Radiation Dose–Volume Effects in the Lung

      The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold “tolerance dose–volume” levels. There are strong volume and fractionation effects.
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        • Mehta V.
        Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: Pulmonary function, prediction, and prevention.
        Int J Radiat Oncol Biol Phys. 2005; 63: 5-24
        • Marks L.B.
        • Yu X.
        • Vujaskovic Z.
        • et al.
        Radiation-induced lung injury.
        Semin Radiother Oncol. 2003; 13: 333-345
        • Kocak Z.
        • Evans E.S.
        • Zhou S.M.
        • et al.
        Challenges in defining radiation pneumonitis in patients with lung cancer.
        Int J Radiat Oncol Biol Phys. 2005; 62: 635-638
        • Marks L.B.
        • Hollis D.
        • Munley M.
        • et al.
        The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests.
        Cancer. 2000; 88: 2135-2141
        • Rancati T.
        • Wennberg B.
        • Lind P.
        • et al.
        Early clinical and radiological pulmonary complications following breast cancer radiation therapy: NTCP fit with four different models.
        Radiother Oncol. 2007; 82: 308-316
        • Kwa S.L.
        • Lebesque J.V.
        • Theuws J.C.
        • et al.
        Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients.
        Int J Radiat Oncol Biol Phys. 1998; 42: 1-9
        • Graham M.V.
        • Purdy J.A.
        • Emami B.
        • et al.
        Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC).
        Int J Radiat Oncol Biol Phys. 1999; 45: 323-329
        • Yorke E.D.
        • Jackson A.
        • Rosenzweig K.E.
        • et al.
        Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy.
        Int J Radiat Oncol Biol Phys. 2002; 54: 329-339
        • Seppenwoolde Y.
        • De Jaeger K.
        • Boersma L.J.
        • et al.
        Regional differences in lung radiosensitivity after radiotherapy for non-small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2004; 60: 748-758
        • Yorke E.D.
        • Jackson A.
        • Rosenzweig K.E.
        • et al.
        Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study.
        Int J Radiat Oncol Biol Phys. 2005; 63: 672-682
        • Hope A.J.
        • Lindsay P.E.
        • El Naqa I.
        • et al.
        Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters.
        Int J Radiat Oncol Biol Phys. 2006; 65: 112-124
        • Bradley J.D.
        • Hope A.
        • El Naqa I.
        • et al.
        A nomogram to predict radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data.
        Int J Radiat Oncol Biol Phys. 2007; 69: 985-992
        • Meadors M.
        • Floyd J.
        • Perry M.C.
        Pulmonary toxicity of chemotherapy.
        Semin Oncol. 2006; 33: 98-105
        • Robnett T.J.
        • Machtay M.
        • Vines E.F.
        • et al.
        Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer.
        Int J Radiat Oncol Biol Phys. 2000; 48: 89-94
        • Hernando M.L.
        • Marks L.B.
        • Bentel G.C.
        • et al.
        Radiation-induced pulmonary toxicity: A dose-volume histogram analysis in 201 patients with lung cancer.
        Int J Radiat Oncol Biol Phys. 2001; 51: 650-659
        • Kong F.M.
        • Ten Haken R.
        • Eisbruch A.
        • et al.
        Non-small cell lung cancer therapy-related pulmonary toxicity: An update on radiation pneumonitis and fibrosis.
        Semin Oncol. 2005; 32: S42-S54
        • Movsas B.
        • Raffin T.A.
        • Epstein A.H.
        • et al.
        Pulmonary radiation injury.
        Chest. 1997; 111: 1061-1076
        • Onishi H.
        • Kuriyama K.
        • Yamaguchi M.
        • et al.
        Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: A good local response but no good survival due to radiation pneumonitis.
        Lung Cancer. 2003; 40: 79-84
        • Tsujino K.
        • Hirota S.
        • Kotani Y
        • et al.
        Radiation pneumonitis following concurrent accelerated hyperfractionated radiotherapy and chemotherapy for limited-stage smallcell lung cancer: Dose-volume histogram analysis and comparison with conventional chemoradiation.
        Int J Radiat Oncol Biol Phys. 2006; 64: 1100-1105
        • Roach 3rd, M.
        • Gandara D.R.
        • Yuo H.S.
        • et al.
        Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors.
        J Clin Oncol. 1995; 13: 2606-2612
        • Bentzen S.M.
        • Skoczylas J.Z.
        • Bernier J.
        Quantitative clinical radiobiology of early and late lung reactions.
        Int J Radiat Biol. 2000; 76: 453-462
        • Lebesque J.V.
        • Keus R.B.
        The simultaneous boost technique: The concept of relative normalized total dose.
        Radiother Oncol. 1991; 22: 45-55
        • Wheldon T.E.
        • Deehan C.
        • Wheldon E.G.
        • et al.
