Radio - Oncology 2008

VICTOR Q. ALABASTRO, MD, FPCR, FUSP, FPROS, FPSO

Historical Perspective: Early Observations of the effects of Ionizing Radiation 1895 - x-rays discovered by Roentgen 1896 - first skin burns reported - first use of x-ray in the treatment of cancer - discovery of radioactivity of Becquerel 1897 – first case of skin damage reported 1899 – first basal cell epithelioma reported cured 1902 – first report of x-ray induced cancer 1911 – first report of leukemia in human and lung cancer form occupational exposure 1911- 94 cases of tumor reported in Germany ( 50 being radiologist)

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER A. SURGERY – for lesions that can be technically removed completely Limitations are: 1. inadequate removal of the gross tumor, leading to a local recurrence 2. inadequate resection of microextensions in tissues adjacent to gross tumor. 3. undetected metastasis to regional lymph nodes 4. systemic micrometastases

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER B. RADIATION THERAPHY – for localized lesions in which surgery may cause anatomically or physiologically undesirable sequelae and for more extensive lesions not amenable to a surgical resection Limitations are: I. Tumor cell burden a. inadequate depopulation of clonogens in the primary tumor which may cause local recurrence b. regional microextensions or metastasis to lymphatics which may not be included in the irradiated volume may cause a recurrence c. clinically unapparent distant metastasis at the time of initial therapy

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER II. Physical and technical factors a. inaccurate tumor localization because of the oncologist inability to define the target volume adequately( geographic miss ) b. inadequate treatment planning, which may result in non-homogenous doses of radiation throughout the target volume c. unreliable daily irradiation techniques, which may result in poor positioning and immobilization (inaccurate treatment)

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER III. Biologic factors a. Hypoxic cell subpopulation which require higher doses of radiation than well oxygenated cells for the same level of cell kill b. Repair of sublethal or potentially lethal damage after irradiation c. Position of the cell in the proliferative cycle. Cells in the late G1 or S phase are more resistant to irradiation than are cells in other portions of the cycle. Cells in the G0 are also more resistant to irradiation than are rapidly proliferating cells

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER d. Tumor cell repopulation during fractionated therapy or after completion of therapy e. Limited tolerance of the surrounding normal tissues to irradiation, thus precluding the delivery of higher doses 3. CHEMOTHERAPY – used in several settings ADJUVANT – to eradicate microscopic metastases or tumor cell dissemination outside the operated or irradiated volume

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER NEOADJUVANT – to reduce the initial tumor cell number before definitive surgery or irradiation or both and potentially to decrease the viability of micrometastases DEFINITIVE THERAPY – in tumors that are chemosensitive and can be controlled with cytotoxic agents alone PALLIATIVE – in the treatment of systemic macrometastases or to relieve symptoms in patients with chemosensitive tumors

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER

Limitations are: I. Pharmacodynamics factors: a. decreased drug diffusions because of abnormal vasculature in the tumor b. decreased drug incorporation and use in the cell II. Biologic factors a. Tumor cell burden – chemotherapy is more effective against a smaller number of tumor cells b. Proportions of clonogenic cells – cytotoxic agents are more effective in proliferating cells and less efficacious in cell with low proliferative activity

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER II. Biologic factors c. Variation of cell sensitivity to drugs throughout the proliferative cell cycle. Some drugs are phase specific ( killing or arresting dividing cells during specific phase of cell cycle such as DNA synthesis), cycle specific (killing proliferating cell more effectively than resting cells) or nonspecific ( equally toxic for resting cycling cells d. Chemoresistance – some cells that initially respond to chemotherapy may later be affected less or not at all by the same drug or combinations, even at a higher dose

MODALITIES TRADITIONALLY USED IN THE MANAGEMENT OF PATIENTS WITH CANCER II. Biologic factors e. mode of administration and timing of administration of one drug in relation to the other, may allow for tumor cell synchronization or sensitization of the tumor cell to the effects of other drugs f. Dose of chemotherapy and frequency of administration – the frequency of administration or higher doses of chemotherapy have a substantial impact on the induction and maintenance of tumor regression

COMBINATION OF THERAPEUTIC MODALITIES IRRADIATION AND SURGERY The following tumors are indications for combined surgery and radiation therapy: 1. tumors with low cure rates by either surgery or radiation therapy alone 2. tumor with great potential for local or regional recurrence 3. tumor with great potential for residual disease after surgery 4. tumors with great potential for lymphatic invasion 5. for preservation of function and the enhancement of cosmesis

RATIONALE FOR PREOPERATIVE RADIATION THERAPY 1. 2. 3. 4. 5.

