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ESMO International Symposium on Chest Tumors Geneva, 2007

Outcomes of randomized clinical trials indicate that chemo-radiotherapy is standard of care (sulcus superior tumors an exception - IASLC 2003)Fatal toxicity uncommon after CT-RT but morbidity can be high in unselected cases; local control is suboptimalNew RT techniques permit improved local contro

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ESMO International Symposium on Chest Tumors Geneva, 2007

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    1. ESMO International Symposium on Chest Tumors (Geneva, 2007) Treatment of stage III NSCLC The role of radiation therapy

    2. Outcomes of randomized clinical trials indicate that chemo-radiotherapy is standard of care (sulcus superior tumors an exception - IASLC 2003) Fatal toxicity uncommon after CT-RT but morbidity can be high in unselected cases; local control is suboptimal New RT techniques permit improved local control

    3. Management of stage III nsclc

    5. Best outcomes per patient subgroup

    6. Concurrent or sequential CT-RT

    7. CTC for Adverse Events v3.0

    8. Is concurrent CT-RT always superior? Not in patients at high risk for toxicity and when sub-optimal chemotherapy schemes used, 2D radiotherapy or elective nodal irradiation, sub-optimal sequencing of CT-RT (possibly) use of post-chemotherapy target volumes

    9. Factors influencing outcomes of radiotherapy Negative patient selection (bulky, multi-station N2/3 disease versus limited volume ‘operable’ disease) 2-Dimensional radiotherapy (leads to ‘geographic miss’ in approx. 12-25% of patients) Co-morbidity in inoperable patients Staging using FDG-PET

    10. INT 0139: Toxicity of 2D CT-RT

    11. Outcomes depending on RT planning

    12. INT 0139: Treatment-related mortality

    13. PET staging before radical RT 153 consecutive patients for curative RT & CT-RT staged with and without FDG-PET [Mac Manus 2001] 30% denied curative RT (unexpected M1 disease or extensive intrathoracic disease) after a PET scan PET stage correlated with survival (P=0 .0041) PET-selected patients have lower early cancer mortality than when conventional imaging used [Mac Manus 2002].

    14. Management of stage III nsclc

    16. Stage III NSCLC: Clinical subgroups Based on tumour extent and performance score, 3 subgroups can be identified: Patients fit for concurrent CT-RT Patients fit for sequential CT-RT Patients requiring a tailored approach, including only palliative care

    17. INT 0139: Exploratory Survival Analysis Is there a survival advantage for CT/RT/S arm when lobectomy can be performed ? Patients in CT/RT/S arm matched with those on CT/RT arm on 4 pre-study factors (KPS, age, sex, T stage) Conclusion: ‘Superior survival’ for surgery when lobectomy possible

    18. Survival after radiotherapy is superior with smaller tumor volumes and low V20 values (comparable to lobectomy cases) Survival after radiotherapy inferior when a geographic miss ocurs (e.g. 19% of CT-RT patients in INT 0139, Turrisi 2003) Exploratory Survival Analysis in INT 0139

    19. Stage III-N2: Surgery for ‘downstaged’ patients? Sterilization of N2 disease is strongest predictor of survival Does ‘downstaging’ identify the best patients for surgery …… or does it identify patients who benefit from full-dose CT-RT? Study of role of surgery requires randomisation of down-staged patients to either surgery or full-dose CT-RT, without delaying treatment completion

    20. Minimise disease progression during treatment

    21. Impact of spilts in CT-RT (for re-staging) Decrease in survival of 1.6% per day when the overall treatment times for RT exceeds 6 weeks [Fowler ‘02]. Risk of death increases by 2% for each day of prolongation in concurrent CT-RT [Machtay ‘05]

    22. Stage III-N2: EORTC 08941 vs INT 0139

    23. Individualised approach to CT-RT

    24. Toxicity & survival in SWOG 0023

    26. Impact of V20 on toxicity & survival

    27. Impact of V5 on toxicity after CT-RT

    28. Individualised approach to CT-RT

    29. Treatment options when V20 high LAMP trial (Belani 2005): Target volume for arms 1 and 2 was the post-chemotherapy volume, and for arm 3 it was based on the original tumor volume. Median overall survival was 13.0, 12.7, and 16.3 months for arms 1, 2, and 3, respectively. Canadian Patterns of Care (Tai P, 2004): Post-chemotherapy tumour volume treated for NSCLC by 42% of respondents.

    30. Gating and IMRT for lung cancer Reduce toxicity of CT-RT ? Enable more patients to undergo CT-RT ??

    31. 4DCT based respiration-gated RT

    32. Respiratory gating to reduce V20

    33. IMRT: non-uniform field intensity maps

    34. Concerns limiting use of IMRT Deleterious effects of low doses of radiation on lung tissue Impact of tumor motion

    35. Concerns limiting use of IMRT Theuws J [2000] : SPECT studies show reduction in local perfusion and ventilation at approx. 10 Gy. Gopal R [2003]: low threshold (13 Gy) for deterioration in DLCO. Yorke E [2005]: severe pneumonitis correlated best with V5-V13 in ipsilateral lung tissue Wang S [2006]: lung spared from 5 Gy is most significant predictor of postoperative lung complications in esophagus ca.

    36. Warning !! Both IMRT and gating required special expertise and competence Both could lead to worse outcomes (more toxicity & recurrences)

    37. Management of stage III-N2 disease Stratify for (i) sub-types of N2 disease and (ii) co-morbidity and toxicity risks Utilize image-guided radiotherapy delivery Planning parameters (V20) are important prognostic parameters for future studies

    38. Two Compartment Model of Combined Modality Therapy for Locally Advanced Lung Cancer

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