Prognostic value of disease distribution in secondary central nervous system diffuse large B cell lymphoma treated with radiation therapy.

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.

Comparative Effectiveness of Computed Tomography- Versus Ultrasound-Guided Percutaneous Radiofrequency Ablation Among Medicare Patients 65 Years of Age or Older With Hepatocellular Carcinoma.

BACKGROUND: For patients with hepatocellular carcinoma (HCC) not eligible for surgical resection, radiofrequency ablation (RFA) is a promising technique that reduces the risk of disease progression. OBJECTIVES: To evaluate whether the trend of image guidance for RFA is moving toward the more expensive computed tomography (CT) technology and to determine the clinical benefits of CT guidance over the ultrasound (US) guidance. METHODS: A cohort of 463 patients was identified from the Surveillance, Epidemiology, and End Results and Medicare-linked database. The temporal trends in use of image guidance were assessed using the Cochrane-Armitage test. The associations between modality of image guidance and survival, complications, and costs were assessed using the Cox regression model, the logistic regression model, and the generalized linear model, respectively. RESULTS: The use of CT-guided RFA increased sharply, from 20.7% in 2002 to 75.9% in 2011. Compared with CT-guided RFA, those who received US-guided RFA had comparable risk of periprocedural and delayed postprocedural complications. Stratified analyses by tumor size also showed no statistically significant difference. In adjusted survival analysis, no statistically significant difference was observed in overall and cancer-specific survival. Nevertheless, the cost of CT-guided RFA ($2847) was higher than that of US-guided RFA ($1862). CONCLUSIONS: Despite its rapid adoption over time, CT-guided RFA incurred higher procedural costs than US-guided RFA but did not significantly improve postprocedural complications and survival. Echoing the American Board of Internal Medicine's Choosing Wisely campaign and the American Society of Clinical Oncology's Value of Cancer Care initiative, findings from our study call for critical evaluation of whether CT-guided RFA provides high-value care for patients with HCC.

Intensity Modulated Radiation Therapy Versus Volumetric Arc Radiation Therapy in the Treatment of Glioblastoma-Does Clinical Benefit Follow Dosimetric Advantage?

PURPOSE: Volumetric modulated arc therapy (VMAT) has been shown by multiple planning studies to hold dosimetric advantages over intensity modulated radiation therapy (IMRT) in the management of brain tumors, including glioblastoma (GBM). Although promising, the clinical impact of these findings has not been fully elucidated. METHODS AND MATERIALS: We retrospectively reviewed consecutive patients with a pathologic-confirmed diagnosis of GBM who were treated between 2014 and 2015, a period that encompassed the transition from IMRT to VMAT at a single institution. After surgery, radiation with VMAT consisted of 2 to 3 coplanar arcs with or without an additional noncoplanar arc or IMRT with 5 to 6 gantry angles with concurrent and adjuvant temozolomide. Actuarial analyses were performed using the Kaplan Meier method. RESULTS: A total of 88 patients treated with IMRT (n = 45) and VMAT (n = 43) were identified. Patients were similar in terms of age, sex, performance status, extent of resection, and the high dose target volume. At a median follow-up time of 27 months (range, .7-32.3 months), the overall survival, freedom from progression, and freedom from new or worsening toxicity rates were not different between the 2 treatment groups (log-rank: P = .33; .87; and .23, respectively). There was no difference in incidences of alopecia, erythema, nausea, worsening or new onset fatigue, or headache during radiation, or temozolomide dose reduction for thrombocytopenia or neutropenia (all P > .05). Patterns of failure were different with more out of field failures in the IMRT group (P = .02). The mean time of treatment (TOT) was significantly reduced by 29% (P < .01) with VMAT (mean TOT: 10.3 minutes) compared with IMRT (mean TOT: 14.6 minutes). CONCLUSIONS: For GBM, treatment with VMAT results in similar oncologic and toxicity outcomes compared with IMRT and may improve resource utilization by reducing TOT. VMAT should be considered a potential radiation modality for patients with GBM.

Complication Rates and Downstream Medical Costs Associated With Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting.

