Clinical significance of completion of radium-223 treatment and acute adverse events in patients with metastatic castration-resistant prostate cancer.

Objectives: In the treatment of castration-resistant prostate cancer (CRPC) with bone metastases, radium-223 dichloride (Ra-223) is the only bone-targeted drug that shows survival benefits. Completing six courses of Ra-223 treatment is thought to be associated with better patient survival, but this treatment has a relatively high rate of acute adverse events. Methods: This retrospective study included 85 patients from 12 institutions in Japan to investigate the clinical significance of the completion of Ra-223 treatment and acute adverse events in CRPC patients. Results: Six courses of Ra-223 treatment were completed in 65.9% of the patients. Grade 3 or higher acute adverse events were observed in 27.1% of patients. The prostate specific antigen and alkaline phosphatase declined at 26.9% and 87.9%, respectively. The overall survival rates at 12 and 24 months were 80.7% and 63.2%, respectively. Both completion of six courses of Ra-223 treatment and absence of grade 3 or higher acute adverse events were associated with longer overall survival. In univariate analysis, factors related to the history of treatment (five or more hormone therapy agents and cytotoxic chemotherapy) and hematological parameters (Prostate specific antigen (PSA) doubling time, alkaline phosphatase, hemoglobin, albumin, and serum calcium) were associated with completing six courses of Ra-223 treatment without experiencing grade 3 or higher acute adverse events. Multivariate analysis showed that a history of chemotherapy, PSA doubling time, hemoglobin, and serum calcium showed statistical significance. We built a predictive score by these four factors. Patients with lower scores showed higher rates of treatment success (p<0.001) and longer overall survival (p<0.001) with statistical significance. Conclusions: Accomplishing six courses of Ra-223 treatment without grade 3 or higher acute adverse events was a prognostic factor in patients with mCRPC treated with Ra-223. We built a predictive score of treatment success and need future external validation.

Radiation Therapy for Advanced Mucinous Carcinoma of the Breast With a Malignant Wound: A Case Report.

Patients with breast cancer who refuse standard treatment often suffer from malignant wounds due to the growth of local tumors. However, treatment strategies for patients with unresectable locally advanced breast cancer who refuse standard treatment remain unclear. Usually, such cases are treated with palliative irradiation and do not achieve local control by irradiation alone. This is the first case report discussing the role of high-dose local irradiation and the treatment course for a patient with a massive breast tumor (mucinous adenocarcinoma) who refused standard treatment. A 44-year-old female was diagnosed with mucinous carcinoma of the breast in the right breast (cT1N0M0, cStage I). She refused standard treatment for six years. She visited the emergency department because of acute bleeding from the right breast with malignant wounds. Macroscopically, the tumor in the right breast measured over 20 cm in diameter. The tumor was exudative, exhibited ulceration and slight bleeding, and emitted an odor. Imaging findings showed multiple lymph nodes and bone metastases, and the final diagnosis was stage IV breast cancer (cT4bN1M1). Although the surgeon recommended chemotherapy for breast cancer, the patient refused chemotherapy or other therapy due to concerns regarding treatment-related complications. Considering the symptoms of advanced breast cancer with malignant wounds, she finally agreed to receive radiation therapy (RT). We performed RT at 70 Gy in 35 fractions over seven weeks. The tumor-associated symptoms disappeared after RT. Three months after RT, the tumor had almost disappeared. We administered luteinizing hormone-releasing hormone agonists after RT. Two years after RT, she died due to multiple liver metastases and ascites; however, there was no disease progression in the right breast. High-dose RT for locally advanced mucinous carcinoma of the breast with malignant wounds is considered an effective therapeutic option.

Clinical experience of pelvic radiotherapy or chemoradiotherapy for postoperative uterine cervical cancer using intensity-modulated radiation therapy.

