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Early stage lung_cancer- jtl

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Early stage lung_cancer- jtl

  1. 1. Early Stage Lung Cancer Wake Forest Baptist Medical Center Radiation Oncology Department John T. Lucas Jr. MD, MSCR PGY2
  2. 2. Outline <ul><li>Management </li></ul><ul><li>Treatment Options </li></ul><ul><li>    Surgery </li></ul><ul><li>    Alternative Ablative Modalities </li></ul><ul><li>    Radiotherapy </li></ul><ul><li>SBRT </li></ul><ul><li>    History </li></ul><ul><li>    Technique </li></ul><ul><li>    Dose, Fractionation </li></ul><ul><li>    Dose Constraints  </li></ul><ul><li>    Side Effects/Complications </li></ul><ul><li>    Post Treatment Surveillance </li></ul><ul><li>    Outcomes </li></ul><ul><li>Ongoing Trials </li></ul><ul><li>           </li></ul>
  3. 3. Surgery <ul><li>- Types of Resection </li></ul><ul><li>- Operability </li></ul><ul><li>- Outcomes </li></ul><ul><li>- QOL </li></ul>
  4. 4. Surgery - Types <ul><li>- Types of Resection </li></ul><ul><li>                     - Pneumonectomy </li></ul><ul><li>                     - Lobectomy </li></ul><ul><li>                     - Sublobar:  </li></ul><ul><li>                         - Segmentectomy </li></ul><ul><li>                             - Sleeve Segmentectomy </li></ul><ul><li>                         - Wedge Resection </li></ul><ul><li>     </li></ul>&quot;Sleeve&quot;
  5. 5. Surgery - Types <ul><li>Operability </li></ul><ul><li>    Min absolute FEV1 for: </li></ul><ul><li>         Pneumonectomy > 2L </li></ul><ul><li>        Lobectomy > 1.5L </li></ul><ul><li>        Wedge < 1.5L (variable) </li></ul><ul><li>     RTOG 0813 def: </li></ul><ul><li>        FEV1 50%, DLCO 50% </li></ul><ul><li>Morbidity Predictors: </li></ul><ul><li>     1. pCO2 <45 mm Hg  </li></ul><ul><li>     2. pO2 <50 mm Hg  </li></ul><ul><li>     3. Preop FEV1 <40% of predicted value  </li></ul><ul><li>     4. Poor exercise tolerance  </li></ul><ul><li>     5. DLCO <50% of predicted value </li></ul><ul><li>     6. Postop FEV1 <0.71 or <30% of predicted value </li></ul><ul><li>     7. Cardiac problems (LV EF<40%, myocardial infarction within 6 mos, arrhythmias)  </li></ul><ul><li>     8. Obesity  </li></ul><ul><li>    9. Ongoing smoker pre and post surgery </li></ul><ul><li>                     </li></ul>
  6. 6. Surgery - Morbidity <ul><li>     </li></ul>Lobectomy vs. Pneumonectomy Tobias Schulte, Bodo Schniewind, Peter Dohrmann, Thomas Küchler and Roland Kurdow. The Extent of Lung Parenchyma Resection Significantly Impacts Long-Term Quality of Life in Patients With Non-Small Cell Lung Cancer. Chest 2009;135;322-329
  7. 7. Surgery - Morbidity <ul><li>     </li></ul>Tobias Schulte, Bodo Schniewind, Peter Dohrmann, Thomas Küchler and Roland Kurdow. The Extent of Lung Parenchyma Resection Significantly Impacts Long-Term Quality of Life in Patients With Non-Small Cell Lung Cancer. Chest 2009;135;322-329
  8. 8. Surgery - Types - Sublobar Resection <ul><li>     </li></ul>Errett LE et al J Thorac Cardiovasc Surg. 1985 Nov;90(5):656-61  - Not a new idea - 1985
  9. 9. Surgery - Types - Sublobar Resection <ul><li>     </li></ul>RJ Ginsberg, LV Rubinstein and Lung Cancer Study Group Ann Thorac Surg 1995;60:615-23 - Prospective, multi-institutional randomized trial - Lobectomy vs. Sublobar for Early Stage NSCLC = 1.26 & .016% = 4.7 & 2.52% = 3.83 & 1.3%
  10. 10. Surgery - Types - Sublobar Resection RJ Ginsberg, LV Rubinstein and Lung Cancer Study Group Ann Thorac Surg 1995;60:615-23 - Lobectomy vs. Sublobar for Early Stage NSCLC
  11. 11. Thermal Ablation Cryoablation (Cooltip) Microwave ablation <ul><li>     </li></ul>Alternative Ablative Modalities
  12. 12. <ul><li>Retrospective Single Center </li></ul><ul><li>420 Patients </li></ul><ul><li>33% w/1o Lung, 67% w/Metastasis </li></ul><ul><li>1000 Cool-tip RFAs </li></ul>Alternative Ablative Modalities AJR Am J Roentgenol. 2011 Oct;197(4):W576-80. Complications after 1000 lung radiofrequency ablation sessions in 420 patients: a single center's experiences. Kashima M, Yamakado K, Takaki H, Kodama H, Yamada T, Uraki J, Nakatsuka A.
