BASICS OF RADIATION THERAPY/RADIATION ONCOLOGY

BASICS OF RADIOTHERAPY/RADIATION ONCOLOGY

1. Basics of radiation therapy DR ANDREA PG RESIDENT DEPARTMENT OF RADIATION ONCOLOGY,FMMCH

2. RADIATION ONCOLOGY Radiation oncology is that discipline of human medicine concerned with the generation, conservation, and dissemination of knowledge concerning the causes, prevention, and treatment of cancer and other diseases involving special expertise in the therapeutic applications of ionizing radiation. Radiation oncology addresses the therapeutic uses of ionizing radiation alone or in combination with other treatment modalities such as biologic and immunologic and cellular therapies, surgery, drugs, oxygen, and heat

3. The aim of radiation therapy is to deliver a precisely measured dose of irradiation to a defined tumor volume with as minimal damage as possible to surrounding healthy tissue , resulting in eradication of the tumor, a high quality of life, and prolongation of survival or palliation of symptoms at a reasonable cost.

4. How are x-rays produced? Natural : radioactive decay Man-made : sudden deceleration of high speed electrons when it hits a tungsten target

5. Mechanism of action of radiation. Target molecules of Radiation Damage- Radiation effects may occur as direct ionizations in a organic molecule or indirectly via free radical processes. As cells consist of mostly water, most ionizations produced by irradiation occur in water molecules leading to r adiolysis of water into hydrogen ion and hydroxyl ion . About 60-70% of cellular DNA damage produced by radiation is by hydroxyl ions.

6. If cells are irradiated with a modest dose of x-rays, many breaks of a single strand occur. SSBs are of little biologic consequence as far a cell killing is concerned because they are repaired readily using the opposite strand as a template. If the breaks in the two strands are opposite one another or separated by only a few base pairs this may lead to a DSB ( double-strand break ), resulting in the cleavage of chromatin into two pieces. DSBs are believed to be the most important lesions produced in chromosomes by radiation SSB DSB

7. When radiation is delivered both the tumour cells as well as normal body cells are damaged , but normal body cells have repair mechanism by which the cell repairs itself whereas the tumour cells do not

8. 6 R’s of Radiobiology Radiobiological principles are important in the daily clinical use of all forms of radiotherapy Repair Radiation results in : lethal damage – ie irreversible damage Sublethally damaged cells are capable of repair if they are allowed sufficient time and if the cell contains all of the necessary DNA repair proteins and enzymes. Repair is essentially complete by 6hr post radiation. If sublethally damaged cells are exposed to further irradiation before repair occurs, the damage may become lethal. Potentially lethal damage- can be manipulated by repair when cells are allowed to remain in non dividing state

9. 2. Redistribution Radiation kills cells in dividing phase of cell kill Cells are most sensitive in mitotic phase(M and G2 phase) Resistance is greater in late s phase If interval b/w doses is 6hrs,then resistant cells move to sensitive phase If >6hrs-cells will repopulate and result in increase of surviving fraction.

10. 3. Repopulation In between fractionation normal cells as well as tumor cells repopulate. So longer the time more difficulty it becomes to control tumor and may be detrimental. Fractionation must be controlled so as to not allow tumor cells to repopulate and at the same time not treating so fast that the acute tolerance is exceeded Accelerated repopulation- Treating with any cytotoxic agent including radiation triggers surviving cells in tumor to divide faster than before. Dose escalation is needed to overcome this repopulation It is better to delay a treatment than to introduce delay during treatment.

11. 4. Reoxygenation Oxygen is radiosensitizer . Cells at center of tumor are hypoxic and resistant. Hypoxic cells get reoxygenated which occurs during a fractionated course of treatment , making them more radiosensitive to subsequent doses of radiation Hence a decreased survival is observed in certain patients with a low initial hemoglobin levels

12. 5. Radiosensitivity More radiosensitive – more response Less dose needed Eg : Seminoma Radioresistant tumors – osteosarcoma,melanoma etc

13. 6. Reactivation of Anti-Tumor Immune Response/Remote bystander effects RT induces modifications resulting in improved ability of immune system in identifying the tumor cells. This activates both innate and adaptive immunity--  anti-tumor immune response The regression of a metastasis outside the irradiated field, known as the abscopal effect , best demonstrates the existence of such a systemic response.

