1 / 37

Chemo-radiation for lung cancer

Chemo-radiation for lung cancer. Chemo-radiation for lung cancer. Radiotherapy issues Benefit of chemo-radiation over radiation alone ? Volume nodal irradiation ? 3-D Conformal radiotherapy ? Dose and fractionation Hyperfractionation ? Schedule (concomitant or sequential)

beata
Download Presentation

Chemo-radiation for lung cancer

An Image/Link below is provided (as is) to download presentation 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. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Chemo-radiation for lung cancer

  2. Chemo-radiation for lung cancer • Radiotherapy issues • Benefit of chemo-radiation over radiation alone ? • Volume • nodal irradiation ? • 3-D Conformal radiotherapy ? • Dose and fractionation • Hyperfractionation ? • Schedule (concomitant or sequential) • Chemotherapy issues • Benefit of chemo + radiation over chemotherapy only ? • Choice of drug(s)

  3. Chemo-radiation for lung cancer • Radiotherapy issues • Benefit of chemo + radiation over radiation alone ? • Dillman NEJM 1990, JNCI 1996 • Sause JNCI 1995 • Le Chevalier Cancer 1994 • Dose, volume and fractionation • nodal irradiation • 3-D Conformal radiotherapy • Hyperfractionation ?

  4. Lung cancer target definition 1 • XRT target volume • +/- nodes • supraclavicular • ipsilateral • contralalteral • contralateral hilum • mediastinum • margins • range 0.35-4.25 cm (Australian study ) MR Pfeffer Chaim Sheba medical center 2000

  5. Lung cancer target definition 2 • relapses in untreated supraclavicular nodes • CHART 0/76 • Ball (1997) 5/159 • 3-D planning study (Hazuka 1993) • Treatment planning including uninvolved nodes - no effect on survival MR Pfeffer Chaim Sheba medical center 2000

  6. 3-D XRT dose escalationHaymanJCO 2001s • Target: clinical disease = primary tumor & nodes >1 cm • dose escalation up to 102.9, 102.9, 84,75.6 Gy, 65.1(2.1 Gy/d) based on NTCP bins (treated lung volume) • 104 patients (24 stage I, 4 stage II, 43 stage IIIA, 26 stage IIIB, 7 local recurrence) • Toxicity: pneumonitis grade 2 - 5 pts, grade3 –2 pts • Survival: stage III and recurrent disease: • median 16 months, 1-, 2-, & 3-year 61%, 36%,& 14% • NO isolated relapses in untreated nodes MR Pfeffer Chaim Sheba medical center 2000

  7. Lung cancer target definition 3 • ~50% cases tumor & extension not adequately covered • atelectasis (use PET?) • respiration effect • CT lung settings (850, -750) best correlated with pathology size MR Pfeffer Chaim Sheba medical center 2000

  8. Impact of virtual simulation on palliative lung radiotherapy • CT based planning and DRRs compared with simulator planned fields • Complete match 5 % • Major mis-match 66 % • Conventional simulation larger 82 % • Mean target under-coverage 16 % • Mean normal tissue over-coverage 25 %

  9. Multi Leaf Collimator

  10. induction chemotherapy • 60 Gy +/- induction cDDP / VBL XRT only chemo-XRT • med surv 13.7 m 9.6 m • 1 yr surv 54% 40% • 3 yr surv 24% 10% • 5 yr surv 17% 6% Dillman JNCI 1996 MR Pfeffer Chaim Sheba medical center 2000

  11. XRT for localized NSCLC • RTOG randomized study 2Gy/d 1.2 Gy bid cDDP/VBL to 60 Gy to 69.6 Gythen 60 Gy • med surv 11.4 mo 12.3 mo 13.8 mo • 3 yr surv 9% 14% 13% Sause JNCI 1995 MR Pfeffer Chaim Sheba medical center 2000

  12. Dose effect for localized non-resectable NSCLC • dose local control (clinical) • 40 Gy 48% • 50 Gy 58% • 60 Gy 67% Perez RTOG 73-01 • <20% bronchoscopic local control @ 65Gy Arriagada IJROBP 1990 MR Pfeffer Chaim Sheba medical center 2000

  13. toxicity dose/volume effect • volume receiving >25 Gygd III pulmonary toxicity >30% 38% <30% 4% • NTCP >12% 29% <12% 0 Armstrong 1997 MR Pfeffer Chaim Sheba medical center 2000

