Early salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: Its impact and optimal candidate.

AIM: We aimed to identify the optimal candidates for early salvage radiotherapy (SRT) among patients with biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS: This multi-institutional retrospective study included 371 patients treated using SRT after RP. The median (range) PSA level at BCR was 0.36 (0.10-2.00) ng/mL. The association between early SRT (ie, starting PSA level < 0.50) and BCR after SRT was tested in each subgroup according to our own risk stratification. RESULTS: The median follow-up time was 51 months. By multivariate analysis, pT3b, Gleason score ≥ 8, negative surgical margins, PSA doubling time < 6 months, and non-early SRT were associated with BCR after SRT. Patients were stratified by four risk factors other than non-early SRT: (1) low risk (0 risk factor), (2) intermediate risk (1 risk factor), and (3) high risk (≥2 risk factors). The BCR-free survival was higher in the early SRT group than the nonearly SRT group in the high-risk subgroup (P = 0.020), whereas that was similar between two groups in the low-risk and intermediate-risk subgroups (P = .79 and .18, respectively). Multivariate analysis revealed that early SRT was beneficial for the high-risk subgroup (P = .032), whereas early SRT was not associated with improved outcomes in the low-risk and intermediate-risk subgroups (P = .92 and 1.0, respectively). CONCLUSIONS: This study suggested that early SRT seemed to contribute to better biochemical control for patients with more adverse features, whereas no benefit was observed in men with no adverse features.

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy.

The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8-5.4, p < 0.001) and use of whole-pelvic radiotherapy (HR 7.6, CI 1.0-56, p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3-7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.

Early response and local control of stage I non-small-cell lung cancer after stereotactic radiotherapy: difference by histology.

To investigate the possible influences of various factors on tumor response to radiation, regression speeds and long-term local control rates of primary adenocarcinoma and squamous cell carcinoma of the lung after stereotactic body radiotherapy were evaluated. Ninety-one patients (65 men and 26 women) with a median age of 76 years were serially examined using computed tomography at 2, 4 and 6 months after treatment. Tumor histology was adenocarcinoma in 62 patients and squamous cell carcinoma in 29 patients. The prescribed dose was 48 Gy in four fractions given twice a week for T1 tumors (≤ 3 cm) and 52 Gy in four fractions given twice a week for T2 tumors (3-5 cm). Tumor shrinkage speed and 3-year local control rates were similar between T1 and T2 tumors and between patients with normal pulmonary function and those with impaired function. Squamous cell carcinomas shrank faster than adenocarcinomas at 2 and 4 months after radiation, but mean relative tumor size at 6 months and local control rates at 3 years did not differ significantly between the two histologies. Tumors in patients with a higher hemoglobin level tended to shrink faster but the control rates were not different. It is concluded that, although squamous cell carcinoma shrinks faster than adenocarcinoma, the two types of lung cancer are of similar radiosensitivity in terms of long-term control rates. Radiosensitivity should not be evaluated by early tumor response.

Regression curves of brain metastases after gamma knife irradiation: Difference by tumor and patient characteristics.

Regression curves and local control rates of brain metastases after gamma knife treatment were evaluated to investigate differences in tumor response to radiation. A total of 203 metastases were serially evaluated using contrast-enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6 months after a 20-Gy dose. Differences were evaluated in regression curves and control rates between tumors ≥10 mm and tumors <10 mm in mean diameter, among three major histological subtypes of lung cancer, among adenocarcinomas of the lung, breast and colorectum, and between tumors in patients with above and below median hemoglobin levels. Smaller tumors shrank faster and yielded better control rates than larger tumors. Metastases from small cell and squamous cell carcinomas of the lung shrank faster than those from lung adenocarcinoma, but 6-month control rates were not different. Breast adenocarcinomas tended to shrink faster than lung adenocarcinomas, but the control rates were not different among adenocarcinomas of the lung, breast and colorectum. Tumors in patients with higher hemoglobin levels tended to shrink faster but the control rates were not different. Small cell and squamous cell carcinomas of the lung regress more rapidly than adenocarcinomas, although local control rates might not differ significantly.

Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas.

BACKGROUND: To examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry. METHODS: Five patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk. RESULTS: In comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors. CONCLUSION: The results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.

Radiotherapy for hilar or mediastinal lymph node metastases after definitive treatment with stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer.

PURPOSE: Management of regional lymph node (LN) recurrence is an important issue in definitive treatment of non-small cell lung cancer (NSCLC). We evaluated clinical outcomes of conventional radiotherapy for hilar or mediastinal LN metastases developing after stereotactic body radiotherapy (SBRT) or surgery for stage I NSCLC. METHODS AND MATERIALS: Between 2004 and 2008, 26 patients with hilar or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 12) were treated with conventional radiotherapy. Twelve of the 14 post-SBRT patients (86%) were judged medically inoperable at the time of SBRT. All patients were treated to the hilum and mediastinum with conventional daily fractions of 2.0 Gy (n = 25) or 2.4 Gy (n = 1). The median total dose for treating metastatic LN was 60 Gy (range, 54-66 Gy) for the post-SBRT patients and 65 Gy (range, 60-66 Gy) for the post-surgery patients. Only 1 of the 14 post-SBRT patients and 8 of the 12 post-surgery patients received chemotherapy. RESULTS: For all 26 patients, the overall and cause-specific survival rates at 3 years from radiation for LN metastases were 36% and 51%, respectively (14% and 39%, respectively, for the 14 post-SBRT patients and both 64% for the 12 post-surgery patients). Three of the SBRT patients were alive at 35 to 43 months with (n = 2) or without (n = 1) further recurrence, and 4 of the post-surgery patients were alive at 36 to 62 months with (n = 2) or without (n = 2) further recurrence. The incidence of ≥grade 2 pulmonary toxicity was 49% at 1 year (53% for post-SBRT patients and 44% for post-surgery patients). A grade 5 pulmonary toxicity was observed in 1 of the post-SBRT patients. CONCLUSIONS: Conventional radiotherapy could successfully salvage LN relapses after SBRT as well as after surgery in 7 of 26 patients. Radiotherapy in this setting appears reasonably well tolerated.

Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity.

www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size.

BACKGROUND: The treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter. METHODS: Between February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions. RESULTS: For all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02). CONCLUSIONS: There was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further.

Stereotactic radiotherapy using Novalis for skull base metastases developing with cranial nerve symptoms.

Skull base metastases are challenging situations because they often involve critical structures such as cranial nerves. We evaluated the role of stereotactic radiotherapy (SRT) which can give high doses to the tumors sparing normal structures. We treated 11 cases of skull base metastases from other visceral carcinomas. They had neurological symptoms due to cranial nerve involvement including optic nerve (3 patients), oculomotor (3), trigeminal (6), abducens (1), facial (4), acoustic (1), and lower cranial nerves (1). The interval between the onset of cranial nerve symptoms and Novalis SRT was 1 week to 7 months. Eleven tumors of 8-112 ml in volume were treated by Novalis SRT with 30-50 Gy in 10-14 fractions. The tumors were covered by 90-95% isodose. Imaging and clinical follow-up has been obtained in all 11 patients for 5-36 months after SRT. Seven patients among 11 died from primary carcinoma or other visceral metastases 9-36 months after Novalis SRT. All 11 metastatic tumors were locally controlled until the end of the follow-up time or patient death, though retreatment for re-growth was done in 1 patient. In 10 of 11 patients, cranial nerve deficits were improved completely or partially. In some patients, the cranial nerve symptoms were relieved even during the period of fractionated SRT. Novalis SRT is thought to be safe and effective treatment for skull base metastases with involvement of cranial nerves and it may improve cranial nerve symptoms quickly.