T. Diwanji

Evaluation of template matching for tumor motion management with cine-MR images in lung cancer patients

PURPOSE Accurate determination of tumor position is crucial for successful application of motion compensated radiotherapy in lung cancer patients. This study tested the performance of an automated template matching algorithm in tracking the tumor position on cine-MR images by examining the tracking error and further comparing the tracking error to the interoperator variability of three human reviewers. METHODS Cine-MR images of 12 lung cancer patients were analyzed. Tumor positions were determined both automatically with template matching and manually by a radiation oncologist and two additional reviewers trained by the radiation oncologist. Performance of the automated template matching was compared against the ground truth established by the radiation oncologist. Additionally, the tracking error of template matching, defined as the difference in the tumor positions determined with template matching and the ground truth, was investigated and compared to the interoperator variability for all patients in the anterior-posterior (AP) and superior-inferior (SI) directions, respectively. RESULTS The median tracking error for ten out of the 12 patients studied in both the AP and SI directions was less than 1 pixel (= 1.95 mm). Furthermore, the median tracking error for seven patients in the AP direction and nine patients in the SI direction was less than half a pixel (= 0.975 mm). The median tracking error was positively correlated with the tumor motion magnitude in both the AP (R = 0.55, p = 0.06) and SI (R = 0.67, p = 0.02) directions. Also, a strong correlation was observed between tracking error and interoperator variability (y = 0.26 + 1.25x, R = 0.84, p < 0.001) with the latter larger. CONCLUSIONS Results from this study indicate that the performance of template matching is comparable with or better than that of manual tumor localization. This study serves as preliminary investigations towards developing online motion tracking techniques for hybrid MRI-Linac systems. Accuracy of template matching makes it a suitable candidate to replace the labor intensive manual tumor localization for obtaining the ground truth when testing other motion management techniques.

Advances in radiotherapy techniques and delivery for non-small cell lung cancer: benefits of intensity-modulated radiation therapy, proton therapy, and stereotactic body radiation therapy

The 21st century has seen several paradigm shifts in the treatment of non-small cell lung cancer (NSCLC) in early-stage inoperable disease, definitive locally advanced disease, and the postoperative setting. A key driver in improvement of local disease control has been the significant evolution of radiation therapy techniques in the last three decades, allowing for delivery of definitive radiation doses while limiting exposure of normal tissues. For patients with locally-advanced NSCLC, the advent of volumetric imaging techniques has allowed a shift from 2-dimensional approaches to 3-dimensional conformal radiation therapy (3DCRT). The next generation of 3DCRT, intensity-modulated radiation therapy and volumetric-modulated arc therapy (VMAT), have enabled even more conformal radiation delivery. Clinical evidence has shown that this can improve the quality of life for patients undergoing definitive management of lung cancer. In the early-stage setting, conventional fractionation led to poor outcomes. Evaluation of altered dose fractionation with the previously noted technology advances led to advent of stereotactic body radiation therapy (SBRT). This technique has dramatically improved local control and expanded treatment options for inoperable, early-stage patients. The recent development of proton therapy has opened new avenues for improving conformity and the therapeutic ratio. Evolution of newer proton therapy techniques, such as pencil-beam scanning (PBS), could improve tolerability and possibly allow reexamination of dose escalation. These new progresses, along with significant advances in systemic therapies, have improved survival for lung cancer patients across the spectrum of non-metastatic disease. They have also brought to light new challenges and avenues for further research and improvement.

Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults

Neoplasms of the central nervous system (CNS) are the most frequently encountered solid tumors of childhood, but are less common in adolescents and young adults (AYA), aged 15–39 years. Gliomas account for 29%–35% of the CNS tumors in AYA, with approximately two-thirds being low-grade glioma (LGG) and the remaining being high-grade glioma (HGG). We review the epidemiology, work-up, and management of LGG and HGG, focusing on the particular issues faced by the AYA population relative to pediatric and adult populations. Visual pathway glioma and brainstem glioma, which represent unique clinical entities, are only briefly discussed. As a general management approach for both LGG and HGG, maximal safe resection should be attempted. AYA with LGG who undergo gross total resection (GTR) may be safely observed. As age increases and the risk factors for recurrence accumulate, adjuvant therapy should be more strongly considered with a strong consideration of advanced radiation techniques such as proton beam therapy to reduce long-term radiation-related toxicity. Recent results also suggest survival advantage for adult patients with the use of adjuvant chemotherapy when radiation is indicated. Whenever possible, AYA patients with HGG should be enrolled in a clinical trial for the benefit of centralized genetic and molecular prognostic review and best clinical care. Chemoradiation should be offered to all World Health Organization grade IV patients with concurrent and adjuvant chemotherapy after maximal safe resection. Younger adolescents with GTR of grade III lesions may consider radiotherapy alone or sequential radiotherapy and chemotherapy if unable to tolerate concurrent treatment. A more comprehensive classification of gliomas integrating pathology and molecular data is emerging, and this integrative strategy offers the potential to be more accurate and reproducible in guiding diagnostic, prognostic, and management decisions.

