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.

Palliative radiotherapy for gastric cancer bleeding: a multi-institutional retrospective study.

BACKGROUND: Palliative radiotherapy for gastric cancer bleeding has been reported to be a safe and effective treatment, but predictive factors for achievement of hemostasis and overall survival have not been established. METHODS: In this retrospective study, 120 courses of palliative radiotherapy for gastric cancer bleeding in 117 patients in 4 institutes in Japan were reviewed with approval of the ethical committee in each institute. The rate of achieving hemostasis was evaluated by 50% or more reduction of red blood cell transfusion before and after the start of radiotherapy, elevation of blood hemoglobin concentration in a period of 4 weeks from the start of radiotherapy or improvement of subjective or objective clinical symptoms in a period of 4 weeks from the start of radiotherapy. Predictive factors for overall survival and achieving hemostasis were investigated with the Cox hazards model. RESULTS: The median overall survival period was 3.7 months. Multivariate analysis showed that absence of metastatic disease, higher biological effective dose, higher serum albumin level, lower blood urea nitrogen level and lower neutrophil-to-lymphocyte ratio (NLR) were associated with longer overall survival. Elevation of hemoglobin concentration in a period of 4 weeks from the start of radiotherapy (mean concentration: 8.2 g/dL vs. 8.9 g/dL, p = 0.006) and decrease in the amount of red cell transfusion from a 4-week period before to a 4-week period after the start of radiotherapy (mean amount: 716 mL vs. 230 mL, p < 0.0001) were observed. The overall rate of achievement of hemostasis was 59.6%. In multivariate analysis, higher biological effective dose was associated with achievement of hemostasis. Grade 2 or higher acute adverse effects related to radiotherapy were observed in 17.5% of cases in 120 treatment courses. Six cases (5.0%) had grade 3 or 4 adverse effects including gastric penetration in 1 patient and anorexia requiring total parental nutrition in 3 patients. No grade 5 adverse effects were observed. CONCLUSIONS: Palliative radiotherapy for gastric cancer bleeding seems to be an effective and safe treatment strategy. Higher treatment dose was associated with longer overall survival and a hemostatic effect. Some hematological parameters may predict overall survival, and they would be helpful for deciding the treatment strategy.

Recurrence of Lymph Node Micrometastases After Radiotherapy for Head and Neck Carcinoma: A Propensity Score-matched Study.

Background: The standard irradiation dose to the elective lymph node area (ELNA) in locally patients with advanced head and neck squamous cell carcinoma (LA-HNSCC) to control lymph node micrometastases (LN-MM) has not changed since it was empirically determined in the 1950s. We investigated the optimal irradiation dose for controlling LN-MM in ELNAs. Patients and Methods: The pattern of recurrence of LA-HNSCC was retrospectively evaluated in patients who underwent concurrent chemoradiotherapy with cisplatin or radiation therapy alone. Results: In total, 162 patients were enrolled. The median observation period was 34 months. No recurrence was found in ELNAs. After propensity score matching, a cisplatin dose of ≥200 mg/m 2 yielded a significantly higher overall survival rate (p≤0.001) and locoregional control rate (p=0.034) than did a dose of <100 mg/m 2 . Conclusion: CCRT with a cisplatin dose of ≥200 mg/m 2 can reduce the irradiation dose to 40-44 Gy at 2 Gy per fraction to control LN-MM.

Quantitative analysis of intra-fractional variation in CT-based image guided brachytherapy for cervical cancer patients.

We quantified intra-fractional dose variation and organ movement during CT-based 3D-image guided brachytherapy (3D-IGBT) in cervical cancer patients. Fifteen patients who underwent CT-based 3D-IGBT were studied. For all patients, pre-delivery CT for treatment planning after applicator insertion and post-delivery CT after dose delivery without changing the applicator position were acquired. Pre- and post-delivery CT were rigidly fused by matching the inserted applicator and planned dose on pre-delivery CT (pre-delivery dose) was mapped on post-delivery CT (post-delivery dose). D2, D1, and D0.1 cm3 of the rectum and bladder were compared between pre- and post-delivery doses with contours on each CT image. Organ movement and deformation was evaluated using deformation vector fields calculated by deformable image registration between pre- and post-delivery CT. We also evaluated dose variation and DVF between with and without a catheter to control filling. Differences in all DVH parameters were <±3% in physical dose and ± 5% in EQD2. However, a > 15% dose difference was found in 13.8% of the fractions in rectum D2 cm3 and in 11.1% of those in bladder D2 cm3. The mean value of DVF for bladder was larger than that of rectum, especially for the superior-inferior (S-I) direction. Insertion catheters in bladder reduced mean dose and DVF variation compared with that of without catheters. In fraction groups with large dose increasing, DVF in the S-I direction was significantly larger than that of other fraction groups. Our results indicated that preparation is needed to reduce changes in the S-I direction affect dose variation.

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.

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.