Its potential ability to eradicate subclinical disease beyond the margins of the surgical resection To diminish tumor implantation by decreasing the number of viable cells within the operative field To sterilize lymph node metastases outside the operative field To decrease the potential for dissemination of clonogenic tumor cells that might produce distant metastases To increase the possibility of resectability

DISADVANTAGE OF PREOPERATIVE IRRADIATION - It may interfere with normal healing of tissues affected by the radiation. ( interference is minimal if radiation doses are below 4500 cGy to 5000 cGy in 5 weeks)

RATIONALE FOR POSTOPERATIVE RADIATION - Based on the facts that it is possible to treat any residual tumor in the operative field by: a. destroying subclinical foci of tumor cells following the surgical procedure b. by eradicating adjacent subclinical foci or cancer ( including lymph node metastases) c. by delivering higher doses than can be achieved with preoperative irradiation – the greater dose being directed to the volume of high risk or known residual disease. Disadvantage: - related to the delay imposed on the initiation of radiation therapy until wound healing is complete - vascular changes produce in tumor bed by surgery may impair radiation effect

IRRADIATION AND CHEMOTHERAPY

- The effects of combined radiation therapy and chemotherapy can be described as independent, additive or interactive - Administration of chemotherapy before radiation therapy produces some cell kill and reduction in the number of cells to be eliminated by the irradiation - use of chemotherapy during radiation therapy has a strong rationale because it could interact with the local treatment ( additive and even supra-additive action) and could also affect subclinical disease early in treatment - Chemotherapy after radiation therapy as an adjuvant has been used primarily for control of subclinical disease

INTEGRATED MULTIMODALITY CANCER MANAGEMENT - Combination of two or even all modalities frequently are used to improve tumor control and patient survival - Steel postulated the biologic basis of cancer therapy as : a. spatial cooperation – in which an agent is active against tumor cells spatially missed by another agent b. addition of anti-tumor effects by two or more agents c. non-overlapping toxicity and protection of normal tissues

RADIATION ONCOLOGY - a clinical and scientific endeavor devoted to: a. management of patients with cancer ( and other disease) by ionizing radiation, alone or combined with other modalities b. investigation of the biologic and physical basis of radiation therapy c. training of professionals in the field

RADIATION THERAPY - a clinical specialty dealing with the use of ionizing radiation in the treatment of patients with malignant neaplasia ( and occasionally benign conditions) - Often use in combination with chemotherapy and surgery - Its goal is to deliver with accuracy a precisely measured dose of radiation 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 at a reasonable cost - it is generally assumed that 50-60 % of cancer patients will benefit from radiotherapy

MAJOR INDICATIONS FOR RADIOTHERAPY 1. Head and neck cancers 2. Gynecological cancers ( eg. Cervix) 3. Prostate CA 4. Other pelvic malignancies ( rectum, bladder) 5. Adjuvant breast treatment 6. Brain Cancer 7. Palliation

TREATMENT APPROACHES IN RADIOTHERAPY 1. CURATIVE TREATMENT – to obtain complete durable remission; it is projected that the patients has an expected probability of surviving after adequate therapy even if that chance is low a. radiotherapy is the sole agent with curative intent for anatomically limited tumors of the retina, optic nerve, brain, spinal cord, nasopharynx, etc. b. radiotherapy is combined with surgery for more extensive cancers of the head and neck, lungs, breast, testis, etc. c. radiotherapy is an adjuvant to chemotherapy for some patients with lymphomas, lung cancer and cancer in children

TREATMENT APPROACHES IN RADIOTHERAPY 2. PROPHYLACTIC TREATMENT – this consists of irradiation of macrocospically uninvolved areas which are thought to be the site of occult subclinical localizations a. radiotherapy to the regional, clinically uninvolved lymphatic chains after surgery and/or radiotherapy to the primary tumor. b. radiotherapy to the lymphatic chains, the spleen and the brain in the absence of clinically evident lesions in malignant lymphomas