  13. 13. <ul><li>Complications </li></ul>Alternative Ablative Modalities
  14. 14. Radiotherapy- Historical Perspective <ul><li>Standard approach involves giving approximately 45-66 Gy total dose in 1.8-2.0 Gy fractions. </li></ul><ul><li>- Relationship in both survival and local control in these patients. - Review of 156 medically inoperable stage I NSCLC patients at Duke University between 1980 and 1995 demonstrated a five-year, cause-specific survival of 32% with radiotherapy alone.          </li></ul><ul><li>     Improved survival was significantly correlated with achieving local control and approached significance for higher radiotherapy dose (p=0.07). </li></ul><ul><li>- Historically treated area included regional lymphatics in the ipsilateral hilum and mediastinum. This “prophylactic” treatment was based on identified risk of occult nodal involvement from surgical series ranging up to 20%, and surgical data indicating better control with more extensive resections. </li></ul><ul><li>- Nonetheless, large  radiotherapy fields are potentially poorly tolerated in this population with limited pulmonary reserve. (Curran WJ, Moldofsky PJ, Solin LJ. Analysis of the influence of elective nodal irradiation on postirradiation pulmonary function. Cancer. 65:2488-93, 1990.) </li></ul><ul><li>Early technique used 1D-2D planning and didn’t: </li></ul><ul><ul><li>visualize the target </li></ul></ul><ul><ul><li>had limitations in selection of beam directions </li></ul></ul><ul><ul><li>limitations in computational algorithms describing deposited dose. </li></ul></ul>Sibley GS, Jamieson TA, Marks LB, Anscher MS, Prosnitz LR. Radiotherapy alone for medically inoperable stage I non-small cell lung cancer: The Duke experience. Int J Radiat Oncol Biol Phys. 40(1): 149-54, 1998.
  15. 15. Radiotherapy- Historical Perspective <ul><li>Researchers at the Karolinska Hospital in Stockholm, Sweden developed an extracranial stereotactic frame and began treatment with the device in 1992. </li></ul><ul><li>- Blomgren, et al., reported on 17 patients treated with stereotactic radiotherapy for intrathoracic metastases with follow-up </li></ul><ul><li>of 3.5 to 25 months. </li></ul><ul><li>25 Tumors ranged in size from 1.8 cm to 7.2 cm.  </li></ul><ul><li>Margin doses ranges from 20 Gy in one fraction to 45 Gy in three fractions. </li></ul><ul><li>Response was measured by repeat CT scans demonstrating: </li></ul><ul><li>Disappearance in 35% </li></ul><ul><li>Reduction in 41% </li></ul><ul><li>Stabilization in 18% </li></ul><ul><li>Progression in only one patient (the largest tumor treated in the report). </li></ul>
  16. 16. SBRT - Rationale <ul><li>-Conventionally fractionated RT (ie, cGy per fraction) operates on a portion of the cell survival curve describing the logarithm of clonagenic survival as a function of dose called the shoulder.  </li></ul><ul><li>-In this shoulder region, an increasing dose per fraction corresponds to small decrements in cell survival due </li></ul><ul><li>to the ability of the tumor cell to repair modest damage (called sublethal damage).  </li></ul><ul><li>-At some point with the increasing dose per fraction, these repair mechanisms become overwhelmed, and the logarithm of clonagenic survival becomes linear with increasing doses (called exponential cell killing).  </li></ul><ul><li>-The dose per fraction and the total dose levels attained with ESR in this trial operated well beyond the shoulder, and its biological potency at disabling tumor clonogenicity should be significant. </li></ul>