Evaluation of rectum and bladder dose accumulation from external beam radiotherapy and brachytherapy for cervical cancer using two different deformable image registration techniques.

We evaluated dose-volume histogram (DVH) parameters based on deformable image registration (DIR) between brachytherapy (BT) and external beam radiotherapy (EBRT) that included a center-shielded (CS) plan. Eleven cervical cancer patients were treated with BT, and their pelvic and CS EBRT were studied. Planning CT images for EBRT and BT (except for the first BT, used as the reference image) were deformed with DIR to reference image. We used two DIR parameter settings: intensity-based and hybrid. Mean Dice similarity coefficients (DSCs) comparing EBRT with the reference for the uterus, rectum and bladder were 0.81, 0.77 and 0.83, respectively, for hybrid DIR and 0.47, 0.37 and 0.42, respectively, for intensity-based DIR (P < 0.05). D1 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 75.1, 81.2 and 78.2 Gy, respectively, for the rectum, whereas they were 93.5, 92.3 and 94.3 Gy, respectively, for the bladder. D2 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 70.1, 74.0 and 71.4 Gy, respectively, for the rectum, whereas they were 85.4, 82.8 and 85.4 Gy, respectively, for the bladder. Overall, hybrid DIR obtained higher DSCs than intensity-based DIR, and there were moderate differences in DVH parameters between the two DIR methods, although the results varied among patients. DIR is only experimental, and extra care should be taken when comparing DIR-based dose values with dose-effect curves established using DVH addition. Also, a true evaluation of DIR-based dose accumulation would require ground truth data (e.g. measurement with physical phantom).

Evaluation of deformable image registration between external beam radiotherapy and HDR brachytherapy for cervical cancer with a 3D-printed deformable pelvis phantom.

PURPOSE: In this study, we developed a 3D-printed deformable pelvis phantom for evaluating spatial DIR accuracy. We then evaluated the spatial DIR accuracies of various DIR settings for cervical cancer. METHODS: A deformable female pelvis phantom was created based on patient CT data using 3D printing. To create the deformable uterus phantom, we first 3D printed both a model of uterus and a model of the internal cavities of the vagina and uterus. We then made a mold using the 3D printed uterus phantom. Finally, urethane was poured into the mold with the model of the internal cavities in place, creating the deformable uterus phantom with a cavity into which an applicator could be inserted. To create the deformable bladder phantom, we first 3D printed models of the bladder and of the same bladder scaled down by 2 mm. We then made a mold using the larger bladder model. Finally, silicone was poured into the mold with the smaller bladder model in place to create the deformable bladder phantom with a wall thickness of 2 mm. To emulate the anatomical bladder, water was poured into the created bladder. We acquired phantom image without applicator for EBRT. Then, we inserted the applicator into the phantom to simulate BT. In this situation, we scanned the phantom again to obtain the phantom image for BT. We performed DIR using the two phantom images in two cases: Case A, with full bladder (170 ml) in both EBRT and BT images; and Case B with full bladder in the BT image and half-full bladder (100 ml) in the EBRT image. DIR was evaluated using Dice similarity coefficients (DSCs) and 31 landmarks for the uterus and 25 landmarks for the bladder. A hybrid intensity and structure DIR algorithm implemented in RayStation with four DIR settings was evaluated. RESULTS: On visual inspection, reasonable agreement in shape of the uterus between the phantom and patient CT images was observed for both EBRT and BT, although some regional disagreements in shape of the bladder and rectum were apparent. The created phantom could reproduce the actual patient's uterus deformation by the applicator. For both Case A and B, large variation was seen in landmark error among the four DIR parameters. In addition, although DSCs were comparable, moderate differences in landmark error existed between the two different DIR parameters selected from the four DIR parameters (i.e., DSC = 0.96, landmark error = 13.2 ± 5.7 mm vs. DSC = 0.97, landmark error = 9.7 ± 4.0 mm). This result suggests that landmark error evaluation might thus be more effective than DSC for evaluating DIR accuracy. CONCLUSIONS: Our developed phantom enabled the evaluation of spatial DIR accuracy for the female pelvic region for the first time. Although the DSCs are high, the spatial errors can still be significant and our developed phantom facilitates their quantification. Our results showed that optimization is needed to identify suitable DIR settings. For determining suitable DIR settings, our method of evaluating spatial DIR accuracy using the 3D-printed phantom may prove helpful.

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.

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study.

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2-135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.

Formula corrected maximal standardized uptake value in FDG-PET for partial volume effect and motion artifact is not a prognostic factor in stage I non-small cell lung cancer treated with stereotactic body radiotherapy.

