Ten-year outcomes of whole-pelvic intensity-modulated radiation therapy for prostate cancer with regional lymph node metastasis.

BACKGROUND: Management of pelvic node-positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole-pelvic (WP) simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). METHODS: A total of 67 consecutive patients with cT1c-4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Neoadjuvant ADT (median: 8.3 months) was administered in all cases. WP SIB-IMRT was designed to simultaneously deliver 78, 66.3, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7 months) was administered in 66 patients. RESULTS: The median follow-up period was 81.6 months (range: 30.5-160.7). Biochemical relapse-free, overall, and prostate cancer-specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco-regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate-specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer-specific survival and progression of castration resistance. The 10-year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. CONCLUSIONS: WP SIB-IMRT can be safely administered to patients with pelvic node-positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.

Long-term safety of high-dose whole pelvic IMRT for high-risk localized prostate cancer through 10-year follow-up.

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and safety of whole pelvic intensity-modulated radiation therapy with a simultaneous-integrated boost (WP-SIB-IMRT) for locally advanced prostate cancer (LAPCa). METHODS: All patients with cT3-4N0M0 prostate cancer treated with WP-SIB-IMRT between February 2006 and September 2009 at our institution were analyzed retrospectively. The prescribed dose was 78 Gy to the prostate and 58.5 Gy to the prophylactic pelvic lymph nodal area in 39 fractions delivered using the simultaneous-integrated boost technique. All patients received short-term neoadjuvant androgen-deprivation therapy alone (median 8.3 months). Propensity-score matching (PSM) analysis was performed to evaluate the additional benefit of prophylactic whole pelvic radiation therapy (WPRT), using the cohort of 203 LAPCa patients treated with prostate-only IMRT (PO-IMRT). RESULTS: In total, 47 consecutive patients were analyzed. The median estimated risk of pelvic lymph node involvement was 57.5%. The median follow-up period was 10.5 years. The 10 year prostate cancer-specific survival and biochemical failure (BF) rates were 92.2 and 54.8%, respectively. The 10 year cumulative incidence rates of ≥ grade 2 late genitourinary and gastrointestinal toxicities were 21.6 and 17.2%, respectively. From a total of 250 patients, PSM analysis identified 76 patients with similar characteristics, and no significant difference in BF rates was observed between WP-SIB-IMRT and PO-IMRT cohorts (p = 0.261). CONCLUSIONS: WP-SIB-IMRT for LAPCa was safe over long-term observation, although no clear benefit of WPRT was observed among our small and highly selected cohort. Regarding the additional efficacy of WPRT, further investigations are needed.

Correlation between urinary dose and delayed radiation cystitis after 78 Gy intensity-modulated radiotherapy for high-risk prostate cancer: A 10-year follow-up study of genitourinary toxicity in clinical practice.

PURPOSE: To investigate the factors associated with the risk of long-term genitourinary (GU) toxicity among high-risk prostate cancer (PC) patients treated with high-dose intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 2000 and 2011, PC patients treated with 78 Gy in 39 fractions delivered by IMRT combined with neo-adjuvant hormonal therapy were selected from among our database. GU toxicities and clinical factors, as well as separate anatomical urinary structures, were evaluated in terms of their associations. RESULTS: A total of 309 patients was included in this study. The median follow-up was 104 months (range: 24-143 months). The most frequently observed late grade ≥2 GU toxicity was hematuria (11.2%: 10-year actuarial risk) with radiation cystitis observed in the majority of patients. In univariate analysis, late grade ≥2 hematuria was associated with the exposure to doses >75 Gy (V75) of the bladder neck and V70 of the bladder wall, as well as with T stage. V75 of the bladder neck remained significant in multivariate analysis (p = 0.049). CONCLUSIONS: At the 10-year follow up of high-dose IMRT, a major concern was proved to be delayed cystitis related to the higher volume of bladder neck dose exposed excess over 75 Gy.