TREATMENT APPROACHES IN RADIOTHERAPY 2. PROPHYLACTIC TREATMENT c. radiotherapy after macroscopically radical surgery for locally advanced cancers at a high risk of local relapse d. radiotherapy to the brain when the primary cancer has a high risk of spreading to the brain (eg. Small cell lung CA ) 3. PALLIATIVE TREATMENT – limited intent of improving the patient’s quality of life and prolonging his survival a. allow for a symptom-free period appreciably longer than the debilitation cause by the irradiation treatment period

TREATMENT APPROACHES IN RADIOTHERAPY 3. PALLIATIVE TREATMENT b. prolong useful or comfortable survival so that other factors might lead to death c. relieve distressing symptoms although survival may not be prolonged d. avert impending symptoms such as hemorrhage, perforation, obstruction etc.

RATIONALE OF RADIATION THERAPY IN METASTATIC DISEASE 1. Relieve severe pain 2. Control hemorrhage 3. Prevent impending pathologic fracture 4. Reverse spinal cord compression before transection takes place 5. Alleviate superior vena cava syndrome 6. Relieve symptoms and disability from brain metastases 7. Prevent obstruction 8. Halt destruction of an organ

A COMPARISON OF MAIN MODALITIES OF RADIOTHERAPY -

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BRACHYTHERAPY Administration of radiation therapy by applying a radioactive material inside the patient or in close approximation to the patient Dose outside the treatment volume can be minimized

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TELETHERAPY Delivery of radiation treatment to the patient from a machine located remote from the body

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Dose outside the treatment volume will in general be greater than in brachytherapy

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Inside the treatment volume, the dose is necessarily non-uniform and dose gradients are often high

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Any required degree of dose uniformity can in principle be achieved inside the treatment volume

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Normally limited to accessible sites, either near the surface of the body or near natural cavities but any volume may be treated using complex array of sources

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No physical limitations to the size of volume that can be treated

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Dose rates are usually relatively low

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Dose rates are usually relatively high

TYPES OF TELETHERAPY 1.

Conventional Roentgen Therapy – consist of the use of x-rays produced by equipment functioning with voltages up to 400 kv a. short distance roentgen therapy – 3-5 cm using voltages form 50-60 Kv b. middle distance roentgen therapy – 15-30 cm using voltages greater than 100 Kv c. deep roentgen therapy – uses voltages from 250-400 Kv

TYPES OF TELETHERAPY 2. External Radiotherapy with high energy photons – most commonly used method for irradiation of deep and semi-deep seated tumors a. Cobalt 60 teletherapy unit b. linear accelerators 3. External Radiotherapy with fast electrons a. Betatrons – up to 45 Mev b. Linac – up to 25 Mev

TYPE OF EQUIPMENTS AND THEIR ENERGY RANGE 1. Superficial x-ray 10 Kv – Grenz Ray 40-140 Kv – superficial 2. Orthovoltage 250 Kv – Deep X-ray; 600 Kv – Radioisotope Teletherapy ( Cs-137) 3. Supervoltage or Megavoltage 2 Mev – Radioisotope Teletherapy ( Co-60) 4-6 MV – low energy Linear accelerator 18-20 MV – high energy Linear accelerator 15-25 MV – dual mode Linear accelerator

AVANTAGES OF TELECOBALT UNITS AND MEGAVOLTAGE GENERATORS OVER ORTHOVOLTAGE 1. Better depth doses – more efficient tumor treatment 2. Less side effects – less radiation sickness 3. No differential absorption by bone – more uniform dosage 4. Skin sparing effects – only skin radiation dermatitis

ELECTRONS BEAMS CAN BE USED IN THE PRINCIPAL TREATMENT OF THE FF: 1. Malignant tumors of the skin and lip 2. Chest wall, neck and brain cancers ( used electrically after radical or conservative surgery or with recurrent disease) 3. Upper respiratory or digestive tract lesion form 1cm to 5cm in depth 4. Lymph nodes, operative scars and residual tumor

TYPES OF BRACHYTHERAPY 1. Interstitial Brachytherapy – this consist of the introduction of variously shaped radioactive sources ( needle, wire, seeds) into the tissue at or near the tumor site. It is used to treat tumors of head and neck, prostate, cervix, ovary, breast, perianal and pelvic region 2. Endocavitary Brachytherapy – this consist of the introduction of radioactive sources contained in “applicators” or in molded devices inside natural, pathological or operative cavities. It is commoly used to treat uterine cancer; researchers also used this for breast, bronchial, cervical, gallbladder, oral, rectal, tracheal, uterine and vaginal cancers