The purpose of this study was to reveal treatment outcomes and toxicity after pelvic intensity-modulated radiotherapy (IMRT) for postoperative uterine cervical cancer of Japanese patients. Consecutive patients who were treated with pelvic IMRT for postoperative cervical cancer in our institute were retrospectively analyzed. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator, and log-rank tests were used to compare differences. From the database, 62 patients were identified. The pathology was squamous cell carcinoma in 44 patients and other pathology in 18 patients. Of the 62 patients, 35 had high-risk prognostic factors and 27 patients had intermediate-risk prognostic factors. The prescribed radiation doses were 50 Gy in 25 fractions for 58 patients and 50.4 Gy in 28 fractions for 4 patients. One patient received a vaginal cuff boost. Chemotherapy was administered in 36 patients. During the median follow-up period of 50.9 months, there was no locoregional failure. Six patients in the high-risk group relapsed, but none of the patients in the intermediate-risk group relapsed (P = 0.02). The 3-year OS and RFS rates were 98.2% and 90.9%, respectively. Significant factors related to RFS were squamous cell carcinoma pathology (P = 0.02), pathological T stage (P = 0.04), surgical margin status (P < 0.01) and multiple lymph nodes metastases (P < 0.01). Grade 3 or more toxicity occurred in 6 patients. Four patients had obstruction of the intestine, and 2 patients had stenosis of the urinary tract. In clinical practice, the use of pelvic IMRT for postoperative cervical cancer of Japanese patients showed a low rate of toxicity without decreasing the efficacy.

Impact of change in serum albumin level during and after chemoradiotherapy in patients with locally advanced esophageal cancer.

BACKGROUND: In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome. METHODS: One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed. RESULTS: The median observation period for patients who survived was 57.2 months, and the 5-year overall survival rate was 35.6% (95% CI 34.2-36.9%). In multivariate analyses, baseline ALB (≥ 3.6 g/dL), higher ΔALB (≥ + 0.3 g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively). CONCLUSIONS: Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.

Oesophageal squamous cell carcinoma: histogram-derived ADC parameters are not predictive of tumour response to chemoradiotherapy.

OBJECTIVES: To evaluate correlations between tumour response to definitive chemoradiotherapy (CRT) in oesophageal squamous cell carcinoma (SCC) and histogram-derived apparent diffusion coefficient (ADC) parameters on diffusion-weighted MR images. METHODS: Forty patients with clinical T3-4 oesophageal SCC underwent concurrent CRT. MR examination at 3 T was performed 1-3 days prior to CRT. Readout-segmented echo-planar diffusion imaging was used to acquire ADC maps. Pre- and post-treatment CT examinations were performed. Histogram parameters (mean, 10th, 25th, 50th, 75th, 90th percentiles, skewness and kurtosis) of the ADC values were compared with post-treatment disease status based on RECIST and the tumour regression ratio. RESULTS: None of the ADC parameters showed significant correlation with post-treatment status (range of Spearman's ρ values - 0.19 to 0.14, range of p values 0.22-0.47) or tumour regression ratio (range of Spearman's ρ values - 0.045 to 0.18, range of p values 0.26-0.96). Neither progression-free survival (PFS) (p = 0.17) nor overall survival (OS) (p = 0.15) was significantly different between the two groups corresponding to the lower (< median) and upper arms (≥ median) of the mean ADC values. CONCLUSIONS: Histogram-derived pretreatment ADC parameters were not predictive imaging biomarkers for tumour response to CRT in patients with oesophageal SCC. KEY POINTS: • Apparent diffusion coefficient (ADC) values are derived from diffusion-weighted MR imaging. • High-resolution diffusion-weighted images are generated by readout-segmented echo-planar diffusion imaging. • Readout-segmented echo-planar diffusion-weighted imaging enabled evaluation of ADC parameters. • Pretreatment ADC parameters do not predict chemoradiotherapy response in patients with oesophageal carcinoma.

Prognostic Value of Radiation Pneumonitis After Stereotactic Body Radiotherapy: Effect of Pulmonary Emphysema Quantitated Using CT Images.

