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radiation therapy in cancers of the head and neck

radiation therapy in cancers of the head and neck

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radiation therapy in cancers of the head and neck

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  1. radiation therapy in cancers of the head and neck robert r johnson february 2, 2012

  2. outline • history of radiation therapy • physics and radiobiology • treatment planning • fractionation • chemoradiation • post-operative radiation • conclusions

  3. history of radiation therapy • wilhelm conrad roentgen • born 1845 in lennep, germany • professor of theoretical physics at university of wurzburg

  4. wilhelm conrad roentgen • accidentally discovered a new kind of “ray” on november 8, 1895 • penetrated wood, metal, human flesh • first x-ray of his wife’s hand on december 22, 1895 • won nobel prize for physics in 1901

  5. timeline • 1896 – radiation first used to treat local relapse of breast cancer • 1896 – henribecquerel discovers spontaneous radioactivity of uranium • 1898 – marie and pierre curie discover radium • 1922 – henricoutard reports first cure of larynx cancer treated with primary radiation therapy • 1934 – coutard reports 23% long-term rate in head and neck cancers

  6. timeline • 1952 – first linear accelerator • 1954 – first use of protons in radiation therapy • 1972 – first ct scanner • independently by housenfeld and cormack • shared nobel prize for medicine in 1979 • 1990s – first use of intensity modulated radiation therapy (imrt) • 2011 – ct scanning, imrt used for nearly all head and neck cancer patients

  7. physics of radiation therapy • commonly used terms • radiation therapy • photon • electron • proton • 3-d conformal radiation therapy • imrt

  8. radiation therapy • use of ionizing radiation to treat cancer • ionizing radiation • radiation with enough energy to eject orbital electrons from an atom • localized release of large amounts of energy • break chemical bonds • dna • x-rays, gamma rays, ultraviolet rays

  9. photon • x-rays and gamma-rays • x-rays produced extra-nuclearly • linear accelerator • gamma-rays produced intra-nuclearly • emitted by radioactive isotopes • cobalt-60, cesium-137, iridium-192

  10. photon • linear accelerator • electrons generated by electrical current • microwave power to accelerate electrons • electrons strike tungsten target

  11. photon

  12. bremsstrahlung • “braking radiation” • electrical field of nucleus slows down electron • energy conserved in form of photon

  13. photon • photons collimated after striking target • field size determined by secondary collimator • field shape determined by tertiary collimator • block or multi-leaf collimator

  14. multi-leaf collimator • made of tungsten • shape field • prevent leakage • modulate beam for imrt

  15. photon • results in dna damage • majority due to indirect action • free radical damages dna • oxygen required to make damage permanent • hypoxia • amifostine scavenges free radicals • radioprotection

  16. electron • accelerated as with photons • target removed • scattering foil used to spread out beam • electron applicator brings beam close to patient surface • scatter in air

  17. photons vs electrons • photons: • spare skin • deposit dose deeper within tissue • attenuate more slowly in tissue • electrons • high skin dose • shallow penetration • fully attenuated within a few centimeters

  18. photons

  19. electrons • energy (MeV)/4 = depth (cm) of 90% isodose line • energy/3 = depth of 80% isodose line • energy/2 = practical range (0% isodose line) of electron • 9 MeV electron: • 90% isodose line at ~ 2 cm • 0% isodose line at ~ 4.5 cm

  20. treatment planning • ct simulation • ct scan in treatment position • supine • neck extended • aquaplast mask • iv contrast

  21. treatment planning • cork and tongue blade • keep tongue still • move palate away from field

  22. treatment planning • intra-oral lead shield • shield oral cavity contents when treating buccal mucosa or parotid bed • covered in wax to absorb backscattered electrons

  23. treatment planning • contour • gtv – gross tumor volume • abnormal disease you see or feel • ctv – clinical target volume • areas at risk for harboring sub-clinical disease • ptv – planning target volume • margin for target motion and changes in daily set-up • uniform circumferential margin

  24. treatment planning

  25. gtv

  26. ctv

  27. ptv

  28. treatment planning • contour cont’d • organs at risk (oar) • normal structures to minimize dose to • especially important for imrt • allows generation of dose volume histogram (dvh)

  29. dvh

  30. 3-d conformal radiation therapy • beam fluence (intensity) is constant across field • ensure contours are within field • beam’s eye view • forward treatment planning • start with fields to calculate dose

