Protocol of Radiotherapy for Small Cell Lung Cancer

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1 107 年 12 月修訂 Protocol of Radiotherapy for Small Cell Lung Cancer Indication of radiotherapy Limited stage: AJCC (8th edition) stage I-III (T any, N any, M0) that can be safely treated with definitive RT doses. Excluding T3-4 due to multiple lung nodules or tumor/nodal volume too large to be encompassed in a tolerable radiation plan. (1) Post lobectomy ct1-2n0 with pathological positive lymph node (2) T3-4N0M0; T1-4N1-3M0 with good PS (0-2) or poor PS (3-4) due to SCLC (3) In patients with limited-stage SCLC who have a good response to initial therapy, PCI decreases brain metastases and increases overall survival (category 1). Extensive stage (ES): AJCC (8th edition) stage IV (T any, N any, M1a/b; or T3-T4 due to multiple lung nodules or tumor/nodal volume too large to be encompassed in a tolerable radiation plan.) (1) Consolidation thoracic RT(TRT) may be beneficial in selected cases responsive to chemotherapy, the principles are similar to those of limited stage cases. Studies have demonstrated that consolidative TRT is well tolerated, results in fewer symptomatic chest recurrences, and improves long term survival in some patients. (2) In patients with extensive-stage SCLC who have responded to chemotherapy, PCI decreases brain metastases. Standards for clinical and technologic expertise and QA and principles of RT simulation, planning, and delivery --are provided in the guideline counterpart for NSCLC. For similar TRT, prescription doses, the normal tissue constrains used for NSCLC appropriate. (Except for that of the PCI section and for that of SABR section) Simulation and Treatment Planning 1. A minimum standard is CT planned 3D conformal RT. Multiple fields should be used, with all fields treated each day. Available technique should be performed to assess tumor movement and motion management should be used to achieve movement of less than 1 cm or the PTV margin should be increased appropriately. (Readers may refer to NSCLC in our hospital and NCCN 2018 guideline in same domain) 2. In patients receiving radiation therapy or chemoradiation with curative intent, treatment interruptions or dose reductions for manageable acute toxicities should be minimized. 3. Vacuum or wing board immobilization was encouraged for daily set-up of thoracic

2 region RT. 4. CT simulation was strongly suggested for treatment planning with IV contrast infusion if feasible. PET-CT is highly recommended for the treatment plan especially in cases with significant atelectasis and when IV contrast is contraindicated. 5. Radiation doses should be calculated with inhomogeneity corrections. General principles for radiation therapy 1. Elective nodal irradiation may not be necessary, particularly in patients staged with both CT and PET; however, low dose (< 50 Gy) could be helpful to control some subclinical nodal metastasis. 2. Wherever possible and suitable, 4DCT, IGRT or Respiratory coordination using a number of technique is needed for breathing motion e.g. Active breathing control, abdominal compression or Cyberknife respiratory tracking system) should be encouraged to be used in thoracic irradiation to minimize the set up uncertainty or internal organ movement error. Respiratory gating is also an option to reduce the irradiated normal lung tissue; however, attention should be paid to irregular breathing and variation in the breathing pattern over the course of the treatment. 3. In clinical practice, if the patient has very poor pulmonary function or a very large GTV, clinical judgment should be applied to balance the optimal tumor coverage and radiation toxicity. Radiation Treatment Fields (1) Gross Tumor Volume (GTV) is defined as all known gross disease as defined by the planning CT and clinical information. The pulmonary extent of lung tumors should be delineated on pulmonary windows, and the mediastinal extent of tumors should be delineated using mediastinal windows. The FDG-PET images can help to categorize suspected mediastinal and hilar adenopathy and differentiate between collapsed lung tissue from tumor. However, false-positive PET scans can be caused by inflammation, and a biopsy is recommended if there is any question. In patients who start chemotherapy before RT, the gross tumor volume (GTV) can be limited to the post induction chemotherapy volume to avoid excessive toxicity. Initially involved nodal regions (but not their entire pre chemotherapy volume) should be covered. (2) Clinical Target Volume (CTV) includes the area of subclinical involvement around the GTV. For the lung parenchymal disease, a margin with typically 6-8 mm is required to cover the gross and microscopic disease expansions of involved nodes of the CTV margins may be manually reduced if there is