Ten-year outcomes of intensity-modulated radiation therapy combined with neoadjuvant hormonal therapy for intermediate- and high-risk patients with T1c-T2N0M0 prostate cancer.

BACKGROUND: We aimed to analyze the 10-year outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant hormonal therapy (HT) for patients with intermediate- and high-risk T1c-T2N0M0 prostate cancer. METHODS: Fifty patients with T1c-T2N0M0 prostate cancer, who were treated with high-dose IMRT combined with neoadjuvant HT, were evaluated. Of these patients, 19 and 31 were classified into the intermediate- and high-risk groups, respectively. Neoadjuvant HT was administered over a median duration of 6 months; 74 and 78 Gy in 2 Gy per fraction were essentially delivered to the intermediate- and high-risk cases, respectively. Adjuvant HT was not administered to any of the patients after the completion of IMRT. RESULTS: Over a median follow-up period of 118 months, the 10-year prostate-specific antigen failure-free survival, prostate-specific antigen failure-free, salvage hormonal therapy-free, prostate cancer-specific survival, and overall survival rates were 70.2 %, 78.7 %, 89.2 %, 100 %, and 88.8 %, respectively. No grade 3 or higher acute or late toxicities were observed. The 10-year likelihoods of developing grade 2 late urinary and rectal toxicities were 13.7 % and 4.2 %, respectively. Compared with the outcomes of a cohort of historical controls who were locally irradiated with 70 Gy by three-dimensional conformal radiotherapy, the prostate-specific antigen failure-free rate was significantly better in the IMRT groups (78.7 % vs. 53.4 % at 10 years; p = 0.027). CONCLUSIONS: High-dose IMRT combined with neoadjuvant HT achieved not only high prostate-specific antigen control, but also excellent survival outcomes with acceptable morbidities, for a Japanese cohort of intermediate- and high-risk T1c-T2N0M0 prostate cancer patients, and these results warrant further investigation.

Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.

PURPOSE: The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer. METHODS AND MATERIALS: A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached. RESULTS: Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction. CONCLUSIONS: A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy.

Clinical effect of multileaf collimator width on the incidence of late rectal bleeding after high-dose intensity-modulated radiotherapy for localized prostate carcinoma.

BACKGROUND: Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. MATERIALS AND METHODS: Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. RESULTS: The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group (n = 132) and 1.8 % for the 5-mm-wide group (n = 73) (p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy (p < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. CONCLUSION: In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity.

Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant androgen deprivation therapy under an early salvage policy for patients with T3-T4N0M0 prostate cancer.

BACKGROUND: Long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) androgen deprivation therapy (ADT) under an early salvage policy in patients with locally advanced prostate cancer (LAPC) were evaluated. METHODS: Data from 120 patients with T3-T4N0M0 adenocarcinoma of the prostate treated with IMRT were analyzed. NA-ADT with a median duration of 6 months was provided in all cases. Seventy-eight Gy, at 2 Gy per fraction, was delivered to the prostate and seminal vesicles. Adjuvant ADT (A-ADT) was not provided for any patient following the completion of IMRT. Salvage ADT (S-ADT) commenced when PSA values >4 ng/ml. RESULTS: The median follow-up period was 97 months. S-ADT was initiated in 39 patients. The median PSA value at the initiation of S-ADT was 5.7 ng/ml. The 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival and S-ADT-free rates were 53.2 % [95 % confidence interval (CI) 43.4, 62.1], 96.6 % (95 % CI 91.2, 98.7), 89.1 % (95 % CI 81.5, 93.7) and 66.6 % (95 % CI 60, 74.6), respectively. The estimated 8-year cumulative incidence rates of grade 2-3 late gastrointestinal, and grade 2-3 genitourinary toxicity were 7.6 and 10.7 %, respectively. No grade 4 toxicity was observed. CONCLUSIONS: High-dose IMRT, combined with NA-ADT for LAPC, was associated with favorable long-term disease-specific and overall survival outcomes, despite non-provision of A-ADT under the early S-ADT provision policy. This approach may represent a viable alternative to uniform provision of long-term A-ADT, because two-thirds of the patients maintained ADT-free status over an 8-year period after IMRT. Prospective trials will be required.