  31. 3-d conformal radiation therapy • 2-6 fields • 3 for head and neck • 2 lateral parallel opposed fields • ap low neck field

  32. 3-d conformal radiation therapy

  33. 3-d conformal radiation therapy • advantages: • easy dose calculation • wider margins • set-up • fast treatment • disadvantages: • wider margins • less conformal • less sparing of organs at risk

  34. imrt • field broken into 3 x 3 x 3 mm voxels • non-uniform fluence delivered through each voxel to optimize composite dose distribution • inverse treatment planning • start with target dose to create fields

  35. imrt • submit request to dosimetry • dose to target(s) • dose limits to oar(s) • computer algorithm generates plan

  36. imrt

  37. dose painting • simultaneously deliver higher dose to gross disease while at risk areas receive lower dose • 2 – 2.25 Gy/fraction to gtv • 1.65 – 1.8 Gy/fraction

  38. imrt • advantages: • highly conformal • better sparing of organs at risk • salivary gland preservation • dose-escalation • disadvantages: • planning and delivery take longer • more comprehensive quality assurance • more expensive

  39. fractionation • standard fractionation • hyperfractionation • hypofractionation • accelerated fractionation • concomitant boost

  40. standard fractionation • 1.8 Gy-2 Gy fractions • total dose 60-70 Gy in 6-8 weeks • used for majority of head and neck cancer • 1.8 Gy/fraction with chemo • 2 Gy/fraction without chemo

  41. hyperfractionation • multiple (two) fractions per day • smaller fraction sizes (1 Gy-1.5 Gy) • separated by 6 hours • allow sublethal damage repair of normal tissues • deliver higher total dose (80 Gy) • minimize late side effects • dose per fraction • worsened acute side effects • mucositis

  42. hyperfractionation • predominantly used for early larynx cancer • 230 patients with T2 glottic carcinoma • 1.1 – 1.2 Gy/fraction to 74 – 80 Gy • twice daily • 2 Gy/fraction to 70 Gy • 2.06 – 2.26 Gy/fraction to 66 – 70 Gy • retrospective chart review from md anderson garden et al. ijropb. 2003:55:322-328.

  43. hyperfractionation • 5-year local control (p = 0.06) • 79% for twice daily treatment • 68% for once daily treatment • 80% for dose > 2.06 Gy • 59% for dose 2 Gy • p < 0.001 • extrapolating • 79% for twice daily • 80% for daily dose > 2.06 Gy garden et al. ijropb. 2003:55:322-328.

  44. hyperfractionation • rtog 95-12 • 250 patients with T2 true vocal cord cancer • 70 Gy in 35 fractions • 79.2 Gy in 66 fractions • twice daily • 5-year • local control: 79% vs 70% • overall survival: 73% vs 62% • trend towards improvement with hyperfractionation

  45. hyperfractionation • also used for re-irradiation • limiting late toxicity important • spinal cord, bone and soft tissues • rtog 99-11 • protocol we follow for re-irradiation • 1.5 Gy/fraction, twice daily during weeks 1,3,5,7 • concurrent cisplatin and paclitaxel • no treatment during weeks 2,4,6

  46. hypofractionation • larger than 2 Gy fraction sizes • 2.1 Gy – 2.25 Gy for head and neck cancers • 6 Gy for melanoma • 34 Gy for non-small cell lung cancer • sbrt • early true vocal cord cancer

  47. hypofractionation • 180 patients with T1 glottic carcinoma • randomized to • arm a – 2 Gy fractions • 60 Gy for <=2/3 of vocal cord • 66 Gy for >2/3 of vocal cord • arm b – 2.25 Gy fractions • 56.25 Gy for <= 2/3 of vocal cord • 63 Gy for > 2/3 of vocal cord yamazaki et al. ijrobp. 2006:64;77-82.

  48. hypofractionation • results • 5 year local control (p=0.004) • arm a (2 Gy) – 77% • arm b (2.25 Gy) – 92% yamazaki et al. ijrobp. 2006:64;77-82.

  49. accelerated fractionation • accelerated fractionation • delivery of total dose over a shorter time period • increases probability of tumor control for given dose by decreasing the opportunity for cell regeneration • traditionally two fractions per day • 1.6 – 1.8 Gy • most patients require break due to acute toxicity • protocols usually build in 2 week break

  50. accelerated fractionation • 6 fractions per week instead of 5 • 2 fractions on monday or friday • 35 fractions given in 6 weeks instead of 7