  17. 17. SBRT <ul><li>    Dose, Fractionation </li></ul><ul><li>    Outcomes </li></ul><ul><li>    Technique </li></ul><ul><li>    Dose Constraints  </li></ul><ul><li>    Side Effects/Complications </li></ul><ul><li>    Post Treatment Surveillance </li></ul>
  18. 18. SBRT Dose/Fractionation Phase 1 Dose Finding Study 37 Stage 1 NSCLC Patients 1o Objective: Est DLT/MTD 8Gy x 3 to the 80% IDL 10Gy x 3 12Gy x 3 14Gy x 3 16Gy x 3 18Gy x 3 20Gy x 3 @ 14Gy stratified to escalate dose independently for T1 & T2 tumors
  19. 19. SBRT Dose/Fractionation - Didnt reach MTD - No diff in Tox b/n T1 or T2 - No heterogeneity correction - No significant cardiopulmonary toxicity - 87% Objective RR, 27% CR - 6 failures in patients all <18Gy/fx 8Gy x 3 to the 80% IDL 10Gy x 3 12Gy x 3 14Gy x 3 16Gy x 3 18Gy x 3 20Gy x 3
  20. 20. SBRT Dose/Fractionation Retrospective Multicenter 257 Stage 1 NSCLC Patients Widely variable dose/fractionation: 18-75Gy, 1-22Fx
  21. 21. SBRT Dose/Fractionation <ul><li>Phase II - Single Center </li></ul><ul><li>70 Patients w/ T1,T2 N0 M0  </li></ul><ul><li>Tx: 60-66Gy / 3 Fx  </li></ul><ul><li>Median f/u 17.5 mo </li></ul>Robert Timmerman, and James Fletcher. J Clin Oncol 24:4833-4839. 2006 LC @ 2 years was 95%   Median OS 32.6 mo  2 yr OS 54.7%
  22. 22. SBRT Dose/Fractionation 2 yr freedom from toxicity -Central: 54% -Peripheral: 83% - Only additional predictor of toxicity was size of GTV, with > 10 cc tumors showing greater toxicity than smaller GTVs. - G3/4 Toxicity events occurred a median of 7.6 mo after completion of SBRT.
  23. 23. SBRT Dose/Fractionation
  24. 24. SBRT Dose/Fractionation Prospective Cohort 27 Patients w/Central NSCLC (Recurrent (14) or Stage 1 (13) Median f/u of 17 mo  - Prescribed dose of 40 Gy (n = 7) to the PTV - Escalated to 50 Gy (n = 20) in 4 consecutive days 1 patient experienced a brachial plexopathy       w/20% of plexus recieving >40Gy LC was poor w/<50Gy~ 3/7 failed Not powered for any objectives, limited conclusions can be drawn      - However 50Gy/4 fractions appears safe for central tumors     - <50Gy is associated w/a higher failure rate
  25. 25. SBRT Dose/Fractionation Central Dose Question is currently being evaluated prospectively w/: RTOG 0813     Phase I/II Study of SBRT in Medically Inoperable Patients w/Centrally Located Stage I NSCLC      Dose Escalation: 50Gy/5fx --> 52.5/5 --> 55/5 --> 57.5/5 --> 60Gy/5fx     - Has high dose conformality index requirements that necessitate noncoplanar beam arrangement     - OARs are limited to <105% of prescribed dose     - Low and High Dose spillage are highly restrictive