Long-term outcomes of dynamic conformal arc irradiation combined with neoadjuvant hormonal therapy in Japanese patients with T1c-T2N0M0 prostate cancer: case series study.

OBJECTIVE: There are few reports of the outcomes of external beam radiotherapy in Asian males with localized prostate cancer. The aim of this study is to evaluate the long-term outcomes of external beam irradiation using three-dimensional two-dynamic conformal arc therapy, combined with neoadjuvant hormonal therapy, in patients with T1c-T2N0M0 prostate cancer. METHODS: Between March 2003 and August 2007, 150 Japanese patients with T1c-T2N0M0 prostate cancer were definitively treated with three-dimensional two-dynamic conformal arc therapy. The median age, pretreatment prostate-specific antigen values and neoadjuvant hormonal therapy period were 73 years, 9.4 ng/ml and 6 months, respectively. In principle, 74 Gy was delivered to the planning target volume, although the total dose was reduced to 70 Gy in patients with unfavorable risk factors, such as severe diabetes mellitus or anticoagulant therapy. No adjuvant hormonal therapy was given to any patient. Salvage hormonal therapy was started when the prostate-specific antigen value exceeded 4 ng/ml in a monotonically increasing manner. RESULTS: The median follow-up period was 79 months. Salvage hormonal therapy was initiated in 10 patients and the median prostate-specific antigen value at the initiation was 4.7 ng/ml. The 5-year Kaplan-Meier estimates of the biochemical relapse-free survival rate, the salvage hormonal therapy -free rate and the overall survival rate were 83.3% (95% confidence interval = 77.1-89.6%), 94.3% (95% confidence interval = 90.4-98.1%) and 96.3% (95% confidence interval = 93.1-99.5%), respectively. The 5-year cumulative incidence rates of developing more than Grade 2 late rectal and urinary toxicities were 5.5 and 2.9%, respectively. CONCLUSIONS: Three-dimensional two-dynamic conformal arc therapy, with up to 74 Gy, in patients with T1c-T2N0M0 prostate cancer with neoadjuvant hormonal therapy was well tolerated and achieved good biochemical control and survival outcomes.

Safety and effectiveness of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation.

BACKGROUND: Pathological diagnosis fails in some pulmonary tumors, although they may be highly suspected to be primary lung cancer. We studied the outcome of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation. METHODS: The current study included 37 patients (39 lesions) treated with stereotactic body radiotherapy who were clinically diagnosed with primary stage I lung cancer between August 1998 and April 2009 at our hospital. Pulmonary tumors were highly suspected to be malignant from physical and imaging examinations. Biopsies were performed for 62 % of patients, although malignancy was not pathologically confirmed. In the other 38 % of patients, a biopsy was not feasible. Median age of the patients was 77 years. Median tumor diameter was 20 mm. A total median dose of 48 Gy was prescribed to the isocenter in four fractions. Median follow-up period was 39 months. RESULTS: The 3-year overall survival, local control, and regional-distant control were 74.2, 94.0, and 68.6 %, respectively. In patients with tumors ≤20 mm, overall survival and regional-distant control were significantly higher than in patients with tumors >20 mm (p ≤ 0.001), whereas no significant difference was observed regarding local control. No grade 3-5 adverse events possibly, probably, or definitely related to the treatment were observed. CONCLUSIONS: Stereotactic body radiotherapy is safe and effective for a clinically diagnosed primary stage I lung cancer when pathological diagnosis is difficult even with repeat biopsies, or a biopsy is not feasible for reasons of the patient's health condition or wishes.

Assessment of interfractional prostate motion in patients immobilized in the prone position using a thermoplastic shell.

