A.P. Wojcieszynski

Gadoxetate for direct tumor therapy and tracking with real-time MRI-guided stereotactic body radiation therapy of the liver.

SBRT is increasingly utilized in liver tumor treatment. MRI-guided RT allows for real-time MRI tracking during therapy. Liver tumors are often poorly visualized and most contrast agents are transient. Gadoxetate may allow for sustained tumor visualization. Here, we report on the first use of gadoxetate during real-time MRI-guided SBRT.

Improved survival with dose-escalated radiotherapy in stage III non-small-cell lung cancer: analysis of the National Cancer Database

BACKGROUND Concurrent chemoradiation is the standard of care in non-operable stage III non-small-cell lung cancer (NSCLC). Data have suggested a benefit of dose escalation; however, results from the randomized dose-escalation trial RTOG 0617 revealed a lower survival rate with high-dose radiation. To evaluate the impact of dose escalation on overall survival (OS) in stage III NSCLC treated with chemoradiotherapy outside the controlled setting of a randomized trial, we carried out an observational, population-based investigation of the National Cancer Database (NCDB). PATIENTS AND METHODS A total of 33 566 patients with stage III NSCLC treated with chemoradiation from 2004 to 2012 and radiation doses between 59.4 and 85 Gy were included. The primary end point was OS, with median survival calculated via Kaplan-Meier. Univariate, multivariable and propensity-score matching analyses were carried out. RESULTS Patients were stratified by dose with median OS of: 18.8, 19.8 and 21.6 months for cohorts receiving 59.4-60, 61-69 and ≥70 Gy, respectively (P < 0.001). Granular dose analyses were carried out demonstrating increased OS with increasing radiation dose: median survival of 18.8, 21.1, 22.0 and 21.0 months for 59.4-60, 66, 70 and ≥71 Gy, respectively. While 66, 70 and ≥71 Gy resulted in increased OS in comparison with 59.4-60 Gy, no significant difference in OS was observed when comparing 66 with ≥71 Gy (P = 0.38). CONCLUSIONS Dose escalation above 60 Gy was associated with improved OS in this cohort of stage III NSCLC patients treated with chemoradiotherapy. A plateau of benefit was observed, with no additional improvement in OS with increased dose (≥71 Gy) compared with 66-70 Gy. With evidence suggesting worse OS and quality of life with increased dose, these data support investigation of the role of intermediate-dose radiation, and in the absence of randomized evidence, may be leveraged to justify utilization of intermediate-dose radiation.

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer.

The addition of chemoradiation (CRT) to surgery has been shown to improve survival in patients with esophageal cancer. In the current study, the authors determined whether the sequencing of CRT has an effect on survival and cardiopulmonary mortality in patients with esophageal cancer.

Dosimetric Comparison of Real-Time MRI-Guided Tri-Cobalt-60 Versus Linear Accelerator-Based Stereotactic Body Radiation Therapy Lung Cancer Plans

Purpose: Magnetic resonance imaging–guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging–guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging–guided radiation therapy plans and internal target volume–based plans utilizing volumetric-modulated arc therapy. Materials and Methods: Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging–guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared. Results: Planning tumor volumes trended larger for volumetric-modulated arc therapy–based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging–guided plans (P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% (P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL (P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 (P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1.25 (P = .98). Conclusion: Magnetic resonance imaging–guided tri-cobalt-60 radiation therapy is capable of delivering lung high-quality stereotactic body radiation therapy plans that are clinically acceptable as compared to volumetric-modulated arc therapy–based plans. Real-time magnetic resonance imaging provides the unique capacity to directly observe tumor motion during treatment for purposes of motion management.

Acute Toxicity From Breast Cancer Radiation Using Helical Tomotherapy With a Simultaneous Integrated Boost

Purpose: To evaluate 2 simultaneous integrated boost treatment planning techniques using helical tomotherapy for breast conserving therapy with regard to acute skin toxicity and dosimetry. Methods: Thirty-two patients were studied. The original approach was for 16 patients and incorporated a directional block of the ipsilateral lung and breast. An additional 16 patients were planned for using a modified approach that incorporates a full block of the ipsilateral lung exclusive of 4 cm around the breast. Dose–volume histograms of targets and critical structures were evaluated. Skin toxicity monitoring was performed throughout treatment and follow-up using the Common Terminology Criteria for Adverse Events. Results: Treatment was well tolerated with patients receiving a median dose of 59.36 Gy. Of the 16 patients in both groups, 8 had grade 2 erythema immediately after radiation. On 3-week follow-up, 10 and 7 patients in the original and modified groups showed grade 1 erythema. On 3- and 6-month follow-up, both groups had minimal erythema, with all patients having either grade 0 or 1 symptoms. No grade 2 or 3 toxicities were reported. Mean treatment time was 7.5 and 10.4 minutes using the original and modified methods. Adequate dose coverage was achieved using both methods (V95 = 99.5% and 98%). Mean dose to the heart was 10.5 and 1.8 Gy, respectively (P < .01). For right-sided tumors, the original and modified plans yielded a mean of 8.8 and 1.1 Gy (P < .01) versus 11.7 and 2.4 Gy for left-sided tumors (P < .01). The mean dose to the ipsilateral lung was also significantly lower in the modified plans (11.8 vs 5.0 Gy, P < .01). Conclusions: Tomotherapy is capable of delivering homogeneous treatment plans to the whole breast and lumpectomy cavity using simultaneous integrated boost treatment. Using the treatment methods described herein, extremely low doses to critical structures can be achieved without compromising acute skin toxicity.

