Alec M. Block

Spatial correspondence of 4D CT ventilation and SPECT pulmonary perfusion defects in patients with malignant airway stenosis

To determine the spatial overlap agreement between four-dimensional computed tomography (4D CT) ventilation and single photon emission computed tomography (SPECT) perfusion hypo-functioning pulmonary defect regions in a patient population with malignant airway stenosis. Treatment planning 4D CT images were obtained retrospectively for ten lung cancer patients with radiographically demonstrated airway obstruction due to gross tumor volume. Each patient also received a SPECT perfusion study within one week of the planning 4D CT, and prior to the initiation of treatment. Deformable image registration was used to map corresponding lung tissue elements between the extreme component phase images, from which quantitative three-dimensional (3D) images representing the local pulmonary specific ventilation were constructed. Semi-automated segmentation of the percentile perfusion distribution was performed to identify regional defects distal to the known obstructing lesion. Semi-automated segmentation was similarly performed by multiple observers to delineate corresponding defect regions depicted on 4D CT ventilation. Normalized Dice similarity coefficient (NDSC) indices were determined for each observer between SPECT perfusion and 4D CT ventilation defect regions to assess spatial overlap agreement. Tidal volumes determined from 4D CT ventilation were evaluated versus measurements obtained from lung parenchyma segmentation. Linear regression resulted in a linear fit with slope = 1.01 (R² = 0.99). Respective values for the average DSC, NDSC(1 mm) and NDSC(2 mm) for all cases and multiple observers were 0.78, 0.88 and 0.99, indicating that, on average, spatial overlap agreement between ventilation and perfusion defect regions was comparable to the threshold for agreement within 1-2 mm uncertainty. Corresponding coefficients of variation for all metrics were similarly in the range: 0.10%-19%. This study is the first to quantitatively assess 3D spatial overlap agreement between clinically acquired SPECT perfusion and specific ventilation from 4D CT. Results suggest high correlation between methods within the sub-population of lung cancer patients with malignant airway stenosis.

Markerless motion tracking of lung tumors using dual‐energy fluoroscopy

PURPOSE To evaluate the efficacy of dual-energy (DE) vs single-energy (SE) fluoroscopic imaging of lung tumors using a markerless template-based tracking algorithm. METHODS Ten representative patient breathing patterns were programmed into a Quasar™ motion phantom. The phantom was modified by affixing pork ribs to the surface, and a cedar insert with a small spherical volume was used to simulate lung and tumor, respectively. Sequential 60 kVp (6 mA) and 120 kVp (1.5 mA) fluoroscopic sequences were acquired. Frame-by-frame weighted logarithmic subtraction was performed resulting in a DE fluoroscopic sequence. A template-based algorithm was then used to track tumor motion throughout the DE and SE fluoroscopy sequences. Tracking coordinates were evaluated against ground-truth tumor locations. Fluoroscopic images were also acquired for two lung cancer patients, neither of which had implanted fiducials. RESULTS For phantom imaging, a total of 1925 frames were analyzed. The algorithm successfully tracked the target on 99.9% (1923/1925) of DE frames vs 90.7% (1745/1925) SE images (p < 0.01). The displacement between tracking coordinates and ground truth for the phantom was 1.4 mm ± 1.1 mm for DE vs 2.0 mm ± 1.3 mm for SE (p < 0.01). Images from two patients, one with a larger tumor and one with a smaller tumor, were also analyzed. For the patient with the larger tumor, the average displacement from physician defined ground truth was 1.2 mm ± 0.6 mm for DE vs 1.4 mm ± 0.7 mm for SE (p = 0.016). For the patient that presented with a smaller tumor, the average displacement from physician defined ground truth was 2.2 mm ± 1.0 mm for DE vs 3.2 mm ± 1.4 mm for SE (p < 0.01). Importantly, for this single patient with the smaller tumor, 15.6% of the SE frames had >5 mm displacements from the ground truth vs 0% for DE fluoroscopy. CONCLUSIONS This work indicates the potential for markerless tumor tracking utilizing DE fluoroscopy. With DE imaging, the algorithm showed improved detectability vs SE fluoroscopy and was able to accurately track the tumor in nearly all cases.

The role of vaginal cuff brachytherapy in endometrial cancer

OBJECTIVE The purpose of this article is to review the data, rationale, and recommendations of vaginal brachytherapy (VBT) in the post-operative treatment of endometrial cancer patients. METHODS The authors performed a thorough review of the medical literature regarding the use of adjuvant VBT in the treatment of endometrial cancer. Relevant data are presented in this review. Additionally, personal and institutional practices from the authors are incorporated where relevant. RESULTS VBT for the adjuvant treatment of early stage endometrial cancer patients results in a low rate of recurrence (0-3.1%) with very low rates of toxicity. PORTEC-2 supports the use of adjuvant VBT versus external beam radiotherapy specifically for high-intermediate risk endometrial cancer patients. VBT has low rates of acute and chronic gastrointestinal and genitourinary toxicity and very low rates of second primary malignancy. The primary toxicity of VBT is vaginal atrophy and stenosis with controversy regarding the use of vaginal dilators for prevention. Data support that patients prefer to be involved in the decision making process for their adjuvant therapy, and patients have a lower minimal desired benefit of adjuvant VBT than do physicians. Guidelines exist from the American Brachytherapy Society and American Society of Radiation Oncology with support from the Society for Gynecologic Oncologists regarding the use of adjuvant VBT. CONCLUSIONS VBT decreases the risk of recurrence with minimal toxicity in the adjuvant treatment of endometrial cancer. Adjuvant therapy should be discussed in a multi-disciplinary setting with detailed counseling of the risks and benefits with the patient so that she ultimately makes an informed decision regarding her adjuvant therapy.

