S. Nagda

Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis

OBJECT Following resection of a brain metastasis, stereotactic radiosurgery (SRS) to the cavity is an emerging alternative to postoperative whole-brain radiation therapy (WBRT). This approach attempts to achieve local control without the neurocognitive risks associated with WBRT. The authors aimed to report the outcomes of a large patient cohort treated with this strategy. METHODS A retrospective review identified 91 patients without a history of WBRT who received Gamma Knife (GK) SRS to 96 metastasis resection cavities between 2007 and 2013. Patterns of intracranial control were examined in the 86 cases with post-GK imaging. Survival, local failure, and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were tested by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses. RESULTS Common primary tumors were non-small cell lung (43%), melanoma (14%), and breast (13%). The cases were predominantly recursive partitioning analysis Class I (25%) or II (70%). Median preoperative metastasis diameter was 2.8 cm, and 82% of patients underwent gross-total resection. A median dose of 16 Gy was delivered to the 50% isodose line, encompassing a median treatment volume of 9.2 cm(3). Synchronous intact metastases were treated in addition to the resection bed in 43% of cases. Patients survived a median of 22.3 months from the time of GK. Local failure developed in 16 cavities, for a crude rate of 18% and 1-year actuarial local control of 81%. Preoperative metastasis diameter ≥ 3 cm and residual or recurrent tumor at the time of GK were associated with local failure (p = 0.04 and 0.008, respectively). Distant intracranial failure occurred in 55 cases (64%) at a median of 7.3 months from GK. Salvage therapies included WBRT and additional SRS in 33% and 31% of patients, respectively. Leptomeningeal carcinomatosis developed in 12 cases (14%) and was associated with breast histology and infratentorial cavities (p = 0.024 and 0.012, respectively). CONCLUSIONS This study bolsters the existing evidence for SRS to the resection bed. Local control rates are high, but patients with larger preoperative metastases or residual/recurrent tumor at the time of SRS are more likely to fail at the cavity. While most patients develop distant intracranial failure, an SRS approach spared or delayed WBRT in the majority of cases. The risk of leptomeningeal carcinomatosis does not appear to be elevated with this strategy.

Comparison of standardized uptake value-based positron emission tomography and computed tomography target volumes in esophageal cancer patients undergoing radiotherapy

PURPOSE To study various standardized uptake value (SUV)-based approaches to ascertain the best strategy for delineating metabolic tumor volumes (MTV). METHODS AND MATERIALS Twenty-two consecutive previously treated esophageal cancer patients with positron emission tomography (PET) imaging and computed tomography (CT)-based radiotherapy plans were studied. At the level of the tumor epicenter, MTVs were delineated at 11 different thresholds: SUV ≥2, ≥2.5, ≥3, ≥3.5 (SUV(n)); ≥40%, ≥45%, and ≥50% of the maximum (SUV(n%)); and mean liver SUV + 1, 2, 3, and 4 standard deviations (SUV(Lnσ)). The volume ratio and conformality index were determined between MTVs, and the corresponding CT/endoscopic ultrasound-based gross tumor volume (GTV) at the epicenter. Means were analyzed by one-way analysis of variance for repeated measures and further compared using a paired t test for repeated measures. RESULTS The mean conformality indices ranged from 0.33 to 0.48, being significantly (p < 0.05) closest to 1 at SUV(2.5) (0.47 ± 0.03) and SUV(L4σ) (0.48 ± 0.03). The mean volume ratios ranged from 0.39 to 2.82, being significantly closest to 1 at SUV(2.5) (1.18 ± 0.36) and SUV(L4σ) (1.09 ± 0.15). The mean value of the SUVs calculated using the SUV(L4σ) approach was 2.4. CONCLUSIONS Regardless of the SUV thresholding method used (i.e., absolute or relative to liver mean), a threshold of approximately 2.5 yields the highest conformality index and best approximates the CT-based GTV at the epicenter. These findings may ultimately aid radiation oncologists in the delineation of the entire GTV in esophageal cancer patients.

Efficacy and safety of stereotactic body radiation therapy for the treatment of pulmonary metastases from sarcoma: A potential alternative to resection.

Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity.

Prospective Evaluation of Dual-Energy Imaging in Patients Undergoing Image Guided Radiation Therapy for Lung Cancer: Initial Clinical Results

PURPOSE A prospective feasibility study was conducted to investigate the utility of dual-energy (DE) imaging compared to conventional x-ray imaging for patients undergoing kV-based image guided radiation therapy (IGRT) for lung cancer. METHODS AND MATERIALS An institutional review board-approved feasibility study enrolled patients with lung cancer undergoing IGRT and was initiated in September 2011. During daily setup, 2 sequential respiration-gated x-ray images were obtained using an on-board imager. Imaging was composed of 1 standard x-ray image at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted logarithmic subtraction of the 2 images was performed offline to create a soft tissue-selective DE image. Conventional and DE images were evaluated by measuring relative contrast and contrast-to-noise ratios (CNR) and also by comparing spatial localization, using both approaches. Imaging dose was assessed using a calibrated ion chamber. RESULTS To date, 10 patients with stage IA to IIIA lung cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in complete suppression of overlying bone in all 57 DE images, with an average improvement in relative contrast of 4.7 ± 3.3 over that of 120 kVp x-ray images (P<.0002). The improvement in relative contrast with DE imaging was seen for both smaller (gross tumor volume [GTV] ≤5 cc) and larger tumors (GTV >5 cc), with average relative contrast improvement ratios of 3.4 ± 4.1 and 5.4 ± 3.6, respectively. Moreover, the GTV was reliably localized in 95% of the DE images versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image set was 0.44 ± 0.03 mGy versus 0.43 ± 0.03 mGy, using conventional kV imaging parameters. CONCLUSIONS Initial results of this feasibility study suggest that DE thoracic imaging may enhance tumor localization in lung cancer patients receiving kV-based IGRT without increasing imaging dose.

