Radiotherapy & chemotherapy /certified fixed orthodontic courses by Indian dental academy

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Radiotherapy & chemotherapy /certified fixed orthodontic courses by Indian dental academy

  1. 1. INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  2. 2. Radiotherapy & Chemotherapy www.indiandentalacademy.com
  3. 3.  INTRODUCTION:  Radiotherapy means treatment using ionizing radiation,i.e radiation that interacts with fluids to produce free ions.  The type of radiation most commonly used is electromagnetic in nature & the energy range 60 kev- 25Mev.  Source: deep x-ray set or linear accelerator or radioactive isotope,especially 60-cobalt www.indiandentalacademy.com
  4. 4.  Radiotherapy dosage is expressed in terms of ABSORBED DOSE. This is the quantity of ionizing radiation energy absorbed per unit mass of tissue.  The SI unit of absorbed dose is “GRAY” www.indiandentalacademy.com
  5. 5.  Biological action of Radiotherapy:  When cells are exposed to radiation due to free radicals the DNA is broken in such a way the cell is unable to go subsequent mitosis  Cell death will occur if the cell attempts to divide, which it may do at an interval after radiotherapy.  This phenomenon of “Mitotic death” is responsible for all the observed effects of radiotherapy on Tumours & Normal tissues. www.indiandentalacademy.com
  6. 6. NORMAL TISSUE TOLERANCE Def: It is the max dose of irradiation that can be given to the volume of tissue being treated without producing an unacceptable incidence of Late damage  It depends on the type of tissue. Eg :it is Low in lens & the spinal cord & High in cases of skin & muscle.  Spinal cord tolerance is 45Gy www.indiandentalacademy.com
  7. 7. Principles of radiotherapy  There are 2 fundamentally diff methods of administering radiotherapy  1)Teletherapy or external beam irradiation  2)brachytherapy Teletherapy uses a machine to deliver beams of irradiation directed at the tumour from outside the pt  Most widely used radiation sources are telecobalt machines emitting gamma rays & linear accelerators producing high energy xrays & electrons.  www.indiandentalacademy.com
  8. 8. Teletherapy( cobalt 60) www.indiandentalacademy.com
  9. 9. PRACTICAL ASPECTS of EXT.BEAM THEARAPY  Pt position: “supine” position is most commonly used to deliver radiation  Pt immobilization: All pts are immobilized with “Thermoplastic masks” individually made in the desired Rx position  A variety of Neck pads & Head holders are now available www.indiandentalacademy.com
  10. 10. Procedures for making MASKS  1) Thermoplastic sheet  attached to a wood/plastic  frame is submerged in warm  water bath(72 c) until it  becomes flexible www.indiandentalacademy.com
  11. 11.  2)sheet is stretched over the head of pt in desired position & the frame is then fixed to head holder by clamps. www.indiandentalacademy.com
  12. 12.  3)care is taken to stretch sheet sufficiently thin to avoid unwanted bolus effect. www.indiandentalacademy.com
  13. 13.  4)Gentle pressure applied to conform sheet to the contour of the face www.indiandentalacademy.com
  14. 14.  5)The mask can be trimmed,if desired www.indiandentalacademy.com
  15. 15. Radioopaque markers & stents  Radioopaque markers are useful for delineating the nodes, normal tissues of interest,& when accesible,the primary lesion.  1)WIRES & SEEDS: placed on skin/mask or inserted into tissues are helpful to mark the boundaries of primary tumors or nodes to indicate relevant structures www.indiandentalacademy.com
  16. 16.  CUSTOM-Made stents use to depress or shield the tongue,to protrude the lip.These devices are of 2 types  a) Shielding stents :they reduce the radiation dose to normal tissues by incorporating shielding materials  b) positional device: displaces normal tissues out of Rx fields www.indiandentalacademy.com
  17. 17. Brachytherapy  When radiotherapy delivered from a radiation source placed in deep seated tumours or superficial neoplasms  Radiation source  The most popular radioactive material for oral cancer is now “iridium-192”.This is produced in the form of fine wire which is inserted into tissues using slotted guides needles  Other materials used are  Iodine-125  Palladium-103  Caesium-137 www.indiandentalacademy.com
  18. 18. www.indiandentalacademy.com
  19. 19. DOSAGE  If an oral cancer is Rx by brachytherapy alone a dose of 65-70Gy is given over a time range of 5 & 8 days at dose rate of 0.3-0.5Gy/hr  Ext radiotherapy & brachythrapy can be used in combination, in which case the ext beam is usually given 1st to a dose of 40Gy over 4 wks,followed by a implant ASAP giving a further 35-40GY at a dose rate of 0.3-0.5Gy/hr www.indiandentalacademy.com
