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
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
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  : SPECT studies show reduction in local perfusion and ventilation at approx. 10 Gy.
Gopal R : low threshold (13 Gy) for deterioration in DLCO.
Yorke E : severe pneumonitis correlated best with V5-V13 in ipsilateral lung tissue
Wang S : 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