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies

Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy.

Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer

Micro‐Abstract: The optimal management of patients with locally advanced recto‐sigmoid cancer is unclear. Using the National Cancer Database, we assessed patterns of care and outcomes associated with upfront surgery versus neoadjuvant chemoradiation followed by surgery. Although neoadjuvant chemoradiation was used in a small percentage of patients, its use was associated with more complete resections, a robust pathologic complete response rate, and improved overall survival. Introduction: The optimal management of locally advanced recto‐sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns‐of‐care and overall survival (OS) associated with these treatment strategies. Patients and Methods: Patients with clinical stage II or III recto‐sigmoid cancer who underwent surgery with or without adjunctive chemotherapy and/or radiotherapy from 2006 to 2014 were identified, and dichotomized into: (1) upfront surgery, and (2) neoadjuvant chemoradiation cohorts. Patterns‐of‐care were assessed using multivariable logistic regression. The association between neoadjuvant chemoradiation use and OS was assessed using Cox proportional hazards analysis with propensity score‐matching. Results: Of 9313 identified patients, 6756 (73%) underwent upfront surgery and 2557 (27%) received neoadjuvant chemoradiation. Treatment at academic facilities and higher clinical T stage were predictors of neoadjuvant chemoradiation use. Compared with upfront surgery, neoadjuvant chemoradiation resulted in fewer positive circumferential resection margins (384 [11%] patients vs. 108 [8%] patients; P = .001), and 478 [18.7%] patients achieved a pathologic complete response at surgery. In propensity score‐matched analysis, neoadjuvant chemoradiation use was associated with improved OS (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90) compared with upfront surgery; 5‐year estimated OS was 77.0% versus 72.0%, respectively. The improvement in OS persisted in landmark analysis of patients who survived at least 12 months. Conclusion: Only a small percentage of patients with locally advanced recto‐sigmoid cancer receive neoadjuvant chemoradiation even though its use might result in improved OS relative to upfront surgery. Prospective research is warranted to validate and standardize therapeutic strategies in patients with recto‐sigmoid cancer.

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiotherapy

Purpose Daily magnetic resonance (MR)–guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment. Methods and materials Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test. Results The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively. Conclusions This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study

PURPOSE The optimum adjuvant treatment for Stage II endometrial cancer patients is unknown. External beam radiation therapy (EBRT) is often considered the standard of care; however, retrospective series suggest that brachytherapy (BT) alone may be sufficient for selected patients. As randomized data are lacking, we used a large database to explore this question. METHODS AND MATERIALS The National Cancer Data Base was queried for patients with pathologic International Federation of Gynecology and Obstetrics Stage II disease. Demographic, clinic-pathologic, and treatment details were compared between patients. Multivariable analysis was used to determine factors associated with receiving radiation therapy (RT). To account for imbalances between groups, a matched-pair analysis was completed. RESULTS Eight thousand one hundred forty patients were included. RT was associated with overall survival (OS), with EBRT (hazard ratio [HR] 0.64), BT (HR 0.47), and combination (HR 0.54) showing increased OS on univariate analysis. Facility, urban location, diagnosis year, hysterectomy type, and chemotherapy did not reach significance. On multivariate analysis, RT was associated with OS, with EBRT (HR 0.69), BT (HR 0.60), and combination (HR 0.54) showing benefit. Using propensity-score matching, RT continued to show improved OS regardless of type: BT (82% vs. 73% 5-year OS) and EBRT (77% vs. 71%). BT as compared to EBRT had equivalent survival (81% vs. 79%, not statistically significant). CONCLUSION This study of over 8,000 patients demonstrates that adjuvant RT confers a survival benefit in Stage II endometrial cancer and supports the continued use of RT in these patients. BT alone may be reasonable in carefully selected patients.

OC-0211: Real-time MRI-guided Radiotherapy for pancreatic cancer

Conclusion: The results indicate the feasibility of VMAT treatments under tumor tracking for selected patients. The arcs available for planning influence the quality of treatment. The L partial arc plans had clinically acceptable quality in four patients. Treatments with reduced margins could be safely delivered by gating the treatment beam if the tumor motion exceeds the margins. Also, a great advantage is that the dose delivered to the tumor could be exactly monitored.