Single-Fraction Stereotactic Ablative Body Radiotherapy to the Lung - The Knockout Punch.

This overview summarises the current evidence on efficacy and safety of single-fraction stereotactic ablative body radiotherapy (SABR) for primary lung cancers and lung metastases, in comparison with the more widely adapted multi-fraction SABR regimens. A literature search using the Medline database through PubMed was carried out using the following key words: ('stereotactic' or 'sabr' or 'sbrt'), ('radiotherapy' or 'radiation therapy'), ('lung' or 'thorax' or 'thoracic' or 'chest'), ('cancer' or 'metasta-' or 'oligometasta-'), alongside: (i) ('single-fraction' or 'single-dose') to identify trials and cohort studies with single-fraction SABR to lung malignant tumours and (ii) ('fraction' or 'schedule') limiting the search to 'clinical trial' and 'randomized controlled trial' to ensure thorough capture of lung SABR trials comparing different fractionations. The review discusses the radiobiological, technical and organ at risk considerations of single-fraction SABR to the lung.

SU-E-J-105: Evaluating Auto-Contouring of Prostate KV Conebeam CTs.

PURPOSE: Auto-contouring of daily kV conebeam CTs (kVCBCT) is critical for online adaptive radiotherapy. We surveyed a set of geometric and dosimetric measures to determine which best assess the suitability of kVCBCT contouring algorithms for use in prostate region adaptive planning. METHODS: Six patients with daily kVCBCT undergoing IMRT of the prostate to 78 Gy were selected. Dose was recalculated with patient density forced to water. Contours were generated on nine kVCBCT for each patient using ABAS (Elekta Ltd.) and also by a physician. The prostate mean dose, D100, D98, where determined and V70 (% and cc) and mean dose for the bladder and rectum for both physician and auto contours. The Dice's Coefficient (DC) was calculated between auto and physician contours, as well as a restricted DC (rDC) which combines geometric and dosimetric information by comparing only the volume within a high dose region. RESULTS: Prostate accuracy can only be discerned with D100, additionally there is no correlation (R2=0.036) between D100 and DC. For all organs, mean dose does not reflect contour suitability. There is large variation in V70 (% and cc) for rectum and bladder, implying V70 is a sensitive indicator of contour suitability. There is however no correlation of V70 with DC. A dose region (>57 Gy) to calculate rDC was chosen to provided optimal correlation (R2>0.81) to V70 (% and cc, rectum and bladder). CONCLUSIONS: V70 for rectum and bladder shows the most sensitivity to contour suitability, by concentrating on where accuracy is most vital. Prostate contouring is less critical due to treatment margins, D100 provides the most discerning metric. DC and mean dose are not useable. In lieu of V70, rDC could be used. The rDC can be approximated by limiting to within 2-3 cm of the prostate contour, alleviating the need to calculate dose. A research version of ABAS was provided by Elekta.

SU-E-T-486: Volume and Location Dependence on the Difference Between Monte Carlo and Pencil Beam Dose Calculations for Lung Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiotherapy has been an efficacious treatment modality for early stage non-small cell lung cancer. The accuracy of dose calculations is in question due to the presence of inhomogeneity. It was required in several clinical trials to calculate dose without heterogeneity correction. However, to better correlate the outcomes with the planned dose, accurate dose calculation with heterogeneity correction is highly desirable. METHODS: We compared the recalculated dose with Monte Carlo (MC) algorithm to the original Pencil Beam (PB) calculations for clinical lung SBRT plans. Thirty-one clinical plans that followed protocol guidelines were retrospectively investigated. Dosimetric parameters D1, D95 and D99 for the PTV and D1 for organs at risk were compared. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. RESULTS: Compared to the PB calculations without heterogeneity correction in clinical plans, we found that in terms of D95 of PTV, (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculation resulted in an average reduction of 23.8% and 15.3% in D95 for island and edge lesions respectively compared to the MC calculation. For organs at risks, no clinical meaningful differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. CONCLUSIONS: Using a single scaling factor to account for the differences in using heterogeneity correction may not be sufficient. To understand dose-response relation in Lung SBRT, accurate dose calculation such as the Monte Carlo algorithms is highly recommended.

