Higher Biological Equivalent Dose Research Articles

Assessing the Benefit of Higher Biologically Effective Dose in Patients With Squamous Cell Carcinoma of the Lung Treated With Stereotactic Body Radiation Therapy

Multiple studies have suggested that patients with early-stage squamous cell carcinoma (SCC) of the lung treated with stereotactic body radiation therapy (SBRT) are more susceptible to local failure when compared to other non-small cell lung cancer (NSCLC) histologies. It is unknown if higher biological equivalent dose (BED) leads to improved outcomes in this patient population. We used the National Cancer Database (NCDB) to compare overall survival (OS) between patients with SCC and non-SCC NSCLC treated with "high" or "low" BED SBRT.The NCDB was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006-2016 and treated with 3-5 fraction SBRT. Patients were grouped by BEDhigh (> 150 Gy) and BEDlow (≤132 Gy). OS was estimated by Kaplan-Meier analysis. Correlation between BED and OS was tested with univariate and doubly-robust multivariable Cox regression analysis (MVA). The MVA included age, sex, Charlson-Deyo score, tumor grade, clinical T stage, and BED group. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to minimize selection bias.We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. For the matched SCC cohorts, BEDhigh was associated with improved OS in both univariate and doubly robust multivariate analysis (MVA HR 0.84 95% CI 0.76-0.92, P < 0.001), with estimated IPTW-adjusted 3-year OS of 49% compared to 41% for the BEDlow group. In contrast, BEDhigh was not associated with improved OS compared to BEDlow for non-SCC NSCLC patients (MVA HR 0.94 95% CI 0.86-1.04, P = 0.23), with estimated IPTW-adjusted 3-year OS of 54% compared to 53% for the BEDlow group.Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens employing the use of BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.

A Single Institution Experience On High Dose MRI-Guided Stereotactic Body Radiotherapy For Pancreatic Cancer: Early Outcomes, Safety And Feasibility

Accumulating evidence has shown a benefit for dose-escalation and stereotactic body radiotherapy (SBRT) in the treatment of unresectable pancreatic cancer. To this end, MR-guided radiotherapy (MRgRT) allows for reduction of dose to organs at risk while accounting for intra- and inter-fraction motion with online treatment plan adaptation to improve target coverage. We sought to report on our early experience in MRgSBRT for pancreatic cancer. This study was a retrospective cohort of biopsy-proven, pancreatic cancer patients that were recommended to undergo high biological equivalent dose (BED) SBRT to their primary disease and were treated on the MR-Linac in 5 fractions. Acute toxicity measured by Common Terminology Criteria for Adverse Events (v5) by a provider during the weekly on-treatment visit, at 1 month following completion of treatment, and at regular 3-month follow-up intervals thereafter. Toxicity occurring greater than 3 months after completion of radiotherapy was deemed late. From April, 2019 until January, 2020 a total of 35 consecutively treated patients (48% borderline resectable, 37% locally advanced; 80% cN0) with a median follow up from diagnosis of 8.3 months were treated to median 45 Gy (Range: 35-50 Gy) on our MRI-Linac. At least three months of induction chemotherapy was given in 88.5% of patients, most commonly FOLFIRINOX (71%) or gemcitabine/abraxane (26%). Twenty-three patients (66%) were treated with online adaptive planning and 4 patients (11%) were treated for locally recurrent, unresectable disease with history of prior radiotherapy (n = 3 prior adjuvant chemoradiation, n = 1 prior definitive SBRT in the lateral decubitus position). Overall, nine patients (25%) experienced any toxicity, predominantly grade 1 fatigue (55%) and nausea (44%). A single patient (2.8%) experienced grade 3 abdominal pain 1.5 weeks after completion of SBRT presumed to be duodenitis from CT imaging. No grade 4/5 or any late toxicity from SBRT has been observed in this cohort to date. At the time of analysis, 9 patients (55% borderline resectable, 22% locally advanced) successfully underwent resection of their primary tumor (100% R0 resection) without perioperative mortality and with 2 reported pathological complete response (TRG 0; 22%), 2 patients with TRG 1 response and 5 patients with TRG 2 response (55%). Overall, no patients had experienced local recurrence based on CT pancreas protocol RECIST criteria and eight patients (22.8%) had distant progression with one reported death (OS: 97%). MRgSBRT for pancreatic cancer appears to be well-tolerated with encouraging early local control and without significant morbidity or increased perioperative mortality. Adaptive treatment parameters and tissue constraints for adaptive and non-adaptive treatment plans minimize toxicity for this increasingly utilized treatment.

Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

PurposeMen with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT). Methods and MaterialsThree hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression. ResultsTen-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001). ConclusionsSurvival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.

Proton and carbon ion radiation therapy for locally advanced pancreatic cancer: A phase I dose escalation study

ObjectiveTo determine the maximum tolerated dose (MTD) of proton and carbon ion radiation therapy (PCRT) for locally advanced pancreatic cancer (LAPC). MethodsA single-institution, phase I dose escalation study was performed. The proton dose of 50.4 GyE in 28 fractions was delivered to clinical target volume, and carbon ion as a boost dose to gross tumor volume escalated from 12 GyE to 18 GyE with 3 GyE per fraction in 3 dose levels. The dose limiting toxicity (DLT) was defined as any treatment-related grade (G)3 or higher of non-hematological toxicity. The MTD was exceeded if ≥2 patients in a dose level developed DLT. ResultsFrom May 2015 to July 2016, ten patients were enrolled, 3 in dose level 1, 4 in dose level 2, and 3 in dose level 3. With a median follow-up of 17.4 months, no patient developed a DLT, and the acute G1-2 of gastrointestinal (GI) and hepatic toxicity occurred in 40% of patients, and G1 of GI late toxicity, in 30%. The median overall survival was 17.3 months. ConclusionHigher than 50.4 GyE could be given by PCRT with slight toxicity and good tolerance for LAPC, and the tumor control and survival had been improved, but not significantly. Better outcome may be achieved using carbon ion radiation therapy with higher biological equivalent dose.

Stereotactic Body Radiation Therapy Versus Conventional Radiotherapy for Hepatic Metastasis from Colorectal Carcinoma

Stereotactic body radiotherapy (SBRT) has been increasingly used for hepatic oligometastasis which is not suggested for surgery and other local ablative therapy. Although burgeoning literature has been discussing SBRT for liver metastasis, there is no evidence comparing the outcome between SBRT and conventional radiotherapy (RT). Moreover, the patients with oligometastasis would continue systemic therapy, how to compare the effect and how to combine radiotherapy with systemic therapy are still under investigation. Therefore, we report our experience comparing SBRT to conventional RT for hepatic metastasis from colorectal carcinoma. Between 2009 June to 2018 December, 11 patients with oligometastatic hepatic nodules from colorectal carcinoma, which were not suggested for resection or other local therapy after multidisciplinary review, received SBRT to their liver metastases. In the comparing subgroup, 21 patients with metastatic hepatic nodules from colorectal carcinoma accepted palliative RT with conventional dose during the same period. Both SBRT and conventional RT were under same protocol for daily image guidance. With mean follow-up as 15.8 months, overall survival was 14.0 months for conventional RT subgroup and 19.2 months for SBRT subgroup. The mean of maximum diameter of hepatic metastasis for both groups was 3.2 cm (range: 1.5 ∼ 5.8cm). Prescribed dose for conventional RT ranges 35 to 50Gy in 10 to 25 fractions while dose for SBRT was 25 to 50Gy in 3 or 5 fractions. Mean biologically effective doses for conventional RT and SBRT was 68.1Gy and 87.1Gy (α/β=5), 56.3Gy and 60.0Gy (α/β=10), respectively. For the best response outcome, by RECIST 1.1, 1 patient had complete remission (CR), 6 patients had partial response (PR), another 6 patients remained stable disease (SD) and the other 8 patients had progressive disease (PD) in conventional RT subgroup; for SBRT subgroup with 11 patients, 2 patients were CR, 6 patients had PR, and 3 patients remained SD. In-field progression-free survival for conventional RT and SBRT was 8.5 and 10.5 months. Out-field (not irradiated area or other organs) progression-free survival for conventional RT and SBRT was 8.8 and 8.8 months, respectively. None of these 32 patients developed ≥grade 3 side effects during or within 1 month after radiotherapy. For liver metastasis not indicated for operation and other local therapy, SBRT offers an ablative but non-invasive option. From our preliminary comparison, SBRT seems to have higher biological equivalent dose and better local control comparing to conventional RT. Further rigorous research comparing conventional RT and SBRT, as well as investigating confounding effect from systemic therapy, would be needed in future.