TYPES OF BRACHYTHERAPY 3. Contact Brachytherapy – this consist of the application through direct contact to the skin surface or other sites ( cornea, external mucous membrane) of radioactive sources ( usually beta-emitting) for the treatment of very superficial neoplasms

TELETHERAPY SOURCES UNIT

150-440 Kvp xray Cesium 137 Cobalt 60 4 MV Linac 6 MV Linac 20-24 MV Betatron and Linac

MEAN ENERGY PHOTONS(MeV)

0.06-0.14 0.66 1.25 1.3 1.8 6.2-7.0

BRACHYTHERAPY SOURCES Half Life

Effective Energy (Mev)

Radium 226 Cesium 137 Iridium 192 Iodine 125 Gold 198

1620yrs 30 yrs 74days 60day 2.7 days

1.2 0.66 0.34 0.027 0.41

THE EFFECTS OF RADIATION ON THE BODY DEPENDS ON: 1. 2. 3. 4.

The volume of tissue irradiated The anatomical site irradiated The radiation dose delivered The rate at which the radiation is delivered 5. Dose fractionation

IRRADIATION FRACTIONATION REGIMEN 1. Conventional fractionation – consist of daily fractions of 1.8 to 2.0 Gy 5 days a week; total dose is determined by type of tumor and tolerance of critical normal tissues.( usually 60 to 75 Gy) 2. Hyperfractionation – uses increased total dose, numbers of fractions is increased, dose per fraction is reduced and overall time is unchanged. 3. Quasi – hyperfractionation – same as hyperfractionation except that total dose is not increased. 4. Accelerated fractionation – overall time is reduced, the number of fractions, total dose and dose per fractions are unchanged or reduced. 5. Quasi – accelerated hyperfractionation – same as accelerated fractionation except the overall time is not reduced because of treatment interruptions

Radiological factor Radiosensitivity

Repair

Mechanism of effect on response Intrinsic

Clinical relevance

Can account for radiosensitivity variable response differs between of tumors. cells of tumors and Curative dose is normal tissue proportional to the types, and strongly log of cell number determines final (so subclinical surviving Cells differfractions in their disease Repair isneeds maximal smaller dose) capacity to repair in late-responding DNA damage, tissues given small particularly after fractions. small doses of Hyperfractionation radiation. may be Repair is usually advantageous . more effective in Treatments need to non-proliferating be well separated cells. The repair in order to avoid

Radiological factor Repopulation

Reoxygenation

Mechanism of effect on response Surviving cells in many tumors and in acuteresponding (but not in lateresponding) normal tissues proliferate more rapidly Hypoxiconce cells, treatment is in which occur progress especially in

Clinical relevance Shortened treatment times (accelerated therapy) may be advantageous for some tumors. Acute (but not late) effects will be increased. Very short Gaps should be avoided treatment times

could lead to tumors, are resistance due to relatively resistant persistence of to radiation. hypoxic cells Hypoxic surviving cells reoxygenate,

Radiological factor Redistribution

Mechanism of effect on response Cells in certain

Clinical relevance

Closely spaced phases of the treatment proliferative cycle fractions could (e.g. late S) are lead to resistance relatively resistant due to persistence and survive of cells in less preferentially. sensitive phases With time between fractions, cells redistribute themselves over all phases of the cycle

TREATMENT PLANNING OBJECTIVE: To achieve a dose distribution inside the volume to be treated(target volume) which is uniform within ±5% of the prescribed dose while limiting the dose to adjacent regions to below tolerance levels 1. Tumor localization and assessment of volume of tissue to be irradiated 2. Choice of radiation quality and selection of treatment machine 3. Selection of radiation dose and dose-time relationship 4. Selection of radiation field arrangement and any necessary beam shaping devices 5. Calculation of radiation dose distribution and daily treatment time 6. Manufacture and use of devices to ensure accurate localization of treatment field and accurate and easily reproducible set-up from day to day 7. Preparation of radiotherapy prescription