SU‐F‐303‐05: DCE‐MRI Before and During Treatment for Prediction of Concurrent Chemotherapy and Radiation Therapy Response in Head and Neck Cancer

Purpose: To determine the ability of pharmacokinetic parameters derived from dynamic contrast-enhanced MRI (DCE- MRI) acquired before and during concurrent chemotherapy and radiation therapy to predict clinical response in patients with head and neck cancer. Methods: Eleven patients underwent a DCE-MRI scan at three time points: 1–2 weeks before treatment, 4–5 weeks after treatment initiation, and 3–4 months after treatment completion. Post-processing of MRI data included correction to reduce motion artifacts. The arterial input function was obtained by measuring the dynamic tracer concentration in the jugular veins. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), rate constant (Kep; Kep = Ktrans/ve), and plasma volume fraction (vp) were computed for primary tumors and cervical nodal masses. Patients were categorized into two groups based on response to therapy at 3–4 months: responders (no evidence of disease) and partial responders (regression of disease). Responses of the primary tumor and nodes were evaluated separately. A linear classifier and receiver operating characteristic curve analyses were used to determine the best model for discrimination of responders from partial responders. Results: When the above pharmacokinetic parameters of the primary tumor measured before and during treatment were incorporated into the linear classifier, a discriminative accuracy of 88.9%, with sensitivity =100% and specificity = 66.7%, was observed between responders (n=6) and partial responders (n=3) for the primary tumor with the corresponding accuracy = 44.4%, sensitivity = 66.7%, and specificity of 0% for nodal masses. When only pre-treatment parameters were used, the accuracy decreased to 66.7%, with sensitivity = 66.7% and specificity = 66.7% for the primary tumor and decreased to 33.3%, sensitivity of 50%, and specificity of 0% for nodal masses. Conclusion: Higher accuracy, sensitivity, and specificity were obtained using DCE-MRI-derived pharmacokinetic parameters acquired before and during treatment as compared with those derived from the pre-treatment time-point, exclusively.

TH‐C‐141‐10: Error of Template Matching for Tracking Tumor Motion Is No Larger Than Inter‐Operator Variability

PURPOSE Recently, template matching has been proposed to track tumor motion using cine-MRI images. However, the technique has been tested primarily on blood vessels in healthy subjects. In this work, we demonstrate the utility of automated template matching in patients with thoracic tumors. We also compare the variability in predicting tumor position using template matching and 3 human operators. METHODS Five patients with non-small cell lung cancer (NSCLC) were recruited in a prospective study. Cine-MRI imaging was performed while the patients were instructed to breathe normally. True FISP (fast imaging in steady state) cine-images were obtained in the sagittal plane. The centroids of the tumors were determined manually by 3 operators and also by the automatic template matching technique. The differences both in the AP and SI directions between the automatic and manual methods and the inter-operator variability were calculated respectively and compared. RESULTS For all patients the variability between automatic and human operators in the SI direction was less than the inter-operator variability. For 4 out of 5 patients the variability between automatic and human operators in the AP direction was less than the inter-operator variability. However, the variability in 1 patient was higher by 14%. This is attributed to out-of-plane motion that currently is not captured using the cine-MRI imaging. CONCLUSION The effectiveness of template matching to estimate tumor position during respiratory motion was tested in patients with lung cancer. Results show that, the difference between the automatic and manual methods was comparable to the inter-operator variability. Future efforts to integrate on-board MRI imaging with linear accelerators can benefit from automated tumor tracking with template matching. Furthermore, the technique can also be utilized to replace the laborious manual tracking process necessary to establish the ground-truth when evaluating external surrogates of tumor motion. NIH/NCICA 122403.