Incidence and Patterns of Locoregional Failure After Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma

PurposeStereotactic body radiation therapy (SBRT) is increasingly utilized in the neoadjuvant and definitive settings for pancreatic adenocarcinoma. The risk of local and regional recurrence after this treatment remains largely unknown. Because of the lack of elective nodal treatment and high fractional dose, we hypothesized that the incidence of regional out-of-field recurrence would predominate after SBRT. Methods and materialsElectronic medical records of all patients treated in our department with SBRT for pancreatic adenocarcinoma were retrospectively reviewed. Patients were separated into those who converted or did not convert to surgical resectability. Demographic, treatment, and outcome data were collected and analyzed. Recurrence was assessed based on the Response Evaluation Criteria In Solid Tumors version 1.1. Treatment plans were reviewed to determine the locations of failure with respect to treatment volume. Statistical comparisons were made using Mann-Whitney U testing for continuous variables and χ2 testing for dichotomous variables. ResultsData on 69 patients was available for analysis. After treatment, 18 patients (26.1%) suffered in-field recurrence and 11 patients (15.9%) recurred regionally out of field. The median time to in-field and out-of-field failures were similar at 120.5 and 108.0 days, respectively (P = .65). Of those who failed out-of-field, 4 of 11 patients (36.4%) were without in-field failure prior to death. In-field failure rates were less in patients who subsequently underwent surgical resection compared with those who did not (2 of 22 patients [9.1%] vs 16 of 47 patients [34.0%]; P = .028), but out-of-field recurrence was unaffected by subsequent surgical resection (3 of 22 patients [13.6%] vs 8 of 47 patients [17.0%]; P = .720). All out-of-field failures occurred in areas that received <2600 cGy. ConclusionsThe incidence of out-of-field failure remains acceptable after SBRT for pancreatic adenocarcinoma. Despite the high biological equivalent dose allowed by SBRT, in-field control remains problematic and continues to signal relative radiation resistance that is associated with bulky disease.

Palliative radiotherapy for gastric cancer: a systematic review and meta-analysis.

Background/PurposeTo review the efficacy and toxicity of palliative radiotherapy (RT) for symptomatic locally advanced gastric cancer (GC) and to determine the optimal RT schedule for symptom palliation.MethodsWe searched MEDLINE and CENTRAL for eligible studies published from 1995 to 2015. Outcomes of interest were relief of bleeding, pain and obstruction.RESULTSSeven non-comparative observational studies were included. There were large variations in RT dose and fractionation. The pooled overall response rates for bleeding, pain and obstruction symptoms were 74%, 67% and 68% respectively. There was no difference in response rate of bleeding between regimens with high biological equivalent dose (BED) of = 39Gy versus regimens with low BED<39Gy regimens (p value =0.39). Grade 3 to 4 toxicities occurred in up to 15% of patients for patients treated with RT alone and up to 25% of patients treated with chemoradiotherapy. Health-related quality of life (HRQL) outcomes were not reported.ConclusionMore than two-thirds of patients receiving RT would have a clinical benefit. Low BED regimens appear to be adequate for symptom palliation. Toxicity rates appear acceptable for patients treated with RT alone. The optimal dose fractionation regimen for symptom palliation remains unclear. Prospective studies to determine the effects of palliative gastric RT on HRQL outcomes are warranted.