BACKGROUND: The aim of this study was to determine the prognostic factors of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: A total of 50 patients (36 male and 14 female) were treated with SBRT for 42 primary lung cancers and 8 metastatic lung cancers. SBRT was performed with 48 Gy in 4 fractions to the isocenter or with 40 Gy in 4 fractions covering 95% of the planning target volume. Percentage of low attenuation area (%LAA) was defined as percentage of the lung area with attenuation of -860 Hounsfield units (HU) or lower (%LAA-860) or of -960 HU or lower (%LAA-960). The dosimetric parameter of V20 Gy, which means percentage volume of the lung receiving 20 Gy or more, was recalculated. RP was assessed using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up period was 39.0 months (range, 7.2-94.5 months). RP of Grade 0, Grade 1, and Grade 2 to 3 was diagnosed in 11, 29, and 10 patients, respectively. Multivariate analyses (MVA) for Grade 1 showed that higher %LAA-860 and higher %LAA-960 were significantly associated with a lower rate of Grade 1 RP. MVA for Grade 2 to 3 showed that lower Brinkman index and lower lung V20 Gy were significantly associated with a lower rate of Grade 2 to 3 RP, and, in contrast, %LAA-860 and %LAA-960 had no association with Grade 2 to 3 RP. CONCLUSION: This result suggests that high %LAA is associated with radiological changes (Grade 1) but that %LAA has no correlation with Grade 2 to 3 RP because symptomatic RP might also be affected by other factors.

Whole-body total lesion glycolysis is an independent predictor in patients with esophageal cancer treated with definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: To determine whether pretreatment whole-body total lesion glycolysis (TLGWB) and metabolic tumor volume (MTVWB) are associated with outcomes in patients with esophageal cancer treated with definitive chemoradiotherapy (dCRT). MATERIALS AND METHODS: Ninety patients with stage II or III thoracic esophageal cancer who underwent FDG-PET/CT within 45 days before dCRT between 2005 and 2013 were reviewed. MTV and TLG of the primary lesion (MTVpri and TLGpri) and the sum of MTV and TLG for all lesions (MTVWB and TLGWB) were calculated. Predictors were analyzed using the Cox proportional hazards model. RESULTS: The median follow-up period was 27.7 months. In multivariate analysis, MTVWB > median was an unfavorable predictor for OS (p = 0.027, hazard ratio [HR]: 2.15), LC (p = 0.039, HR: 1.98) and PFS (p = 0.041, HR: 1.96). TLGWB > median was an unfavorable predictor for OS (p = 0.019, HR: 2.26), LC (p = 0.015, HR: 2.36) and PFS (p = 0.014, HR: 2.33). SUVmax was not a predictor, and the HR of TLGWB was higher than that of MTVWB for OS, LC and PFS in multivariate analysis. CONCLUSION: TLGWB and MTVWB are independent predictors in patients with esophageal cancer.

Elective nodal irradiation is not necessary in chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer.

PURPOSE: The purposes of the present study were to evaluate prognostic factors for patients with postoperative loco-regional recurrent esophageal cancer treated with chemoradiotherapy by multivariate analysis and to determine which irradiation is better, involved field irradiation or elective nodal irradiation, by matched-pair analysis. METHODS: We reviewed records for 80 patients with postoperative loco-regional recurrent esophageal cancer treated by chemoradiotherapy between 2000 and 2014. The median follow-up period was 62.0 months. Thirty-one cases were treated with elective nodal irradiation and were randomly matched by risk factors to 49 cases treated with involved field irradiation (1:1). RESULTS: Fifty-one patients had disease recurrence again, and irradiated-field failure was observed in 26 patients. The 5-year overall survival rate was 30.5% with a median survival period of 26.5 months. Grade 3 or higher late toxicity was observed in only one patient. In multivariate analysis, short disease-free interval and anastomotic recurrence were statistically significant unfavorable prognostic factors for overall survival (hazard ratios: 2.1 and 2.5, respectively). Matched-pair analysis including disease-free interval, pattern of recurrence and number of recurrent regions revealed that overall survival rate and irradiated-field control rate in patients treated with involved field irradiation were significantly better than those in patients treated with elective nodal irradiation (P = 0.016 and P = 0.014, respectively). CONCLUSIONS: Short disease-free interval and anastomotic recurrence are unfavorable factors and elective nodal irradiation is not necessary in chemoradiotherapy for patients with postoperative loco-regional recurrent esophageal cancer.

