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James D. Cox



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    MS 16 - Future Direction of Chemoradiotherapy for Inoperable Non-small Cell Lung Cancer (ID 538)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Radiotherapy
    • Presentations: 1
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      MS 16.05 - High-Dose Boost Radiation Using SBRT/ IMRT (ID 7720)

      15:45 - 17:30  |  Presenting Author(s): James D. Cox

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Chemotherapy combined with radiation therapy has become standard treatment for inoperable non-small cell lung cancer (NSCLC). The combination was first proposed in the 1970s. Although induction (neoadjuvant) chemotherapy followed by radiation therapy was initially considered preferable owing to concerns about toxicity, it eventually became clear that concurrent treatment was more effective. Similarly, low-dose radiation therapy was thought to be the safest, and radiation oncologists were loath to use any dose/fractionation regimen that exceeded standard approaches with radiation therapy alone. Chemotherapy evolved in a similar fashion. At first, single agents were used, followed by tests of various combinations of different drugs, with eventual acceptance of 2-drug combination regimens, usually consisting of a platinum compound with another agent. These regimens were combined with standard radiation therapy, usually to a dose of 60 Gy in 30 fractions using three-dimensional conformal radiation therapy (3D CRT), planned on the basis of computed tomography (CT); this combination produced tolerable adverse effect profiles that were less severe than those after the previous standard of 2D treatments based on plane radiography. The next iteration of external-beam radiation therapy was intensity-modulated radiation therapy (IMRT), which involves directing multiple beamlets at the tumor while limiting the doses to surrounding critical structures. IMRT, which depends on CT imaging for staging and treatment planning, also allowed higher fraction sizes and total doses to be tested in attempts to increase tumor control. However, use of higher total doses has had potentially intimidating results in clinical trials. In a recent prospective clinical trial of the Radiation Therapy Oncology Group (RTOG 0617) in which standard-dose 60 Gy in 30 fractions given over 6 weeks was compared with high-dose 74 Gy in 37 fractions over 7 1/2 weeks, the higher total dose actually led to poorer local control. It has been hypothesized that failure to adequately cover the gross tumor volume in the high-dose arm resulted in the higher local failure rate. For small (T1 or T2) tumors of the lung, investigators have tested very-high-dose treatments based on 3D targeting of every fraction, an approach that requires 3D imaging capability. In the United States, achieving such precise targeting has required collaborations with medical physicists in the delivery of each fraction. The next generation of radiation therapy, stereotactic body radiation therapy or SBRT, began as a treatment for lesions in the brain. In Sweden, Leksell and colleagues developed an approach that came to be known as stereotactic radiation therapy. Considered an alternative to surgical resection, stereotactic radiation therapy was predicated on immobilizing the patient with a stereotaxic frame, using multiple cobalt-60 sources in a helmet-like configuration, and administering the radiation in a single fraction. Because the goal of this approach was controlled necrosis rather than a surgical defect, this approach also came to be known as stereotactic radiosurgery. Approximately 25 years later, a similar approach was developed in which linear accelerators were used to deliver SBRT. Similar principles were used: precise imaging with of the tumor with CT and, more recently, with fluorodeoxyglucose positron emission tomography; careful and secure immobilization with various body frames; management of respiratory motion for lesions in the thorax; intensity-modulated treatment planning; and image-guided targeting. From 1 to 5 or even 10 fractions are delivered in this manner, with both the treating physician and collaborating physicist attending each treatment to ensure consistent image guidance. This approach allows the delivery of very high biological doses. SBRT has been shown to result in local control rates of 85% to 95% for tumors up to 4 cm in diameter. Proton beam therapy is the latest means to control NSCLC, particularly for tumors that are larger than the T1 or T2 tumors usually treated with SBRT. Protons differ from photons in their interactions with tissues in the body; protons are heavy particles that produce different ionization tracks and deposit most of their energy at the end of their range. Where they come to a stop is a function of their energy when they enter the body. Protons have lower energy than photons until they reach their prescribed depth, at which point they produce a peak of ionizations, the Bragg peak. This Bragg peak can be spread out to cover the tumor in depth, and the beam can be shaped in the other two dimensions by electronic or physical means to achieve a high-dose volume that has the same size and shape of the tumor. Properly directed proton therapy essentially delivers no dose beyond the gross tumor volume. The relative biologically effective dose (RBE) of proton beam therapy is approximately the same as that of x-rays, so the effects of the doses in the tumor and the surrounding normal tissues (organs at risk) are well understood. Proton beam therapy and chemotherapy interact in predictable ways, and so the toxicity patterns are similar to those with chemotherapy and photons. However, proton therapy seems to have less severe effects on blood counts. In clinical trials to date, whether with IMRT, SBRT, or protons, the greatest need seems to be to enhance the effectiveness of the systemic treatment. Considerable interest has been expressed in combining each of these radiation delivery methods with immunotherapy. The occurrence of an occasional abscopal effect with radiation therapy has given rise to cautious enthusiasm for further exploration of this area.

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    PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation (ID 585)

    • Event: WCLC 2017
    • Type: Plenary Session
    • Track: Early Stage NSCLC
    • Presentations: 1
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      PL 02.08 - James Cox Lectureship Award Presentation (ID 10868)

      08:15 - 09:45  |  Presenting Author(s): James D. Cox

      • Abstract
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      Abstract not provided

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