  20. 20. Types of brachytherapy  1)permanent: when a removable implant can not be performed for technical or medical reasons, a permanent implant with gold-198 seeds is done.  It is not desirable to use iodine-125 for perm implants for SCC of head & neck becoz the dose rate from such implants is too low in relation to the proliferative potential of tumour www.indiandentalacademy.com
  21. 21.  2) Temporary brachytherapy  Most common used for orofacial cancer  Iridium-192 wires are used which are inserted into Teflon catheters or s.s needle depending on tumour site.  3)Molds:A surface mold loaded with ir192 or cs-137 occasionally used for lesions on the hard palate or alveolar ridge www.indiandentalacademy.com
  22. 22. PALLIATIVE RADIOTHERAPY  AIM:To relieve the symptoms of the disease, without attempting to cure the pt  It is only appropriate for pts with incurable disease & a short life expectancy  It is useful for relieving bleeding or pressure symptoms caused by the bulk of tumour such as pain or obstruction  This approach is useful for palliation of Metastases, specially in bone, brain or skin www.indiandentalacademy.com
  23. 23. COMBINED RADIOTHERAPY & SURGERY  SALVAGE SURGERY  Where radical radiotherapy fails & there is residual or recurrent tumour,surgical cure may yet be possible.surgery performed after the failure of radiotherapy is termed as salvage surgery.  It carries high risk of complications such as wound healing,fistula formation,wound breakdown & carotid artery rupture  The complication rate is lowest when surgery is performed with in 3 months of completion of radiotherapy. www.indiandentalacademy.com
  24. 24. Fractionation & Types  A course of external beam radiotherapy is fractionated i.e the total dose is divided into a number of smaller doses delivered over a period of several weeks  AIM of fractionation: To increase the differential effect of the radiation on the tumour compared with normal tissues www.indiandentalacademy.com
  25. 25. Relationship of cell cycle & ionizing Radiation  Cell cycle has 4 phases  1) s (synthesis) – DNA synthesis  2) G2( Gap) -- A period of apparent cellular activity  3) M (mitosis) _ cellular division into 2 daughter cells  4) G1(Gap) _ period of apparent cellular inactivity  MOST SENSITIVE phases www.indiandentalacademy.com are G2 & M
  26. 26. OXYGEN EFFECT  The ability of ionizing radiation to cause biologic change is very much dependent on AMOUNT of oxygen present in the TISSUES environment  Cells in 100% oxygen are 3 times more radiosensitive than cells in complete anoxia  It is the oxygen that reacts with the DNA damage & prevents its repair which ultimately leads to cellular death www.indiandentalacademy.com
  27. 27. Radiobiologic Basis of Fractionation  The use of multiple fractions over many weeks of radiation therapy is based on the principle of the IMPROVING the therapeutic ratio between normal tissues & tumours  The GOAL is to maximize the cell death of tumours & to minimize unacceptable damage to normal cells.  multiple Fractions is explained by the 4 radiobiologic processes     1)Repair 2)Re-oxygenation 3)Re population 4)Re distribution www.indiandentalacademy.com
  28. 28.  REPAIR:  Both normal & malignant cells suffer radiation induced DNA damage of 3 types. Lethal, Potentially lethal & sublethal Repair may occur to a greater degree in slowly dividing normal tissues compared to tumours & this may contribute to a beneficial therapeutic ratio  RE-OXYGENATION:    Buckly tumours have centers that are relatively hypoxic due to there location away from blood vessel.tumour cells located in this region would be more resistant to radiation due to LOW oxygen tension Due to fractionated radiation therapy is administered ,the better oxygenated malignant cells at outer regions are killed & results in tumour mass shrinkage & brings the previously hypoxic central cells closer to B.V’s & thus allowing there oxygenation This increases radiosensitivity and increased potential for their cell www.indiandentalacademy.com kill
  29. 29.  RE-POPULATION   In tumours ,there exists CLONOGENS that can proliferate during a course of fractionationed radiotherapy.As cell death occurs over the weeks,an accelerated rate of cellular proliferation may occur which is called REPOPULATION This reduces the NET effect of Rx & ultimately will contribute to LOCAL Rx failure  RE-DISTRIBUTION  When a tissue is irradiated, a certain % of the cells are killed & these are generally located in more radiosensitive phases such as G2 & M. www.indiandentalacademy.com
  30. 30.  The surviving cells may go into a MITOTIC DELAY such as in G2 arrest, or may progress into the next phase of the cell cycle which may be more radiosensitive.  The net effect is that there will be an increase in the % of cells in the more radiosensitive phase www.indiandentalacademy.com