THE PRESCRIPTION OF RADIATION IS BASED ON THE FOLLOWING PRINCIPLES 1. Evaluation of the full extent of the tumor (staging) by whatever means available including radiographic, radioisotope and other studies 2. Knowledge of the pathologic characteristic of the disease including potential areas of spread that may influence choice of therapy ( that is the rationale for elective irradiation of the lymphatics in the neck or the pelvis) 3. Definition of goals of therapy (cure vs palliation) 4. Selection of appropriate treatment modalities which may be irradiation alone or combined with surgery, chemotherapy or both

THE PRESCRIPTION OF RADIATION IS BASED ON THE FOLLOWING PRINCIPLES 5. Determination of the optimal dose of radiation and the volume to be treated which is made according to the anatomic location, histologic type, stage and other characteristics of the tumor and the normal structures present in the region 6. Periodic evaluation of the patients general condition, tumor response and status of the normal tissues treated

CURATIVE DOSES OF RADIATION FOR DIFFERENT TUMOR TYPES 2000-3000 cGy Seminoma Dysgerminoma Acute Lymphocytic Leukemia 3000-4000 cGy Seminoma (bulky) Wilm’s tumor Neuroblastoma 4000-4500 cGy Hodgkin’s disease Lymphosarcoma Histiocytic cell sarcoma Skin Cancer( basal cell)

CURATIVE DOSES OF RADIATION FOR DIFFERENT TUMOR TYPES 5000-6000 cGy Lymph nodes, metastatic (No,N1) Squamous Cell CA, cervix CA, head and neck CA Embryonal CA, Ewing tumor, Breast CA (excised) Breast CA, Ovarian CA, Medulloblastoma, Retinoblatoma 6000-6500 cGy Larynx (< 1cm) Breast cancer( T1)

CURATIVE DOSES OF RADIATION FOR DIFFERENT TUMOR TYPES 7000-7500 cGy Oral cavity ( <2cm, 2-4cm) Oro-naso-laryngo-pharyngeal CA Breast CA(T2), Bladder CA, Cervix CA, Uterine fundal CA Ovarian CA, Lymph nodes, metastatic (1-3cm), Lung CA (<3cm) 8000 cGy or above Head and Neck CA (>4cm), Breasts CA (>5cm), Glioblastoma, Osteogenic sarcoma, Melanomas, Soft tissue sarcomas(>5cm), Thyroid CA, Lymph nodes, metastatic (>6cm)

RESPONSE TO TREATMENT 1. Complete remission – no clinically detectable cancer is formed following treatment 2. Partial remission – measurable tumor is decreased by 50% following treatment; no new area of cancer can be found and no area of tumor shows progression 3. Minimal remission – same as partial remission but not meeting the criteria of 50% reduction 4. Progression – increased of tumor mass by more than 25%; appearance of new lesions or tumorinduced death 5. Stable disease – measurable tumor does not meet the criteria for CR, PR, MR, or progression

CAUSES OF FAILURE IN RADIATION THERAPY 1. Error of judgment eg. – wrong diagnosis – wrong treatment - failure to detect metastasis before exposing the patient to radical treatment for the primary tumor 2. Error of Omission eg. – failure to give an adequate level of dosage 3. Error of Commission eg. – habitual use of a poor technique will in time be reflected in a lower cure rate than might have been expected - error in dose calculation - badly positioned xray applicator which can lead to the so called “ geographic miss” with an inevitable result of failure to control growth

POSSIBLE SPECIFIC SEQUELAE OF THERAPY ANATOMIC SITE

ACUTE SEQUELAE

LATE SEQUELAE

BRAIN

Earache, headache, dizziness, hair loss, erythema

Hearing loss, damage to middle or inner ear, pitiutary gland dysfunction, cataract formation, brain necrosis

HEAD AND NECK

Odynophagia, dysphagia, hoarseness, xerostomia dysgeusia, weight loss

Subcutaneous fibrosis, skin ulceration, necrosis, thyroid dysfunction, persistent hoarseness, dysphonia, xerostomia, dysgeusia, cartilage necrosis, osteoradionecrosis of mandible, delayed wound healing, fistula, dental decay, damage to middle &inner ear, apical pulmonary fibrosis rare: myelopathy