Importance: The Centers for Medicare & Medicaid Services added lung cancer screening with low-dose computed tomography (LDCT) as a Medicare preventive service benefit in 2015 following findings from the National Lung Screening Trial (NLST) that showed a 16% reduction in lung cancer mortality associated with LDCT. A challenge in developing and promoting a national lung cancer screening program is the high false-positive rate of LDCT because abnormal findings from thoracic imaging often trigger subsequent invasive diagnostic procedures and could lead to postprocedural complications. Objective: To determine the complication rates and downstream medical costs associated with invasive diagnostic procedures performed for identification of lung abnormalities in the community setting. Design, Setting, and Participants: A retrospective cohort study of non-protocol-driven community practices captured in MarketScan Commercial Claims & Encounters and Medicare supplemental databases was conducted. A nationally representative sample of 344 510 patients aged 55 to 77 years who underwent invasive diagnostic procedures between 2008 and 2013 was included. Main Outcomes and Measures: One-year complication rates were calculated for 4 groups of invasive diagnostic procedures. The complication rates and costs were further stratified by age group. Results: Of the 344 510 individuals aged 55 to 77 years included in the study, 174 702 comprised the study group (109 363 [62.6%] women) and 169 808 served as the control group (106 007 [62.4%] women). The estimated complication rate was 22.2% (95% CI, 21.7%-22.7%) for individuals in the young age group and 23.8% (95% CI, 23.0%-24.6%) for those in the Medicare group; the rates were approximately twice as high as those reported in the NLST (9.8% and 8.5%, respectively). The mean incremental complication costs were $6320 (95% CI, $5863-$6777) for minor complications to $56 845 (95% CI, $47 953-$65 737) for major complications. Conclusions and Relevance: The rates of complications after invasive diagnostic procedures were higher than the rates reported in clinical trials. Physicians and patients should be aware of the potential risks of subsequent adverse events and their high downstream costs in the shared decision-making process.

Dosimetric advantages of stereotactic radiosurgery as a boost to adjuvant conventional radiotherapy in the setting of adenoid cystic carcinoma of the parotid with skull base invasion.

This study highlights gamma knife stereotactic radiosurgery (GK-SRS) as boost therapy in a patient with adenoid cystic carcinoma of the parotid involving the skull base and invasion of the facial nerve. Using GK-SRS, dose to the brainstem and temporal lobe were reduced when compared to less conformal radiotherapy techniques.

Response-adapted radiation therapy for newly diagnosed primary diffuse large B-cell lymphoma of the CNS treated with methotrexate-based systemic therapy.

BACKGROUND: For patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL), whole-brain radiation therapy (WBRT) to doses of ≥45 Gy are often given after a partial response (PR) to methotrexate-based induction chemotherapy. We conducted an exploratory analysis to determine whether lower-dose WBRT, given with a boost to sites of persistent disease, might be a reasonable alternative. METHODS AND MATERIALS: We retrospectively reviewed the records of 22 patients with PCNSL who received WBRT, with or without a boost, after methotrexate-based induction chemotherapy. Outcomes were compared among patients according to response to chemotherapy using the Kaplan-Meier method. RESULTS: Median follow-up was 52 months. All patients with a complete response (CR) (n = 5) received WBRT to 23.4 Gy. One CR patient died after an in-field relapse. Patients with partial response (PR) (n = 10) received a median whole-brain dose of 23.4 Gy with (n = 8) or without (n = 2) a boost; there were 2 relapses within the central nervous system (CNS). All PR patients were alive at the time of analysis. The overall survival (P = .127) and freedom from relapse within the CNS (P = .967) were not different for patients with CR versus PR. Baseline and follow-up neurocognitive evaluations were available for 4 PR patients, and there were no significant differences between pre- and post-treatment evaluations (P > .05 for language, memory, visual-spatial, attention, or motor functions). All patients who progressed or did not respond to chemotherapy and then received WBRT had died at a median time of 3.4 months. Patients who progressed or did not respond to chemotherapy had worse overall survival (P = .001) and freedom from CNS relapse (P = .005) compared with CR patients. CONCLUSIONS: Among patients with a PR to induction chemotherapy, reduced-dose WBRT with a boost to residual PCNSL may be a viable treatment approach that merits further investigation.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

BACKGROUND: Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. METHODS: A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. RESULTS: Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HRadjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HRadjusted 9.53; 95% CI 3.04-27.06). CONCLUSION: Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival.

Radiation Therapy as an Effective Salvage Strategy for Secondary CNS Lymphoma.

PURPOSE: We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma. METHODS AND MATERIALS: The cohort comprised 44 patients with systemic diffuse large B-cell lymphoma (DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse that was treated with RT. RESULTS: Of these patients, 29 (66%) were in systemic remission when CNS disease was diagnosed. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% confidence interval 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation after RT, and had brain parenchymal (vs leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: 1 involved the brain parenchyma, and 7 involved the spine and/or cerebrospinal fluid and/or meninges. CONCLUSIONS: We conclude that RT is associated with high response rates and may contribute to long-term OS. In addition, RT may provide CNS disease control that facilitates successful salvage with stem cell transplantation in patients with chemotherapy-refractory disease.