  31. 31. Types of Fractionation  Conventional fractionation: It uses 180 to 200 cGy per fraction, 1 fraction per day, 5 days per week for 6 to 7 weeks to a total dosage of 6500 to 7000 cGy has been the standard,regimen of curative head & neck radiation therapy for many years.  ALTERED FRACTIONATION  Goal:To improve the therapeutic ratio by maximizing the tumour killing effect & minimizing acute & late toxicities.  A)Hyperfractionation  B)Accelerated fractionation www.indiandentalacademy.com
  32. 32.  Hyperfractionation: is the term for radiation with more than one fractionation per day  Total daily dose & weekly dose is kept equivalent to conventional fractionation & total Rx time is kept constant  An improvement in the therapeutic ratio is obtained through “redistribution” of the tumor cells into more radiosensitive phases due to multiple fractions. www.indiandentalacademy.com
  33. 33. Characters  1)decreased size of the dose per fraction(115 to 120 cGy) compared with conv. Fract(180 to 200 cGy)  2)bid to tid fractionation  3)increase total dosage (7,400 to 8160 cGy) over conv fraction (7000 cGy)  4)similar overall Rx duration to conv fraction www.indiandentalacademy.com
  34. 34. ACCELERATED FRACTIONATION 1. Describes a fractionation which shortens the overall Rx time by giving more than 1 fraction/day 2. The single dose is slightly reduce & weekly dose is increased 3. It is based on the concept that tumour clonogens undergo an accelerated rate of proliferation 3 to 5 wks after initiation of conv fraction radiotherapy. 4. By shortening the overall Rx duration, the opportunity for accelerated repopulation would be reduced. 5. It is felt that this treatment scheme would be best for very rapidly growing tumours. www.indiandentalacademy.com
  35. 35. Methods of improving results of EB Therapy  The presence of VIABLE HYPOXIC cells in tumours but not in normal tissues is believed to be one of the MAJOR cause of radiotherapy failure  Several methods of overcoming the oxygen effect have been tried in oral cancers, they are  1)Hyperbaric oxygen:  The most obvious approach to the radiosensitive hypoxic tumour cell is to provide it directly with MORE 02.in order to bring reduction in the proportion of hypoxic cells,02 must be inhaled at raised pressure. www.indiandentalacademy.com
  36. 36.  2)Neutron therapy:  Another approach to the problem of 02 effect is the use of types of radiation that are LESS DEPENDENT on the presence of 02 for their killing effect  FAST Neutrons have been used.  There is a greater risk of late normal tissue complications,such as “Fibrosis & Necrosis” www.indiandentalacademy.com
  37. 37. Side effects of radiotherapy  ACUTE Side effects:    Mucositis Anorexia,nausea,malaise Alopecia/ Epilation  LATE Side effects:       Skin; ischemia,ulceration BONE: Necrosis,fracture MOUTH:Xerostomia,sialitis,ulceration LUNG:Fibrosis HEART:Cardiomyopathy,pericardialfibrosis GONADS:infertility,menopause www.indiandentalacademy.com
  38. 38. Management of Radiotherapy pt DENTAL CARE:  The teeth of a pt Rx by radiotherapy for oral cancer are at risk both from the direct effect of radiation & from the sec effects of XEROSTOMIA  Teeth receiving a high dose of radiation suffer killing of odontoblasts & atrophy of pulp  Salivary changes is a more potent factor provoking caries.The reduction in volume & increased viscocity of saliva after radiotherapy encourages “Bacterial growth”  To prevent radiation caries meticulous dental hygiene & supervision are essential. www.indiandentalacademy.com
  39. 39. Preparation of dentition for radiotherapy        Every tooth must be carefully inspected for pathologic conditions & restored to the best state of health. A thorough prophylaxis & topical fluoride application should be performed before radiotherapy Any sharp cusps should be rounded to prevent mechanism irritation. Pt should rinse his mouth twice a day with chlorhexidine mouth rinses to minimize bacterlial or fungal levels. TOPICAL FLUROIDE APPLICATION: It reduces the incidence of caries. Fl must be applied to the whole surface of all teeth to have a protective effect Custom built carriers are made for each pt.The pt is provided with a NaF gel & instructed to put 10 drops on trays & apply to the for 5min/day www.indiandentalacademy.com
  40. 40. Method of preirradiation extractions  In general the principles of atraumatic exodontia apply  Concepts of bone preservation is disregarded,& an attempt is made to remove a good portion of the alveolar process along with the teeth & achieve a primary soft tissue closure.  Burs & files should be used to smooth the bony edges under irrigation, since remodeling capability of the tissues is greatly decreased after radiotherapy  REMEMBER: The DENTIST is in a race against time. if the wound fails to heals, the radiotherapy will be delayed or if radiation is delivered anyway, the wound will take months or even years to heal. www.indiandentalacademy.com
