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Pulmonary & Critical Care Bulletin
Vol. VII, No. 3, July 15, 2001
In this issue :
From Editor's Desk
RADIOTHERAPY FOR CARCINOMA LUNG
The discovery of radioactivity dates back to the late 19th century when Henry Becquerel (1889) discovered that radium, which had been accidentally kept in his vest pocket, caused local skin erythema followed by ulceration.
Regaud can be accredited with the discovery of the concept of fractionation in radiotherapy (RT). He discovered that, for sterilization of ram's testes, fractionating the total radiation dose achieved the purpose without causing overlying skin necrosis, whilst use of single dose radiation resulted in the same.
The concept of brachytherapy (implantation of radioactive material within body cavities or within tumors) was used initially in France and later in the United Kingdom in the treatment of carcinoma cervix.
Modern day radiotherapy involves the use of following two modalities.
a. Teletherapy wherein RT is delivered from outside the body.
b. Brachytherapy wherein radioactive material is placed within the body.
The sources of radiation in teletherapy are X-rays and gamma rays; the former being produced by linear accelerators and the latter by radioactive cobalt or caesium.
PHYSICAL AND BIOLOGICAL BASIS OF RADIOTHERAPY
At the atomic level, radiation energy produces effects based on the energy of the incident photon (a photon is a packet of energy). At higher energies, two phenomena can occur namely: a. Compton effect wherein a high energy photon undergoes the so called 'billiard ball' collision with the electron in the valence shell of the atom and ejects it from its shell, thus transferring its kinetic energy to the electron; (b) Pair production effect wherein the photon strikes the nucleus of the atom and produces a positron electron pair which strikes the target cell.
At lower energies, the photoelectric effect is produced when the incident photon strikes and ejects one of the electron in the inner shells of the atom thus causing the valence electron to 'jump' to lower shells thus releasing more energy.
These physical interactions translate into breakage of chemical bonds in DNA molecules resulting in irreversible damage due to formation of 'DNA adducts'. The latter is mediated either by free radical formation or by direct impact of the charged particles on the DNA molecule. At this point, it would be pertinent to note that cells in the 'M' or 'late G2' phase of the cell cycle are sensitive to radiation induced damage while cells in the 'late s' phase are resistant to these effects.
RADIOTHERAPY FOR CARCINOMA LUNG
The tissues comprising the respiratory system display differential sensitivity to radiation; while the trachea and bronchi suffer little damage at radiation doses upto 50 Gy(Grays), the pulmonary parenchyma is exquisitely radiosensitive and pneumonitis occurs with doses as low as 25 Gy. This probably explains the relative radioresistance of squamous cell carcinoma as opposed to the radiosensitivity of small cell carcinoma of the lung.
For therapeutic purposes lung cancer has been classified into the small cell and nonsmall cell varieties. Small cell carcinoma (SCLC) is of neuroendocrine origin and is a systemic disease with as many as two thirds of patients having extensive disease at presentation, thus precluding surgery as the treatment modality of choice. Nonsmall cell cancer (NSCLC) on the other hand is localised at presentation in about 1/3 of patients and amenable to limited resection in another one thirds; thus surgical resection is an important treatment option in these patients. Unfortunately, even for nonsmall cell lung cancer, most patients in this country are inoperable when first seen.
1. Radiotherapy in small cell carcinoma lung
Small cell carcinoma is managed with a combination of chemotherapy (CT) and radiotherapy (RT) in almost all cases:
a) Timing of radiotherapy: It has been amply demonstrated that combined modality therapy in small cell Ca lung enhances both tumor control and survival.
Perez et al studied 304 patients of SCLC wherein they found that there was a 36% failure rate and 40% survival in patients receiving chemotherapy and radiotherapy when compared with patients receiving chemotherapy only, where the failure rate was 52% and survival was only 23%
In another prospective randomized controlled trial (Perry et al) to study the effect of radiotherapy and timing of RT in SCLC the number of complete remissions, relapse free survival and the interval before treatment failure were favourable in patients receiving radiotherapy also.