Prognostic Factors as a Function of Disease-free Interval After Definitive (Chemo)radiation for Non-Small Cell Lung Cancer Using Conditional Survival Analysis.

PURPOSE: We analyzed overall and disease-free survival (OS and DFS) after definitive (chemo)radiation for stage III non-small cell lung cancer with 2 statistical methods: Kaplan-Meier (KM) analysis, with diagnosis as index date, and conditional survival (CS) analysis, with a variety of disease-free index dates, and determined whether prognostic factors varied based on the reference date. MATERIALS AND METHODS: All 651 patients analyzed received definitive (chemo)radiotherapy for stage III non-small cell lung cancer in November 1998 to December 2010 at a single institution; all had Karnofsky performance status scores ≥60 and received ≥60 Gy. OS and DFS were first calculated with the KM method, and then CS was used to calculate 2 outcomes: OS conditioned on DFS time (OS|DFS) and DFS conditioned on DFS time (DFS|DFS). Factors predicting OS and DFS conditioned on 1-, 2-, and 3-year DFS were sought in univariate and multivariate analyses. RESULTS: KM analysis produced 1-, 2-, and 3-year DFS rates of 48%, 30%, and 26%; OS rates were 64%, 41%, and 29%. By CS analysis, both OS|DFS and DFS|DFS showed an increase in 5-year OS after 6 months, and CS after 30 months approached 100%. On multivariate analyses, age and concurrent chemoradiation predicted OS|DFS; age, smoking history, tumor histology, disease stage, and radiation dose predicted DFS|DFS. CONCLUSIONS: CS analysis showed that the probability of long-term survival increases sharply after 6 months with no evidence of disease; factors predicting survival differed based on the method and endpoint used.

Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

BACKGROUND: The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). METHODS: The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). RESULTS: In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718-0.988; 45-59.9 Gy: HR, 0.596; 95% CI, 0.479-0.743; 60-75 Gy: HR, 0.419; 95% CI, 0.339-0.517) correlated with OS. The RT dose-survival correlation for patients who received higher (60-75 Gy) versus lower (45-59.9 Gy) therapeutic doses was confirmed by propensity-score matching. CONCLUSIONS: Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653-1661. © 2017 American Cancer Society.

Prognostic value of pretherapy platelet elevation in oropharyngeal cancer patients treated with chemoradiation.

The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. A total of 433 oropharyngeal cancer patients (OPC) treated with intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data were extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT ) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (p < 0.03, p < 0.04 and p < 0.0001, respectively) for patients with PLTpre-chemoRT value of ≥350 × 10(9) /L. Actuarial 5-year locoregional control (LRC) and FDM were 83 and 85% for non-thrombocythemic patients while patient with high platelets had 5-year LRC and FDM of 73 and 74%, respectively. Likewise, 5-year OS was better for patients with normal platelet counts by comparison (76 vs. 57%; p < 0.0001). Comparison of univariate parametric models demonstrated that PLTpre-chemoRT was better among tested models. Multivariate assessment demonstrated improved performance of models which included pretherapy platelet indices. On Bayesian information criteria analysis, the optimal prognostic model was then used to develop nomograms predicting 3-, 5- and 10-year OS. In conclusion, pretreatment platelet elevation is a promising predictor of prognosis, and further work should be done to elucidate the utility of antiplatelets in modifying risk in OPC patients.

Propensity score-matched analysis of comprehensive local therapy for oligometastatic non-small cell lung cancer that did not progress after front-line chemotherapy.

PURPOSE: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. METHODS AND MATERIALS: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. RESULTS: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. CONCLUSIONS: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score-matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

Nomogram for predicting symptom severity during radiation therapy for head and neck cancer.

OBJECTIVES: Radiation therapy (RT), with or without chemotherapy, can cause significant acute toxicity among patients treated for head and neck cancer (HNC), but predicting, before treatment, who will experience a particular toxicity or symptom is difficult. We created and evaluated 2 multivariate models and generated a nomogram to predict symptom severity during RT based on a patient-reported outcome (PRO) instrument, the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN). STUDY DESIGN: This was a prospective, longitudinal, questionnaire-based study. SETTING: Tertiary cancer care center. SUBJECTS AND METHODS: Subjects were 264 patients with HNC (mostly oropharyngeal) who had completed the MDASI-HN before and during therapy. Pretreatment variables were correlated with MDASI-HN symptom scores during therapy with multivariate modeling and then were correlated with the composite MDASI-HN score during week 5 of therapy. RESULTS: A multivariate model incorporating pretreatment PROs better predicted MDASI-HN symptom scores during treatment than did a model based on clinical variables and physician-rated patient performance status alone (Akaike information criterion = 1442.5 vs 1459.9). In the most parsimonious model, pretreatment MDASI-HN symptom severity (P < .001), concurrent chemotherapy (P = .006), primary tumor site (P = .016), and receipt of definitive (rather than adjuvant) RT (P = .044) correlated with MDASI-HN symptom scores during week 5. That model was used to construct a nomogram. CONCLUSION: Our model demonstrates the value of incorporating baseline PROs, in addition to disease and treatment characteristics, to predict patient symptom burden during therapy. Although additional investigation and validation are required, PRO-inclusive prediction tools can be useful for improving symptom interventions and expectations for patients being treated for HNC.