        The linear-quadratic transformation of dose-volume histograms in fractionated radiotherapy.
        Radiother Oncol. 1998; 46: 285-295
        • Fryer C.J.
        • Fitzpatrick P.J.
        • Rider W.D.
        • et al.
        Radiation pneumonitis: Experience following a large single dose of radiation.
        Int J Radiat Oncol Biol Phys. 1978; 4: 931-936
        • Ozsahin M.
        • Belkacémi Y.
        • Pène Fo
        • et al.
        Interstitial pneumonitis following autologous bone-marrow transplantation conditioned with cyclophosphamide and total-body irradiation.
        Int J Radiat Oncol Biol Phys. 1996; 34: 71-77
        • Sampath S.
        • Schultheiss T.E.
        • Wong J.
        Dose response and factors related to interstitial pneumonitis after bone marrow transplant.
        Int J Radiat Oncol Biol Phys. 2005; 63: 876-884
        • Timmerman R.D.
        • Park C.
        • Kavanagh B.D.
        The North American experience with stereotactic body radiation therapy in non-small cell lung cancer.
        J Thorac Oncol. 2007; 2: S101-S112
        • Timmerman R.
        • Galvin J.
        • Michalski J.
        • et al.
        Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using stereotactic body radiation therapy in lung cancer.
        Acta Oncol. 2006; 45: 779-786
        • Timmerman R.
        • Papiez L.
        • McGarry R.
        • et al.
        Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer.
        Chest. 2003; 124: 1946-1955
        • Hara R.
        • Itami J.
        • Komiyama T.
        • et al.
        Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors.
        Chest. 2004; 125: 340-344
        • Yamashita H.
        • Nakagawa K.
        • Nakamura N.
        • et al.
        Exceptionally high incidence of symptomatic grade 2-5 radiation pneumonitis after stereotactic radiation therapy for lung tumors.
        Radiat Oncol. 2007; 2: 21
        • Miller K.L.
        • Shafman T.D.
        • Anscher M.S.
        • et al.
        Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?.
        Int J Radiat Oncol Biol Phys. 2005; 61: 64-69
        • Yom S.S.
        • Liao Z.
        • Liu H.H.
        • et al.
        Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy.
        Int J Radiat Oncol Biol Phys. 2007; 68: 94-102
        • Sura S.
        • Gupta V.
        • Yorke E.
        • et al.
        Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience.
        Radiother Oncol. 2008; 87: 17-23
        • Allen A.M.
        • Czerminska M.
        • Jänne P.A.
        • et al.
        Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma.
        Int J Radiat Oncol Biol Phys. 2006; 65: 640-645
        • Rice D.C.
        • Smythe W.R.
        • Liao Z.
        • et al.
        Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma.
        Int J Radiat Oncol Biol Phys. 2007; 69: 350-357
        • Miles E.F.
        • Larrier N.A.
        • Kelsey C.R.
        • et al.
        Intensity-modulated radiotherapy for resected mesothelioma: The Duke experience.
        Int J Radiat Oncol Biol Phys. 2008; 71: 1143-1150
        • Novakova-Jiresova A.
        • van Luijk P.
        • van Goor H.
        • et al.
        Pulmonary radiation injury: Identification of risk factors associated with regional hypersensitivity.
        Cancer Res. 2005; 65: 3568-3576
        • van Luijk P.
        • Novakova-Jiresova A.
        • Faber H.
        • et al.
        Radiation damage to the heart enhances early radiation-induced lung function loss.
        Cancer Res. 2005; 65: 6509-6511
        • Wiegman E.M.
        • Meertens H.
        • Konings A.W.T.
        • et al.
        Loco-regional differences in pulmonary function and density after partial rat lung irradiation.
        Radiother Oncol. 2003; 69: 11-19
        • Komaki R.
        • Lee J.S.
        • Milas L.
        • et al.
        Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial.
        Int J Radiat Oncol Biol Phys. 2004; 58: 1369-1377
        • Antonadou D.
        • Coliarakis N.
        • Synodinou M.
        • et al.
        Randomized phase III trial of radiation treatment ± amifostine in patients with advanced-stage lung cancer.
        Int J Radiat Oncol Biol Phys. 2001; 51: 915-922
        • Antonadou D.
        • Throuvalas N.
        • Petridis A.
        • et al.
        Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2003; 57: 402-408
        • Movsas B.
        • Scott C.
        • Langer C.
        • et al.
        Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: Radiation Therapy Oncology Group trial 98-01.
        J Clin Oncol. 2005; 23: 2145-2154
        • Ozturk B.
        • Egehan I.
        • Atavci S.
        • et al.
        Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: A double-blind randomized trial.
        Int J Radiat Oncol Biol Phys. 2004; 58: 213-219
        • Fu X-L.
        • Huang H.
        • Bentel G.
        • et al.
        Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V30 and transforming growth factor [beta].