OBJECTIVE: It is known that the partial volume effect and respiratory motion blur affect quantitative parameters such as the maximum standardized uptake value (SUVmax) in FDG-PET, especially in small lesions. The purpose of this study was to assess the prognostic value of corrected SUVmax, which was corrected SUVmax for the partial volume effect and respiratory motion blur, in patients with stage I non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT). METHODS: Fifty-one patients who were treated with SBRT between 2005 and 2011 in our institute were enrolled. The median tumor diameter was 2.2 cm (range 0.9-3.9 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 of irradiation fields. Each raw SUVmax was corrected using the recently proposed formula, and the correlations of raw SUVmax and corrected SUVmax with local control rate (LCR) were analyzed retrospectively. RESULTS: Median raw SUVmax before SBRT was 6.4 (range 0.6-22.8). Median corrected SUVmax was 8.0 (range 0.8-22.8), which was significantly increased (p < 0.01). The median follow-up period for survivors was 45.3 months (range 18.5-82.0 months). The 3-year LCR and overall survival rates were 81.8 and 65.2 %, respectively. In univariate analysis, raw SUVmax [per 1 increase; p = 0.02, hazard ratio (HR) 1.20, 95 % confidence interval (CI) 1.03-1.42] was significantly correlated with LCR, but corrected SUVmax did not show a significant correlation with LCR (per 1 increase; p = 0.15, HR 1.07, 95 % CI 0.96-1.19). Other factors significantly correlated with LCR were diagnosis (pathological diagnosis vs. clinical diagnosis; p = 0.04, HR 6.17, 95 % CI 1.08-116) and tumor diameter (per 1 mm increase; p < 0.01, HR 1.33, 95 % CI 1.15-1.61). CONCLUSIONS: Tumor diameter was the most significant predictor of LCR after SBRT. Correction for the partial volume effect and respiratory motion blur may weaken the prognostic value of SUVmax.

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.

Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study.

BACKGROUND: To evaluate the dose-effect relations for myocardial metabolic disorders after mediastinal radiotherapy (RT) by performing iodine-123 ß-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. METHODS: Between 2011 and 2012, we performed I-123 BMIPP scintigraphy for patients with esophageal cancer before and six months after curative mediastinal RT. Single photon emission computed tomography (SPECT) images of pre-RT and post-RT were registered into RT dose distributions. The myocardium was contoured, and the regional RT dose was calculated. Normalization is required to compare pre- and post-RT SPECT images because the uptake pattern is changed due to the breathing level. Normalization was applied on the mean of SPECT counts in regions of the myocardium receiving less than 5 Gy. Relative values in each dose region (interval of 5 Gy) were calculated on the basis of this normalization for each patient. The reduction in the percent of relative values was calculated. RESULTS: Five patients were enrolled in this study. None of the patients had a past history of cardiac disease. The left ventricle was partially involved in RT fields in all patients. The patients received RT with median total doses of 60-66 Gy for the primary tumor and metastatic lymph nodes. Concomitant chemotherapy consisting of cisplatin or nedaplatin and 5-fluorouracil with RT was performed in 4 patients. All patients had reduced uptake corresponding to RT fields. Dose-effect relations for reduced uptake tended to be observed at 6 months after RT with mean decreases of 8.96% in regions at 10-15 Gy, 12.6% in regions at 20-25 Gy, 15.6% in regions at 30-35 Gy, 19.0% in regions at 40-45 Gy and 16.0% in regions at 50-55 Gy. CONCLUSIONS: Dose-effect relations for myocardial metabolic disorders tended to be observed. We may need to make an effort to reduce high-dose mediastinal RT to the myocardium in RT planning.

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.

Evaluation of various deformable image registration algorithms for thoracic images.

We evaluated the accuracy of one commercially available and three publicly available deformable image registration (DIR) algorithms for thoracic four-dimensional (4D) computed tomography (CT) images. Five patients with esophagus cancer were studied. Datasets of the five patients were provided by DIR-lab (dir-lab.com) and consisted of thoracic 4D CT images and a coordinate list of anatomical landmarks that had been manually identified. Expert landmark correspondence was used for evaluating DIR spatial accuracy. First, the manually measured displacement vector field (mDVF) was obtained from the coordinate list of anatomical landmarks. Then the automatically calculated displacement vector field (aDVF) was calculated by using the following four DIR algorithms: B-spine implemented in Velocity AI (Velocity Medical, Atlanta, GA, USA), free-form deformation (FFD), Horn-Schunk optical flow (OF) and Demons in DIRART of MATLAB software. Registration error is defined as the difference between mDVF and aDVF. The mean 3D registration errors were 2.7 ± 0.8 mm for B-spline, 3.6 ± 1.0 mm for FFD, 2.4 ± 0.9 mm for OF and 2.4 ± 1.2 mm for Demons. The results showed that reasonable accuracy was achieved in B-spline, OF and Demons, and that these algorithms have the potential to be used for 4D dose calculation, automatic image segmentation and 4D CT ventilation imaging in patients with thoracic cancer. However, for all algorithms, the accuracy might be improved by using the optimized parameter setting. Furthermore, for B-spline in Velocity AI, the 3D registration error was small with displacements of less than ∼10 mm, indicating that this software may be useful in this range of displacements.