The aim of this study was to evaluate the interfractional prostate motion of patients immobilized in the prone position using a thermoplastic shell. A total of 24 patients with prostate calcifications detectable using a kilo-voltage X-ray image-guidance system (ExacTrac X-ray system) were examined. Daily displacements of the calcification within the prostate relative to pelvic bony structures were calculated by the ExacTrac X-ray system. The average displacement and standard deviation (SD) in each of the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were calculated for each patient. Based on the results of interfractional prostate motion, we also calculated planning target volume (PTV) margins using the van Herk formula and examined the validity of the PTV margin of our institute (a 9-mm margin everywhere except posteriorly, where a 6-mm margin was applied). In total, 899 data measurements from 24 patients were obtained. The average prostate displacements ± SD relative to bony structures were 2.8 ± 3.3, -2.0 ± 2.0 and 0.2 ± 0.4 mm, in the SI, AP and LR directions, respectively. The required PTV margins were 9.7, 6.1 and 1.4 mm in the SI, AP and LR directions, respectively. The clinical target volumes of 21 patients (87.5%) were located within the PTV for 90% or more of all treatment sessions. Interfractional prostate motion in the prone position with a thermoplastic shell was equivalent to that reported for the supine position. The PTV margin of our institute is considered appropriate for alignment, based on bony structures.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy.

OBJECTIVES: Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. METHODS: Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. RESULTS: Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥ 8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥ 0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥ 2 predictors, respectively. CONCLUSION: In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies.

Differences in the dose-volume metrics with heterogeneity correction status and its influence on local control in stereotactic body radiation therapy for lung cancer.

The purpose of this study is to evaluate the dose-volume metrics under different heterogeneity corrections and the factors associated with local recurrence (LR) after stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). Eighty-three patients who underwent SBRT for pathologically proven stage I NSCLC were reviewed retrospectively. The prescribed dose was 48 Gy in four fractions at the isocenter (IC) under heterogeneity correction with the Batho power law (BPL). The clinical plans were recalculated with Eclipse (Varian) for the same monitor units under the BPL and anisotropic analytical algorithm (AAA) and with no heterogeneity correction (NC). The dose at the IC, dose that covers 95% of the volume (D95), minimum dose (Min), and mean dose (Mean) of the planning target volume (PTV) were compared under each algorithm and between patients with local lesion control (LC) and LR. The IC doses under NC were significantly lower than those under the BPL and AAA. Under the BPL, the mean PTV D95, Min and Mean were 8.0, 9.4 and 7.4% higher than those under the AAA, and 9.6, 9.2 and 4.6% higher than those under NC, respectively. Under the AAA, all dose-volumetric parameters were significantly lower in T1a patients than in those with T1b and T2a. With a median follow-up of 35.9 months, LR occurred in 18 patients. Between the LC and LR groups, no significant differences were observed for any of the metrics. Even after stratification according to T-stage, no significant difference was observed between LC and LR.

[Salvage hormonal therapy against recurrence after curative external beam radiotherapy for locally advanced prostate cancer at Kyoto University Hospital].

Fifty-three patients with biochemical relapse (BCR) after receiving external beam radiotherapy (EBRT) against locally advanced prostate cancer (stage III : International Union Against Cancer [UICC] 6th edition) between September 1997 and January 2006 at our institution, who were treated with salvage hormonal therapy (HTx), were followed for a mean period of 75.5 months. There was progression to castrationresistant prostate cancer (CRPC) during the follow-up period in 17 patients (32.0%). The median time to CRPC after initial HTx was 17 months. Univariate analysis revealed that time to BCR after EBRT was significantly associated with progression to CRPC (p＝0.022), while PSA-doubling time just before salvage HTx was marginally associated with irradiation dose (p＝0. 088, p＝0.128 respectively). Multivariate analysis showed that time to BCR after EBRT was the only significant predictor of progression to CRPC (p＝ 0.035, Hazard ratio ; 0.252, 95% confidence interval ; 0.070-0.905) conclusion, time to BCR after EBRT might be a good predictor for the efficiency of salvage HTx after EBRT against locally advanced prostate cancer.