  14. XRT for localized NSCLC • conformal radiotherapy • treat visible disease only • dose based on NTCP lung volume TD 5/5 TD 50/5 1/3 45 Gy 65 Gy 2/3 30 Gy 40 Gy whole lung 17.5 Gy 24.5 Gy MR Pfeffer Chaim Sheba medical center 2000

  15. 3-D XRT dose escalationHaymanJCO 2001s • Target: clinical disease = primary tumor & nodes >1 cm • dose escalation up to 102.9, 102.9, 84,75.6 Gy, 65.1(2.1 Gy/d) based on NTCP bins (treated lung volume) • 104 patients (24 stage I, 4 stage II, 43 stage IIIA, 26 stage IIIB, 7 local recurrence) • Toxicity: pneumonitis grade 2 - 5 pts, grade3 –2 pts • Survival: stage III and recurrent disease: • median 16 months, 1-, 2-, & 3-year 61%, 36%,& 14% • NO isolated relapses in untreated nodes MR Pfeffer Chaim Sheba medical center 2000

  16. Fractionation of XRT for localized NSCLC • traditional fractionation • 2Gy/d 60 Gy 6w • hyperfractionation • 1.15-1.2 Gy bid 70 Gy 6w • CHART • 1.5 Gy tid 54 Gy 12d MR Pfeffer Chaim Sheba medical center 2000

  17. XRT for localized NSCLC • CHART randomized study SaundersLancet 1997 • inoperable, suitable for radical XRT 1.5 Gy tid, 54 Gy,12d v 2 Gy/d, 60 Gy, 6w • 1 yr surv 63% 55% • 2 yr surv 29% 20% • dysphagia (acute) 19% 3% • pneumonitis 10% 19% • symptomatic late fibrosis 16% 4% MR Pfeffer Chaim Sheba medical center 2000

  18. Cisplatin and radiotherapy:EORTC study NEJM 1992 • 55 Gy/ 20 fx /6w1 yr surv 3 yr surv • XRT alone 46% 2% • XRT + daily cDDP 54% 16% • XRT + weekly cDDP 44% 11% • improved local control • no effect on distant metastases • effect of daily cDDP not seen in other series (Blenke, Trove) MR Pfeffer Chaim Sheba medical center 2000

  19. Concurrent v sequential chemo-radiation • cDDP/vindesine/MMC x 2 & 56 Gy(split course) (Furuse JCO 1999) • cDDP/VBL & 60 Gy XRT (RTOG 94-10) Median survival Sequentialconcomitant Furuse 13.3m 16.5 m RTOG 14.6m 17.0 m (n.s.)

  20. Concurrent v sequential chemo-radiation Furuse JCO 1999

  21. Issues in chemo-radiation of localized NSCLC • chemotherapy • adjuvant induction chemotherapy • moderate survival benefit • reduces distant mtastases • newer (better?) drugs • concomitant chemotherapy • cDDP may be beneficial • does it improve therapeutic ratio? MR Pfeffer Chaim Sheba medical center 2000

  22. Agents studied in chemo-radiation of lung cancer • Cisplatin • taxanes • gemcitabine • irinotecan • tiripazamine • vinorelbine

  23. Taxol & concurrent XRT – study designs Taxol dose escalationWillner Lung Cancer 2001 • 2 cycles induction PX/carboplatin followed by 3D-conformal radiotherapy (60 Gy/6 weeks) with weekly taxol. • DLT:esophagitis III°, interruption of XRT @ taxol 70 mg/m2. • Pneumonitis 36% no clear correlation with PX dose. • 1- and 2-year survival 73% and 34%. XRT dose escalationSocinski Cancer 2001 • 2 cycles carbo/taxol > XRT + weekly carbo (AUC 2)/taxol 45/m2) • XRT (GTV tumor & regional nodes) escalating dose to 74 Gy • 1, 2, yr survival 71%, 52%, Esophagitis gd 3-4 8%

  24. XRT for localized NSCLC • medically inoperable T1-2 • tumor size • dose • T <3 cm, 90% control @ 65 Gy Dosoretz 1992 MR Pfeffer Chaim Sheba medical center 2000

  25. Chemo-radiation for lung cancer • Chemotherapy issues • Benefit of chemo-radiation over chemotherapy only ? • Schedule (concomitant or sequential) • Choice of drug(s)

