Basic principles of Radiobiology

1. The critical target for radiation injury for most cell types is DNA.

2. Inonizing radiation in sufficient dosage will produce cell death and then loss of clonogenic capacity

3. Disruption of plasma membranes is the other form of cell damage

4. Unit of dosage: Gray (1 joule/kg); 1 Gray = 100 rad; centigray (cGy) is the unit of current pratice, 1 cGy = 1 rad.

5. Fractionation: A single dose of radiation (eg 600cGy) will result in fewer surviving cells than the same total dose given in several smaller fractions ( eg 300 cGy x 3). But, fractionated radiation provides chance of repair of normal tissue damage between fractions.

6. Radiosensitivity correlates with the presence of oxygen. Keep Hb ³ 10 will enhance the radiation sensitivity.

7. hyperthermia: 42 - 43 C sensitizes cell to radiation.

Radiation Techniques: radiation therapy is delivered in three ways

1. Teletherapy ( External beam):given  with megavoltage  or supervoltage equipment

1) Photons: a quantum of high-energy electromagnetic radiation to cause ionization. Photon may be gamma ray or x-rays

2) Electrons: generated from betatrons or high-energy accelerators. For superficial lesion

2. Brachytherapy:

Radiation Therapy in Gynecologic Malignancies

A. Cervical Cancer:

1. Indications:

1) When surgery is not possibile: stage ³ IIb, age > 70 y/o, general condition not suitable for surgery, contraindication of anesthesia

2) Adjuvant therapy of radical hysterectomy:

parametrium involvement (+),

pelvic lymph node metastases (+),

cervicix invasion depth > 2/3,

section margin with cancer,

Section margin with CIN III in patient receiving neoadjuvant chemotherapy (bulky tumor)

inadequate surgical margin

3) Recurrent cancer (local recurrence): often combined with chemotherapy, single or combination regimen.

4) Palliation in advanced disease: short courses, eg 2000 cGy in 5 fractions, 3000 cGy in 10 fractions

5) Interstitial implants (& COBRT): to provide small volume boost in patients after external therapy, also in recurrent focus of previous radiation therapy ( central, sidewall)

2. Irradiation administration:

1) External radiation: dose is limited due to the adjacent normal organ.

      Brachy therapy: to achieve a higher cintral tumor dose

2) Treatment dosage: 4000-5000 cGy for local control of microscopic tumor, 6000 cGy or more to obvious tumor

3) Reference points:

Point A: 2 cm later and 2 cm superior to the external cx os

Point B: 3 cm later to point A and corresponds to the pelvic sidewall

4) The summated dose to point A for adequate central control is 7500 - 8500 cGy. The dose to point B is 4500 - 6500 cGy for parametrium and sidewall control

5) Box technique: may spare rectum and sigmoid colon and small bowel to reduce side-effect

6) Extented field: to cover para-aortic lymph node, up to T-12. used in PA L/N (+)

7) Drainage of pyometra before radiation to prevent sepsis from rupture of pyometra

3. Toxicity:

1) Late complication (5-15%)

Hematuria, radiation cystitis: Tx with normal siline irrigation, hyperbaric oxygenation

Hemorrhagic proctitis: Tx with cort-enema

Fistula: rectovaginal fistula is most often, Tx with colostomy. Vesicovaginal fistula, Tx with long term foley catherization and repair, PCN.

Stricture: of ureter, PCN if hydronephrosis occurs.

perforation of hallo organ: rectum, sigmoid, small bowel, pyometra.

2) Acute toxicity:

a) Abdominal cramping and diarrhea in (60%) : Tx with antidiarrhea medications (eg. kaopectin)

b) Anorexia, nausea, vomiting (75%): Tx with novamin, primperan, zofran

c) General fatigue (100%): supportive Tx

d) thrombocytopenia and neutropenia (10%): Isolation to prevent secondary infection, prophylactic antibiotics, G-CSF.

e) Pneumonitis (15%): most often self-limiting and resolves spontaneously

f) Liver damage(40%): GOT, Alk-p elevation: observation and supportive Tx

g) Abdominal bloating (10%): symptomatic relief

B. Endometrial Cancer:

1. Adjuvant therapy: myometrial invasion ³ 1/2

2. Localized endometrial cancer --- curative intent

3. Toxicities are same as in cervical cancer

C. Ovarian Cancer:

1. Indication:

1) For selected patient of ovarian cancer, eg focal residual tumor in p’t of poor liver and renal function and chemotherapy is not suitable

2) Improving local control of microscopic lesion in some specific condition

2. Irradiation administration:

1) Whole abdominopelvic radiation; moving-strip techniqe, open-field technique

2) Acute toxicity was similar for both techniques. Late complication s were nore frequent with the strip technique.

3) Open technique was more favored

3. Toxicity:

1) Abdominal cramping and diarrhea in (60%) : Tx with antidiarrhea medications (eg. kaopectin)

2) Anorexia, nausea, vomiting (75%): Tx with novamin, primperan, zofran

3) General fatigue (100%): supportive Tx

4) thrombocytopenia and neutropenia (10%): Isolation to prevent secondary infection, prophylactic antibiotics, G-CSF.

5) Pneumonitis (15%): most often self-limiting and resolves spontaneously

6) Liver damage(40%): GOT, Alk-p elevation: observation and supportive Tx

7) Abdominal bloating (10%): symptomatic relief

D. Combined Operative Brachy Radiation Therapy (COBRT): for focal residual tumor (mainly CX Ca) after a debulking surgery (most often exenteration surgery) in patient who had reciieved full dose external radiation

E. Vulva Cancer:

1. Indication:

1) In patient of advanced diseses to reduced the postoperative locoreginal failure

2) Poor candidate of surgery or anesthesia

3) Inguinopelvic irradiation is used for adjuvant therapy in patient of positive node.

4) Local irradiation when the surgical margin or deep margin ( periosteum) is not adequate

2. Radiation Administration:

1) 4500 - 5000 cGy for microscopic disease, 6000 - 6400 cGy for macroscopic lesion

2) Fraction size should be minimized to 160 - 175 cGy to reduced radiarion sequelae

3) 5-FU or cisplatin can be used as radiation sensitizer

4) Electron beam is used in superficial lesion

3. Toxicity:

1) Acute moist desquamation

2) Late complication: lymphedema, atrophy and fibrosis of skin and subcutaneous tissues

3) Hip fracture

F. Vaginal Cancer: advanced stage

The side-effect and its management of radiation therapy

* Radiation Cystitis (hemorrhagic cystitis)的處理原則:

1. 2 combined antibiotics

2. on 3 way foley

3. Ringer lactate solution irrigation(最好是冰的)180ml/hr

4. 照會骨科for高壓氧治療(Hyperbaric Oxygenation HBO)

* Hemorrhagic proctitis

1. On low residual dilt or soft diet.

2. Cort-enema for sectum suppositary retention