2. Nuclear Physics - a Blessing to Mankind: Recent Advances in Radiation Therapies for Cancer Ruprecht Machleidt Department of Physics, University of Idaho Renfrew Colloquium Sept. 10, 2013

3. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/20132 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 Renfrew Colloquium 09/10/20133

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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. Machleidt6 Radiation Therapies Renfrew Colloquium 09/10/2013

8. How does radiation therapy work? Radiation causes ionization.Radiation causes ionization. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/20137

9. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/20138 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.

10. Healthy cells versus cancer cells R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/20139

11. 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 Renfrew Colloquium 09/10/201310

12. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201311 “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. Example:

13. 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 Renfrew Colloquium 09/10/201312

14. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201313 What radiations are there? And what are the differences?

15. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201314 Passage of radiation through matter: Energy deposition Photons Heavy Ions Bragg Peak Electrons

16. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201315 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.

17. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201316 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?

18. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201317 PHOTONS Tumor

19. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201318 PHOTONS

20. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201319 PROTONS

21. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201320 PROTONS more energy Deeper lying Tumor

22. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201321 PHOTONS PRO- TONS “Bragg Peak”

23. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201322 PHOTONS PROTONS more energy “Bragg Peak”

24. Reducing the disadvantage of photons: “Multi-field” R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201323 Further refinements: Intensity Modulated Radiation Therapy (IMRT): Five or more fields with different intensities. But the same is done with protons and then multi-field is even more effective, because you start from a better beam: Intensity Modulated Proton Therapy (IMPT).

25. Shaping the proton beam for 3D conformal irradiation of the tumor R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201324

26. Comparison Protons - Photons for a brain tumor R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201325

27. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201326 Comparing different treatment protocols for prostate cancer

28. R. Machleidt27 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. 2012 16,000-th proton patient treated at Loma Linda; 39 proton centers world-wide; more than 96,000 patients treated world-wide.

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30. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201329 Loma Linda

31. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201330 The Proton Center at Loma Linda

32. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201331 The proton beam treatment room (gantry) from the patients view

33. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201332 In contrast: a photon treatment “center”

34. 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 Renfrew Colloquium 09/10/201333

35. The cost: example Proton therapy: ≈$60,000Proton therapy: ≈$60,000 Photon (X-ray, “conventional”): ≈$30,000Photon (X-ray, “conventional”): ≈$30,000 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 Renfrew Colloquium 09/10/201334

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39. R. Machleidt Radiation Therapies Renfrew Colloquium 09/10/201338 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 Renfrew Colloquium 09/10/201339 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.