Jordan Maier

Lung SBRT: dosimetric and delivery comparison of RapidArc, TomoTherapy, and IMRT

This study seeks to compare fixed‐field intensity‐modulated radiation therapy (FF IMRT), RapidArc (RA), and helical tomotherapy (HT) to discover the optimal treatment modality to deliver SBRT to the peripheral lung. Eight patients with peripheral primary lung cancer were reviewed. Plans were prescribed a dose of 48 Gy and optimized similarly with heterogeneity corrections. Plan quality was assessed using conformality index (CI100%), homogeneity index (HI), the ratio of the 50% isodose volume to PTV (R50%) to assess intermediate dose spillage, and normal tissue constraints. Delivery efficiency was evaluated using treatment time and MUs. Dosimetric accuracy was assessed using gamma index (3% dose difference, 3 mm DTA, 10% threshold), and measured with a PTW ARRAY seven29 and OCTAVIUS phantom. CI100%,HI, and R50% were lowest for HT compared to seven‐field coplanar IMRT and two‐arc coplanar RA (p<0.05). Normal tissue constraints were met for all modalities, except maximum rib dose due to close proximity to the PTV. RA reduced delivery time by 60% compared to HT, and 40% when compared to FF IMRT. RA also reduced the mean MUs by 77% when compared to HT, and by 22% compared to FF IMRT. All modalities can be delivered accurately, with mean QA pass rates over 97%. For peripheral lung SBRT treatments, HT performed better dosimetrically, reducing maximum rib dose, as well as improving dose conformity and uniformity. RA and FF IMRT plan quality was equivalent to HT for patients with minimal or no overlap of the PTV with the chest wall, but was reduced for patients with a larger overlap. RA and IMRT were equivalent, but the reduced treatment times of RA make it a more efficient modality. PACS numbers: 87.53.Ly87.55.N‐, 87.55.D‐, 87.56.bd

Sunitinib plus androgen deprivation and radiation therapy for patients with localized high-risk prostate cancer: Results from a multi-institutional phase 1 study

PURPOSE To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. METHODS AND MATERIALS Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. RESULTS Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. CONCLUSIONS The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

Abstract 741: Sunitinib plus hormone ablation and radiation therapy for patients with high-risk localized prostate cancer: Results from a multi-institutional phase I study

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: Novel strategies are needed to improve the long-term outcomes of patients (pts) with high-risk prostate cancer treated with hormonal ablation and external beam radiation therapy (XRT). Preclinical data suggest that angiogenesis inhibitors normalize vasculature, reduce hypoxia, and improve the therapeutic index of XRT. To assess the feasibility of combined VEGFR/PDGFR inhibition in combination with XRT, a Phase I study with sunitinib was initiated. Methods: Seventeen men with adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or PSA > 20ng/ml received initial hormonal ablation (leuprolide 22.5mg every 12 weeks + oral bicalutamide 50mg daily) for 4-8 weeks prior to oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks post XRT (prostate and proximal seminal vesicles received 75.6 Gy in 42 fractions with at least 50 Gy for the distal seminal vesicles). A 3+3 sequential dose-escalation design was employed to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose (MTD) of sunitinib. Results: The first 4 pts enrolled on 37.5 mg experienced a DLT during lead-in. *With 2 pts unexpectedly experiencing Grade 3 neutropenia and a third experiencing Grade 3 thrombocytopenia, a drug-interaction with bicalutamide was suspected. The protocol was revised to replace these pts and omit concurrent bicalutamide. Of these first 4 pts, 3 were dose reduced to 25 mg and successfully completed full treatment, while 1 pt withdrew. Of the next 3 pts subsequently enrolled at 37.5 mg, 2 of 3 on concurrent therapy have experienced DLTs (G3 diarrhea with concomitant sunitinib-induced thyrotoxicosis; G3 proctitis). Conclusions: Using a daily dosing regimen and a lead-in phase, the MTD of concurrent sunitinib, hormonal ablation and XRT was 37.5mg daily. The recommended Phase 2 dose of sunitinib for further study is 25mg daily. ![Figure][1] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 741. doi:1538-7445.AM2012-741 [1]: pending:yes