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Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

      Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women’s Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy.
      Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m2). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test.
      Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5–57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3–22.3%), 15.2 Gy (range, 13.3–17 Gy), and 98.6% (range, 81–100%), respectively, as compared with 10.9% (range, 5.5–24.7%) (p = 0.08), 12.9 Gy (range, 8.7–16.9 Gy) (p = 0.07), and 90% (range, 66–98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis.
      Conclusions: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.

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      References

        • Vogelzang N.J.
        • Rusthoven J.J.
        • Symanowski J.
        • et al.
        Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
        J Clin Oncol. 2003; 21: 2636-2644
        • Pass H.I.
        • Kranda K.
        • Temeck B.K.
        • et al.
        Surgically debulked malignant pleural mesothelioma.
        Ann Surg Oncol. 1997; 4: 215-222
        • Rusch V.W.
        • Piantadosi S.
        • Holmes E.C.
        • A Lung Cancer Study Group trial
        The role of extrapleural pneumonectomy in malignant pleural mesothelioma.
        J Thorac Cardiovasc Surg. 1991; 102: 1-9
        • Sugarbaker D.J.
        • Flores R.M.
        • Jaklitsch M.T.
        • et al.
        Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma.
        J Thorac Cardiovasc Surg. 1999; 117: 54-65
        • Ahamad A.
        • Stevens C.W.
        • Smythe W.R.
        • et al.
        Promising early local control of malignant pleural mesothelioma following postoperative intensity modulated radiotherapy (IMRT) to the chest.
        Cancer J. 2003; 9: 476-484
        • Forster K.M.
        • Smythe W.R.
        • Starkschall G.
        • et al.
        Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma.
        Int J Radiat Oncol Biol Phys. 2003; 55: 606-616
        • Ahamad A.
        • Stevens C.W.
        • Smythe W.R.
        • et al.
        Intensity-modulated radiation therapy.
        Int J Radiat Oncol Biol Phys. 2003; 55: 768-775
        • Rusch V.W.
        • Rosenzweig K.
        • Venkatraman E.
        • et al.
        A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.
        J Thorac Cardiovasc Surg. 2001; 122: 788-795
        • Baldini E.H.
        • Recht A.
        • Strauss G.M.
        • et al.
        Patterns of failure after trimodality therapy for malignant pleural mesothelioma.
        Ann Thorac Surg. 1997; 63: 334-338
        • Yajnik S.
        • Rosenzweig K.E.
        • Mychalczak B.
        • et al.
        Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma.
        Int J Radiat Oncol Biol Phys. 2003; 56: 1319-1326
        • Dawson L.A.
        • Normolle D.
        • Balter J.M.
        • et al.
        Analysis of radiation-induced liver disease using the Lyman NTCP model.
        Int J Radiat Oncol Biol Phys. 2002; 53: 810-821
        • Kwa S.L.
        • Lebesque J.V.
        • Theuws J.C.
        • et al.
        Radiation pneumonitis as a function of mean lung dose.
        Int J Radiat Oncol Biol Phys. 1998; 42: 1-9
        • Hernando M.L.
        • Marks L.B.
        • Bentel G.C.
        • et al.
        Radiation-induced pulmonary toxicity.
        Int J Radiat Oncol Biol Phys. 2001; 51: 650-659
        • Trotti A.
        • Colevas A.D.
        • Setser A.
        • et al.
        CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment.
        Semin Radiat Oncol. 2003; 13: 176-181
        • Rusch V.W.
        • Figlin R.
        • Godwin D.
        • Piantadosi S.
        Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions.
        J Clin Oncol. 1991; 9: 313-319
        • Tohda Y.
        • Iwanaga T.
        • Takada M.
        • et al.
        Intrapleural administration of cisplatin and etoposide to treat malignant pleural effusions in patients with non–small cell lung cancer.
        Chemotherapy. 1999; 45: 197-204
        • Colleoni M.
        • Sartori F.
        • Calabro F.
        • et al.
        Surgery followed by intracavitary plus systemic chemotherapy in malignant pleural mesothelioma.
        Tumori. 1996; 82: 53-56
        • van Putten J.W.
        • Price A.
        • van der Leest A.H.
        • et al.
        A Phase I study of gemcitabine with concurrent radiotherapy in stage III, locally advanced non–small cell lung cancer.
        Clin Cancer Res. 2003; 9: 2472-2477
        • Thomas A.L.
        • Cox G.
        • Sharma R.A.
        • et al.
        Gemcitabine and paclitaxel associated pneumonitis in non–small cell lung cancer.
        Eur J Cancer. 2000; 36: 2329-2334
        • Blackstock A.W.
        • Lesser G.J.
        • Fletcher-Steede J.
        • et al.
        Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non–small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2001; 51: 1281-1289
        • Bischof M.
        • Weber K.J.
        • Blatter J.
        • et al.
        Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and irradiation in vitro.
        Int J Radiat Oncol Biol Phys. 2002; 52: 1381-1388
        • Seiwert T.Y.
        • Mauer A.M.
        • Hoffman P.C.
        • et al.
        A phase I dose-escalating study of combination pemetrexed-based chemotherapy and concomitant radiotherapy for locally advanced or metastatic non–small cell lung or esophageal cancer. ASCO, Orlando, FL2005
        • 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
        • 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
        • Kocak Z.
        • Yu X.
        • Zhou S.M.
        • et al.
        The impact of pre-radiotherapy surgery on radiation-induced lung injury.
        Clin Oncol (R Coll Radiol). 2005; 17: 210-216
        • Della Volpe A.
        • Ferreri A.J.
        • Annaloro C.
        • et al.
        Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total body irradiation.
        Int J Radiat Oncol Biol Phys. 2002; 52: 483-488
        • 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
        • 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
        • Wang S.L.
        • Liao Z.
        • Vaporciyan A.A.
        • et al.
        Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.
        Int J Radiat Oncol Biol Phys. 2006; 64: 692-699
        • Holloway C.L.
        • Robinson D.
        • Murray B.
        • et al.
        Results of a phase I study to dose escalate using intensity modulated radiotherapy guided by combined PET/CT imaging with induction chemotherapy for patients with non–small cell lung cancer.
        Radiother Oncol. 2004; 73: 285-287

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