Proton beam therapy for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare disease with a poor prognosis. Surgical techniques have made incremental improvements over the last few decades while new systemic therapies, including immunotherapies, show promise as potentially effective novel therapies. Radiation therapy has historically been used only in the palliative setting or as adjuvant therapy after extrapleural pneumonectomy, but recent advances in treatment planning and delivery techniques utilizing intensity-modulated radiation therapy and more recently pencil-beam scanning (PBS) proton therapy, have enabled the delivery of radiation therapy as neoadjuvant or adjuvant therapy after an extended pleurectomy and decortication or as definitive therapy for patients with recurrent or unresectable disease. In particular, PBS proton therapy has the potential to deliver high doses of irradiation to the entire effected pleura while significantly reducing doses to nearby organs at risk. This article describes the evolution of radiation therapy for MPM and details how whole-pleural PBS proton therapy is delivered to patients at the Maryland Proton Treatment Center.

Advances in proton therapy in lung cancer

Lung cancer remains the leading cause of cancer deaths in the United States (US) and worldwide. Radiation therapy is a mainstay in the treatment of locally advanced non-small cell lung cancer (NSCLC) and serves as an excellent alternative for early stage patients who are medically inoperable or who decline surgery. Proton therapy has been shown to offer a significant dosimetric advantage in NSCLC patients over photon therapy, with a decrease in dose to vital organs at risk (OARs) including the heart, lungs and esophagus. This in turn, can lead to a decrease in acute and late toxicities in a population already predisposed to lung and cardiac injury. Here, we present a review on proton treatment techniques, studies, clinical outcomes and toxicities associated with treating both early stage and locally advanced NSCLC.

How Histopathologic Tumor Extent and Patterns of Recurrence Data Inform the Development of Radiation Therapy Treatment Volumes in Solid Malignancies

The ability to deliver highly conformal radiation therapy using intensity-modulated radiation therapy and particle therapy provides for new opportunities to improve patient outcomes by reducing treatment-related morbidities following radiation therapy. By reducing the volume of normal tissue exposed to radiation therapy (RT), while also allowing for the opportunity to escalate the dose of RT delivered to the tumor, use of conformal RT delivery should also provide the possibility of expanding the therapeutic index of radiotherapy. However, the ability to safely and confidently deliver conformal RT is largely dependent on our ability to clearly define the clinical target volume for radiation therapy, which requires an in-depth knowledge of histopathologic extent of different tumor types, as well as patterns of recurrence data. In this article, we provide a comprehensive review of the histopathologic and radiographic data that provide the basis for evidence-based guidelines for clinical tumor volume delineation.

Advances in the use of motion management and image guidance in radiation therapy treatment for lung cancer

The development of advanced radiation technologies, including intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT) and proton therapy, has resulted in increasingly conformal radiation treatments. Recent evidence for the importance of minimizing dose to normal critical structures including the heart and lungs has led to incorporation of these advanced treatment modalities into radiation therapy (RT) for non-small cell lung cancer (NSCLC). While such technologies have allowed for improved dose delivery, implementation requires improved target accuracy with treatments, placing increasing importance on evaluating tumor motion at the time of planning and verifying tumor position at the time of treatment. In this review article, we describe issues and updates related both to motion management and image guidance in the treatment of NSCLC.

Improving Outcomes through Immune System Modulation in the Treatment ofGynecological Malignancies

The treatment of gynecological cancers continues to evolve with combination of different therapies. There has been a significant effort to induce stimulation of the immune system through treatment with interferons and interleukins in the past. More recently, the remarkable results of clinical trials demonstrating efficacy of checkpoint inhibitor immunotherapies in multiple cancer types has generated considerable interest within the gynecological community. Here, we review the findings of efforts to augment the humoral immune system and review the pre-clinical and clinical evidence for checkpoint inhibitors. The Abscopal effect, a phenomenon whereby localized radiation therapy results in immune mediated tumor regression in distant sites is currently also discussed in the context of gynecological cancers. The combination of various immunotherapies in gynecological cancer and emerging clinical evidence for the combinations may lead to improved treatment outcomes.