  26. 26. SBRT Dose/Fractionation - RTOG 0236 <ul><li>Phase 2 Multi-center Trial </li></ul><ul><li>Peripheral Stage 1 NSCLC - Medically Inoperable  </li></ul><ul><li>1 o Objective: Eval Toxicity and Efficacy in high risk patients </li></ul><ul><li>Of 55 evaluable patients, 44 had T1 & 11 had T2 tumors.  </li></ul><ul><li>Tx: 60Gy /3 fx --> Didnt correct for tissue inhomogeneity but retrospective analysis  </li></ul><ul><li>     shows a total dose of 54Gy / 3 fx </li></ul><ul><li>Median f/u 34.4 mo </li></ul><ul><li>The study was activated in May 2004 and opened in 8 sites, after those sites had completed the          </li></ul><ul><li>     credentialing process.  RTOG 0236 was closed October 2006.  </li></ul>
  27. 27. SBRT Dose/Fractionation - RTOG 0236 <ul><li>1o Failure =   2.4% @ 3yrs (CI 0.3-15.7%) </li></ul><ul><li>1 patient </li></ul><ul><li>Involved Lobe Failure = Local failure - 1o Failure = 10.4%-2.4% = 8% </li></ul><ul><li>Local Failure = 1o failure + Involved lobe failure =   10.4% @ 3 yrs (CI 3.5-24%) </li></ul><ul><li>3 patient (involved lobe 2nd 1o) </li></ul><ul><li>Regional Failure  = hilum + mediastinum = local regional - local failure = 12.8%-10.4% = 2.4% </li></ul><ul><li>2 involved lobe & mediastinum, 1 hilum alone  </li></ul><ul><li>  </li></ul><ul><li>Local-regional Failure =1o Failure+Involved lobe+hilum+mediastinum= 12.8%@3yrs (CI 5.3%-29%) </li></ul><ul><li>Disseminated Failure =  22.1% @ 3yrs (CI 12.3%-37.8%) </li></ul><ul><li>11 patients  </li></ul><ul><li>     1 mediastinum & dissem </li></ul><ul><li>     8 dissem alone </li></ul><ul><li>     2 NOS </li></ul><ul><li>   - 30.7% Adeno, 6% SCC  </li></ul>
  28. 28. SBRT Dose/Fractionation - RTOG 0236 <ul><li>- 3yr DFS 48.3% (95% CI, 34.4%-60.8%) </li></ul><ul><li>    - 34.4 Mo (95% CI 34.4 mo-NA) </li></ul><ul><li>- 3 yr OS 55.8% (95% CI, 41.6%-67.9%) </li></ul><ul><li>     - Median OS 48.1 mo (95% CI, 29.6- NA) </li></ul><ul><li>     10 patients died of lung cancer </li></ul><ul><li>    16 patients died of other causes </li></ul><ul><li>         5 of comorbid problems: - Stroke, MI, COPD exacerbation, & 2nd malignancy </li></ul><ul><li>         2 of nonprotocol medical interventions </li></ul><ul><li>        9 of unknown causes </li></ul>
  29. 29. SBRT Dose/Fractionation - RTOG 0236 <ul><li>Toxicities </li></ul><ul><li>Median f/u of 38.7 mo </li></ul><ul><li>- 1 (2%) G4 pulmonary </li></ul><ul><li>- 2/7 reported PFT decrease </li></ul><ul><li>- 1/7 reported cough/dyspnea </li></ul><ul><li>- 1 reported hypoxia </li></ul><ul><li>- 1 reported pneumonitis </li></ul><ul><li>- 1 reported cough </li></ul><ul><li>- 1 patient reported PNX  </li></ul><ul><li>- 1 G3 dermatitis  </li></ul><ul><li>- 1 G3 syncope reported as related to protocol treatment.  </li></ul><ul><li>- 7 (13%) G3 pulmonary/upper respiratory adverse events 2/2 protocol </li></ul><ul><li>*Median Time to Toxicity not evaluated </li></ul><ul><li>- No treatment related deaths have been reported. </li></ul>