Dosimetric evaluation of the impacts of different heterogeneity correction algorithms on target doses in stereotactic body radiation therapy for lung tumors.

Heterogeneity correction algorithms can have a large impact on the dose distributions of stereotactic body radiation therapy (SBRT) for lung tumors. Treatment plans of 20 patients who underwent SBRT for lung tumors with the prescribed dose of 48 Gy in four fractions at the isocenter were reviewed retrospectively and recalculated with different heterogeneity correction algorithms: the pencil beam convolution algorithm with a Batho power-law correction (BPL) in Eclipse, the radiological path length algorithm (RPL), and the X-ray Voxel Monte Carlo algorithm (XVMC) in iPlan. The doses at the periphery (minimum dose and D95) of the planning target volume (PTV) were compared using the same monitor units among the three heterogeneity correction algorithms, and the monitor units were compared between two methods of dose prescription, that is, an isocenter dose prescription (IC prescription) and dose-volume based prescription (D95 prescription). Mean values of the dose at the periphery of the PTV were significantly lower with XVMC than with BPL using the same monitor units (P < 0.001). In addition, under IC prescription using BPL, RPL and XVMC, the ratios of mean values of monitor units were 1, 0.959 and 0.986, respectively. Under D95 prescription, they were 1, 0.937 and 1.088, respectively. These observations indicated that the application of XVMC under D95 prescription results in an increase in the actually delivered dose by 8.8% on average compared with the application of BPL. The appropriateness of switching heterogeneity correction algorithms and dose prescription methods should be carefully validated from a clinical viewpoint.

Dose--volume metrics associated with radiation pneumonitis after stereotactic body radiation therapy for lung cancer.

PURPOSE: To identify dose-volume factors associated with radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer. METHODS AND MATERIALS: This study analyzed 74 patients who underwent SBRT for primary lung cancer. The prescribed dose for SBRT was uniformly 48 Gy in four fractions at the isocenter. RP was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3. Symptomatic RP was defined as grade 2 or worse. Optimal cut-offs dividing the patient population into two subgroups based on the incidence of symptomatic RP were sought using the following dose-volume metrics: PTV volume (ml), mean lung dose (Gy), and V5, V10, V15, V20, V25, V30, V35, and V40 (%) of both lungs excluding the PTV. RESULTS: With a median follow-up duration of 31.4 months, symptomatic RP was observed in 15 patients (20.3%), including 1 patient with grade 3. Optimal cut-offs for pulmonary dose-volume metrics were V25 and V20. These two factors were highly correlated with each other, and V25 was more significant. Symptomatic RP was observed in 14.8% of the patients with V25 <4.2%, and the rate was 46.2% in the remainder (p = 0.019). PTV volume was another significant factor. The symptomatic RP rate was significantly lower in the group with PTV <37.7 ml compared with the larger PTV group (11.1% vs. 34.5%, p = 0.020). The patients were divided into three subgroups (patients with PTV <37.7 ml; patients with, PTV ≥37.7 ml and V25 <4.2%; and patients with PTV ≥37.7 ml and V25 ≥4.2%); the incidence of RP grade 2 or worse was 11.1%, 23.5%, and 50.0%, respectively (p = 0.013). CONCLUSIONS: Lung V25 and PTV volume were significant factors associated with RP after SBRT.

Preliminary report of late recurrences, at 5 years or more, after stereotactic body radiation therapy for non-small cell lung cancer.