14. Time Dose Fractionation Overall Treatment time Radiation dose Types of fractionation. 1. CONVENTIONAL 2. ALTERED- Hyperfractionation Accelerated fractionation Split course radiation Hypofractionation .

15. FRACTIONATION OF THE RADIOTHERAPY COURSE Fractionation Allows repair of normal tissue Allows repopulation of normal tissue Allows re-oxygenation of tumour Allows re-distribution But Allows repair of tumour Allows proliferation of tumour

16. Unit Gray (Gy) Absorbed energy per unit mass of tissue. 1 gray = 1 Joule/kilogram also equals 100 rad.

17. INDICATIONS OF RADIATION NEOADJUVANT DEFINITIVE ADJUVANT DEFINITIVE PALLIAITIVE

18. INDICATIONS NEOADJUVANT / PRE-OPERATIVE DEFINITIVE ADJUVANT / POST OPERATIVE CARCINOMA RECTUM CARCINOMA ESOPHAGUS HEAD AND NECK CANCERS CARCINOMA CERVIX CARCINOMA ESOPHAGUS CARCINOMA PROSTATE TESTICULAR MALIGNANCIES LYMPHOMAS CARCINOMA LUNG PLASMA CELL NEOPLASMS SKIN CANCERS PAEDIATRIC MALIGNANCIES HEAD AND NECK CANCERS GYNAEC MALIGNANCIES CARCINOMA BREAST SOFT TISSUE SARCOMAS CNS TUMOURS CARCINOMA STOMACH CARCINOMA LUNG SCC OF EXTREMITIES PITUITARY ADENOMAS

19. TYPES OF RADIATION THERAPY EXTERNAL BEAM RADIATION THERAPY BRACHYTHERAPY

20. EXTERNAL BEAM RADIATION THERAPY (EBRT) EBRT is the most common type of Radiation therapy used. A machine is used to aim high energy X-rays , produced in the machine to the tumour within the body. The most commonly used machine is a LINAC – LINEAR ACCELERATOR

21. EBRT can be delivered by TELECOBALT MACHINE CYBER KNIFE PROTON THERAPY LINAC

22. TELECOBALT THERAPY Cobalt 60- Gamma rays Capital Investment less Easy Installation Few Staff required Maintenance/Repair Easy Currently – Largely being replaced by LINAC in most of the places

23. LINEAR ACCELERATOR (LINAC) The linear accelerator is a device that uses high frequency electromagnetic waves to accelerate charged particles such as electrons to high energies through a linear tube.

24. Historical image of Gordon Issacs , first patient treated with LINAC

25. Why LINAC? Higher energy beams High dose rate Multiple energies – 6MV , 10 MV , 15 MV , 18 MV etc Highly sophisticated plans possible No radiation exposure when machine is on standby / off

26. PROTON THERAPY Proton therapy is the most technologically advanced method to deliver radiation therapy. The advantage is that , with proton therapy we can accurately deliver very high doses to tumour and reduce the doses to surrounding tissue , better than the a LINAC

27. CYBER KNIFE The CYBER KNIFE is a linear accelerator mounted on a robotic arm which delivers highly focused multiple beams (around 150-200) to the tumour

28. METHODS OF DELIVERING RT 2D RT 3D CRT IMRT IGRT SRS / SBRT

29. 2D RT Treatment plan based on Bony Anatomy Area to be treated drawn on xray Based on XRAYS Simple but not very accurate Side effects are higher

30. 3D CRT Three dimensional conformal Radiation therapy , are based on 3D anatomical information and treatment fields are used that match as closely as possible to the tumour and normal organs 2D VS 3DRT

31. IMRT – INTENSITY MODULATED RADIATION THERAPY IMRT is an advanced form of 3DCRT in which multiple “beamlets” are shaped to fit exactly the shape of the tumour thereby delivering a high dose to the tumour and minimal dose to the surrounding structures TREATMENT AREA 2DRT 3DCRT IMRT DOSE TO SURROUNDING AREAS MORE DOSE TO SURROUNDING AREAS LESS