  30. 30. SBRT Outcomes <ul><li>Recently Closed </li></ul><ul><li>RTOG 0915 - Closed 3/22/2011  </li></ul><ul><li>     A Randomized Phase II Study Comparing 2 SBRT Schedules (48Gy/4fx vs. 34Gy/1) for Medically  </li></ul><ul><li>     Inoperable Patients with Stage I Peripheral Non-Small Cell Lung Cancer  </li></ul><ul><li>RTOG 0618 - Closed 5/17/10 - Analysis planned for 6/2012 </li></ul><ul><li>     A Phase II Trial of SBRT in the Treatment of Patients with Operable Stage I/II NSCLC </li></ul><ul><li>ROSEL   - Closed 4/4/11 due to poor accrual </li></ul><ul><li>     Radiosurgery or Surgery for Operable Stage 1 NSCLC - Netherlands Trial  </li></ul>
  31. 31. SBRT Outcomes <ul><li>Current Trials </li></ul><ul><li>ACOSOG RTOG 1021  </li></ul><ul><li>   Phase 3 Sublobar Resection +/- Brachytherapy vs. SBRT (54Gy/3fx) </li></ul><ul><li>STARS -  </li></ul><ul><li>    Phase 3 Randomized Study to Compare Cyberknife to Surgical Resection (any) in Stage 1 NSCLC </li></ul><ul><li>      Central lesion: 15 Gy x 4 fractions = 60 Gy; Peripheral lesion: 20 Gy x 3 fractions = 60 Gy   </li></ul>
  32. 32. SBRT Technique <ul><li>  </li></ul>
  33. 33. SBRT Technique <ul><li>  </li></ul>
  34. 34. SBRT Technique <ul><li>  </li></ul>Composite 4d (MIP) Breath Hold CT
  35. 35. SBRT Technique <ul><li>  </li></ul>Med Phys. 2004 Dec;31(12):3179-86. Four-dimensional (4D) PET/CT imaging of the thorax. Nehmeh SA, Erdi YE, Pan T, Pevsner A, Rosenzweig KE, Yorke E, Mageras GS, Schoder H, Vernon P, Squire O, Mostafavi H, Larson SM, Humm JL.
  36. 36. SBRT Technique <ul><li>  </li></ul>
  37. 37. SBRT Technique - Constraints <ul><li>AAPM Task Group 101  </li></ul>AAPM Task Group 101 SBRT Dose Constraints
  38. 38. SBRT Post Treatment Surveillance <ul><li>Monitor for: </li></ul><ul><li>- Early treatment effects </li></ul><ul><li>- Late radiotherapy effects (median time to G3/4 tox ~8mo) </li></ul><ul><li>- Appearance of occult disease </li></ul><ul><li>- Failure at primary site </li></ul><ul><li>- Failure at distant site </li></ul>
  39. 39. SBRT Post Treatment Surveillance <ul><li>Early Stage- f/u visits </li></ul><ul><li>     Post Tx: @ 2 mo then q4mo thereafter for 2 yrs </li></ul><ul><li>         2 mo visit to establish baseline CT prior to tx change </li></ul><ul><li>         q4mo visits: CT w/out contrast if no concerns </li></ul><ul><li>     2 Yrs Post Tx: q6mo for 5 yrs w/CT </li></ul><ul><li>     5 yrs Post Tx: q1yr w/CT </li></ul>
  40. 40. <ul><li>Monitor for: Early treatment effects </li></ul><ul><li>- PFT changes </li></ul><ul><li>    - No SS change in FEV1 or DLCO </li></ul><ul><li>    - If <6 mo out, pneumonitis possible </li></ul>SBRT Post Treatment Surveillance J Thorac Oncol. 2009 Jul;4(7):838-44. Comprehensive analysis of PFT changes after SBRT for stage I lung cancer in medically inoperable patients. Stephans KL, Djemil T, Reddy CA, Gajdos SM, Kolar M, Machuzak M, Mazzone P, Videtic GM.
  41. 41. SBRT Post Treatment Surveillance <ul><li>Monitor for: Early treatment effects - PFT changes </li></ul>J Thorac Oncol. 2009 Jul;4(7):838-44. Comprehensive analysis of pulmonary function Test (PFT) changes after stereotactic body radiotherapy (SBRT) for stage I lung cancer in medically inoperable patients. Stephans KL, Djemil T, Reddy CA, Gajdos SM, Kolar M, Machuzak M, Mazzone P, Videtic GM.
