Tecniche Radioterapiche U. Ricardi

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1 Tecniche Radioterapiche U. Ricardi UNIVERSITA DEGLI STUDI DI TORINO

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6 Should we always rely on stage? T4N0M0 Stage IIIB T2N3M0

7 Early stage NSCLC The treatment of choice for early-stage NSCLC is anatomic surgical resection Certain patients can be considered medically or functionally not amenable with surgery For these patients, radiotherapy is the alternative treatment, although with considerably worse outcome UNIVERSITA DEGLI STUDI DI TORINO

8 Early stage NSCLC The effect of tumor size on curability of stage I NSCLC (7620 resected pts) Survival 12 yrs 5-15 mm 69% mm 63% mm 58% mm 53% >45 mm 43% Radiation therapy for the treatment of unresected stage I NSCLC (3842 pts who did not receive surgical resection) 5 yrs survival rate: 15% (local failure rates ranging from 30% to 70%) Wisnivesky JP et al., Chest, 2004 Wisnivesky JP et al., Chest, 2005 UNIVERSITA DEGLI STUDI DI TORINO

9 Suboptimal local control after radiation therapy in lung cancer Inadequate dose to tumor Excessive dose to normal tissues Tumor extension beyond treatment volume UNIVERSITA DEGLI STUDI DI TORINO

10 SBRT in early stage lung tumors Early stage NSCLC Small volume Peripheral location Treatment simulation: all relevant information on target definition is incorporated (CT-PET, 4D-CT) Treatment planning: involves selection of delivery technique and approach for optimizing target Dose escalation coverage and normal tissue avoidance Radiation delivery and treatment verification UNIVERSITA DEGLI STUDI DI TORINO

11 Stereotactic Body Radiation Therapy (SBRT) An external beam radiation therapy method used to very precisely deliver a high dose of radiation to an extracranial target within the body, using either a single dose or a small number of large fractions Specialized treatment planning results in high target dose and steep dose gradients beyond the target The challenge is to hit the entire extent of the tumor with extremely potent and biologically damaging therapy, while simultaneously avoiding surrounding normal tissue (tumor ablation and normal tissues sparing) UNIVERSITA DEGLI STUDI DI TORINO

12 SBRT for lung University of Torino Standard treatment for early stage NSCLC since May, 2003 Patients medically or functionally unfit for surgery, or Sx refusal More than 200 pts have been University of Torino UNIVERSITA DEGLI STUDI DI TORINO

13 STEREOTACTIC BODY RADIOTHERAPY LUNG: primary metastatic 245 patients 153 patients other sites: 48 patients (adrenal glands, liver, lymphnodes, spinal) UNIVERSITA DEGLI STUDI DI TORINO

14 Prospective Phase II trial of SBRT Eligibility Criteria Histological confirmation or clinical proof of NSCLC Stage IA or IB (T2aN0) Contra-indication to surgery or refusal Performance status ECOG FDG CT-PET scan (mandatory) Written informed consent Exclusion criteria Lesions located less than 2 cm away from airways or less than 1 cm away from major blood vessels UNIVERSITA DEGLI STUDI DI TORINO

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16 Response to treatment At treatment After 3 months After 90 months UNIVERSITA DEGLI STUDI DI TORINO

17 Severe Pulmonary Toxicity No Pts Dose Grade 3+ Toxicity Uematsu Gy 5-15 fx 0% Nakagawa Gy 1 fx 0% Nagata Gy 4 fx 0% Wulf Gy 1-3 fx 3% Hara Gy 1 fx 4% Hof Gy 1 fx 0% Onimaru Gy 8 fx 2% Whyte Gy 1 fx 0% Blomgren Gy 2-3 fx 6% Ricardi Gy/3fx or 26 Gy/1fx 3% UNIVERSITA DEGLI STUDI DI TORINO

