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      A Current Review of Dose-escalated Radiotherapy in Locally Advanced Non-small Cell Lung Cancer

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          Abstract

          Background

          The mainstay therapy for locally advanced non-small cell lung cancer is concurrent chemoradiotherapy. Loco-regional recurrence constitutes the predominant failure patterns. Previous studies confirmed the relationship between increased biological equivalent doses and improved overall survival. However, the large randomized phase III study, RTOG 0617, failed to demonstrate the benefit of dose-escalation to 74 Gy compared with 60 Gy by simply increasing fraction numbers.

          Conclusions

          Though effective dose-escalation methods have been explored, including altered fractionation, adapting individualized increments for different patients, and adopting new technologies and new equipment such as new radiation therapy, no consensus has been achieved yet.

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          Most cited references44

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          Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study.

          Hiroshi Onishi, Hiroki Shirato, Yasushi Nagata … (2007)
          Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57-180 Gy) based on alpha/beta = 10. During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p < 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p < 0.05). Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.
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            A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study

            Jacob G Scott, Anders Berglund, Michael Schell … (2017)
            Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose.
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              Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer

              Zhongxing Liao, J. Lee, Ritsuko Komaki … (2018)
              Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF). Patients and Methods Eligible patients had stage IIB to IIIB NSCLC (or stage IV NSCLC with a single brain metastasis or recurrent lung or mediastinal disease after surgery) who were candidates for concurrent chemoradiation therapy. Pairs of treatment plans for IMRT and PSPT were created for each patient. Patients were eligible for random assignment only if both plans satisfied the same prespecified dose-volume constraints for at-risk organs at the same tumor dose. Results Compared with IMRT (n = 92), PSPT (n = 57) exposed less lung tissue to doses of 5 to 10 Gy(RBE), which is the absorbed Gy dose multiplied by the relative biologic effectiveness (RBE) factor for protons; exposed more lung tissue to ≥ 20 Gy(RBE), but exposed less heart tissue at all dose levels between 5 and 80 Gy(RBE). The grade ≥ 3 RP rate for all patients was 8.1% (IMRT, 6.5%; PSPT, 10.5%); corresponding LF rates were 10.7% (all), 10.9% (IMRT), and 10.5% (PSPT). The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that the RP and LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% (before) versus 18.2% (after) for the IMRT group (P = .047) and 31.0% (before) versus 13.1% (after) for the PSPT group (P = .027). Conclusion PSPT did not improve dose-volume indices for lung but did for heart. No benefit was noted in RP or LF after PSPT. Improvements in both end points were observed over the course of the trial.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Radiol Oncol
                Journal ID (iso-abbrev): Radiol Oncol
                Journal ID (publisher-id): raon
                Journal ID (pmc): raon
                Title: Radiology and Oncology
                Publisher: Sciendo
                ISSN (Print): 1318-2099
                ISSN (Electronic): 1581-3207
                Publication date Collection: March 2019
                Publication date (Electronic): 03 March 2019
                Volume: 53
                Issue: 1
                Pages: 6-14
                Affiliations
                [1 ]Department of Radiation Oncology, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Shenzhen, 518116, China
                [2 ]Department of VIP Medical Services, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100021, China
                [3 ]Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100021, China
                Author notes
                [* ] Zhouguang Hui, M.D., Department of VIP Medical Services & Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Panjiayuan Nanli 17, Chaoyang District, Beijing 100021, China. Phone: + 861087787656 huizg@ 123456cicams.ac.cn
                Article
                Publisher ID: raon-2019-0006
                DOI: 10.2478/raon-2019-0006
                PMC ID: 6411023
                PubMed ID: 30840594
                SO-VID: 19c39aba-40bb-440c-a658-41d2118e61cc
                Copyright © © 2019 Li Ma, Yu Men, Lingling Feng, Jingjing Kang, Xin Sun, Meng Yuan, Wei Jiang, Zhouguang Hui published by Sciendo
                License:

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

                History
                Date received : 31 August 2018
                Date accepted : 05 January 2019
                Page count
                Pages: 9
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: non-small cell lung cancer,dose escalation,hyperfractionation,hypofractionation,adaptive radiotherapy,proton radiotherapy,carbon ion radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: non-small cell lung cancer, dose escalation, hyperfractionation, hypofractionation, adaptive radiotherapy, proton radiotherapy, carbon ion radiotherapy

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