  42. 42. SBRT Post Treatment Surveillance <ul><li>Monitoring for Occult Disease </li></ul><ul><li>    - PET </li></ul><ul><li>         Sensitivity - 86% </li></ul><ul><li>        Specificity - 88% </li></ul><ul><li>    - Mediastinoscopy </li></ul><ul><li>        Sensitivity - 93% </li></ul><ul><li>        Specificity - 100% </li></ul><ul><li>    - EBUS </li></ul><ul><li>        Sensitivity - 76% </li></ul><ul><li>        Specificity - 97% </li></ul>Chest. 2003 Jan;123(1 Suppl):137S-146S. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Toloza EM, Harpole L, McCrory DC. PET
  43. 43. SBRT Post Treatment Surveillance <ul><li>Monitoring for Primary Site Failure </li></ul><ul><li>- Complicated by: </li></ul><ul><li>    - Post RT changes </li></ul><ul><li>        - Radiation pneumonitis </li></ul><ul><li>        - Radiation fibrosis </li></ul><ul><li>        - Effusion </li></ul><ul><li>    - Other disease processes w/in the lung </li></ul><ul><li>        - Infection/Pneumonia </li></ul><ul><li>        - Bronchiectasis </li></ul><ul><li>        - Atelectasis </li></ul><ul><li>    - Actual Treatment Failure </li></ul><ul><li>        - Local progression </li></ul><ul><li>        - Subclinical lyphmangitic spread </li></ul>Larici. Lung Abnormalities at Multimodality Imaging after Radiation Therapy for NSCLC. May 2011 RadioGraphics, 31, 771-789.
  44. 44. SBRT Post Treatment Surveillance <ul><li>Monitoring for Primary Site Failure </li></ul><ul><li>Post Radiation Treatment Changes </li></ul><ul><li>- 1-6 mo RT Pneumonitis </li></ul><ul><li>    - Ground glass opacities, consolidation w/in radiation port </li></ul><ul><li>    - Potential ipsiateral pleural effusion </li></ul><ul><li>    - 4 patterns (Ikezoe) </li></ul><ul><li>        - ground glass opacities </li></ul><ul><li>        - patchy consolidation and ground glass opacities </li></ul><ul><li>        - patchy ground glass opacities </li></ul><ul><li>        - scar like  </li></ul><ul><li>- 6-12 mo Radiation Fibrosis </li></ul><ul><li>    - Well defined area of volume loss w/linear scar or </li></ul><ul><li>consolidation w/parenchymal distortiona and traction  </li></ul><ul><li>         bronchiectasis conforming to treatment portals </li></ul>Larici. Lung Abnormalities at Multimodality Imaging after Radiation Therapy for NSCLC. May 2011 RadioGraphics, 31, 771-789. 2 months 3 months 6 months Before
  45. 45. SBRT Post Treatment Surveillance <ul><li>Monitoring for Primary Site Failure </li></ul><ul><li>Algorithm for post treatment CT surveillance </li></ul>Site Abnormality  - after comparison to prior CT scans Significant + in size w/no air bronchograms Moderate + in size PET Scan vs. Biopsy Short interval f/u w/CT Empiric Tx w/ roids & abtx Short interval f/u w/CT
  46. 46. SBRT Post Treatment Surveillance <ul><li>Role of PET in f/u s/p SBRT </li></ul><ul><li>     Sensitivity and specificity of FDG-PET/CT for detecting recurrence has historically been estimated to </li></ul><ul><li>range from 93% to 100% and 82% to 92%, respectively </li></ul><ul><li>More recently found to be controversial </li></ul>Mac Manus MP, Ding Z, Hogg A, et al. Association between pulmonary uptake of fluorodeoxyglucose detected by positron emission tomography scanning after radiation therapy for nonsmall-cell lung cancer and radiation pneumonitis. Int J Radiat Oncol Biol Phys. [Epub ahead of print July 31, 2010].
  47. 47. SBRT Post Treatment Surveillance <ul><li>Role of PET in f/u s/p SBRT </li></ul><ul><li>- Hoopes et al demonstrated that  </li></ul><ul><li>     moderate HM activity may persist </li></ul><ul><li>     for up to 2 yrs after completion of </li></ul><ul><li>     SBRT w/out definite evidence of </li></ul><ul><li>     recurrence.  </li></ul><ul><li>Validated prospectively w/a </li></ul><ul><li>small number of patients </li></ul>Mac Manus MP, Ding Z, Hogg A, et al. Association between pulmonary uptake of fluorodeoxyglucose detected by positron emission tomography scanning after radiation therapy for nonsmall-cell lung cancer and radiation pneumonitis. Int J Radiat Oncol Biol Phys. [Epub ahead of print July 31, 2010].