INTRODUCTION: Long-term outcomes remain unknown after stereotactic body radiation therapy (SBRT). We observed a few patients who developed disease progression late, at 5 years or more, after SBRT. In this report, we describe the characteristics of those patients with late recurrence after SBRT. METHODS: We retrospectively reviewed patients who underwent SBRT for non-small cell lung cancer with histological confirmation between January 1999 and December 2005 at our institution. During this period, 48 Gy of SBRT in four fractions at the isocenter was prescribed for all patients. RESULTS: In total, 66 patients were eligible. With a median follow-up period of 35.9 months, the 5-year overall survival and disease-free survival rates were 44.6% (95% confidence interval, 33.5-59.5%) and 33.8% (95% confidence interval, 23.6-48.4%), respectively. Of the patients, 16 survived without disease progression for 5 years or more after SBRT. Of these, four patients developed late recurrence at 76, 101, 108, and 109 months after SBRT. Three of the patients were females with adenocarcinomas; the other was a male with squamous cell carcinoma. The initial sites of recurrence were local in two patients, distant in one, and simultaneously local and distant in one. A total of two patients with local recurrence alone were still alive at 138 months after SBRT. CONCLUSIONS: The rate of late recurrence was not negligible in long-term survivors after SBRT. Our experiences indicate that long-term follow-up is needed after SBRT for non-small cell lung cancer.

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with T1c-T2N0M0 prostate cancer.

BACKGROUND: The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with T1c-T2N0M0 prostate cancer, with initiation of salvage hormonal therapy (SHT) at a relatively early phase, were analyzed. METHODS: Fifty-nine Japanese patients with T1c-T2N0M0 prostate cancer who received radical 3D-CRT between January 1999 and January 2003 were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were: 72 years, 9.4 ng/ml, and 6 months, respectively. Seventy Gy was given in 35 fractions confined to the prostate ± seminal vesicles. AHT was not administered after 3D-CRT in any patients. RESULTS: The median follow-up period was 89 months. The median PSA value at the time of initiation of SHT was 4.7 ng/ml (range 0.1-21.6 ng/ml). The overall, disease-specific, PSA failure-free (based on the Phoenix definition), and SHT-free survival rates at 8 years were 82.8% (95% confidence interval [CI] 72.4-93.2), 100%, 62.4% (47.1-77.8), and 82.6% (71.3-94.0), respectively. Only one patient developed grade 3 late toxicity. CONCLUSIONS: The PSA control rates in our series of Japanese patients with stage T1c-T2N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed at least comparable to those reported from Western countries; as well, the patients had excellent outcomes. The present outcomes can be used as basic data for evaluating the impact of dose escalation with intensity-modulated radiation therapy for Japanese patients with prostate cancer in the future.

Detailed dosimetric evaluation of intensity-modulated radiation therapy plans created for stage C prostate cancer based on a planning protocol.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been employed as a precision radiation therapy with higher conformity to the target. Although clinical outcomes have been reported for many investigations, detailed treatment planning results have not been mentioned to date. The aim of this study was to evaluate the dose specifications of our IMRT treatment plans for locally advanced prostate cancer. METHODS: Seventy-seven clinically applied IMRT plans treated between September 2003 and December 2005, in which patients were irradiated with 78 Gy in the prone position, were retrospectively analyzed. Dosimetric data output from dose volume histograms were evaluated in detail. RESULTS: The mean dose ± standard deviation, homogeneity index, and conformity index to the planning target volume (PTV) were 78.3 ± 0.7 Gy (100.4 ± 0.9%), 13.7 ± 3.0, and 0.83 ± 0.04, respectively. For the clinical target volume, the mean dose was 80.3 ± 0.7 Gy (102.9 ± 0.9%).The V40, V60, and V70 Gy of the rectal wall were 58.3 ± 2.8, 29.6 ± 2.7, and 15.2 ± 3.0%, respectively. Planning difficulties were encountered in patients whose bowels were displaced downward, as constraints imposed by the bowel position altered the dose index of the PTV. In many cases, additional bowel optimization parameters were required to satisfy constraints for organs at risk. However, major deviation could be avoided by inverse planning with computer optimization. CONCLUSION: IMRT allowed the creation of acceptable and practical treatment plans for locally advanced prostate cancer. Reports regarding detailed dosimetric evaluations are mandatory for interpreting clinical outcomes in the future.