  26. Chemo-radiation for lung cancer • Locally advanced non-resectable disease • (IIIA non resectable or IIIB or bulky N2)

  27. chemo-radiation timing • Radiosensitizer (low dose-daily) • Sequential CT -> XRT -> CT • Concurrent • Sequential and concurrent MR Pfeffer Chaim Sheba medical center 2000

  28. EORTC 08912 phase I/II study inoperable SqCLC daily cDDP?XRT • Inoperable patients, 37/40 were N2 or T4 • 2 Gy/fx to GTV with 2 cm margin + mediastinum. Simultaneous boost 0.75 Gy to GTV with 1 cm margin • MTD: 66 Gy/2.75 Gy/24 fx combined with daily cDDP 6 mg/m(2) given over 5 weeks • Actuarial 1- and 2-year survival 53% and 40%. • 1- and 2-year local disease-free interval 65% and 58%.

  29. Vinorelbine and radiotherapy • In vitro radiosensitizer • maximum effect in cell lines with G2/M arrest after radiation (cells with mutant p53) • MTD for daily iv NVB 4 mg/m2/d • clinical studies NP or NIP (weekly NVB 25-30 mg/m2) plus XRT • median survival 43-65 weeks (similar to other chemo-radiation phase II studies

  30. Vinorelbine and radiotherapy • Czech study (Zatloukal IASLC 2000) • randomized study - total 40 pts • 3 cycles cDDP 80/m2 q 4w + NVB 25/m2 d1,8,15 • XRT 60 Gy/30fr/6w starting cycle 2 or post chemo • RR 85% (35% CR) v 45% (15% CR) (p=0.028) • MS 20 v 14 m • increased neutropenia and esophagitis (30% v 0%)

  31. Vinorelbine and radiotherapy • CALGB randomized phase II study 181pts • 2 cycles chemo -> chemo/xrt • cDDP + NVB 0r GZR or Taxol • CR OR MS 1 yr S esophagitis (gd 3-4) • NVB 10% 69% 17.7m 65% 24% • GZR 2% 70% 18.4m 68% 52% • TXL 12% 64% 14.7 m 63% 40% • conclusion: all combinations are safe

  32. Vinorelbine and radiotherapy • Arriagada ASCO 2001 • ChartWEL

  33. Radiosensitizer studies • Ideal radio-sensitizer • minimal toxicity • can be given on every day of radiation therapy • increases effect of radiation against tumor • does not increase side effects of radiation • easily administered, preferably per os • for disease with high risk of metastases, useful to have independent anti-tumor activity (spatial co-operation)

  34. induction chemotherapy • cDDP based • Dillman JNCI 1996 • newer agents cave toxicity • gemcitabine (full dose) • gd 5 pneumonitis • weekly 50 mg/m2 Taxol + XRT • interstitial pneumonitis MR Pfeffer Chaim Sheba medical center 2000

  35. Carbo/Paclitaxel or Carbo/Vinorelbine Followed by Accelerated Hyperfractionated Conformal Radiation Therapy: Phase I Trial • Concurrent boost 1.6 and 1.25 cGy BID to GTV and CTV • Starting dose 73.6 Gy; escalated to 80 and 86.4 Gy. • Carb/Taxol and 86.4 Gy: 2/7 patients developed grade 4 toxicity, 80.0 Gy is considered the MTD following C/T. • Carb/NVB arm: enrollment continues at 86.4 Gy, escalation to 92.8 Gy will be considered. • Survival (both groups combined): median 16.2 months, 1 year 67%, 2 year 39%.

  36. Do Elderly Patients (pts) with Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Benefit from Combined Modality Therapy? A Secondary Analysis of RTOG 94-10 • n survival (MST) in the elderly favored concurrent chemoradiation: 22.4 mos for CON-QD vs. 16.4 mos for CON-BID vs. 10.8 mos for SEQ (p=0.069), whereas the MST for those <70 was 15.5 vs. 16 vs. 15.7 mos, respectively.

  37. Issues in radiation therapy of localized NSCLC - summary • XRT dose - dose response exists for local control and toxicity • fractionation - hyperfractionation:moderate benefit • volume - ensure adequate tumor coverage • CT planning • Beam’s Eye View • volume - avoid treating uninvolved organs • lung, heart, esophagus • use NTCP to define dose MR Pfeffer Chaim Sheba medical center 2000

More Related