102P Ablative robotic radiosurgery for inoperable patients with stage IA–IB non small cell lung cancer

Background: The gold standard treatment for early stage non small-cell lung cancer (NSCLC) is surgical resection. For patients (pts) considered medically or functionally not amenable with surgery, radiotherapy is the alternative treatment. In the last years impressive local control (LC) rates have been reported using stereotactic radiotherapy treatment (SBRT) that provides an attractive option to deliver high dose per fraction and a high biological equivalent dose (BED). The purpose of our study is to evaluate outcome and follow-up data on our pts who underwent Cyberknife (CK) Radiosurgery for early NSCLC. Methods: Since February 2005 to October 2013, a total of 90 pts, median age of 76 years (range 42–90) with pathologically proven NSCLC, diagnosed as 41 stage IA and 56 stage IB were referred to our Radiotherapy Department for CK-SBRT. Selected tracking modalities depended on tumor size, location and extent of respiratory movement were performed. 27 pts with lower lobe lesions were treated with fiducial markers (1–3), in the others 70 fiducialless X sight option was used. The median tumor volume was 30 cc (range, 4–143). Depending on tumor size and location different curative dose regimens were used, but in all pts a high BED (>100Gy) was delivered to the tumor. The SBRT treatment dose of 25–60Gy was prescribed to the 75–85% isodose lines in 1–5 fractions. Median follow-up was 30 months (range, 2–102). Results: The Kaplan–Meier LC rate at 1, 3 and 5 years was respectively 98%, 88.5% and 81%. Reported acute side effects have generally been mild including esophagitis, fatigue, chest wall tenderness and cough. For the evaluation of toxicity we used the RTOG/EORTC scale. We detected a late radiation-induced local fibrosis using CT imaging in most pts, in 3 we observed grade 3 pneumonitis, in 1 patient chest wall pain and rib fracture and in another one G3 radiation induced mielopathy at an interval of 30 months following CK/SRS treatment. Conclusions: CK/SBRT for limited-stage primary lung cancer has been shown to be a promising treatment with high LC rates and very low toxicity. Prospective studies should be performed to determine whether this therapy may be an alternative option for surgery. Legal entity responsible for the study: Centro Diagnostico Italiano Funding: Centro Diagnostico Italiano Disclosure: All authors have declared no conflicts of interest. 103P Lobectomy for non-small cell lung cancer in octogenarians: A 7-year single center experience

High-dose-rate interstitial brachytherapy in early stage oral tongue cancer - 15 year experience from a tertiary care institute.

PurposeTo determine outcomes of interstitial high-dose-rate brachytherapy (HDR-BT) in patients with early stage oral tongue cancer.Material and methodsNinety-two patients with stage I and II oral tongue cancer were treated with HDR-BT between 1999 and 2014: brachytherapy alone = 62 (67.4%), and combination of external beam radiotherapy (EBRT) and brachytherapy = 30 (32.6%). Median follow-up was 53.5 months. Patterns of failure, overall survival (OS), disease-free survival (DFS), local control rates (LCR), and nodal control rates (NCR) were determined.Results5-year OS, DFS, LCR, and NCR were 73.2%, 58.2%, 64.2%, and 83.8%, respectively. In total, 43 patients (46.7%) failed treatment: isolated local failures = 28 (30.4%), isolated nodal failures = 8 (8.7%), both local and regional failures = 7 (7.6%). While in T1 stage, 5 year LCR were significantly higher in brachytherapy alone group compared to combined EBRT and brachytherapy group (81.7% vs. 62.5%, p = 0.04), the isolated nodal failure rates were not significantly different among the two groups. For T2 stage, NCR were higher in combined EBRT and brachytherapy group compared to brachytherapy alone (92.9% vs. 74.3%). Acute mucositis (grade ≥ 2) was seen more in brachytherapy alone group compared to the combined modality group (87% vs. 66%), and this correlated significantly with the higher biological equivalent dose (BED) in the brachytherapy alone group.ConclusionsOur study recommends treating patients with brachytherapy alone in T1 stage, and demonstrates the need for addressing nodal region either by neck dissection or nodal irradiation in T2 stage patients. Also, the study highlights the need for dose escalation (from the doses used in the study) in both T1 and T2 stage tumors when using interstitial brachytherapy either as sole modality or as a boost.