  48. 48. SBRT Post Treatment Surveillance <ul><li>A study from the University of Pittsburgh demonstrated a significant correlation with mean SUV and treatment response. (mean SUV decreases) </li></ul><ul><li>     Complete responders, 94%,  </li></ul><ul><li>     Partial responders 48%,  </li></ul><ul><li>     Stable disease 28% </li></ul><ul><li>Patients with progressive disease had an SUV decrease of only 0.4%. </li></ul><ul><li>However this study only had once LR, so their definition of CR, PR, SD is arbitrary and w/out clinical </li></ul><ul><li>relevance </li></ul>Clin Lung Cancer. 2008 Jul;9(4):217-21. Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning. Coon D, Gokhale AS, Burton SA, Heron DE, Ozhasoglu C, Christie N.
  49. 49. SBRT Post Treatment Surveillance <ul><li>Monitoring for Distant Failure </li></ul><ul><li>Evaluate bony, mediastinal windows for recurrence </li></ul><ul><li>- Mediastinal changes suspicious include + size of LAD or loss of fatty hilum </li></ul><ul><li>- Complicating factors can include associated comorbidities such as: </li></ul><ul><li>    - CHF exacerbation </li></ul><ul><li>    - Chronic Bronchitis </li></ul><ul><li>    - TB/MAC infection i.e. HIV patients </li></ul><ul><li>Algorithm for post treatment CT surveillance </li></ul>High Suspicion @ Primary Site  for recurrence Restage w/PET C/A/P
  50. 50. Fin
  51. 51. SBRT Treatment Failure - Salvage <ul><li>To be discussed at a later date… </li></ul>
  52. 52.   <ul><li>1. maximal tolerated dose for peripheral primary tumors less than 7 cm is 60 to 66 Gy in three  fractions. </li></ul><ul><li>2. The maximal tolerated dose for centrally located primary tumors less than 7 cm is unknown but is exceeded by doses of 60 to 66 Gy in three fractions.  </li></ul><ul><li>3. A prescription dose less than 54 Gy in three frac- tions is associated with maximal local control of approximately 70% to 80% for patients treated in </li></ul><ul><li>prospective trials with adequate follow-up in North America and Europe. </li></ul><ul><li>4. A prescription dose of 54 Gy or more in three fractions has been demonstrated to achieve local control in more than 90% of treated tumors in prospective testing. </li></ul><ul><li>5. Despite clinical staging, isolated hilar and mediastinal nodal failures occur in less than 5% of patients after SBRT. </li></ul><ul><li>6. Despite staging with whole body PET scans, ap- proximately 20% of patients develop distant meta- static disease. </li></ul><ul><li>7. Although it is well-known that toxicity after large dose per fraction treatment occurs late, it is also recognized that tumor recurrence likewise occurs </li></ul><ul><li>late after treatment with the median time to recur- rence of 16 to 24 months after therapy.  </li></ul><ul><li>8. Despite excellent local control after SBRT, patient survival for medically inoperable early-stage lung cancer is very poor, mainly due to severe and life- threatening coexisting morbidities and the eventual appearance of metastatic disease. </li></ul>
  53. 53.   <ul><li>How do we stage early stage lung cancer patients who are planned for surgical eval? </li></ul><ul><li>Why do PET only staged patients who go for SBRT have lower regional failures? </li></ul><ul><li>What is the most appropriate group for comparing surgical vs. nonsurgical (SBRT) intervention for early stage lung cancer? </li></ul><ul><li>     - 20% to 25% of patients with earlystage lung cancer are not considered candidates for lobar resection </li></ul><ul><li>         because of concomitant severe cardiac or pulmonary comorbidities </li></ul><ul><li>    - Varying modilty of choice by location?  </li></ul><ul><li>        - Peripherally located tumors 3 cm, sublobar resection by an anatomic segmentectomy (rather than  </li></ul><ul><li>         a wedge resection) may result in OS & CSS ~ to lobectomy </li></ul><ul><li>        - Centrally located within a lobe or close to the lobar bronchi have no viable surgical option other than lobectomy which, in this patient population, may be associated with a prohibitive morbidity & higher mortality.  </li></ul>