Presently, it is recommended that radiotherapy be given in the later part of the chemotherapy regimen, as concurrent RT and CT is associated with a high incidence of side effects.
b) Dose and fractionation of RT: The current guidelines recommend 45 Gy of RT to be given according to the standard fractionation schedule; i.e. 1.8 - 2 Gy/d for 5 days a week over 4-6 wks. However, Choi et al found that better tumor control was achieved with 50 Gy of RT given according to an accelerated fractionation schedule (i.e. 2 fractions/day over 2 wks) before starting chemotherapy.
c) Prophylactic cranial irradiation (PCI)
Brain metastases occurs in over 50% of patients with SCLC and prophylactic cranial irradiation decreases the overall incidence of brain metastases to less than 5%. However PCI confers no survival advantage and is associated with a high incidence of neurological side effects like dementia, psychomotor retardation, hemiparesis and optic atrophy. Thus PCI is recommended only in those patients in whom the disease is in complete remission after chemotherapy and local radiotherapy.
2. Radiotherapy for Nonsmall cell carcinoma lung
Since NSCLC has diverse clinical presentations, radiotherapy can be offered in the following settings:
a) Neoadjuvant Radiotherapy: This form of RT is given in clinical N2 and superior sulcus tumors. The dose is 45 Gy in standard fractions given preoperatively; surgery is undertaken 3-4 weeks later after restaging. Alternatively, preoperative brachytherapy using Iridium192 or even intraoperative RT have been given in selected patients.
b) Adjuvant RT: Radiotherapy is given postoperatively in the following subsets of patients: 1) positive or close surgical margins. ii) residual tumor after resection; iii) N2 disease; iv) local recurrence. The role of post operative RT is controversial in patients with clear surgical margins and in those with N1 disease. The dose is 50 Gy given according to the standard fractionation schedule.
An intergroup protocol study is underway to determine the utility of combined therapy (chemo-irradiation) in the above mentioned patient subsets.
This is indicated in: (a) loco-regionally advanced disease (stage IIIA/B); (b) medically inoperable patients; (c) post operative recurrence of tumors.The dose of RT is 60-70 Gy according to the standard fractionation schedule.
In patients with locoregionally advanced disease who have a good performance status, chemoirradiation has been tried as follows:
a. Cis-platinum based chemo treatment followed by RT.
b. Concurrent chemo treatment and RT
c. Chemotherapy with hyperfractionated RT
d. RT + Newer chemo therapeutic agents (docetaxel or paclitaxel plus Cisplatinum or carboplatinum).
This form of RT is recommended in patients with stage III/IV disease with poor performance status. 20-40 Gy are given in standard number of doses.
BRACHYTHERAPY IN CARCINOMA LUNG
Brachytherapy, the implantation of radioactive material endobronchially or within tumors is indicated in the following situations:
a. Tumors entailing removal of a large volume of the lung.
b. Tumors adherent to the major vessels, trachea, esophagus, chest wall or spine.
Brachytherapy is contraindicated in anaplastic carcinomata and extensive small cell Ca lung. Radiation is given using either permanent implantation of I125or with Ir192 which is introduced through a teflon catheter advanced into the tumor. In the latter technique, a 10 curie source of Ir192 is used and 6-8 Gy are given in 2 sessions, a week apart.
TOXICITY OF RT
Esophagitis Pneumonitis (25-30 Gy)
Cough Esophageal stricture (60Gy)
Skin reaction Cardiac: Constrictive pericarditis,
Fatique pericardial effusion, cardiomyopathy
Lhermitte's syndrome Myelopathy Brachial Plexopathy 45Gy
1. Perez & Brady. Principles and Practice of Radiation Oncology. III ed. Philadelphia Lippincott Raven 1998.
2. Fishman Alfred P: Pulmonary disease and disorders. 3rd Ed. New York McGraw Hill 1998.
3. Moss & Cox: Radiation Oncology: Rationale, technique and results. 6th ed. Toronto, The CV Mosby Company 1989.
Dr. Uma Maheswari K, M.D. (Med) Senior Resident, Deptt. of Pulmonary Medicine, P.G.I., Chandigarh.
Dr. Uma Maheswari K, M.D.
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