MP62-16 FACTORS AFFECTING METASTASIS AND LONG-TERM SURVIVAL FOLLOWING PROSTATE BRACHYTHERAPY

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 2015MP62-16 FACTORS AFFECTING METASTASIS AND LONG-TERM SURVIVAL FOLLOWING PROSTATE BRACHYTHERAPY Nelson Stone and Richard Stock Nelson StoneNelson Stone More articles by this author and Richard StockRichard Stock More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2390AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine the prognostic and treatment related variables associated with metastases and decreased cause specific survival (CSS) following prostate brachytherapy. METHODS 1669 men with T1-T3 prostate cancer were followed a minimum of 5 years and treated with implant alone (683, 40.9%), implant plus external beam irradiation (EBRT, 88, 5.3%), implant plus hormone therapy (HT, 417, 25%) or implant plus HT and EBRT (481, 28.9%). 898 (53.8%) were treated with a median of 6 months of HT (range 1-34). Median patient age was 66 years and mean PSA 9.7 ng/ml. There were 757 (45.5%) patients at low, 642 (38.5%) intermediate and 267 (16%) high risk. Radiation dose was converted to the biological equivalent dose (BED) and was a median of 198 Gy2. Patients were followed a mean of 9.2 years (median 8.8, range 5-21). Men were diagnosed with metastatic disease (Metz) had a positive bone or CT scan. Associations were compared by ANOVA and Chi-square. Survival function was estimated by Kaplan Meier method with comparisons by log rank and cox regression proportion hazard rates RESULTS The 10 and 15 year freedom from Metz and CSS were 97.1 and 94% and 98.2 and 94.6%, respectively. Freedom from Metz and CSS decreased by risk group (table). When high risk patients were stratified by very high risk (Gleason score ≥ 8 and PSA > 20 ng/ml) there was no difference in CSS. BED was significantly higher in low risk patients free of Metz (198 vs 176 Gy, p=0.041) and in low (198 vs 172 Gy, p=0.023) and high risk (193 vs 169 Gy, p=0.005) patients not dying from prostate cancer. Cox regression revealed stage (p=0.012, HR 1.45, 95%CI 1.08-1.94), Gleason score (p=0.037, HR 1.40, 95%CI 1.02-1.91) and BED (p=0.044, HR 1.01, 95%CI 1-1.03) as significant for Metz. Cox regression for CSS was significant for stage (p=0.014) and Gleason score (p=0.002). Use of HT, patient age, and PSA did not influence Metz or CSS. CONCLUSIONS Radiation dose significantly influences metastases and survival following prostate brachytherapy. Unlike studies which report a beneficial effect of HT combined with EBRT in intermediate and high risk disease, no benefit was experienced when radiation doses are high. Those patients with very high risk disease experienced the same high 10 and 15-year CSS as patients without the highest risk features. These positive results also most likely reflect the high BED. Low Risk Intermediate Risk High Risk P Value Freedom from Metastases 10 Year 99.2% 97.6% 90.8% 15 Year 96.1% 94.5% 86.5% P < 0.001 CSS 10 Year 99.5% 98.8% 92.3% 15 Year 96.8% 96.6% 80.5% P < 0.001 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e786-e787 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nelson Stone More articles by this author Richard Stock More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRT or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.

