2. Nuclear Physics – a Blessing to Mankind: Recent Advances in Radiation Therapies for Cancer Ruprecht Machleidt Department of Physics, University of Idaho UI Physics Colloquium Sept. 14, 2009

3. R. Machleidt Radiation Therapies UI Colloq 09/14/092 Outline Cancer factsCancer facts How does radiation therapy work?How does radiation therapy work? Passage of radiation through matterPassage of radiation through matter Differences between electron, photon and proton/heavy ion radiationsDifferences between electron, photon and proton/heavy ion radiations The Bragg peak and its use in cancer therapyThe Bragg peak and its use in cancer therapy Proton/heavy ion facilitiesProton/heavy ion facilities ConclusionsConclusions

4. Cancer facts Cancer is the second largest killer.Cancer is the second largest killer. R. Machleidt Radiation Therapies UI Colloq 09/14/093

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7. Cancer facts Cancer is the second largest killer.Cancer is the second largest killer. How to fight cancer: detect it (early!) and erase it.How to fight cancer: detect it (early!) and erase it. One way of detection: Imaging (CT, MRI, PET, …)One way of detection: Imaging (CT, MRI, PET, …) Erasing cancer:Erasing cancer: Surgery, chemo (both are invasive), Surgery, chemo (both are invasive), Radiation (non-invasive, involved in 50% of cancer treatments) Radiation (non-invasive, involved in 50% of cancer treatments) R. Machleidt Radiation Therapies UI Colloq 09/14/096

8. How does radiation therapy work? Radiation causes ionization.Radiation causes ionization. Most ionization occurs on water (80% of our body)Most ionization occurs on water (80% of our body) Generates free radicals, e.g., OH*, chemically extremely reactive.Generates free radicals, e.g., OH*, chemically extremely reactive. Radicals react with other molecules, disrupting and disabling them, e.g., DNA.Radicals react with other molecules, disrupting and disabling them, e.g., DNA. Cell with damaged DNA can continue to live, but dies at next cell division.Cell with damaged DNA can continue to live, but dies at next cell division. R. Machleidt Radiation Therapies UI Colloq 09/14/097

9. Healthy cells versus cancer cells R. Machleidt Radiation Therapies UI Colloq 09/14/098

10. Healthy cells versus cancer cells under radiation Healthy cells are able to repair themselves.Healthy cells are able to repair themselves. Cancer cells less able, and they divide more often (recall: cell-death occurs upon cell division).Cancer cells less able, and they divide more often (recall: cell-death occurs upon cell division). Thus, more damage is done to cancer cells.Thus, more damage is done to cancer cells. R. Machleidt Radiation Therapies UI Colloq 09/14/099

11. “Fractionation” Total dose: 80 Gray (Gy)Total dose: 80 Gray (Gy) R. Machleidt Radiation Therapies UI Colloq 09/14/0910 Example:

12. Talking about units … The unit for absorbed dose isThe unit for absorbed dose is 1 Gray (Gy) = 1 Joule/kg = 100 rad 1 Gray (Gy) = 1 Joule/kg = 100 rad 10 -3 Gy/year is safe.10 -3 Gy/year is safe. 10 2 is lethal.10 2 is lethal. R. Machleidt Radiation Therapies UI Colloq 09/14/0911

13. R. Machleidt Radiation Therapies UI Colloq 09/14/0912 “Fractionation” Total dose: 80 Gray (Gy)Total dose: 80 Gray (Gy) This is broken up into 40 portions: 2 Gy per portionThis is broken up into 40 portions: 2 Gy per portion 5 portions per week (weekend free, healthy cells can recover)5 portions per week (weekend free, healthy cells can recover) Total radiation treatment: 8 weeks.Total radiation treatment: 8 weeks. Fractionation enhances the survival of the healthy cells.Fractionation enhances the survival of the healthy cells. R. Machleidt Radiation Therapies UI Colloq 09/14/0912 Example:

14. Goal of all cancer therapies Do lethal damage to the cancer (tumor).Do lethal damage to the cancer (tumor). Do minimal damage to healthy tissue.Do minimal damage to healthy tissue. Not so easy!Not so easy! What radiation is best suited to reach the above goal?What radiation is best suited to reach the above goal? R. Machleidt Radiation Therapies UI Colloq 09/14/0913

15. R. Machleidt Radiation Therapies UI Colloq 09/14/0914 What radiations are there? And what are the differences?

16. R. Machleidt Radiation Therapies UI Colloq 09/14/0915 Passage of radiation through matter: Energy deposition Photons Heavy Ions Bragg Peak Electrons

17. R. Machleidt Radiation Therapies UI Colloq 09/14/0916 Differences in the energy depositions Electrons: small depth, “superficial”. The light electrons bounce off heavy atoms: chaotic zigzag path. The electrons are not getting anywhere.Electrons: small depth, “superficial”. The light electrons bounce off heavy atoms: chaotic zigzag path. The electrons are not getting anywhere. Photons: Exponential fall-off, like light passing through milky/foggy glass.Photons: Exponential fall-off, like light passing through milky/foggy glass. Protons and heavy ions: They have a mass; so they stop after losing their kinetic energy. Shortly before stopping, they do maximum ionization: Bragg peak.Protons and heavy ions: They have a mass; so they stop after losing their kinetic energy. Shortly before stopping, they do maximum ionization: Bragg peak.

