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      Moderately Hypofractionated Radiotherapy Alone for Stage I-IIB Non-small Cell Lung Cancer

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          Abstract

          Introduction: The optimal management of patients with early non-small cell lung cancer (NSCLC) not amenable to surgical resection or stereotactic body radiotherapy (SBRT) or those with hilar nodal involvement ineligible for surgery or concurrent chemoradiotherapy is unclear. This report describes survival outcomes and toxicity profiles of patients treated with hypofractionated radiotherapy (HRT) alone.

          Methods: A total of 52 patients with Stage I-IIB NSCLC treated with HRT alone between 2010-2018 were reviewed. Patients were categorized as having ultracentral tumors if the planning target volume contacted or overlapped the proximal bronchial tree, esophagus, pulmonary vein or artery. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and the competing risk cumulative incidence of locoregional failure (LRF) and distant failure (DF) were estimated using death without failure as a competing risk. Pneumonitis and esophagitis rates were evaluated as per Acute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

          Results: Of the 52 patients analyzed, 50 patients were treated with radiotherapy alone to a dose of 70.2 Gy in 26 fractions, one patient was treated with 68 Gy in 25 fractions and one patient was treated with 65 Gy in 26 fractions. The median age was 72 (range 48-89), 42% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2-3, 46% were stage I and 54% were stage II. Hilar nodal involvement was present in 21% of patients and 74% of node-negative patients had ultracentral primary tumors. Median OS was 39.6 months and the median PFS was 21.0 months. Overall three-year cumulative incidence of LRF and DF were 32% and 34%, respectively. Grade 3 pneumonitis occurred in two (4%) patients. No grade 3+ acute esophagitis or grade 4-5 toxicities were observed.

          Conclusion: Hypofractionated thoracic radiotherapy consisting of 70.2 Gy is well-tolerated and results in favorable locoregional control for stage I-IIB patients who are not candidates for SBRT, surgery, or concurrent chemoradiotherapy.

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          Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer.

          Surgical resection is standard therapy in stage I non-small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Eligible patients included clinically staged T1 or T2 (< or = 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors. High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.
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            Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study.

            The 50-month results of a prospective Phase II trial of stereotactic body radiation therapy (SBRT) in medically inoperable patients are reported. A total of 70 medically inoperable patients had clinically staged T1 (34 patients) or T2 (36 patients) ( 20 cc) did not significantly impact survival: MS was 36.9 months (95% CI, 18.1-42.9), 34.0 (95% CI, 16.9-57.1), 32.8 (95% CI, 21.3-57.8), and 21.4 months (95% CI, 17.8-41.6), respectively (p = 0.712). There was no significant survival difference between patients with peripheral vs. central tumors (MS 33.2 vs. 24.4 months, p = 0.697). Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors (10.4%) and in 6 of 22 patients (27.3%) with central tumors (Fisher's exact test, p = 0.088). Based on our study results, use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC.
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              Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus.

              To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT. Published by Elsevier Inc.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                22 June 2019
                June 2019
                : 11
                : 6
                : e4969
                Affiliations
                [1 ] Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, USA
                [2 ] Epidemiology, Wake Forest School of Medicine, Winston-Salem, USA
                Author notes
                Article
                10.7759/cureus.4969
                6701921
                31453041
                ae31c269-2b81-44a2-8c2c-524fc10a5612
                Copyright © 2019, Hughes et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 May 2019
                : 22 June 2019
                Categories
                Radiation Oncology
                Oncology

                hypofractionated radiation therapy,non-small cell lung cancer,ultracentral,medically inoperable,surgically inoperable

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