LUNGS AND MEDIASTINUM OR ESOPHAGUS

Odynophagia, dysphagia, hoarseness,cough, pneumonitis, carditis

Progressive fibrosis of lung, dyspnea, chronic cough, esophageal stricture, rare: chronic pericarditis, myelopathy

BREAST OR CHEST WALL

Odynophagia, dysphagia, hoarseness, cough, pneumonitis, carditis, cytopenia

Fibrosis, retraction of breast, lung fibrosis, arm edema, chronic endocarditis, MI, rare:osteonecrosis of ribs

ABDOMEN OR PELVIS

Nausea, vomiting, abd. pain, diarrhea, urinary frequency, dysuria, nocturia, cytopenia

Proctitis, sigmoiditis, rectal or sigmoid stricture, colonic perforation or obstruction, contracted bladder, urinary incontinence, hematuria due to chronic cystitis

Vesicovaginal fistula,rectovaginal fistula,leg edema, scrotal edema, sexual impotency,vaginal retraction,or scarring,sterilization,d amage to liver or kidney

EXTREMITIES

Erythema, dry/moist desquamation

Subcutaneous fibrosis, ankylosis, edema, bone/soft tissue necrosis

OTHER METHODS OF TREATMENT I. INTRAOPERATIVE RADIATION THERAPY - a form of external radiation that is given during surgery - it is used to treat localized cancers that cannot be completely removed or that have a high risk of recurring in nearby tissues - one large high energy dose of radiation is aimed directly at the tumor site during surgery(nearby healthy tissue is protected with special shield - it is costly, time consuming procedure because of the necessity of combining the operating room’s sterile technique with the high energy equipment in a shielded room. - it may be used in the treatment of thyroid and colorectal cancers, gynecological, small intestinal and pancreatic cancers - its is also being studied in clinical trials to treat some types of brain tumor and pelvic sarcomas in adults

OTHER METHODS OF TREATMENT II. STEREOTACTIC RADIOSURGERY - uses a stereotactic frame, a radiation delivery system computer hardware and treatment planning hardware - the patient head is placed in a special frame, which is attached to the patients skull. The frame is used to aim high-dose radiation beams directly at the tumor inside the brain - it is often performed on outpatient basis and is a time consuming process involving the placement of the stereotactic frame determination of target size and location and treatment planning and treatment delivery

OTHER METHODS OF TREATMENT This can be done in 3 ways: 1. Linac based stereotactic radiosurgery – uses a linear accelarator to administer highenergy photon radiation to the tumor 2. Gamma knife – uses Cobalt 60 to deliver radiation 3. Heavy charged particle beam therapy – uses protons and helium ions to deliver radiation Indications: the presence of a suitable size( generally less than 4 cm) radiographically distinct lesion that has potential to respond to a single large dose of radiation

- the largest worldwide experience has been in to treatment of arteriovenous malformations - Low grade and high grade gliomas - 2nd most common indication is primary or secondary treatment of brain metastasis ( up to 3 brain metastases) - Middle fossa meningiomas - Acoustic neurinomas STEREOTACTIC RADIOTHERAPY - Uses essentially the same approach as stereotactic radiosurgery to deliver radiation to the target tissue - However, it uses multiple small fractions of radiation as opposed to one large dose - Giving multiple smaller doses may improve outcome and minimizes side effects - Is used to treat tumors in the brain as well as other part of the body

III. TOTAL BODY IRRADIATION - has been used as a form of systemic therapy for various disease Indications: 1. a. patients with autoimmune disease - <2 Gy given as single fraction b. allogenic bone marrow transplantation - >9.5 Gy if used alone to prevent graft rejection c. patient with aplastic anemia for bone marrow transplantation – single dose of 3 Gy in conjunction with cyclosphosphamide to reduce the probability of graft rejection 2. Low-Dose Systemic Therapy for Chronic Lymphocytic Leukemia and Non-Hodgkins Lymphoma – 0.05 to 0.15 Gy 2x to 5x a week for leukocystosis 3. High-Dose Cytoreductive Therapy before bone marrow or Peripheral blood Stem Cell transplantation – 1.2 Gy 3x/day with partial lung blocks

