT on the primary tumor were categorized based on the number of tumor cells destroyed. RESULTS The median overall survival time was 74.5 months and 3-year and 5-year survival rates were 64.3% and 54.5%, respectively. Dose-volume parameters of radiation such as D33 with a cut-off value of 51.6 Gy were correlated significantly with HE (p=.0230). Lesions having received GEM>7625 mg/m(2) before surgical resection more frequently showed positive HE (p=.0002). Multivariate logistic regression analysis demonstrated that both D33 and cumulative GEM dose were significant predictors of definite HE (p=.0110 and <.0001, respectively). CONCLUSIONS Our retrospective analysis showed that dose intensity of radiation and GEM is significantly related to HE of preoperative CRT for PC.

Neoadjuvant Gemcitabine-based Accelerated Hyperfractionation Chemoradiotherapy for Patients with Borderline Resectable Pancreatic Adenocarcinoma

OBJECTIVE We report the response to pre-operative gemcitabine-based chemoradiotherapy for pancreatic adenocarcinoma. METHODS Thirty-five consecutive patients with borderline resectable pancreatic adenocarcinoma of UICC Stage II or III with portal vein invasion or tumor abutment of artery received radiotherapy (twice daily fractions of 1.5 Gy, 5 days/week, total dose: 36 Gy; 30 Gy for Phase I Level 1) with weekly intravenous infusions of gemcitabine (400, 600 and 800 mg/m(2)) at Days 1 and 8 for Phase I and 800 mg/m(2) for Phase II. Restaging was repeated after completion of chemoradiotherapy. RESULTS Twenty-six of the 35 (74.3%) patients underwent resection. The dose-limiting toxicities were Grade 4 neutropenia and thrombocytopenia. The recommended regimen was total radiation dose of 36 Gy with gemcitabine 800 mg/m(2). Surgical resection was conducted in 11 of the 15 (73.3%) patients in Phase I study and 15 of the 20 (75.0%) in Phase II. After recommended dose chemoradiotherapy and surgical resection, the median disease-free survival was 17.4 months (5-year survival rate = 14.3%). The median overall survival time and 5-year survival rate were 41.2 months and 28.6%, respectively, for the 21 patients who underwent resection and 10.0 months and 0%, respectively, for those 5 who did not (P = 0.004). CONCLUSION Our pre-operative gemcitabine-based chemoradiotherapy was well tolerated and safe.

Monotherapeutic high-dose-rate brachytherapy for prostate cancer: A dose reduction trial

PURPOSE To report preliminary results of our second regimen with 45.5 Gy/7 fractions aiming to reduce toxicity, compared with our first regimen with 54 Gy/9 fractions, using high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer. MATERIALS AND METHODS From 2005 through 2010, 63 patients with localized prostate cancer were treated with HDR brachytherapy alone in 45.5 Gy/7 fractions for 4 days. Thirty-four patients were considered as intermediate-risk and 29 as high-risk. Thirty-seven patients also received neoadjuvant and/or adjuvant hormonal therapy. Biologically effective dose assuming α/β=1.5 Gy (BED₁.₅) was reduced from 270 Gy to 243 Gy, and BED₃.₀ from 162 Gy to 144 Gy, compared to previous 54 Gy/9 fractions for 5 days. RESULTS Median follow-up time was 42 months (range 13-72). Grade 2 acute toxicities occurred in six (9.5%), late toxicities in five (7.9%) patients, and Grade 3 or higher in none. Grade 2 late gastrointestinal toxicity rate was 1.6%, compared with 7.1% for the 54 Gy regimen. Three-year PSA failure-free rates for intermediate- and high-risk patients were 96% and 90%, which were comparable to 93% and 85% for the 54 Gy regimen. CONCLUSIONS Compared to the 54 Gy/9 fractions regimen, dose-reduced regimen of 45.5 Gy/7 fractions using HDR brachytherapy as monotherapy preliminarily showed an equivalent or lower incidence rate for acute and late toxicities without compromising the excellent PSA failure-free rate. Further studies with more patients and longer follow-up are warranted.

Significance of Tumor Volume Related to Peritumoral Edema in Intracranial Meningioma Treated with Extreme Hypofractionated Stereotactic Radiation Therapy in Three to Five Fractions

BACKGROUND To investigate the treatment results of intracranial meningiomas treated with hypofractionated stereotactic radiation therapy in three to five fractions. METHODS Thirty-one patients (32 lesions) with intracranial meningioma were treated with hypofractionated stereotactic radiation therapy in three to five fractions using CyberKnife. Fifteen lesions were diagnosed as Grade I (World Health Organization classification) by surgical resection and 17 lesions were diagnosed as meningioma based on radiological findings. The median follow-up time was 48 months. The median planning target volume was 6.3 cm(3) (range, 1.4-27.1), and the prescribed dose (D90≤) ranged from 21 to 36 Gy (median, 27.8) administrated in three to five fractions. RESULTS Five-year overall and progression-free survival rate of all 31 patients with intracranial meningioma was 86 and 83%, respectively. Five-year progression-free rate of all 32 lesions was 87%. Six of the 31 patients (19%) developed marked peritumoral edema, three of whom were asymptomatic and three symptomatic, the latter with late adverse effects of more than or equal to Grade 3. The mean planning target volume of the six lesions with marked peritumoral edema was 15.6 cm(3), and for the remaining 26 lesions without marked peritumoral edema was 7.1 cm(3) (P = 0.004). The threshold diameter of 2.56 cm for meningioma was calculated from the planning target volume (11 cm(3)) and was used as marker of developing peritumoral edema (P = 0.003). CONCLUSIONS Tumor volume is a significant indicative factor for peritumoral edema in intracranial meningioma treated with hypofractionated stereotactic radiation therapy in three to five factions.

Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife

The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm3 for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm3 (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted.