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Radiotherapy
Presented by: Dr. Nikil Jain
contents
Introduction
The Basis of Radiotherapy
Radiation Techniques
Side effects of radiotherapy
Future Development in Radiotherapy
What is Radiotherapy
Use of ionising radiation to treat cancers
Source of ionising radiation : Natural : Uranium,
Plutonium, Radium Cobalt, Iodine, Gold, Iridium
Man made : LINAC, cyclotrons
Introduction1898 - Roentgen discovers x-rays1903 - Gruber treats Ca Breast with radiotherapy1950 - Cobalt teletherapy
- Gamma knife1970 - LINAC1990 - “Conformal RT techniques”
- Stereotactic Radiotherapy- 3D conformal RT- Inverse treatment planning- cyberknife, - intra-operative RT- chemo-RT- altered fractionation
Role of RT
50% of all Ca will require RT
2/3 of these for curative intent
Curative Role : Head and Neck Ca Ca Cervix Anal and skin Ca Prostate Ca Bladder Ca Early Lung Ca Early Ca Oesophagus Seminoma Hodgkin’s disease and NHL Medulloblastomas and some brain
tumours
How are x-rays produced?
Natural : radioactive decay
Man-made : sudden deceleration of high speed electrons when it hits a tungsten target
Biological Effects of RT
1. RT causes “ionization” in tissue
2. This forms “free radicals”
3. Free radicals - interact and damage DNA
4. During mitosis, abnormal DNA unable to
replicate, causing cell death
Cellular Effects of Radiation
Inhibition of specific biochemical processes in
cells (eg respiration, protein synthesis)
require very high doses (10-100Gy)
Chromosomal aberrations (1Gy)
Inhibition of reproductive ability :< 10Gy - divide a few times> 20Gy - lyse without entering mitosis
Interaction of RT and Matter Direct action
direct interaction with critical targets in cells
Indirect actionreacts with H20 to form free radicalfree radical highly reactivefree radicals diffuse to DNA- produce damage to DNA
biological effects results
Biological Effects of RT DNA strand breaks
Breaks in the chromosomes
results in - restitution (rejoin)
- aberration (fail to rejoin)
- rejoin other broken ends (give rise to gross
distortion)
Outcome of Radiation Damage
Cell survives
Cell dies - mitotic cell death
- intermitotic death
(lymphocytes, ova, salivary
gland cells)
Cell repairs - given time, energy and
nutrientsItself
Chromosome aberrations in human lymphocytes
Used as biomarkers of radiation exposure
Blood samples taken within days-weeks
Lymphocytes stimulated to divide and
incidence of dicentrics and rings is scored
Dose can be estimated by comparing with in-
vitro cultures exposed to known doses
repair Radiation results in : lethal damage - ie
irreversible sublethal damage - ie can be repaired unless 2nd dose of RT
repair - because of shoulder in cell survival curve
repopulation When RT administered, some cells die,
some cells repair or escape damage with time these cells will replicate and
replace or repopulate the dead cells if the rate of repopulation exceeds the rate of cell
death, then the tumour will grow despite treatment thus repopulation
good for normal tissue bad for tumour
fractionation Allows repair of normal tissue Allows repopulation of normal tissue
Allows re-oxygenation of tumour Allows re-assortment
But
Allows repair of tumour Allows proliferation of tumour
Treatment plan is based on
Staging of disease using TNM classification
age of patient
co-morbid conditions-MedicalDentalSpeechNutritionPsychosocialSocioeconomic
Treatment Options
Primary surgery
Adjuvant Radiotherapy
Concurrent Chemotherapy
OR Primary Radiotherapy
Concurrent Chemotherapy
Surgery for Salvage
+/-
+/-
+/-
+/-
No treatment
Palliation
Radiation therapy is indicated following surgery if:soft tissue margin positiveone or more lymph nodes exhibit
extracapsular invasionbone invasion presentmore than one lymph node positive in the
absence of extracapsular invasioncomorbid immunosuppressive disease
present, or perineural invasion occurre
Aims of radiation Deliver a precise dose of radiation to a
defined tumor volume with as minimal damage as possible to surrounding normal tissues
- Eradication of the tumor- Improvement of quality of life- Prolongation of survival
Terms used in Radiotherapy Gray is Radiation Absorption Dose in the
medium= RAD 1 Gy = 100 rads 1 cGy = 1 rad Field or portal = The name of the radiation
beam entering thro’ the anatomical site of body. Eg) Rt lateral, Lt lateral face portals
DIFFERENT TYPES OF RADIOTHERAPY External beam therapy Brachytherapy Combined external beam and interstitial
brachytherapy Modification of tumor hypoxia Modified radiation fractionation Combined chemotherapy/radiotherapy Combined modified radiation fractionation
and simultaneous chemotherapy Intensity modulated radiotherapy or IMRT
Process of radiation oncology Clinical evaluation- Pathology- Staging work up- Patterns of spread and failure Therapeutic decision:goal of therapy- Curative:definitive,neoadjuvant or adjuvant- Palliative Selection of therapeutic modalities- Integration with surgery(pre op or post op)- Integration with chemotherapy Periodic evaluation (during treatment) and follow-
up- Careful assessment of acute and late toxicity
Pt-Radiation Processing Decision made for Treatment Consent CT Simulation with markers From CT Scan CT cuts are exported to TPS In TPS ,target volume/ critical structures are
contoured by Oncologists Medical physicist plans for RT with TPS Once plan is ready- for approval by Oncologist Plan exported to workstation Treatment setup done Setup verification done thro Portal Vision Treatment delivered Documentation
Treatment Machines Tele Cobalt-60 Cobalt 60- Gamma rays Capital Investment less Useful in most Practical Situations. Easy Installation Few Staff required Maintenance/Repair Easy Medical Linac Electrically Driven Investment more Sharper Beams. Higher tissue penetration Technically Superior Can produce Electron beams ,used to treat Neck nodes.
Medical Linac Electrically Driven Investment more Sharper Beams. Higher tissue penetration Technically Superior Can produce Electron beams ,used to treat
Neck nodes.
Medical Linear Accelarator
Linac Treatment Options X- Rays : Simple Complex 3D Conformal IMRT Electrons : In Head & Neck for LN, any Skin Cancers,Recurrence
IMRTIMRT Intensity modulated radiotherapy
Advanced form of 3D - conformal radiotherapy
based on the use of optimised non uniform beam intensities
determined by computer-based optimisation techniques (Inverse planning)
Clinical Processing for IMRT
Aquaplast Face Mask
Intra Oral Cone therapy Localized radiation technique More suitable for anteriorly located lesions RT by Intra oral cones uses 250 KeV x rays or
Electron beams Indications same like Brachytherapy Used after Ext Beam RT
Interstitial Brachytherapy Depends upon volume of growth. May be single plane,double plane, volume
implants. 0.5 – 1.0 cm margin around the growth. Stainless steel needles or after loading
catheters used for this. LDR (Caesium ) or HDR (Iridium) isotope used
thro after loading catheter.
• How much?
• Where?
Radiation dosimetry
1 “rad” = 1 centiGray (cGy)
200 cGy per day 5 days per week 1000 cGy per week Total dose ranges from 6000 cGy – 7000 cGy
6 – 7 WEEKS of treatment
Dental Care and Radiation Dental care should be a comprehensive part Evaluation before RT For dental carries Teeth Extn before RT RT will be delayed for 2 weeks after Extn. Sound teeth or teeth in good repair need not
be sacrificed. Post RT dental Extn possible with antibiotic
coverage,but better avoided within short period
Treatment Recommendations Lip Cancers T1 N0 :Surgery or RT if commissural
involvement or poorly different. Cancers T2 N0 :Surgery or RT Post op RT if margin +ve ; node +ve T 3-4 N0: Surgery ? Cosmetic/Functional
Outcome Post op RT +/- Chemo if +ve margin; node
+ve Alternatively Concomitant Chemo+RT first
and Surgery for Salvage.