Dose escalation using helical tomotherapy improves local control in spine metastases from primary hepatic malignancies

This study was designed to reveal the prognostic significance of dose-escalated radiotherapy with tomotherapy in local control for spine metastases of primary hepatic tumours. From April 2006 to May 2012, 23 hepatocellular carcinoma patients and 7 intrahepatic cholangiocellular carcinoma patients (total 30 patients, 42 spinal lesions) were treated for metastatic spine lesions with helical tomotherapy (HT). The gross tumour volume (GTV) was defined as a tumour evident from computed tomography and magnetic resonance imaging. Median values were as follows: GTV total dose of 48 Gy (range 21-51), fraction size of 6 Gy (range 3-8) and eight fractions (range 3-17). Pain response was checked according to visual analogue scale (from 0 to 10). The median follow-up was 5.6 months. Six events of local failure occurred, including five lesions in which spinal canals were involved at radiotherapy. Local control rate at 3 months was 86.6%. Biological equivalent dose (BED) was correlated with local control (AUC = 0.833). Higher BED (>56.0 Gy10 ) was associated with increased local control (P = 0.004). The median time to local progression in patients receiving ≤56.0 Gy10 and >56.0 Gy10 were 3 and 20.8 months respectively. Dose escalation (BED > 56.0 Gy10 ) was also associated with improved progression-free survival (median 14.7 vs. 2.8 months, P = 0.010). Pain reduction was observed in 90.9% (20/22) of patients with painful bone metastases. Dose-escalated radiotherapy (BED > 56.0 Gy10 ) using HT improved local control in spinal metastases of hepatic malignancies.

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases

The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. In two consecutive periods, 41patients with 46brain metastases received SRT with 1 fraction of 15Gy, while 51patients with 65brain metastases received FSRT with 3fractions of 8Gy. We included patients with brain metastases with a planning target volume of > 13cm(3) or metastases in the brainstem. The minimum follow-up of patients still alive was 22months. Comparing 1fraction of 15Gy with 3fractions of 8Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. The 1-year local progression and pseudo progression rates after 1 fraction of 15Gy or 3fractions of 8Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary.

A Survey of Liver Stereotactic Body Radiation Therapy Practice Patterns in the United States

Although stereotactic body radiotherapy (SBRT) has shown promising results in liver tumors, little is known about its usage in clinical practice. A survey was performed among US radiation oncologists, with results regarding SBRT adoption reported elsewhere (Pan, Cancer 2011). This study presents further analysis of prescriptions, fractionation, and fiducial marker (FM) usage in liver SBRT from that survey. A random sample of 1600 US radiation oncologists was surveyed regarding SBRT usage. Physicians were asked about their practice (type, size, and location), years in practice, years of SBRT experience, use of FM and body frame, target localization techniques, motion management, and most common prescription. A biological equivalent dose (BED) was calculated using the linear quadratic model with α/β = 10. Chi-square tests were performed to identify differences in fractionation and dose per fraction. Spearman's rank correlation coefficients (rs) were calculated to identify associations with BED and FM usage. Of the 1600 physicians surveyed, 40% of contactable physicians responded; 64% of evaluable respondents used SBRT, of which 55% treated liver. Of liver SBRT users, 141 (89%) supplied their most common prescription. The reported prescriptions were varied, with the most common being 15 Gy x 3 (19%), 10 Gy x 5 (14%), and 20 Gy x 3 (12%). The most common number of fractions used was 3 (48%), 5 (38%), and 4 (9%). Practice type, use of body frame and FM, years of SBRT experience, and target localization techniques were not associated with significant differences in fractionation. The median dose per fraction among all prescriptions was 12 Gy. A fraction size of ≥15 Gy for liver SBRT was reported more frequently by respondents who adopted SBRT at any disease site earlier (2000-2008) as compared to more recently (2009-2010) (48% vs 32%, p = 0.02). = The median BED was 106 Gy (12 Gy x 4), including 12% of respondents who treated with BED of 180 Gy (20 Gy x 3). The use of body frame (rs = 0.20, p = 0.02), and practice in an academic center (rs = 0.20, p = 0.02) were associated with higher BED, while increased number of fractions (rs: -0.41, p<0.001) and additional years in practice (rs: -0.17, p = 0.04) were associated with lower BED. Of liver SBRT users, 57% reported the use of FM. Rank correlation identified the use of planar imaging (rs = 0.27, p = 0.001) and gating for motion management (rs = 0.20, p = 0.03) as positively associated with FM usage, while the use of a body frame (rs: -0.18, p = 0.03) had a negative association. There is wide variation in prescription patterns among US radiation oncologists for liver SBRT, with no single prescription accounting for more than a fifth of responses. Further study is required to ascertain optimal dose and fractionation schemes in liver SBRT.