SU-E-J-10: Accuracy of Image Guidance Using Cone-Beam CT with Multiple Breath Hold Using Active Breathing Coordination.

PURPOSE: To complete a CBCT for a treatment using ABC, multiple breath hold (BH) (>3) were used due to the slow gantry rotation and the short BH period. Inter-BH tumor position variability may introduce distortion in the reconstructed images. This study aims to determine a threshold of the inter-BH scan displacement so that the inconsistency can be identified from the CBCT images. METHODS: A numerical phantom was constructed to represent the thorax region of a human body. To simulate the inter-BH displacements, known magnitudes of motion (s = 0, 1, 3, 5 mm) along the longitudinal direction were introduced for the 'tumor' and 'diaphragm' in the phantom. Two different irregular motion patterns (s1=s3=/=s2 and s1=/=s2=/=s3) during CBCT scans were tested. Furthermore, a physical phantom with a movable insert was scanned using a commercial CBCT system. The insert of the phantom was programmed to move in the longitudinal direction according to the same motion patterns as designed in the numerical simulations. Subsequently, nine CBCT's in 'half-fan' mode for the physical phantom were acquired with the insert in various positions. These CBCT images were then fused to the reference CT by aligning to either the body of the phantom or the 'tumor' inside the insert. RESULTS: Based on numerical simulation, position variation >1mm can be observed from the reconstructed CBCT images. Based on acquired CBCTs of the physical phantom, position variations of >3mm or 5mm were observed, depending on the motion pattern during the data acquisition. Because of the use of half-fan mode, we observed the order of position displacements of the tumor during CBCT acquisition drastically affected the outcome of imaging registration. CONCLUSIONS: Using ABC device, the inter-BH variability during a CBCT acquisition affects accuracy of tumor localization. A patient individualized planning margin might be necessary to account for this effect.

Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals.

Although high frequencies of T lymphocytes specific for certain tumor-associated antigens have been detected in some cancer patients, increasing evidence suggests that these T cells may be functionally defective in vivo and fail to induce meaningful clinical responses. One strategy to overcome this limitation is to target novel antigens that are ignored during the natural antitumor immune response but are nevertheless capable of triggering effector T-cell responses against tumors after optimal presentation by antigen-presenting cells. Here, we show that the telomerase catalytic subunit (hTERT)-a nearly universal tumor antigen identified by epitope deduction rather than from patient immune responses-is immunologically ignored by patients despite progressive tumor burden. Nevertheless, HLA-A2-restricted CTLs against hTERT are equivalently induced ex vivo from patients and healthy individuals and efficiently kill human tumor cell lines and primary tumors. Thus, telomerase-specific T cells from cancer patients are spared functional inactivation because of immunological ignorance. These findings support clinical efforts to target the hTERT as a tumor antigen with broad therapeutic potential.

Phase I study of recombinant human CD40 ligand in cancer patients.

PURPOSE: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation. PATIENTS AND METHODS: Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin's lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression. RESULTS: Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 +/- 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL). For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient was taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biopsy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which was sustained in four patients through four courses. CONCLUSION: The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.

Zinc elevates neuropeptide Y levels in rat pheochromocytoma cells by a mechanism independent of L-channel mediated inhibition of release.

Both zinc and neuropeptide Y (NPY) have been implicated as playing a role in seizures and feeding behavior. We investigated the hypothesis that zinc could regulate levels of NPY, and found that chronic exposure to 50-100 microM zinc increased levels of cellular NPY in cultured PC12 cells grown in the presence of nerve growth factor. Zinc's effect on NPY was specific, time- and concentration-dependent, and independent of inhibition of NPY release secondary to blockade of dihydropyridine-sensitive calcium channels. These results are consistent with a role for zinc in regulating hippocampal NPY following high-frequency neuronal activity.