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      Protons Safely Allow Coverage of High-Risk Nodes for Patients with Regionally Advanced Non-Small-Cell Lung Cancer

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          Abstract

          Our objective was to determine if protons allow for the expansion of treatment volumes to cover high-risk nodes in patients with regionally advanced non-small-cell lung cancer. In this study, 5 consecutive patients underwent external-beam radiotherapy treatment planning. Four treatment plans were generated for each patient: 1) photons (x-rays) to treat positron emission tomography (PET)-positive gross disease only to 74 Gy (XG); 2) photons (x-rays) to treat high-risk nodes to 44 Gy and PET-positive gross disease to 74 Gy (XNG); 3) protons to treat PET-positive gross disease only to 74 cobalt gray equivalent (PG); and 4) protons to treat high-risk nodes to 44 CGE and PET-positive gross disease to 74 CGE (PNG). We defined high-risk nodes as mediastinal, hilar, and supraclavicular lymph nodal stations anatomically adjacent to the foci of PET-positive gross disease. Four-dimensional computed tomography was utilized for all patients to account for tumor motion. Standard normal-tissue constraints were utilized. Our results showed that proton plans for all patients were isoeffective with the corresponding photon (x-ray) plans in that they achieved the desired target doses while respecting normal-tissue constraints. In spite of the larger volumes covered, median volume of normal lung receiving 10 CGE or greater (V10Gy/CGE), median V20Gy/CGE, and mean lung dose were lower in the proton plans (PNG) targeting gross disease and nodes when compared with the photon (x-ray) plans (XG) treating gross disease alone. In conclusion, proton plans demonstrated the potential to safely include high-risk nodes without increasing the volume of normal lung irradiated when compared to photon (x-ray) plans, which only targeted gross disease.

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          A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.

          Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC). A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048). IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.
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            Involved-field radiation therapy for inoperable non small-cell lung cancer.

            Dose escalation has been shown to improve local control in non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy, but with increased complications. We implemented the use of involved-field radiotherapy (IFRT) in an effort to reduce toxicity while treating the gross tumor to higher doses. This analysis reports failure rates in uninvolved nodal regions with the use of IFRT. A total of 524 patients with NSCLC treated with three-dimensional conformal radiotherapy at Memorial Sloan-Kettering Cancer Center between 1991 and 2005 were reviewed. Only lymph node regions initially involved with tumor by either biopsy or radiographic criteria were included in the clinical target volume. Elective nodal failure (ENF) was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. Only 32 patients (6.1%) with ENF were identified. The 2-year actuarial rates of elective nodal control and primary tumor control were 92.4% and 51%, respectively, with a median follow-up of 41 months in survivors. In patients who achieved local disease control, the 2-year elective nodal control rate was 91%. The median time to ENF was 6 months (range, 0 to 56 months). Many patients experienced treatment failure in multiple lymph node regions simultaneously. The use of IFRT did not cause a significant amount of failure in lymph node regions not included in the tumor volume. Therefore, IFRT remains an acceptable method of treatment that allows for dose escalation while minimizing toxicity.
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              CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan.

              Accurate delineation of the mediastinal and hilar lymph node regions is essential for a reproducible definition of target volumes used in conformal irradiation of non-small-cell lung cancer. The goal of this work was to generate a consensus to delineate these nodal regions based on definitions from the American Joint Committee on Cancer. A dedicated thoracic radiologist, thoracic surgeon, medical physicist, and three radiation oncologists were gathered to generate a three-dimensional radiologic description for the mediastinal and hilar nodal regions on axial CT scans. This paper proposes an atlas of most of the lymph node stations described by Mountain and Dresler. The CT boundaries of lymph node stations 1-2, 3, 4, 5, 6, 7, 8, 10-11 were defined on axial CT, along with image illustrations. These CT-based illustrative definitions will provide guidelines for clinical practice and studies evaluating incidental radiation in radiotherapy. Studies are ongoing at the University of Michigan to measure quantitatively the incidental nodal radiation received by patients with non-small-cell lung cancer.
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                Author and article information

                Journal
                Technol Cancer Res Treat
                Technol. Cancer Res. Treat
                TCT
                sptct
                Technology in Cancer Research & Treatment
                SAGE Publications (Sage CA: Los Angeles, CA )
                1533-0346
                1533-0338
                August 2011
                August 2011
                : 10
                : 4
                : 317-322
                Affiliations
                [1 ] University of Florida, Proton Therapy Institute, Jacksonville, FL, USA
                [2 ] University of Florida, Department of Surgery and Internal Medicine, Jacksonville, FL, USA
                [3 ] University of Florida, Department of Pulmonary Medicine, Jacksonville, FL, USA
                [4 ] University of Florida, Division of Medical Oncology, Jacksonville, FL, USA
                Author notes
                [*] [* ]Romaine C. Nichols, Jr. M.D. E-mail: rnichols@ 123456floridaproton.org
                Article
                10.7785_tcrt.2012.500208
                10.7785/tcrt.2012.500208
                4527458
                21728388
                2c8f5591-d887-4faa-8583-21bc15b61532
                ©Adenine Press (2011)
                History
                : 1 October 2010
                : 14 February 2011
                Categories
                Articles

                proton therapy,normal-tissue sparing,non-small-cell lung cancer,elective nodal irradiation

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