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“You Can Stereo That, Right?”

“You Can Stereo That, Right?”. The Unavoidable Uses of Lung SBRT. Matthew Harkenrider, MD James Graham Brown Cancer Center University of Louisville School of Medicine, Louisville, KY. Case #1. 87 year old caucasian male Presented to PCP with lower extremity edema CXR – LLL lung nodule

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“You Can Stereo That, Right?”

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  1. “You Can Stereo That, Right?” The Unavoidable Uses of Lung SBRT Matthew Harkenrider, MD James Graham Brown Cancer Center University of Louisville School of Medicine, Louisville, KY

  2. Case #1 • 87 year old caucasian male • Presented to PCP with lower extremity edema • CXR – LLL lung nodule • CT Chest – 2.9x2.6cm LLL spiculated nodule • PET/CT – SUV 6.4, no enlarged nodes, no mets • PMH – hypertension, arthritis • SH - 30 pack h/o smoking, no significant EtOH use

  3. Case #1

  4. Case #1 • CT-guided biopsy • Very few epitheliod cells, amorphous non-cellular debris, rare histiocytes and rare fibrovascular tissue • Non-diagnostic • Patient experienced hemorrhage during the procedure • Patient evaluated by thoracic surgeon but declined VATS lobectomy or wedge resection • Referred to radiation oncology for SBRT

  5. Unbiopsied Lung Cancer • Radiographic characteristics of malignancy • Irregular, spiculated appearance • Enlarging on serial imaging • Hypermetabolic on FDG-PET • Sensitivity of PET is 95-100% Sazon et al. AmJ Respir Crit Car Med, 1996. Dewan et al. Chest, 1993.

  6. Unbiopsied Lung Cancer • Patients often have poor pulmonary function and emphysematous blebs • Complications of CT-guided biopsy • Pneumothorax - 4-27% • Chest tube insertion – 1-5% • Pulmonary hemorrhage – 0.3-4% Priola et al. Acta Radiol, 2010. Laspas et al. J Med Imaging Radiat Oncol, 2008 Chakrabarti et al. Respir Med, 2009. Chojniak, et al. Sao Paulo Med, 2006.

  7. SBRT for UnbiopsiedEarly Stage Lung Cancer – A Multi-Institutional Analysis Matthew Harkenrider, MD, Matthew Bertke, MSE, and Neal Dunlap, MD James Graham Brown Cancer Center University of Louisville School of Medicine, Louisville, KY

  8. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis • Patients and Methods • University of Louisville and University of Virginia • Retrospectively analyzed 34 patients (17 from each institution) • Inclusion Criteria • Parenchymal lung nodule without pathologic diagnosis • No nodal or metastatic disease and no concurrent diagnosis of cancer • No previous local therapy • Radiographic imaging consistent with primary lung cancer

  9. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis • Patients and Methods • All patients evaluated by a thoracic surgeon • Medically inoperable or declined surgery • Too high risk for biopsy • Pretreatment Imaging • Serial Chest CT • PET/CT

  10. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis • Treatment Planning • U of L • 4D-CT in vacuum immobilization bag • Maximum intensity projection (MIP) images used to segment the internal target volume (ITV) • PTV = ITV + 0.5 cm • Treated with static field SBRT or VMAT • UVA • 3D-CT in body fix immobilization device • PTV = GTV + 1 cm • Treated with 7-9 noncoplanar beams

  11. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis • Dose • 50 Gy median dose (range 30-55 Gy) • Median of 5 fractions • Median BED 100 Gy (range 48-151.2 Gy) • Response measured using RTOG 0915 criteria of longest measured dimension on CT • Endpoints – LC, Regional Control, Distant Metastasis-Free survival, OS, Acute and Chronic Toxicity

  12. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis Patient and Tumor Demographics Median f/u 16.7 months

  13. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis

  14. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis

  15. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis

  16. “Clinical Proof of Malignancy” Beitler, et al. IJROBP, 2006 Lagerwaard et al. IJROBP, 2008 Baumann, et al. JCO, 2009 Ricardi, et al. Lung Cancer, 2010.