Definitive Chemoradiotherapy for Advanced Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer with a poor prognosis. We herein report on a case of pulmonary sarcomatoid carcinoma that was treated successfully by concurrent chemoradiotherapy. A 65-year-old man was diagnosed to have pulmonary pleomorphic carcinoma (clinical T4N2M0 stage IIIB). He received concurrent chemoradiotherapy (60 Gy of radiotherapy in 30 fractionations and two courses of chemotherapy with carboplatin and paclitaxel). After chemoradiotherapy, a significant reduction of the tumor size was observed. Two courses of adjuvant chemotherapy were performed. He is currently alive at 15 months after the first treatment without any recurrence or metastasis.

Metabolic tumor volume on FDG-PET/CT is a possible prognostic factor for Stage I lung cancer patients treated with stereotactic body radiation therapy: a retrospective clinical study.

The aim of this study was to determine whether metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are associated with outcomes in Stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT). Thirty-eight patients underwent [18F] fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) within 60 days before SBRT at our institution between January 2001 and December 2011. The maximum standardized uptake value (SUVmax), MTV2, MTV4, MTV6, TLG40%, TLG50% and TLG60% were calculated. Prognostic factors for overall survival (OS) and local control (LC) were analyzed using Cox's proportional hazards model, and survival curves were calculated using the Kaplan-Meier method. Receiver operating characteristics (ROC) curves of PET parameters for OS and LC were calculated. The median follow-up period for survivors was 37.7 months. Three-year OS and LC rates were 56.4% and 70.5%, respectively, and 5-year OS and LC rates were 36.8% and 70.5%, respectively. In univariate analyses, tumor diameter (P = 0.019), single dose ≥10 Gy (P = 0.017), MTV2 (P = 0.030) and MTV4 (P = 0.048) were significant predictors for OS. Tumor diameter (P < 0.001), single dose ≥10 Gy (P = 0.007), SUVmax (P = 0.035), MTV2 (P < 0.001), MTV4 (P = 0.003), MTV6 (P = 0.017), TLG40% (P < 0.001), TLG50% (P = 0.001) and TLG60% (P = 0.003) were significant predictors for LC. SUVmax was not a significant predictor for OS. We made the ROC curves at PET parameters, and the largest area under the curve value for OS was MTV2 and for LC was TLG40% Tumor diameter, single dose ≥10 Gy, MTV2 and MTV4 are prognostic factors for OS and LC rates and MTV2 is a better prognostic factor for OS than other PET parameters.

Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma.

BACKGROUND: Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC). METHODS: A total of 14 patients (11 males, 3 females) who received SBRT for RCC at Tohoku University Hospital between April 2010 and February 2014 were analyzed. The median serum creatinine level was 1.1 mg/dl and two patients had a single kidney. Nine patients were implanted with fiducial markers. The median tumor diameter was 30 mm. SBRT was delivered at 70 Gy in 10 fractions for 7 tumors, at 60 Gy in 10 fractions for 2 tumors, and at 50 Gy in 10 fractions for 5 tumors with 6 and/or 15 MV X-ray using 5 to 8 multi-static beams. Renal atrophy was assessed using post-SBRT CT images after 12-24 months intervals. Correlations were examined by Spearman rank correlation analysis. Differences between two groups were evaluated by the Mann-Whitney test, and pairwise comparisons were made by the Wilcoxon signed-rank test. RESULTS: The median tumor volume shrunk from 14.8 cc to 10.6 cc (p = 0.12), and the median irradiated kidney volume changed from 160.4 cc to 137.1 cc (p < .01). The median peak creatinine level was 1.6 mg/dl after treatment (p < .01). Percentage volumes of the irradiated kidney receiving at least 10 Gy (V10, p = 0.03), V20 (p < .01), V30(p < .01), V40 (p = 0.01), mean irradiated kidney dose (p < .01), and magnitude of overlap between PTV and kidney volume (p = 0.03) were significantly correlated with post-treatment irradiated kidney volume in percent, and V20-V30 had strong correlation (r < -0.70, p < .01). Patients with implanted fiducial markers showed a significantly lower ratio of renal atrophy (p = 0.02). CONCLUSIONS: Significant renal atrophic change was observed. Dose distribution of SBRT at 20-30 Gy had a strong correlation with renal atrophy when irradiation was performed in 10 fractions.