  41. 41. INTERVAL btw preirradiation & beginning of radiotherapy  There is no correct answer to how long one should wait after extraction  before beginning radiation.  However, radiotherapy should delay for 3 wks after extraction. This helps to ensure that sufficient soft tissues healing has occurred.  If a Local wound dehiscence has occurred, daily IRRIGATION & post op antibiotics are mandatory until the soft tissues have healed www.indiandentalacademy.com
  42. 42. CHEMOTHERAPY   INTRODUCTION: Chemotherapy has been around since the days of ancient greeks. However, its Rx for cancers began in 1940,s with the use of Nitrogen mustard. since then many more drugs has been developed & tried.  These are also referred as Anticancer drugs or Antineoplastics.    The other chemotherapy agents are A. Harmone therapy B. Monoclonal antibodies. www.indiandentalacademy.com
  43. 43. Uses of chemotherapy  1)To cure a specific cancer  2)To control tumour growth ,when cure is not possible  3)To shrink tumour b4 surgery or radiotherapy  4)To relieve symptoms (such as pain)  5)To destroy microscopic cancer cells that may be present after the known tumour is removed by surgery (called adjuvant therapy) www.indiandentalacademy.com
  44. 44. PRINCIPLES OF CHEMOTHERAPY  CHEMOTHERAPY employs systemically administered drugs that directly damage cellular DNA. It kills cells by promoting APOPTOSIS & sometimes by NECROSIS  Most tumours rapidly developed resistance to single agent on their own. For this reason the principle of “intermittent combination chemotherapy” was developed.  Several drugs has been combined on basis of diff MOA. These drugs are given over a period of a few days followed by a REST of few wks, during which normal tissues have opportunity for RE-GROWTH www.indiandentalacademy.com
  45. 45. TYPES OF CHEMOTHERAPY  1) DNA DAMAGING:  a. Alkylating agents:  They act by covalently binding alkyl groups, & their major effect is to interfering with DNA synthesis & causing breakage of DNA strands  eg: cyclophosphamide, chlorambucil, busulfan  B. platinum compounds:  cisplatin, carboplatin  They are regraded as NON-CLASSICAL alkylating agents. www.indiandentalacademy.com
  46. 46. ANTIMETABOLITIES         These are usually structural analogues of normal substances with in the cells,that interfere with normal synthesis of nucliec acids by falsely substituting PURINES & PYRIMIDINES in metabolic pathways a. Folic acid antagonist: Methotrexate B. pyrimidine antagonist: 5-fluorouracil C. purine antagonist: 6-mercapto purine, 6-thio guanine DNA REPAIR INHIBITORS Topoisomerase inhibitors They interfere with the action of topoisomerase enzymes 1 & 2. During the process of chemoRx control the manipulation of the structure of DNA necessary for REPLICATION Eg: etoposide & teniposide www.indiandentalacademy.com
  47. 47. ANTITUMOUR ANTIBIOTIES        They are produced by a species of soil fungus called STREPTOMYCES They act by inhibiting DNA repair Eg: Doxorubicin, bleomycin , mitomycin ANTI TUBULIN AGENTS Vinka alkaloids: They are used in the RX of haematological cancers. Eg: vinblastine, vincristine www.indiandentalacademy.com
  48. 48. Chemotherapy Approaches  1) single agent chemotherapy  2) combination chemotherapy     3) combination with Local radical treatment a. Adjuvant chemotherapy b. Neo-adjuvant / Induction chemotherapy c. concomitant chemotherapy    4) palliative chemotherapy 5) Intralesional chemotherapy 6)Topical chemotherapy www.indiandentalacademy.com
  49. 49.       1) single agent chemotherapy: A number of drugs have single agent activity in s.c.c of head & neck.These include methotrexate, cisplatin, 5-fluorouracil . Methotrexate is the most commonly used drug & can be safely administration by weekly I.V inj at 40-60mg/m2 in outpatient setting. 2) combination chemotherapy: The aim of combination chemotherapy using 2 or 3 drugs is to improve survival rates, decrease morbidity & quality of life. The combination of cisplatin & 5-FU has been shown to have a higher response rate than single agent methotrexate www.indiandentalacademy.com
  50. 50.       A) Adjuvant chemotherapy: Its given subsequent to definitive Locoregional therapy (surgery , radiotherapy or both ) AIM: To sterilize a possible small population of residual cancer cells at primary site or in the neck, & also to eliminate MICROmetastases B) Neo-adjuvant / induction chemotherapy: Given “ BEFORE” local RX AIM: To reduce the bulk of the disease,thereby either increasing the chance of radiotherapy success or facilitating surgery www.indiandentalacademy.com