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.

Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy

The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle‐invasive bladder cancer (MIBC).

Improved overall survival with adjuvant radiotherapy for high-intermediate and high risk Stage I endometrial cancer

BACKGROUND/PURPOSE To perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. MATERIAL/METHODS 132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. RESULTS 104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT+VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p<0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731-0.867; p<0.001) and 0.783 (95% CI: 0.693-0.885; p<0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. CONCLUSIONS In Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival.

The integration of radiation therapy and immunotherapy in melanoma management

Melanoma has long been considered an “immunologic” malignancy because of numerous reports of spontaneous regression as well as abscopal phenomena along with its relative responsiveness to cancer immunotherapy. Over the past few years, there has been a resurgence of interest in cancer immunotherapy with particular focus on melanoma. Many new immunotherapeutic interventions have arisen, some with notable clinical efficacy. One such example is the current generation of checkpoint inhibitors. In this article, we shall review the recent data on checkpoint inhibition in melanoma along with a brief review of other immunotherapeutic approaches, including the encouraging and expanding role of radiation therapy in integrated immunotherapy.

SU‐E‐J‐44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique Angles

PURPOSE To characterize the contrast improvement of simulated tumors in an anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on-board imager (OBI) at oblique angles. METHODS An Alderson lung/chest anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar images were obtained in pairs every 100 in a full (3600) rotation using the OBI (Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component images were determined byvarying the x-ray exposure time, while maintaining a constant tube current. DE images were created to best suppress the bone overlaying the simulated tumors. Tumor visibility in DE images was quantified using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image relative to a single image (standard protocol) was evaluated as a function of gantry angle. RESULTS CNR was improved with DE imaging by an average ratio of 1.66 over all gantry angles. The greatest improvement occurred at gantry angles where the tumor was obstructed by the ribs alone. More modest improvements were observed where the tumor overlapped other soft tissue structures (such as the heart) or the dense spine, on a given projection. CONCLUSIONS This study illustrates the feasibility of performing DE imaging at oblique gantry angles using a clinical on-board imaging system. Incorporating DE imaging into clinical practice may allow for verification of tumor position at oblique gantry angles, and may facilitate the development of markerless motion tracking techniques. Supported by a grant from Varian Medical Systems.

Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database

OBJECTIVE To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC). METHODS 4298 patients treated from 1998 to 2011 with Stage I-IVA CCC were identified within the National Cancer Database. FIGO 2009 staging system was used. Adjuvant groups included: hysterectomy (HYS); HYS+vaginal brachytherapy (VBT); HYS+chemotherapy (CT); HYS+external beam radiation therapy (EBRT); HYS+CT+EBRT; and HYS+CT+VBT. Univariable (UVA) and multivariable (MVA) frailty survival analyses were performed. RESULTS On UVA, higher stage was associated with an increased risk of death. Compared to stage I-IA, the risk of death for stage IB was HR 1.75 (95% CI, 1.50-2.04; p<0.001), stage II was HR 1.77 (95% CI, 1.50-2.10; p<0.001), stage III-IIIB was HR 3.29 (95% CI, 2.86-3.80; p<0.001), stage IIIC-IIIC2 was HR 3.33 (95% CI: 2.94-3.77; p<0.001), and stage IVA was 8.59 (95% CI: 6.60-11.18; p<0.001). Other meaningful predictors of death included black race (p<0.001), public insurance (p<0.001), geographic education attainment (p=0.001), greater comorbidity score (p=0.001), increasing age (p<0.001), and increasing tumor size (p<0.001). After controlling for stage, insurance, race, education attainment, comorbidity score, age, and tumor size adjuvant treatment was not associated with decreased risk of mortality (p=0.26). CONCLUSION Adjuvant therapy did not have a meaningful effect on survival in this sample from the National Cancer Center Database. Given the aggressive nature of the disease, clinical trials are required to determine the optimal adjuvant therapy in patients with non-metastatic CCC to improve clinical outcomes.

Low-dose total body irradiation: an overlooked cancer immunotherapy technique

Low-dose total body irradiation (LD-TBI) has been shown to be an effective therapy for patients with hematologic malignancies. The application of this method has fallen out of favor as newer systemic therapies have been developed. Nevertheless, for management of many of these hematologic malignancies, no prospective randomized trial has shown that any other treatment is unequivocally superior to LD-TBI. The precise mechanism of action is uncertain but it is believed by some to be at least partly immunologically mediated. In this review, we shall discuss the clinical data on this method along with some new potential applications. We also discuss some of the potential immunological mechanisms behind LD-TBI and consider future possibilities.