HEMIBODY IRRADIATION (HBI) - Was developed as a method to treat patients with disseminated tumors involving multiple sites - Line passing across the bottom of L4 is commonly used to separate upper and lower HBI - Most effective dose were: 6 Gy for upper HBI, 8 Gy for lower and middle HBI with 80% pain improvement in 1 week - Comparing HBI added to local irradiation with local radiation therapy alone. Studies showed that adjuvant single dose HBI: a. delayed the progression of existing disease b. reduced the frequency of new disease c. delayed as well as reduced the need for retreatment

NONSEALED RADIONUCLIDE THERAPY -

Use of radioactive materials which may be taken by mouth or injected into the body ( SYSTEMIC RADIATION THERAPY) Currently approved non-sealed radionuclide sources are: 1. Sodium iodine (131I)- treatment of hyperthyroidism ( diffuse toxic goiter, toxic multinodular goiter, solitary toxic thyroid nodule) - definite adjuvant therapy and palliation of same thyroid carcinomas (papillary, follicular) 2. Sodium phosphate (32P)- treatmentj of myeloproliferative disorders such as polycythemia vera and thrombocytosis

NONSEALED RADIONUCLIDE THERAPY 3. Colloidal chromic phosphate (32P)- intracavitary therapy for malignant ascitis, malignant effusion, brain cysts 4. Samarium (153Sm)- palliation of painful bone metastases 5. Strontium chloride (89Sr)- palliation of painful bone metastases

OTHER METHODS TO IMPROVE EXTERNAL RADIATION THERAPY I.

THREE DIMENSIONAL CONFORMAL RADIATION THERAPY - uses computer technology to allow doctors to more precisely target a tumor with radiation beams (using width, height and depth) - A 3-D image of a tumor can be obtained using CT scan, MRI etc. - using information from the image, special computer programs design radiation beams that “conforms” to the shape of the tumor. Because the healthy tissue surrounding the tumor is largely spared by this technique, higher doses of radiation can be used to treat the tumor - improved outcomes have been reported for nasopharyngeal, prostate, lung, liver and brain cancers

OTHER METHODS TO IMPROVE EXTERNAL RADIATION THERAPY II. INTENSITY MODULATED RADIATION THERAPY ( IMRT) - A new type of 3-D conformal radiation therapy that uses radiation beams (usually X-rays) of varying intensities to deliver different doses of radiation to small areas of tissue at the same time - The technology allows for the delivery of higher doses of radiation within the tumor and lower doses to nearby healthy tissue - Some techniques deliver a higher dose of radiation to the patient each day potentially shortening the overall treatment and improving the success of treatment

OTHER METHODS TO IMPROVE EXTERNAL RADIATION THERAPY II. INTENSITY MODULATED RADIATION THERAPY ( IMRT) - The radiation is delivered by a linear accelarator that is equipped with a multileaf collimator ( a collimator that helps to shape or sculpt the beams of radiation) - The equipment can be rotated around the patient so that radiation beams can be sent from the best angles - This new technology has been used to treat tumors in the brain, head and neck, nasopharynx, breast, liver, prostate and uterus

FLOW CHART OF FUNCTIONS IN RADIATION THERAPY Clinical evaluation and staging, e.g. TNM Treatment intent: radical or palliative Choice of treatment: surgery, radiotherapy, chemotherapy

FLOW CHART OF FUNCTIONS IN RADIATION THERAPY Description of treatment Method of patient immobilization Image acquisition of tumor and patient data for planning Delineation of volumes (GTV, CTV, PTV) Choice of technique and beam modification Computation of dose distribution

FLOW CHART OF FUNCTIONS IN RADIATION THERAPY Dose prescription Implementation of treatment Verification Monitoring treatment Recording and reporting treatment

Evaluation of outcome

Squamous cell CA of the balanopreputial region with extension into the glands. Patient was treated with 120kVp xray, 0.3-mmCu half-value layer, receiving skin dose of 6000 cGy in 5 weeks

Same patient 4 years later with no evidence of disease

Patient with a 4 cm epidermoid Ca in the labia and clitoris

Portal used to deliver external irradiation to treat the pelvis and vulvar areas to 5000 cGy. Bolus was used over right inguinal areas

Posttreament photograph 3 years later shows excellent cosmetic results. Patient is tumor free

Patient with squamous cell CA of the ear

External mould used with a high-dose rate remote control afterloading device.

Posttreatment photograph showing complete tumor-regression and satisfactory cosmetic results

Medial tangential portal

Lateral tangential portal

AMDG (ad majorem de glorium)

the end