T 1-4 Any N :Surgery +/- Contra lateral ND Post Op Chemo RT as indicated Margin + ve ; Margin close Node(s) + ve ; Poorly Different.Cancers Lympho Vascular Space invasion
Treatment Recommendations Floor of mouth Cancers T1 N0 : Surgery or RT +/- Brachytherapy Post
op RT as indicated . T2 N0 ,T3N0(Resectable):Surgery Post op Chemo RT as indicated. T1-4 N+ :Surgery Post op Chemo RT as indicated Locally advanced –unresectable Chemoradiation first Surgery for salvage
Treatment Recommendations Oral Tongue Cancers T1 & Early T2 N0:Surgery or RT In both Neck Treatment is required Post op RT as indicated Large T2 N0: Surgery Post Op Chemo RT If inoperable -Definitive RT T3-4 N0 or T1-4 N+ :Surgery Post op Chemo RT Alternatively Chemo RT first Surgery for Salvage if any nodes or residual
primary disease.
Treatment recommendation buccal mucosa External beam therapy most commonly used
for T1 and T2 tumors
Larger T3 and operable T4 tumors are more approptietly treated with surgery and post operative RT.
Treatment modalities lower alveolar mucosaClose proximity to underlying mandible ,bone
invation occurs
T1 and T2 tumors most frequently treated with external beam therapy
Extensively advanced tumor with more extensive require surgery and postoperative radiotherapy to include prophylactic lymphnode iiradiation
Treatment modalitiesretromolar trigone T1 and T2 Tumors can be effectively treated
with external beam therapy
Important to include ant. border of ramus and ptrygoid fossa superiorly to skull base with elective irradiation to ipsilateral lymphnode drainage
More advanced tumor require surgery followed by radiotherapy
Post op rt
Advantages- Benefit of pathology,surgical findings Better staging,no need to over treat
Disadvantages Larger RT fields to cover surgical bed Poorer blood suply – RT less effective More late morbidity
Pre-op RT
Advantages -Downstage tumour, less multilating
surgery-Sterilise surgical margins-Remove RT damaged parts during surgery
Disadvantages- Clinical staging, therefore treat some unnecessary-What if tumour not sensitive to RT?-May increase surgical morbidity
What Happens To A Patient Undergoing RT
Acute sequale General- Weight loss - Nausea - Fatigue- Depression Extra-Oral Intra-Oral- Cutaneous burns mucositis- Alopecia erythema- Xeroderma ulceration
Side Effects of RT
Epidermal layers of skin, GIT - fast turnover Thus RT kills the epidermal layers as they go into
mitosis Lower layers insufficient time to repopulate Thus de-sloughing occurs :-
-skin : erythema, dry then moist desquamation “sun burn”
-mucosa : mucositis, oesophagitis, gastritis, colitis proctitis, cystitis
- marrow : pan-cytopaenia
Side effects of RT to head & neck Xerostomia
From day 1 - Pilocarpine 5-10mg tid - Saliva substitutes (oral balance) - Ethyol (amifostine)
Serous component of saliva affected most often
-Bicarbonate mouth rinses
Mucositis
direct mucosal (basal layer) damage secondary infectionTreatment
- good oral hygiene- anti-fungals- salt water rinses- pain killers, steroids- lidocaine- soft diet- avoid spices, smokes, spirits
Hypoalimentation
nutrition counselling enteral feeding appetite stimulants (Megace,
anabolic steroids)
Skin Reactions
Erythema Dry desquamation (peeling)
hydrocortisone 1%
Moist desquamation (dermis exposed and oozes serum) gentian violet paraminol cream healing within 2-4 weeks after RT
Sialadenitis 5% develop it within 12 hrs of
1st RT transient painless enlargement
of salivary gland usually disappears within a week
despite continuation of treatment
Skin reactions Sense of Taste-
Begins with in one week Recovers with in 1-3 months
Alopecia
Only in areas which are irradiated Begins during the 3rd week of RT
