Dose escalated, hypofractionated radiotherapy using helical tomotherapy for inoperable non-small cell lung cancer: preliminary results of a risk-stratified phase I dose escalation study.

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to < or = 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTD(mean) (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% +/- 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.

Quality assurance of a helical tomotherapy machine.

Helical tomotherapy has been developed at the University of Wisconsin, and 'Hi-Art II' clinical machines are now commercially manufactured. At the core of each machine lies a ring-gantry-mounted short linear accelerator which generates x-rays that are collimated into a fan beam of intensity-modulated radiation by a binary multileaf, the modulation being variable with gantry angle. Patients are treated lying on a couch which is translated continuously through the bore of the machine as the gantry rotates. Highly conformal dose-distributions can be delivered using this technique, which is the therapy equivalent of spiral computed tomography. The approach requires synchrony of gantry rotation, couch translation, accelerator pulsing and the opening and closing of the leaves of the binary multileaf collimator used to modulate the radiation beam. In the course of clinically implementing helical tomotherapy, we have developed a quality assurance (QA) system for our machine. The system is analogous to that recommended for conventional clinical linear accelerator QA by AAPM Task Group 40 but contains some novel components, reflecting differences between the Hi-Art devices and conventional clinical accelerators. Here the design and dosimetric characteristics of Hi-Art machines are summarized and the QA system is set out along with experimental details of its implementation. Connections between this machine-based QA work, pre-treatment patient-specific delivery QA and fraction-by-fraction dose verification are discussed.

Antideuteron yield at the AGS and coalescence implications

We present Experiment 864's measurement of invariant antideuteron yields in 11.5A GeV/c Au+Pt collisions. The analysis includes 250x10(6) triggers representing 14x10(9) 10% central interactions sampled for events with high mass candidates. We find (1/2pip(t))d(2)N/dydp(t) = 3.5+/-1.5(stat)+0.9-0.5(syst)x10(-8) GeV-2 c(2) for 1.8 = 0.35 GeV/c ( y(c.m.) = 1.6) and 3.7+/-2.7(stat)+1.4-1.5(syst)x10(-8) GeV-2 c(2) for 1.4 = 0.26 GeV/c, and a coalescence parameter B2; of 4.1+/-2. 9(stat)+2.3-2.4(syst)x10(-3) GeV2 c(-3). Implications for coalescence and antimatter annihilation are discussed.