Locoregional tumor failure after definitive radiation for patients with stage III non-small cell lung cancer.

BACKGROUND: Locoregional tumor failure (LRF) after definitive chemoradiation for patients with stage III NSCLC remains unacceptably high. This analysis sought to further define where LRF occurs relative to radiation dose received and pre-treatment PET scan-defined maximum standard uptake value (SUVmax). METHODS: This was a retrospective study analyzing patients with stage III NSCLC treated with definitive radiation between 2006 and 2011. LRF was defined as failure within the ipsilateral lung, hilum or mediastinum. The CT simulation scan with the radiation dose distribution was registered to the CT or PET/CT documenting LRF. The region of LRF was contoured, and the dose to 95% of the volume (D95) of LRF was extracted. The pre-treatment SUVmax was also extracted for the anatomic region of LRF. RESULTS: Sixty-one patients were identified. Median follow-up time was 19.1 months (range 2.37-76.33). Seventy four percent of patients were treated with 3-D conformal technique (3DCRT), 15% were treated with Intensity Modulated Radiotherapy (IMRT), and 11% were treated with a combination of 3DCRT and IMRT. Median prescribed radiation dose for all patients was 66 Gy (39.6-74). Concurrent chemotherapy was delivered in 90% of patients. Twenty-two patients (36%) developed a LRF, with a total of 39 anatomic regions of LRF identified. Median time to LRF was 11.4 months (3.5-44.6). Failures were distributed as follows: 36% were in-field failures, 27% were out-of-field failures, 18% were in-field and out-of-field failures, and 18% were in-field and marginal (recurrences within the field edge) failures. There were no isolated marginal failures. Of the patients that developed a LRF, 73% developed a LRF with an in-field component. Sixty-two percent of LRFs were nodal. The median pre-treatment SUVmax for the anatomic region of LRF for patients with an in-field failure was 13. The median D95 of in-field LRF was 63 Gy. CONCLUSIONS: LRF after definitive chemoradiation are comprised primarily of in-field failures, though out-of field failures are not insignificant. Marginal failures are rare, indicating field margins are appropriate. Although radiation dose escalation to standard radiation fields has not yielded success, using PET parameters to define high-risk regions remains worthy of further investigation.

Small cell carcinoma of the anus in the setting of prior squamous dysplasia and carcinoma in situ.

Small cell carcinoma of the anus is a rare tumor that has been infrequently described in the literature. In contrast to squamous cell carcinoma, which is known to be associated with high-risk subtypes of human papillomavirus (HPV), the etiology of small cell carcinoma of the anal canal is not established. We present a case of a patient with small cell carcinoma of the anal canal in the setting of prior squamous dysplasia and carcinoma in situ. In conjunction with recently published data demonstrating the presence of HPV in tumor specimens from patients with small cell carcinoma of the anal canal, our patient's clinical course suggests a possible link between HPV and this rare malignancy.

Quantitative analysis of pre- and post-treatment PET-CT scans using deformable image registration methods.

BACKGROUND AND PURPOSE: To investigate the utility of quantitative PET analysis for early prediction of local control following stereotactic body radiation therapy (SBRT). MATERIAL AND METHODS: An initial test cohort of fourteen cases and a validation cohort of twenty-three cases were analyzed. All patients had metastatic or recurrent cancer and underwent PET-CTs pre- and post- SBRT to a variety of sites. Local failure was defined as biopsy proven persistent/recurrent disease or progressive disease on radiologic imaging. Using deformable registration, radiation dose was transferred to the PET-CTs. Using the prescription isodose as the volume of interest (VOI), response was assessed by generating metabolic volume histograms (MVH). MVH curves examine metabolic heterogeneity in the VOI. Exploratory analyses of the test cohort evaluated the viability of multiple iso-SUV and iso-volumetric points selected from the MVH curves to serve as novel markers of response. Standard PET response markers (maximum/mean SUV and qualitative analysis) were also assessed. RESULTS: In the initial cohort, ten of fourteen patients achieved local control at last follow-up, a median of 225 days following post-SBRT PET. Three out of four local failures had an increase in max SUV, while all patients who achieved local control had a reduction in max SUV (p=0.01). Exploratory analyses using multiple iso-SUV and iso-volumetric points did not yield any factors associated with local control (p>0.05). In the validation cohort, lower post- treatment max SUV (p=.03) and reduction in max SUV (p<0.05) were significantly associated with local control. CONCLUSIONS: Reduction in max SUV following SBRT is associated with local control.

Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review.

Spinal metastasis is a problem that afflicts many cancer patients. Traditionally, conventional fractionated radiation therapy and/or surgery have been the most common approaches for managing such patients. Through technical advances in radiotherapy, high dose radiation with extremely steep drop off can now be delivered to a limited target volume along the spine under image-guidance with very high precision. This procedure, known as stereotactic body radiosurgery, provides a technique to rapidly treat selected spinal metastasis patients with single- or limited-fraction treatments that have similar to superior efficacies compared with more established approaches. This review describes current treatment systems in use to deliver stereotactic body radiosurgery as well as results of some of the larger case series from a number of institutions that report outcomes of patients treated for spinal metastatic disease. These series include nearly 1400 patients and report a cumulative local control rate of 90% with myelopathy risk that is significantly less than 1%. Based on this comprehensive review of the literature, we believe that stereotactic body radiosurgery is an established treatment modality for patients with spinal metastatic disease that is both safe and highly effective.

Evaluation of automatic atlas-based lymph node segmentation for head-and-neck cancer.

PURPOSE: To evaluate if automatic atlas-based lymph node segmentation (LNS) improves efficiency and decreases inter-observer variability while maintaining accuracy. METHODS AND MATERIALS: Five physicians with head-and-neck IMRT experience used computed tomography (CT) data from 5 patients to create bilateral neck clinical target volumes covering specified nodal levels. A second contour set was automatically generated using a commercially available atlas. Physicians modified the automatic contours to make them acceptable for treatment planning. To assess contour variability, the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm was used to take collections of contours and calculate a probabilistic estimate of the "true" segmentation. Differences between the manual, automatic, and automatic-modified (AM) contours were analyzed using multiple metrics. RESULTS: Compared with the "true" segmentation created from manual contours, the automatic contours had a high degree of accuracy, with sensitivity, Dice similarity coefficient, and mean/max surface disagreement values comparable to the average manual contour (86%, 76%, 3.3/17.4 mm automatic vs. 73%, 79%, 2.8/17 mm manual). The AM group was more consistent than the manual group for multiple metrics, most notably reducing the range of contour volume (106-430 mL manual vs. 176-347 mL AM) and percent false positivity (1-37% manual vs. 1-7% AM). Average contouring time savings with the automatic segmentation was 11.5 min per patient, a 35% reduction. CONCLUSIONS: Using the STAPLE algorithm to generate "true" contours from multiple physician contours, we demonstrated that, in comparison with manual segmentation, atlas-based automatic LNS for head-and-neck cancer is accurate, efficient, and reduces interobserver variability.

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy.

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.

A comparison of the expected costs of high dose rate brachytherapy using 252Cf versus 192Ir.

A cost analysis to compare high dose rate (HDR) brachytherapy using either californium-252 (252Cf) or 192Ir was performed to determine the prospects of widespread clinical implementation of HDR 252Cf. Interest in the neutron-emitting 252Cf radioisotope as a radiotherapy nuclide has undergone a resurgence given recent efforts to fabricate HDR remotely afterloaded sources, and other efforts to create a miniature source for improved accessibility to a variety of anatomic sites. Therefore, HDR 252Cf brachytherapy may prove to be a potential rival to the use of HDR 192Ir remotely afterloaded brachytherapy--the current standard-of-care treatment modality using HDR brachytherapy. Considering the possible improvements in clinical efficacy using HDR 252Cf brachytherapy and the enormous costs of other high-LET radiation sources, the cost differences between 252Cf and 192Ir may be well-justified.