  51. 51.  c.concomitant chemotherapy:  It is given at the SAME TIME as radiotherapy with the objective of increasing the chance of a radiotherapy cure  It improve the locoregional control & eradicate systemic micrometastasis by the following mechanism -- decreases the ability of radiotherapy damaged tumour cells to REPAIR -- Has cytotoxic activity against radioresistant tumour cells -- Has selective cytoproctective properties for Normal tissues, allowing higher radiation    www.indiandentalacademy.com
  52. 52.  4) Intralesional chemotherapy:  Intralesional Injection of vinblastine, vincristine or alphainterferon has been shown to be effective in the locoregional control of epidemic kaposi sarcoma   5) Topical chemotherapy: ACTINIC KERATOTIC lesions have been effectively RX with appli of 5% “Florouracil cream twice daily It is not effective in “invasive lesions” & results in needless delay in definitive RX  www.indiandentalacademy.com
  53. 53.  6) palliative chemotherapy:  The primary goal of it is to improve quality of life.This can be accomplished by relieving pain, preserving or improving organ fn & preventing obstruction of airway.  Although in some instances survival may be prolonged but survival is not the primary goal of palliative chemotherapy  Single agent methotrexate therapy has been the standard for head & neck cancer. It is well tolerated, convenient & inexpensive. www.indiandentalacademy.com
  54. 54. Targeted Therapy  Targeted therapy is about identifying other features of cancer cells. It looks for specific diff btw cancer cells & the normal cells. This information is used to attack cancer cells without damaging normal cells, thus leading to fewer side effects.  They interfere with the ability of cancer cells to Growth ,Divide , Repair or Communicate with other cells.  Target therapy includes use of Monoclonal antibodies ,Anti-angiogenesis drugs or Both www.indiandentalacademy.com
  55. 55. Monoclonal antibodies Therapy  In the lab, scientists analyze specific Ag on the surface of cancer cells to determine a protein to match the Ag.  A special antibody is created using animal or human protein which will get attached to target Ag  This technology allows RX to target specific cells ,causing less toxicity to healthy cells  Eg : Alemtuzumab  Gemtuzumab  Rituximab www.indiandentalacademy.com
  56. 56. Anti-angiogenesis/ Angiogenesis Inhibitors  Anti-angiogenesis is the process of stopping formation of new blood vessels.  Tumour needs new blood vessels to Grow & Spread.  Angiogenesis inhibitors stops the development of blood vessels & STRAVES the tumour to death  Drugs like “ alpha-interferon & Thalidomide ” are believed to some ability to inhibit with angiogenesis www.indiandentalacademy.com
  57. 57. TUMOUR VACCINES        Research are developing the vaccines that may encourage pt,s immune system to recognize cancer cells .These works in the similar way as vaccines like measles,mumps & small pox. The diff in cancer RX is the vaccine are used after somebody has cancer. The use of vaccine continues to be studied in clinical trails. HARMONE THERAPY It is based on the observation that receptors for specific harmones that are needed for cellgrowth are present on some of the tumour cells. It works by stopping the production of certain harmones or blocking harmone receptors, which cannot be used by www.indiandentalacademy.com tumour cell.
  58. 58.  The diff harmone therapy types are categorized by the type of harmone that is effected.  Eg: adrenal steroids inhibitors  Androgens  Anti-androgens  Anti-estrogens www.indiandentalacademy.com
  59. 59. Chemoprotective agents:          These types of drugs are used with “certain types” of chemotherapy to minimize the side effects of chemotherapy. Common chemoprotective agents include AMIFOSTINE MESNA DEXRAZOXANE CHEMOTHERAPY RESISTANCE It occurs cancers that has been responding to chemotherapy suddenly starts Growing POSSIBLE REASONS FOR RESISTANCE: 1) Some of the cells that are not killed by chemotherapy MUTATE & become resistant.once they multiply they are more resistance than the cells that are more sensitive to chemotherapy. www.indiandentalacademy.com
  60. 60.  2) cancer cell can PUMP OUT the drug as fast as it is going in by using a molecule called p-gylcoprotein  3)Cancer cell may stops taking in the drug becoz the protein that transport the drug across the wall stops working  4) cancer cell may devp a mech that inactivates the drug. www.indiandentalacademy.com
  61. 61. THANK YOU www.indiandentalacademy.com

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