Risk of Lung Cancer Following Therapy for Hodgkin's Disease

 

Radiation Dose >= 5 Gy	Alkylating Agents Used	Smoking	Risk Ratio	95% CI
no	no	not moderate to heavy	1.0
no	no	moderate to heavy	6.0	1.9 to 20.4
yes	no	not moderate to heavy	7.2	2.9 to 21.2
yes	no	moderate to heavy	20.2	6.8 to 68
no	yes	not moderate to heavy	4.3	1.8 to 11.7
no	yes	moderate to heavy	16.8	6.2 to 53
yes	yes	not moderate to heavy	7.2	2.8 to 21.6
yes	yes	moderate to heavy	49.1	15.1 to 187

from Table 5, page 189

 

where:

• Gy = Gray, or J/kg. An absorbed dose of 100 rads is equivalent to 1 Gy. Radiation exposure >= 5 Gy is a marked exposure.

• Moderate to heavy smoking: one or more packs a day (moderate 1-2, heavy >= 2).

• Not moderate to heavy smoking: never smoked, former smoker, light cigarette smoker (< 1 pack per day), intermittent smoker, pipe or cigar smoker.

• I would expect a person with heavy cigar or pipe smoking would be at some increased risk.

• The MOPP regimen includes mechlorethamine (nitrogen mustard) and procarbazine. The latter exerts an effect on DNA similar to an alkylating agent after metabolism by the P450 cytochrome system in the liver (Melmon and Morrelli's Clinical Pharmacology).

• Other alkylating agents include cyclophosphamide (cytoxan), ifosfamide, melphalan, chlorambucil, thiotepa and busulfan.

 

General observations:

(1) Risk increases with increasing number of cycles of chemotherapy using an alkylating agent and with increasing radiation dose. The risk when both are used together matches the summation of the individual risk (rather than the product).

(2) The risk of lung cancer following an alkylating agent can be seen in 1-4 years after therapy, while the risk after radiotherapy can be seen from to 20 or more years.

(3) Smoking significantly increases the risk of lung cancer. It tends to multiply the risk based on radiation therapy and alkylating agent use.