Challenge of dose escalation in locally advanced unfavourable prostate cancer using HDR brachytherapy

In men with locally advanced/high-risk prostate cancer, there is an ongoing challenge to achieve improved results. Dose escalation studies using three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) have shown benefit particularly in the intermediate and poor risk groups of patients. Of concern, however, is the increase in documented rectal toxicity. High-dose rate brachytherapy (HDR-BT) as a boost in combination with external beam radiotherapy (EBRT) is an alternative strategy of dose escalation that can potentially achieve an even higher biological equivalent dose (BED) to the tumour. The results so far are very encouraging for men with poor prognosis disease. Moreover the technique is associated with very low rates of acute and late toxicity.

Lack of benefit at 5 years from a short course of neoadjuvant/concurrent androgen deprivation for unfavorable prostate cancer patients treated to a high total radiation dose

Purpose/Objective: To assess the survival impact of a course of ≤6 months of adjuvant/concurrent androgen deprivation in patients with unfavorable prostate cancer treated to a very high radiation dose with external beam (EBRT) and high dose rate (HDR) brachytherapy boosts. Materials/Methods: Between 1986 and 2002, 579 patients (pts) were treated for clinically localized prostate cancer in two prospective trials of pelvic EBRT and dose escalating HDR brachytherapy boosts. There were 201 pts treated at Kiel University and 378 pts at William Beaumont Hospital with 222 pts receiving androgen deprivation therapy (ADT) for a period of ≤6 months. For this analysis, the patient had to have a follow-up ≥18 months (3 times greater than the exposure to ADT) leaving a total sample of 475 pts. All pts had 1 of the following poor prognostic factors: Stage ≥T2b, Gleason score ≥7 and pretreatment PSA of ≥10. Pts were stratified by any one factor, 219 pts, any 2 factors 194 pts, and to improve comparability, all 3 factors in 138 pts. The ASTRO definition for biochemical failure (BF) was used. Results: The mean follow-up time for all patients was 5.1 years and for those patients with all 3 poor prognostic factors was 6.1 years (range 1.7–14.5 yrs). The 5-year actuarial analysis: a) all patients, b) ADT patients c) patients without ADT and d) patients with all 3 poor prognostic factors are listed in Table 1. We analyzed overall survival (OS), cause-specific survival (CSS), biochemical control (BC), disease free survival (DSF) and clinical local recurrence (c-LR). Of great significance is that the pts receiving a short course of ADT had a lower CSS when all 475 were analyzed p=0.015. For pts with all 3 poor risk factors giving ADT resulted not only in lower CSS p=0.009 but also in lower OS p=0.05. Multivariate analysis for biochemical control demonstrated decreasing age (p=0.039), increasing stage (p=0.008), and increasing Gleason score (<0.001) were significant for biochemical failure. While increasing PSA values, the addition of ADT, the increasing number of poor prognostic factors and the increasing length of follow-up were not predictive variables. Conclusions: EBRT with conformal HDR boosts produces excellent long term outcome in terms of OS, CSS, DFS, BC and c-LR in patients with unfavorable prostate cancer. With the high biological equivalent dose delivered with this technique, the addition of a course of <6 months of neoadjuvant/concurrent ADT to this treatment protocol does not appear to confer a therapeutic advantage. In fact, ADT, did not prevent cancer deaths, has decreased OS, resulted in lower CSS and has added side effects (sexual impotence) as well as the significant cost of hormonal treatment.