Late Effects Of RTXerostomia dependent on dose (>35Gy) to parotids
Teeth pathologic changes secondary to diminished
salivary flow radiation caries
Trismus fibrosis of muscles of mastication expecially if treated with Sx+RT
Late effects of RT Brain Necrosis – Demyellination with loss of focal areas of
white matter necrosis Time interval : 8 months to 2 years Symptoms : dizziness
- Impaired memory, headache,- Confusion, fits, personality change- 16% - no sign or symptoms
Treatment - steroids
Soft tissue and bone necrosis Due to avascular effect of RT
Bone itself tolerates high dose of RT well, so long as tissues overlying the bone remain intact and the bone is not subjected to excessive stress or trauma
After RT, extraction of nonrestorable teeth within high dose areas is to be avoided unless all other measures fail. Try root-canal therapy
RT caries in teeth outside the field of RT does not predispose to osteonecrosis since the bone at this point has not received high-dose RT
Management Small exposures - conservative
- patience (mths)
HBO - 30-60 divesof 2.4atm/90min/day/5day/week
Surgical resection
Cranial nerve Optic Nerve Neuropathy
8% at doses of 60-73Gy No effective treatment Steroids, HBO
Hypoglossal Nerve esp if large subdiagastric LN RT -> fibrosis, nerve entrapment RT+RND - less risk
Brachial Plexus occur 6-24 mths later rare at 2Gy/# associated with large dose/#
RT induced 2nd Malignancies 1st case in1902 - hand of RT technician
RT induced Mucosal CA
MDAH - 1163 patients (Radiology 1975)- no excess new SCC
UCLA - 2125 patients (IJROBP 1988)- no diff in risk of 2nd Ca
RTOG - NPC database (Cancer 1922)- cf age-matched grp
- less 2nd Ca after RT
Rt induced sarcoma Incidence (Hatfield; Philips; Seydel; Bataini) 1-2 cases per 1000, 5yr survivor
Assuming 1 per 500, 5yr survivorAnd overall 5 yr surv for RT is 40%
Most are : high grade sarcomas, advanced stage difficult to operate respond poorly to chemo and consequently poor prognosis
RT Induced Thyroid Ca
Latent period : 10-30 yrs
Low doses of RT (<20Gy)
Advances in rt techniques Altered Fractionation Regiments Balance between tumour & normal tissue :
repair, re-oxygenation, re-assortment, re-population
Accelerated Fractionation overcome tumour repopulation
Hyperfractionation reduce dose/fraction to reduce late side
effects and permit higher total doses to be given to tumour
Chemo-RT “Spatial co-operation”
eg ALL (CNS) ‘hypoxic’ drugs
Synergistic actions eg 5FU, DDP, Paclitaxel
Sequencing chemo and RT
Neo-adjuvant Concomitant Adjuvant
Most evidence suggest concomitant chemo-RT is sequence which will result in improved results
H&N, lung, esophagus, cervix
Improving oxygenation HBO Hypoxic cell sensitiser Erythropoeitin Carbogen (95%CO2, 5%O2) Nicotinamide
Angiogenesis Endothelial cell biology Vascular targetting
Ratioprotectors (Ethyol)
Improved technology Fusion of CT/MRI/PET images 3D conformal RT Inverse treatment planning Real time target localisation
Cyberknife BAT u/s system
“Tomotherapy” - like CT Scan
Charged particles Precise dose localisation possible
eg protons
high LET (less dependence on O2)eg neutrons
“stars” - causes disintegration of nucleuseg pions (-ve pi mesons)
Conclusion Early detection of lesions is critical to
allow conservative treatment and protect the patient’s quality of life.
Many avenues constantly under investigation, are available to treat oral cancers, with improved methods
A multidisciplinary team can help oral cancer patients deal with the aftermath of treatment.
references Text book for oral cancer by Jatin P. Shah
Text book of oral &maxillofacial surgery by Peter Ward Booth.
Text book of radiology white & ferrow
Thank you