18 [Ricardi U et al., 2009] UNIVERSITA DEGLI STUDI DI TORINO

19 Acute Toxicity - Skin toxicity Late Toxicity - Rib fracture - Chest wall pain UNIVERSITA DEGLI STUDI DI TORINO

20 Dunlap N.E. et al.: IJROBP, 76, 3, , 2010 Targets for chest wall toxicity include muscle, connettive tissue, neurovascular bundle and bone; injury of the peripheral nerves from radiation as mechanism of local pain The Chest Wall volume receiving 30 Gy in 3 to 5 fractions should be limited to < 30 cm 3 to reduce the risk of toxicity UNIVERSITA DEGLI STUDI DI TORINO

21 Location inside ----outside p=0.004 [Timmerman R et al., 2006] T1 tumors: 20 Gy x 3 fractions (60 Gy total) T2 tumors: 22 Gy x 3 fractions (66 Gy total) UNIVERSITA DEGLI STUDI DI TORINO

22 Lesions were considered to be within central thorax if they were located in the mediastinum, hilum and/or met the RTOG 0236 protocol guidelines for central thoracic lesions, namely within 2 cm in all directions around the proximal bronchial tree Institution Patient population Prescribed dose (Gy) Fraction dose (Gy) BED2 (Gy) Toxicity IndianaU. Stage I NSCLC Fold increase risk of severe-fatal toxicity Hokkaido U NSCLC and Mts of 9 with severe toxicity U. Texas, San Antonio NSCLC and Mts of 9 asymptomatic airway collapse Air Force General Hospital Stage I-II NSCLC No severe toxicity VU Amsterdam Stage I NSCLC No severe toxicity Technical U. NSCLC and Mts No severe toxicity Moderately hypofractionated SBRT to central thoracic lesions is effective with respect to local control and toxicity. Radiother Oncol, 2009 UNIVERSITA DEGLI STUDI DI TORINO

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24 University of Turin Local tumor control dependent on BED Local tumor control dependent on BED (a/b=10) of different irradiation regimens. UNIVERSITA DEGLI STUDI DI TORINO

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27 Stereotactic radiation therapy: changing treatment paradigms for stage I NSCLC In patients with stage I NSCLC who do not undergo surgery, SBRT achieves superior survival as compared to treatment using conventionally fractionated radiotherapy The role of SBRT in operable patients remains to be defined within randomized trials In patients identified to be at high risk for surgical complications, SBRT appears to provide an effective alternative with low risks of hospitalization and 30-day mortality Future treatment algorithms should include individualized assessment of surgical risks, and the consideration of SBRT for high-risk patients, in order to develop a personalized treatment approach UNIVERSITA DEGLI STUDI DI TORINO

28 Unresectable stage III NSCLC At present, concurrent chemotherapy with radiotherapy to a dose of 60 Gy in 30 daily fracbons is considered to be the standard treatment Indirect evidence suggests that radiabon dose- escalabon may improve survival also in the context of chemo- radiabon UNIVERSITA DEGLI STUDI DI TORINO

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31 Suboptimal local control after radiation therapy in lung cancer Inadequate dose to tumor Excessive dose to normal tissues Tumor extension beyond treatment volume UNIVERSITA DEGLI STUDI DI TORINO

32 Unresectable stage III NSCLC At present, concurrent chemotherapy with radiotherapy to a dose of 60 Gy in 30 daily fracbons is considered to be the standard treatment Indirect evidence suggests that radiabon dose- escalabon may improve survival also in the context of chemo- radiabon UNIVERSITA DEGLI STUDI DI TORINO

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35 Radiotherapy schedules other than conventional fractionation ones for dose intensification? UNIVERSITA DEGLI STUDI DI TORINO

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37 Is there an optimal fractionation schedule for maximizing the therapeutic ratio? Hypofractionation is not beneficial for normal tissue sparing SABR in early stage lung cancer Can adapted hypofractionation be applied to lung cancer patients with larger tumors? Hi-Tech Radiotherapy: very steep dose gradient between tumor and healthy tissues UNIVERSITA DEGLI STUDI DI TORINO

38 Summary ObjecBves of XRT for lung cancer - OpBmize local control - Reduce toxicity Technical advances that improve ability to target treatment and reduce toxicity - Incorporate PET- CT into radiabon planning - 4D- CT to account for tumor mobon - IMRT and IGRT to limit PTV margins UNIVERSITA DEGLI STUDI DI TORINO

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