  17. “Clinical Proof of Malignancy” • Beitler et al found no difference in overall survival without pathology • Ricardi et al found no difference in cancer specific survival without pathology

  18. “Clinical Proof of Malignancy” • Inoue, IJROBP 2010 • 115 medically inoperable patients from 12 institutions treated on Japanese Clinical Oncology Group trial • Diagnosed with enlargement of the lesion on serial CT +/- FDG-PET avidity • 30-70 Gy delivered in 2-7 fractions

  19. “Clinical Proof of Malignancy” • Local Control • <2 cm – 96.4% • >2 cm – 94.7% • One grade 5 pneumonitis occurring 1.5 months after SBRT for T2 lesion • Three grade 3 toxicities all managed conservatively

  20. Local Control Ginsberg et al. Ann Thorac Surg, 1995 Timmerman et al. JAMA, 2010.

  21. Case #1 • PET/CT 6 mos. post-SBRT

  22. SBRT for Unbiopsied Early Stage Lung Cancer – A Multi-Institutional Analysis • Conclusions • SBRT can be safely delivered for unbiopsied primary lung tumors • Favorable rates of local control can be achieved • Tissue diagnosis should still be obtained if biopsy can be safely performed

  23. Case #2 • 71 year old female • Acute onset DOE • History of a lung nodule in the left apex • CXR on admission showed enlargement of the nodule • CT confirmed growth now measuring 2.9x2.3 cm • PET/CT showed SUV of 4.8 • PMH – COPD, HTN, 2L home oxygen • SH – 2.5 ppd smoking for 66 years • Biopsy reveals SCC of the lung • Not a surgical candidate

  24. Case #2 • Treated with 3D-CRT to 70 Gy in 2 Gy fractions without chemotherapy • Plan changed at 56 Gy to avoid brachial plexus • 3 month CT – decreased to 1.2 cm • 6 month PET/CT - stable size, decreased SUV • 9 month CT – stable size • 12 month PET/CT – spiculated 2.3x1.9 cm lesion with SUV 10.3 at the site of previously treated disease

  25. Case #2 • 12 month PET/CT

  26. Options for Local Failure • Chemotherapy • Surgery • Re-Irradiation • Palliation

  27. Case #2 • 50 Gy in 5 fractions to 95% of PTV

  28. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients Matthew Harkenrider, MD, Matthew Bertke, MSE, Neal Dunlap, MD, and Anthony Dragun, MD James Graham Brown Cancer Center University of Louisville School of Medicine, Louisville, KY

  29. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients • University of Louisville • 22 patients (7 of which had recurrent disease) • Inclusion criteria • >6 months follow up • No biopsy of recurrence • Radiographic characteristics of malignancy • Spiculation • Enlarging size on CT • FDG avidity on PET scan

  30. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients Patient and Tumor Demographics Median f/u 15.3 months

  31. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients

  32. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients

  33. Case #2 • 10 month PET/CT s/p salvage SBRT

  34. SBRT as Re-Irradiation Coon et al. Clin Lung Cancer, 2008. Kelly et al. IJROBP, 2010

  35. SBRT for Non-Pathologically Diagnosed Lung Cancer Patients • There were no acute or chronic grade 3 or greater toxicities with SBRT for recurrent tumors • Conclusions • SBRT can be safely delivered for patients with recurrent NSCLC • Encouraging rate of local control can be achieved

  36. Lung SBRT for Oligometastatic Disease

  37. Lung SBRT for Oligometastatic Disease • Halsted theory of cancer spread • Local  Lymphatic  Systemic • Systemic theory of cancer spread • If the tumor is to metastasize, then it has already done so, and is hence a systemic disease • Hellman and Weichselbaum theory • Combination of the two theories • Describes low volume and number of metastases that is potentially curable