The influence of 18flourodeoxyglucose positron emission tomography on the management of gastroesophageal junction carcinoma

BACKGROUND The influence of positron emission tomography (PET) scanning with flourodeoxyglucose (FDG) on decision making for the treatment of patients with esophagogastric junction (EGJ) carcinoma is unclear as is the utility of the maximum standardized uptake value (SUV) as a prognostic indicator. METHODS This study was a retrospective review of EGJ carcinoma cases at a single institution during a 5-year period. RESULTS FDG-PET altered treatment in 13 of 64 patients (20%). Of these, 21 patients had PET scans before and after undergoing neoadjuvant chemoradiation (CRT) as well as surgery. Patients who had a decrease in SUV >50% had a 12-month disease-free survival advantage over patients a decrease in SUV <50% (93% vs 43%, P = .025). CONCLUSIONS FDG-PET alters treatment in a significant number of patients with EGJ carcinoma. A >50% decrease in SUV after CRT is associated with an improved prognosis.

Local control dependence on consecutive vs. nonconsecutive fractionation in lung stereotactic body radiation therapy

BACKGROUND Recent reports demonstrate impaired tumor re-oxygenation 24-48h after stereotactic body radiation therapy (SBRT), suggesting that non-consecutive treatment delivery may be advantageous. To test this hypothesis clinically, we compared local control in patients treated in consecutive daily fractions vs. nonconsecutive fractions. METHODS We retrospectively reviewed 107 lung SBRT patients (117 tumors) treated for T1-T2N0 NSCLC with LINAC based SBRT (50 or 60Gy/5fractions). Patients were characterized as having been treated in consecutive daily fractions vs. in non-consecutive fractions. Local control, survival and toxicity end points (CTCAE V4.0) were compared. Propensity score matching and Cox regression analyses were performed in order to determine the effect of fractionation on local control. RESULTS With a median follow up of 23.7months, 3-year local control was superior at 93.3% vs. 63.6% in the non-consecutive and consecutive group, respectively (p=0.001). Multivariate analysis and propensity score matching showed that consecutive fractionation was an independent predictor of local failure. Overall survival trended toward improvement in the non-consecutive group, but this was not statistically significant (p=0.188). Development of any grade 2 toxicity was not significantly different between the two groups (p=0.75). CONCLUSION Five-fraction SBRT delivered over non-consecutive days imparts superior LC and similar toxicity compared to consecutive fractionation. These results should be validated in independent datasets and in a prospective fashion.

Comparison of acute toxicities between contemporary forward-planned 3D conformal radiotherapy and inverse-planned intensity-modulated radiotherapy for whole breast radiation

The use of inverse‐planned intensity‐modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward‐planned field‐in‐field 3D conformal radiotherapy and tangential inverse‐planned intensity‐modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward‐planned field‐in‐field 3D conformal radiotherapy or intensity‐modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field‐in‐field 3D conformal radiotherapy and intensity‐modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity‐modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first‐line use of field‐in‐field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity‐modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity‐modulated radiotherapy.

TH‐E‐218‐02: Deformable Registration Techniques for Dual Energy Imaging in Clinical Radiotherapy

Purpose: To demonstrate a deformable registration algorithm to reduce cardiac and respiratory motion artifacts in planar dual energy (DE) subtraction images obtained using a clinical on‐board imaging (OBI) system. Methods: A Demons‐based deformable registration algorithm was developed to reduce motion artifacts between sequential planar x‐ray images obtained on the OBI. The algorithm was applied to paired (120 kVp and 60 kVp) chest x‐rays, deforming the low energy image to the high energy image. To test the algorithm, a total of 20‐paired scans were obtained from 6 lungcancer patients. All images were obtained using respiratory gating (RPM, Varian Medical Systems, Palo Alto, CA). In order to quantify the reduction in image artifacts, homologous landmarks were chosen using soft‐tissue features on both sets of images. Landmarks were placed throughout the images to examine both cardiac and respiratory motion. The root‐mean‐square (RMS) difference between the individual points was calculated both before and after application of deformable registration. Results: A total of 160 landmarks were evaluated. Measurement of the RMS distances between the landmarks in the high and low energy deformed images showed improvement in all sectors. For points with 2 mm RMS difference, the corresponding reduction was 64%. Qualitatively, DE images produced using Demons deformation showed fewer artifacts, and more defined tumor edges. Conclusions: The Demons algorithm reduced motion artifacts across all DE planar images. The greatest improvements were observed in regions near the diaphragm and the heart. In particular, artifacts due to cardiac motion showed the most improvement as these are not taken into account when performing respiratory gating. The iterative, matrix‐based algorithm would greatly benefit from integration of GPU parallel‐processing and will be implemented in future investigations. Supported by a grant from Varian Medical Systems.

Evaluation of RTOG Guidelines for Monte Carlo-based Lung SBRT Planning

Twelve lung SBRT plans calculated with heterogeneity corrected PB algorithm on the Brainlab iPlan were normalized to deliver 50Gy PTV dose in 5 fractions using 8-12 non-coplanar, conformal 6MV fields. (PB) Treatment plans were then recalculated using MC algorithm without changing any beam parameters (MC Non-Optimized). Next, MUs in MC plans were optimized (MC Optimized) to satisfy PTV prescription dose at 50Gy. PTV dose parameters Dmin, Dmax, Dmean, D90, D2cm, R50% and conformality index (CI), were evaluated and compared per RTOG 0813 guidelines for PB, MC Non-Optimized and MC Optimized plans.