3 confidence that microscopic disease does not exist in a specified region. (3) Planning Target Volume (PTV) provide margin around the CTV to account for daily setup error and target motion. The setup uncertainty can be reduced to 5 mm, if a daily image-guided setup is used. KV image-guided setup is used. And 3-5 mm for cone beam CT Tumor motion is best assessed individually for each patient. For patients with tumor motion of < 5mm, simple expansion for the GTV margin is adequate. Radiation dose 1. Preoperatively, a dose of Gy in 1.8 to 2 Gy /fraction size is recommended. 2. Postoperative radiation dose should be based on margin status. Lung tolerance to radiation after surgery seems to be remarkably smaller than those with the presence of both lungs. Every effort should be made to minimize the dose of radiation therapy. 3. For definitive radiation therapy, the commonly prescribed dose is Gy. 4. In extensive stage patient, dosing and fractionation of consolidative thoracic RT should be individualized within the range of 30 Gy in 10 daily fractions to 60 Gy in 30 daily fractions, or equivalent regimens in this range. 5. In patients who receive postoperative radiotherapy, CTV may consist of the bronchial stump and high-risk draining lymph node stations. Postoperative radiation therapy, more strict DVH parameters should be considered for the lung. Treatment Type Total Dose Fraction Size Treatment Duration Preoperative Gy 4-5 weeks Postoperative Negative margins Extracapsular nodal extension or microscopic positive margins Gross residual tumors 50-54Gy Gy 60 to 70 Gy 5-6 weeks 5-6 weeks 6-7 weeks Definitive RT with or without Concurrent chemotherapy Gy weeks Constraints of OAR Structures Limits OAR Constraints in fractions Spinal Cord Max 50 Gy in

4 fractions Lung V % V5 65% MLD < 20 Gy Heart V40 80 % V45 60% V60 30% Mean 35 Gy Esophagus Mean dose 34 Gy Max 105% of the prescription dose Brachial Plexus Max 66 Gy * Modification of above constraint should be considered according to each patient s condition PCI (Prophylactic Cranial Irradiation): Administrate PCI after resolution of acute toxicity of initial therapy. CTV should encompass the whole brain..the field edges should be at least 1 cm from the outer skull margin or with treated with conformal RT technique with adding 3-5 mm margin to become PTV if no image guide RT can be used. Typically recommended dose is arround 8-15 fractions totally 24 Gy to 30 Gy. A shorter course (eg, 20 Gy in 5 fractions) may be appropriate in selected patients with extensive-stage disease. Concurrent systemic therapy and high total RT dose (>30 Gy) should be avoided in patients receiving PCI. Reference 1. Small Cell Lung Cancer. NCCN practice guidelines in oncology 2018 verion 1. Available at: 2. Pignon JP, Arriagada A, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992;3: Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341: Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small cell lung cancer. N Engl J Med 2007;357: Liengswangwong V, Bonner JA, Shaw EG, et al. Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic

5 radiotherapy. J Clin Oncol 1994;12(3): Roof KS et al ; Radiation dose escalation in limited small cell lung cancer. Int J Radiat Oncol Bio Phys 2003; 57 (3): Bogart JA et al; 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited stage small cell lung cancer : analysis pf cancer and leukemia group b study Int J Radiat Oncol Bio Phys 2004; 59 (2): Keall PJ, et al. The management of repsiratory motion in radiation oncology report AAPM task group 76. Med Phys 2006;33: Kim TH, et al Dose-volimetric parameters in the prediction of severe radiation pneumonitis after three-dimensional confromal radiation therapy for lung cancer. Radiology 2005;235: Komaki R, Swann RS, Ettinger DS, et al. Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: report of Radiation Therapy Oncology Group (RTOG) protocol Int J Radiat Oncol Biol Phys 2005;62(2): p. 965p. 966p. 967p Komaki RU, Paulus R, Ettinger D, et al. Patterns of first failure in a phase ii study of accelerated high dose thoracic radiation therapy (TRT) with concurrent chemotherapy for limited small-cell lung cancer (LSCLC): Radiation Therapy Oncology Group (RTOG) Int J Radiat Oncol Biol Phys 2009;75(3 Suppl 1):S34 S Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet Jan 3;385(9962): doi: /S (14) Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol Aug;18(8): Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol May;18(5):