Chemoradiotherapy for T4 and/or M1 lymph node esophageal cancer: experience since 2000 at a high-volume center in Japan.

PURPOSE: To review data for patients with stage T4 and/or M1 lymph node (lym) esophageal cancer who have been treated with definitive chemoradiotherapy since 2000 at a high-volume center in Japan. PATIENTS AND METHODS: We retrospectively reviewed all patients with T4 and/or M1 lym esophageal cancer who were treated by definitive chemoradiotherapy between 2000 and 2010. The eligibility criteria included (1) histopathologically proven esophageal cancer, (2) T4 and/or M1 lym (UICC 2002), (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with ≥ 50 Gy, and (6) having no other active malignant tumor during treatment. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0). RESULTS: Data from 128 patients (70 with clinical stage III, 58 with clinical stage IV) were used for analysis in this study. The median observation period for survivors was 46.3 months. The 2- and 4-year overall survival rates were 32.8 and 24.4 %, respectively. The overall survival of patients without M1 lym was significantly better than that of patients with Ml lym (4-year, 32.6 vs 11.7 %, log-rank test; p = 0.04). Overall survival in more recent patients (2006-2010) did not show improvement when compared with past patients (2000-2005). Eight patients had late toxicities of grade ≥3. CONCLUSIONS: T4 patients without M1 lym showed a relatively good 4-year survival rate of approximately 33 %; however, the results did not show significant improvement after 2000.

Long-term results of chemoradiotherapy for stage II-III thoracic esophageal cancer in a single institution after 2000 -with a focus on comparison of three protocols.

BACKGROUND: To evaluate the long-term results of chemoradiotherapy (CRT) for stage II-III thoracic esophageal cancer mainly by comparing results of three protocols retrospectively. METHODS: Between 2000 and 2012, 298 patients with stage II-III thoracic esophageal cancer underwent CRT. Patients in Group A received two cycles of cisplatin (CDDP) at 70 mg/m(2) (day 1 and 29) and 5-fluorouracil (5-FU) at 700 mg/m(2)/24 h (day 1-4 and 29-32) with radiotherapy (RT) of 60 Gy without a break. Patients in Group B received two cycles of CDDP at 40 mg/m(2) (day 1, 8, 36 and 43) and 5-FU at 400 mg/m(2)/24 h (day 1-5, 8-12, 36-40 and 43-47) with RT of 60 Gy with a 2-week break. Patients in Group C received two cycles of nedaplatin at 70 mg/m(2) (day 1 and 29) and 5-FU at 500 mg/m(2)/24 h (day 1-4 and 29-32) with RT of 60-70 Gy without a break. Differences in prognostic factors between the groups were analyzed by univariate and multivariate analyses. RESULTS: The 5-year overall survival rates for patients in Group A, Group B and Group C were 52.4, 45.2 and 37.2%, respectively. The 5-year overall survival rates for patients in Stage II, Stage III (non-T4) and Stage III (T4) were 64.0, 40.1 and 22.5%, respectively. The 5-year overall survival rates for patients who received 1 cycle and 2 cycles of concomitant chemotherapy were 27.9 and 46.0%, respectively. In univariate analysis, stage, performance status and number of concomitant chemotherapy cycles were significant prognostic factors (p < 0.001, p = 0.008 and p < 0.001, respectively). In multivariate analysis, stage, protocol and number of concomitant chemotherapy cycles were significant factors (p < 0.001, p = 0.043 and p < 0.001, respectively). CONCLUSIONS: The protocol used in Group A may be an effective protocol of CRT for esophageal cancer. It may be important to complete the scheduled concomitant chemotherapy with the appropriate intensity of CRT.