32. IGRT – IMAGE GUIDED RADIATION THERAPY USE OF IMAGE GUIDANCE DURING THE DELIVERY OF RADIATION XRAY / CT machine is attached onto the linear accelerator to provide real time image and tumour tracking during the treatment. If there is any slight change in the tumour position the machine will reorient itself and treat only the tumour

33. ON -BOARD CT IMAGING

34. SRS - STEROTACTIC RADIOSURGERY A single dose of very high dose of Radiation is delivered in a single sitting. Lesion should be small in size (<2cm) “ RADIOSURGERY “ – Because all the dose is delivery in single sitting Used in Intracranial neoplasms

35. SBRT – STEREOTACTIC BODY RADIATION THERAPY Similar to SRS , but dose given in 4-5 fractions over few days Used in Lung cancer , HCC , Bone Metastasis etc

36. STEPS IN RADIATION THERAPY PLANNING WORKUP AND DIAGNOSIS WITH DETAILED HISTOPATHOLOGY REPORT STAGING PREPARATION OF THE PATIENT FOR MOULDING/IMMOBILIZATION Dental prophylaxis , Bowel protocol etc

37. IMMOBILISATION As patients need to be treated daily in the exact same position a thermoplastic mould or VACLOC is used to immobilise the patient during treatment RT PLANNING CT A contrast CT of the region is taken usually 2.5mm / 5 mm cuts

38. CT ACQUISITION All the CT images are transferred to the Radiation Therapy Department Server CONTOURING The tumour and the nearby normal organs are drawn on each CT slice PLANNING Using the suitable machine (COBALT / LINAC / CYBER KNIFE ) and the suitable method (2D/3D/IMRT/IGRT/SRS/SBRT) the a radiotherapy plan is prepared which will deliver a high dose to tumour and minimal dose to surrounding areas

39. TREATMENT DELIVERY AFTER DAILY VERIFICATION FOLLOW UP Daily follow up of the patient in Wards/ OPD ASSESMENT OF TUMOUR RESPONSE AND TOXICITIES COMPLETION OF TREATMENT COURSE

40. BRACHYTHERAPY Greek :“ Brachys ” - short A form of radiotherapy in which a sealed radioactive source is placed inside or in close proximity to the tumour

41. Merits Brachytherapy alone is used in few early stage cancers Used in treatment of cancers of Head and Neck , Breast , Gynecological , Genitourinary , GI tract , Skin, STS etc High Dose delivered to the tumour with minimal dose to the normal tissues Cost effective

42. Types of brachytherapy INTRACAVITARY BRACHYTHERAPY INTERSTITIAL BRACHYTHERAPY INTRALUMINAL BRACHYTHERAPY ENDOBRONCHIAL BRACHYTHERAPY SURFACE MOULD BRACHYTHERAPY

43. GYNECOLOGICAL MALIGNANCIES INTRACAVITARY BRACHYTHERAPY

44. Carcinoma Breast Cervical Cancer Vaginal and Vulval Cancer Head and neck tumours Ano -Rectal tumours Soft Tissue Sarcomas INTERSTITIAL BRACHYTHERAPY

45. CARCINOMA ESOPHAGUS Definitive Palliative HEPATOBILIARY TRACT MALIGNANCIES INTRALUMINAL BRACHYTHERAPY

46. CARCINOMA TRACHEA / BRONCHUS / LUNG ENDOBRONCHIAL BRACHYTHERAPY

47. SURFACE TUMOURS SKIN TUMOURS SCALP TUMOURS SCC/BCC KELOIDS SURFACE MOULD BRACHYTHERAPY

48. SIDE EFFECTS OF RADIATION THERAPY Depends on the site and duration of treatment. Settles by 2-3 weeks post completion of treatment ACUTE EFFECTS SKIN : erythema, dry then moist desquamation MUCOSA : mucositis, esophagitis , colitis proctitis, cystitis MARROW : pan- cytopenia XEROSTOMIA

49. LATE EFFECTS Soft tissue and bone necrosis Neuropathy Second malignancy - rare

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