  54. 54. SBRT Outcomes <ul><li>  </li></ul>Timmerman, Journal of Thoracic Oncology • Vol. 2, No. 7, Supplement 3, July 2007
  55. 55. SBRT vs. Wedge Resection
  56. 56. Radiotherapy- Historical Perspective <ul><li>A key issue that must be considered when comparing these modalities based on available literature is that the definitions of local recurrence, local control, and regional recurrence are not uniform. This has led to </li></ul><ul><li>different perceptions and interpretations of the published literature relating to these modalities. In the </li></ul><ul><li>surgical literature, local recurrence variably includes recurrence occurring within the same lobe, sometimes another lobe within the same ipsilateral lung, hilar and sometimes ipsilateral mediastinal lymph nodes [2,18,102].  </li></ul><ul><li>In the SBRT literature, local recurrence usually is synonymous with primary tumor control, i.e., limited to recurrence within and sometimes within 1cm of the planning treatment volume (PTV) [12,101]. The more </li></ul><ul><li>appropriate convention for characterizing recurrence definitions is a reflection on the original TNM staging. </li></ul><ul><li>As such, a recurrence of the original primary tumor (originally characterized by the T of the TNM staging </li></ul><ul><li>including the primary tumor and involved lobe) is deemed a local recurrence. A recurrence in the primary </li></ul><ul><li>tumors draining lymph nodes (hilar and mediastinal as originally characterized by the N of the TNM staging) is deemed a regional recurrence. Finally, a recurrence in distant sites (originally characterized by the M of the TNM staging) is deemed a disseminated recurrence. By this convention, both the more recent surgical literature and SBRT literature have been guilty of inappropriate recurrence definitions making comparisons difficult. </li></ul>
  57. 57. Surgery -  -Lobectomy vs.  Sublobar Resection <ul><li>     </li></ul>Sublobar resection for lung cancer.  SERIES ‘‘LUNG CANCER’’ Number 2 in this Series.   R. Rami-Porta* and M. Tsuboi#  Edited by C. Brambilla.  
  58. 58. Radiotherapy- Historical Perspective <ul><li>At Indiana University, a phase I dose escalation protocol has been completed for the treatment of </li></ul><ul><li>medically inoperable patients with AJCC Stage I lung cancer. 26 SBRT (a.k.a. extracranial </li></ul><ul><li>stereotactic radioablation) with large doses per fraction was delivered in an extracranial </li></ul><ul><li>stereotactic body frame, which includes a system to decrease respiratory motion. The starting </li></ul><ul><li>dose was 8 Gy times 3 (24 Gy total), and fraction dose was escalated by 2 Gy per fraction for </li></ul><ul><li>each cohort. The target lesion was outlined by a physician and designated as the gross tumor </li></ul><ul><li>volume (GTV). An additional 0.5 cm in the axial plane and 1.0 cm in the longitudinal plane was </li></ul><ul><li>added to the GTV to constitute the PTV based on validation measurements for this commercially </li></ul><ul><li>available system.27-29 Typically, 7-10 non-coplanar beams were used to encompass the PTV. </li></ul><ul><li>Dose was prescribed to the 80% line; however, higher isodoses (hotspots) occurred within the </li></ul><ul><li>central core of the target mimicking the heterogenous dose profile common to intracranial </li></ul><ul><li>stereotactic radiosurgery. The higher dose in the tumor core is intended to give extra dose in </li></ul><ul><li>areas of presumed greatest tumor hypoxia and radioresistance. The treatment isocenter was </li></ul><ul><li>identified with 3-D coordinates defined stereotactically and localized on verniers attached to the </li></ul><ul><li>frame. No skin or bony landmarks were used to set the treatment isocenter, however; orthogonal </li></ul><ul><li>port films were used on a daily basis for isocenter verification. 30 Separate dose escalations were </li></ul><ul><li>carried out independently for patients with T1 versus T2 small (< 5 cm) versus T2 large (5-7 cm) </li></ul><ul><li>tumors at diagnosis. </li></ul>

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