Impact of tumor attachment to the pleura measured by a pretreatment CT image on outcome of stage I NSCLC treated with stereotactic body radiotherapy.

BACKGROUND: Pleural invasion status is known to be a predictor of survival after pulmonary resection for non-small cell lung cancer. Our goal was to determine whether the length of tumor attachment to the pleura on a pretreatment CT image has prognostic value as an alternative to pleural invasion status for stage I non-small cell lung cancer treated with stereotactic body radiotherapy (SBRT). METHODS: A total of 90 tumors in 87 patients (males: 68, females: 19) who received SBRT between March 2005 and September 2011 in our institution were reviewed. The median age of the patients was 78 years (range, 48-90 years). The median tumor diameter was 2.2 cm (range, 0.9-4.2 cm). The prescribed dose was typically 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions to the isocenter with 6 MV X-ray using 4 non-coplanar and 3 coplanar static beams. The lengths of attachment were measured using pretreatment CT images at the lung window. Cumulative incidence rates were calculated using Kaplan-Meier curves, and univariate and multivariate analyses for in-field tumor control, locoregional control (LRC), freedom from distant metastasis and freedom from progression (FFP) were performed using a Cox proportional hazards model. RESULTS: Of the 90 tumors, 42 tumors were attached to the pleura (median, 14.7 mm; range, 4.3-36.0 mm), 21 tumors had pleural indentation and 27 tumors had no attachment. The median follow-up period for survivors was 46.1 months. The 3-year in-field control, LRC, FFP and overall survival rates were 91.2%, 75.3%, 63.8% and 68.6%, respectively. SBRT dose and tumor diameter were independently significant predictors of in-field control (p = 0.02 and p = 0.04, respectively). Broad attachment to the pleura, the length being more than 14.7 mm, was a negative independent predictor of LRC and FFP (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Pleural attachment status on a pretreatment CT image might be an important predictor of LRC and FFP.

Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors.

BACKGROUND: The goal of this study was to determine the prognostic factors associated with an improved overall outcome after stereotactic body radiotherapy (SBRT) for primary lung cancer and metastatic lung tumors. METHODS: A total of 229 lung tumors in 201 patients were included in the study. SBRT of 45 Gy in 3 fractions, 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions was typically used to treat 172 primary lungs cancer in 164 patients and 57 metastatic lung tumors in 37 patients between January 2001 and December 2011. Prognostic factors for local control (LC) and overall survival (OS) were analyzed using a Cox proportional hazards model. RESULTS: The median biologically effective dose was 105.6 Gy based on alpha/beta = 10 (BED10). The median follow-up period was 41.9 months. The 3-year LC and OS rates were 72.5% and 60.9%, and the 5-year LC and OS rates were 67.8% and 38.1%, respectively. Radiation pneumonitis of grades 2, 3 and 5 occurred in 22 patients, 6 patients and 1 patient, respectively. Multivariate analyses revealed that tumor origin (primary lung cancer or metastatic lung tumor, p < 0.001), tumor diameter (p = 0.005), BED10 (p = 0.029) and date of treatment (p = 0.011) were significant independent predictors for LC and that gender (p = 0.012), tumor origin (p = 0.001) and tumor diameter (p < 0.001) were significant independent predictors for OS. CONCLUSIONS: SBRT resulted in good LC and tolerable treatment-related toxicities. Tumor origin and tumor diameter are significant independent predictors for both overall survival and local control.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan.

BACKGROUND: Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer. METHODS: In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2-88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. RESULTS: The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥ 8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2-3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed. CONCLUSIONS: These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.