18. R. Machleidt Radiation Therapies UI Colloq 09/14/0917 How are photons absorbed? Photon reaction mechanisms as a function of energy:

19. R. Machleidt Radiation Therapies UI Colloq 09/14/0918 Passage of Particles through Matter Phys 465/565 13-Sept-06 Photon absorption by pair creation

20. R. Machleidt Radiation Therapies UI Colloq 09/14/0919 Medical applications in cancer treatment Electrons: Skin cancer (“superficial”)Electrons: Skin cancer (“superficial”) Photons (X-ray): deeper lying tumorsPhotons (X-ray): deeper lying tumors Protons and heavy ions: deeper lying tumorsProtons and heavy ions: deeper lying tumors What’s the difference between photons and protons?

21. R. Machleidt Radiation Therapies UI Colloq 09/14/0920 PHOTONS Tumor

22. R. Machleidt Radiation Therapies UI Colloq 09/14/0921 PHOTONS

23. R. Machleidt Radiation Therapies UI Colloq 09/14/0922 PROTONS

24. R. Machleidt Radiation Therapies UI Colloq 09/14/0923 PROTONS more energy Deeper lying Tumor

25. R. Machleidt Radiation Therapies UI Colloq 09/14/0924 PHOTONS PRO- TONS “Bragg Peak”

26. R. Machleidt Radiation Therapies UI Colloq 09/14/0925 PHOTONS PROTONS more energy “Bragg Peak”

27. Reducing the disadvantage of photons: “Multi-field” R. Machleidt Radiation Therapies UI Colloq 09/14/0926 But the same is done with protons and then it’s even more effective.

28. R. Machleidt Radiation Therapies UI Colloq 09/14/0927 Some History 1905 W. H. Bragg and R. Kleeman, University of Adelaide, discover the “Bragg Peak” using alpha particles from radium; Phil. Mag. 10, 318 (1905). 1946 R. R. Wilson proposes medical use of protons; Radiology 47, 487 (1946). 1954 First human treated at Berkeley. 1961 Harvard starts proton therapy (9000 patients treated by 2003). 1988-90 First hospital-based proton accelerator (synchrotron) built at Loma Linda University Medical Center, S. California. 2009 12,000-th proton patient treated at Loma Linda; more than 55,000 patients treated world-wide.

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30. R. Machleidt Radiation Therapies UI Colloq 09/14/0929 Loma Linda

31. R. Machleidt Radiation Therapies UI Colloq 09/14/0930 Comparing different treatment protocols for prostate cancer

32. R. Machleidt Radiation Therapies UI Colloq 09/14/0931 The Proton Center at Loma Linda

33. R. Machleidt Radiation Therapies UI Colloq 09/14/0932 The proton beam treatment room (gantry) from the patients view

34. R. Machleidt Radiation Therapies UI Colloq 09/14/0933 In contrast: a photon treatment “center”

35. The cost Proton facilities are expensive, but when run efficiently [16 hours per day (two shifts), 64 patients per treatment room per day, 3 rooms: 192 patients per day], the cost per patients gets within a factor of two to photon (X-ray, “conventional”) radiation therapy.Proton facilities are expensive, but when run efficiently [16 hours per day (two shifts), 64 patients per treatment room per day, 3 rooms: 192 patients per day], the cost per patients gets within a factor of two to photon (X-ray, “conventional”) radiation therapy. R. Machleidt Radiation Therapies UI Colloq 09/14/0934

36. The cost: example Proton therapy: ≈$40,000Proton therapy: ≈$40,000 Photon (X-ray, “conventional”): ≈$20,000Photon (X-ray, “conventional”): ≈$20,000 BUT: you have to add the follow-up cost. With large side effects, there are large follow-up costs. $5,000 follow-up costs per year (for a photon case with severe side effects) generates costs of $50,000 in 10 years, $100,000 in 20 years, …BUT: you have to add the follow-up cost. With large side effects, there are large follow-up costs. $5,000 follow-up costs per year (for a photon case with severe side effects) generates costs of $50,000 in 10 years, $100,000 in 20 years, … R. Machleidt Radiation Therapies UI Colloq 09/14/0935

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39. R. Machleidt Radiation Therapies UI Colloq 09/14/0938 Some useful links www.protons.comwww.protons.comwww.protons.com www.proton-therapy.orgwww.proton-therapy.org www.protonbob.comwww.protonbob.com

40. R. Machleidt Radiation Therapies UI Colloq 09/14/0939 Conclusions Nuclear physics saves lives every day.Nuclear physics saves lives every day. Radiation treatment using beams of heavy charged particles (protons, ions) allows to focus on localized tumors due to the Bragg peak, thus, dramatically reducing negative side effects.Radiation treatment using beams of heavy charged particles (protons, ions) allows to focus on localized tumors due to the Bragg peak, thus, dramatically reducing negative side effects. It is the preferred method for the removal of tumors that are difficult to reach by surgery (scull base, back of the eye) or where surgery has typically large side effects (prostate cancer).It is the preferred method for the removal of tumors that are difficult to reach by surgery (scull base, back of the eye) or where surgery has typically large side effects (prostate cancer). Proton therapy has been used for 50 years and is well tested with long- term (10y) follow-up studies. It is not experimental.Proton therapy has been used for 50 years and is well tested with long- term (10y) follow-up studies. It is not experimental. Medicare and most (but not all!) health insurances pay nowadays for proton therapy.Medicare and most (but not all!) health insurances pay nowadays for proton therapy. However your doctor may have never heard about proton therapy or thinks that it is something very weird and untested.However your doctor may have never heard about proton therapy or thinks that it is something very weird and untested.