  38. Lung SBRT for Oligometastatic Disease • International Registry of Lung Metastases • 5,206 cases of lung metastatectomy • 5 year survival – 36% • 15 year survival – 22% • Phase I/II multi-institutional trial of SBRT • Patients with 1-3 lesions • Grade 3 toxicity 8% • No grade 4 toxicity “Long-term results of lung metastasectomy…” J Thorac Cardiovasc Surg, 1997. Rusthoven et al. JCO, 2009

  39. Lung SBRT for Oligometastatic Disease “Long-term results of lung metastasectomy…” J Thorac Cardiovasc Surg, 1997. Rusthoven et al. JCO, 2009 Okunieff et al. Acta Oncologica, 2006 Fritz et al. Radiation Onology, 2006

  40. Lung SBRT for Oligometastatic Disease • Acute and chronic toxicity is minimal • Local control rates are comparable to early stage NSCLC • Long term survival is possible • Single organ • Limited number • Low volume

  41. Tumor Volume Change Before, During and After Stereotactic Body Radiotherapy (SBRT) for Early Stage Lung Cancer (ESLC): Evaluating the potential for Adaptive SBRT (A-SBRT) Aashish D. Bhatt, M.D., Geetika Bhatt, M.B.B.S., Matthew Harkenrider, M.D., Albert Zacarias, Ph.D., A. CahidCivelek, M.D., Jianmin Pan, Ph.D., Shesh N. Rai, Ph.D., and Moataz N. El-Ghamry, M.D. James Graham Brown Cancer Center University of Louisville School of Medicine, Louisville, KY

  42. Background • Usual SBRT Tx -> Plan once • Tumor regression -> ↓GTV -> ⇑PTV (relative) • Result -> ↑Integral dose

  43. Purpose • Quantify GTV change before, during and after SBRT • Evaluate predictive factors to GTV shrinkage • Possible timing of Adaptive SBRT (A-SBRT)

  44. Methods • Retrospective analysis • 24 patients with 25 treated lung tumors • Dose – 50 Gy/5 fxs @ 10 Gy/fx • 7 GTV’s contoured – 1. Initial diagnCT (CTPRE), 2-6. 5 Cone Beam CT’s (CBCT1-5 ) 7. 1st f/u CT post RT (CTPOST)

  45. Methods • Primary Endpoint – Quantify GTV change on 7 serial CT scans • T-test (two sided): compare mean GTV changes • Secondary Endpoint – Univariate and Multivariate analyses to correlate GTV changes to predictive patient factors

  46. SBRT Technique • Maximum intensity projection (MIP) based motion encompassing ITV derived using a 4D-CT • PTV = 0.5 cm expansion of ITV • 95% of the PTV received 100% of the dose • Double vacuum based immobilization system • Initially static field, then VMAT (RapidArc®) • IGRT (CBCT’s) on Varian TrilogyTM ITV – Internal target volume VMAT – Volume Modulated Arc Therapy

  47. Results GTV changes from CTPRE CBCT1 CBCT5CTPOST

  48. Results Volume of GTV changes T-Test results between the 7 GTV’s *- Equivalent 2 mm CT thickness volume (cc)

  49. Results CTPRETUMOR SIZE - 2.10 x 2.35 cms VOLUME– 8.33 cc Illustration of GTV changes on serial CT scans CBCT1TUMOR SIZE - 3.12 x 3.10 cms VOLUME– 13.61 cc CBCT4TUMOR SIZE - 3.08 x 2.6 cms VOLUME– 9.79 cc CBCT5TUMOR SIZE - 2.5 x 2.2 cms VOLUME– 9.11 cc CTPOSTTUMOR SIZE - 1.72 x 1.41 cms VOLUME– 4.3 cc

  50. Results • Univariate linear regression analyses CBCT1to CTPOST : 2 significant covariates • “Time from CBCT5 to CTPOST” (p=0.0271) & • “T-Stage” (p=0.0027) • Multivariate analyses: “T-stage” remained signif. • No signif. correlation of GTV shrinkage to any other impact factors

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