Malfunctions of implantable cardiac devices in patients receiving proton beam therapy: incidence and predictors.

PURPOSE: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. METHODS AND MATERIALS: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. RESULTS: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. CONCLUSIONS: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.

Use of the LQ model with large fraction sizes results in underestimation of isoeffect doses.

PURPOSE: To test the appropriateness of the linear-quadratic (LQ) model to describe survival of jejunal crypt clonogens after split doses with variable (small 1-6 Gy, large 8-13 Gy) first dose, as a model of its appropriateness for both small and large fraction sizes. METHODS: C3Hf/KamLaw mice were exposed to whole body irradiation using 300 kVp X-rays at a dose rate of 1.84 Gy/min, and the number of viable jejunal crypts was determined using the microcolony assay. 14 Gy total dose was split into unequal first and second fractions separated by 4 h. Data were analyzed using the LQ model, the lethal potentially lethal (LPL) model, and a repair-saturation (RS) model. RESULTS: Cell kill was greater in the group receiving the larger fraction first, creating an asymmetry in the plot of survival vs size of first dose, as opposed to the prediction of the LQ model of a symmetric response. There was a significant difference in the estimated ßs (higher ß after larger first doses), but no significant difference in the αs, when large doses were given first vs small doses first. This difference results in underestimation (based on present data by approximately 8%) of isoeffect doses using LQ model parameters based on small fraction sizes. While the LPL model also predicted a symmetric response inconsistent with the data, the RS model results were consistent with the observed asymmetry. CONCLUSION: The LQ model underestimates doses for isoeffective crypt-cell survival with large fraction sizes (in the present setting, >9 Gy).

Preclinical evaluation of sunitinib, a multi-tyrosine kinase inhibitor, as a radiosensitizer for human prostate cancer.

BACKGROUND: Many prostate cancers demonstrate an increased expression of growth factor receptors such as vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) which have been correlated with increased resistance to radiotherapy and poor prognosis in other tumors. Therefore, response to radiation could potentially be improved by using inhibitors of these abnormally activated pathways. We have investigated the radiosensitizing effects of sunitinib, a potent, multi-tyrosine kinase inhibitor of the VEGFR and PDGFR receptors, on human prostate cancer cells. METHODS: The radiosensitizing effects of sunitinib were assessed on human prostate cancer cell lines DU145, PC3 and LNCaP by clonogenic assay. Sunitinib's ability to inhibit the activities of its key targets was determined by immunoblot analysis. The radiosensitizing effects of sunitinib in vivo were tested on human tumor xenografts growing in nude mice where response was assessed by tumor growth delay. RESULTS: Clonogenic survival curve assays for both DU145 and PC3 cells showed that the surviving fraction at 2 Gy was reduced from 0.70 and 0.52 in controls to 0.44 and 0.38, respectively, by a 24 hr pretreatment with 100 nM sunitinib. LNCaP cells were not radiosensitized by sunitinib. Dose dependent decreases in VEGFR and PDGFR activation were also observed following sunitinib in both DU145 and PC3 cells. We assessed the ability of sunitinib to radiosensitize PC3 xenograft tumors growing in the hind limb of nude mice. Sunitinib given concurrently with radiation did not prolong tumor growth delay. However, when animals were treated with sunitinib commencing the day after fractionated radiation was complete, tumor growth delay was enhanced compared to radiation alone. CONCLUSIONS: We conclude, based on the in vivo results, that sunitinib and radiation do not interact directly to radiosensitize the PC3 tumor cells in vivo as they did in vitro. The fact that tumor growth delay was enhanced when sunitinib was given after radiotherapy was completed suggests that sunitinib may be acting on the irradiated tumor stroma and suppressing its ability to sustain regrowth of the irradiated tumor. Based on these preclinical findings, we suggest that the combination of sunitinib and radiation for the treatment of prostate cancer deserves further development.