        Int J Radiat Oncol Biol Phys. 2001; 50: 899-908
        • Moiseenko V.
        • Deasy J.O.
        • Dyk J.V.
        Radiobiological modeling for treatment planning.
        in: Van Dyk J. The modern technology of radiation oncology: A compendium for medical physicists and radiation oncologists. Vol. 2. Medical Physics, Madison, WI2005
        • Seppenwoolde Y.
        • Lebesque J.V.
        • de Jaeger K.
        • et al.
        Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability.
        Int J Radiat Oncol Biol Phys. 2003; 55: 724-735
        • Tucker S.L.
        • Liu H.H.
        • Wang S.
        • et al.
        Dose-volume modeling of the risk of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.
        Int J Radiat Oncol Biol Phys. 2006; 66: 754-761
        • Kong F.M.
        • Hayman J.A.
        • Griffith K.A.
        • et al.
        Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1075-1086
        • Wang S.
        • Liao Z.
        • Wei X.
        • et al.
        Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT).
        Int J Radiat Oncol Biol Phys. 2006; 66: 1399-1407
        • Martel M.K.
        • Ten Haken R.K.
        • Hazuka M.B.
        • et al.
        Dose-volume histogram and 3-D treatment planning evaluation of patients with pneumonitis.
        Int J Radiat Oncol Biol Phys. 1994; 28: 575-581
        • Kwa S.L.
        • Theuws J.C.
        • Wagenaar A.
        • et al.
        Evaluation of two dose-volume histogram reduction models for the prediction of radiation pneumonitis.
        Radiother Oncol. 1998; 48: 61-69
        • Oetzel D.
        • Schraube P.
        • Hensley F.
        • et al.
        Estimation of pneumonitis risk in three-dimensional treatment planning using dose-volume histogram analysis.
        Int J Radiat Oncol Biol Phys. 1995; 33: 455-460
        • Rancati T.
        • Ceresoli G.L.
        • Gagliardi G.
        • et al.
        Factors predicting radiation pneumonitis in lung cancer patients: A retrospective study.
        Radiother Oncol. 2003; 67: 275-283
        • Kim T.H.
        • Cho K.H.
        • Pyo H.R.
        • et al.
        Dose-volumetric parameters for predicting severe radiation pneumonitis after three-dimensional conformal radiation therapy for lung cancer.
        Radiology. 2005; 235: 208-215
        • Willner J.
        • Jost A.
        • Baier K.
        • et al.
        A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer treated with 3-D conformal radiotherapy.
        Strahlenther Onkol. 2003; 179: 548-556
        • Tsujino K.
        • Hirota S.
        • Endo M.
        • et al.
        Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer.
        Int J Radiat Oncol Biol Phys. 2003; 55: 110-115
        • Armstrong J.G.
        • Zelefsky M.J.
        • Leibel S.A.
        • et al.
        Strategy for dose escalation using 3-dimensional conformal radiation therapy for lung cancer.
        Ann Oncol. 1995; 6: 693-697
        • Schallenkamp J.M.
        • Miller R.C.
        • Brinkmann D.H.
        • et al.
        Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates.
        Int J Radiat Oncol Biol Phys. 2007; 67: 410-416
        • Newton K.A.
        Total thoracic irradiation combined with intravenous injection of autogenous marrow.
        Clin Radiol. 1960; 11: 14-21
        • Newton K.A.
        • Spittle M.F.
        An analysis of 40 cases treated by total thoracic irradiation.
        Clin Radiol. 1969; 20: 19-22
        • Salazar O.M.
        • Rubin P.
        • Keller B.
        • et al.
        Systemic (half-body) radiation therapy: Response and toxicity.
        Int J Radiat Oncol Biol Phys. 1978; 4: 937-950
        • Van Dyk J.
        • Keane T.J.
        • Kan S.
        Radiation pneumonitis following large single dose irradiation: A re-evaluation based on absolute dose to lung.
        Int J Radiat Oncol Biol Phys. 1981; 7: 461-467
        • Rab G.T.
        • Ivins J.C.
        • Childs J.
        • Donald S.
        • et al.
        Elective whole lung irradiation in the treatment of osteogenic sarcoma.
        Cancer. 1976; 38: 939-942
        • Breur K.
        • Cohen P.
        • Schweisguth O.
        • et al.
        Irradiation of the lungs as an adjuvant therapy in the treatment of osteosarcoma of the limbs. An E.O.R.T.C. randomized study.
        European Journal of Cancer. 1978; 14: 461-471
        • Burgers J.M.
        • van Glabbeke V.
        • Busson A.
        • et al.
        Osteosarcoma of the limbs. Report of the EORTC-SIOP 03 trial 20781 investigating the value of adjuvant treatment with chemotherapy and/or prophylactic lung irradiation.
        Cancer. 1988; 61: 1024-1031


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