Radioimmunotherapy of Non-Hodgkin’s Lymphoma

TO THE EDITOR:

The contrast between 2 papers on this topic published side by side in The Journal of Nuclear Medicine is quite striking. The first, by Koral et al. (1), concentrates on tumor dosimetry and response using ¹³¹I-tositumomab therapy. The second, by Wiseman et al. (2) on radiation dosimetry results with ⁹⁰Y-ibritumomab tiuxetan, never mentions tumor dosimetry, and the authors appear to have measured tumor dosimetry in only 9 patients in previous studies (3,4). The basic principle of nuclear medicine therapy is to use the therapeutic agent on tumors that are shown by imaging to take up the agent. Whether lack of uptake be shown for ¹³¹I or ¹²³I for ¹³¹I therapy of differentiated thyroid cancer, ¹²³I-metaiodobenzylguanidine (MIBG) for ¹³¹I-MIBG therapy of neuroendocrine tumors, or ¹¹¹In-octreotide imaging before therapy with ⁹⁰Y-octreotide derivatives for somatostatin receptor–bearing tumors, the principle is the same. Failure to demonstrate uptake of the potential agent helps to exclude from unnecessary radiation treatment those patients whose tumors are without avidity for the agent (5). This principle is already being eroded when ¹³¹I therapy for thyroid cancer is given on the basis of the patient’s thyroglobulin being raised and ¹³¹I tracer findings being negative. This situation, which may arise because ¹³¹I tracer is a poor imaging agent, is being solved through the use of 185 MBq (5 mCi) of ¹²³I (6,7). No outcome benefit from the treatment of non–iodine-avid differentiated thyroid cancer with ¹³¹I therapy has been published. The arguments for dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer are given in a paper (8) in the same issue as the papers by Koral et al. (1) and Wiseman et al. (2).

Assessing the therapeutic dose to the tumor, whether visually (e.g., tumor uptake is greater than or equal to liver uptake for therapy or is less than liver uptake for no therapy, as in the Novartis trial for the use of ⁹⁰Y-OctreoTher) or by detailed dosimetry as in the paper by Koral et al. (1), is a basic principle of radionuclide therapy. In no example above was the therapeutic dose calculated using body weight, and in no way can body weight determine the dose to a tumor. The fact that on a whole-body–based calculation, it can be argued that the bone marrow dose can be minimized does not justify giving the therapy for a tumor that has not been shown to take up the agent. In our first case of non-Hodgkin’s lymphoma treated with ⁹⁰Y-ibritumomab, in which we calculated the dose using the body weight as stipulated by the manufacturers, we in fact gave approximately one third the dose limit of the bone marrow. In other words, on the basis of our dose calculation, the amount of activity that could have been given to treat this patient’s tumor was 3 times that determined on a body-weight basis. Whereas there may be an upper limit above which a further increase in therapeutic dose has no benefit to the patient with a tumor, there is clearly a lower limit at which insufficient therapy has no benefit to the patient with a tumor.

We face, therefore, a dilemma. Should we insist on the nuclear medicine approach to cancer therapy, in which potential nonresponders are excluded by imaging, or should we follow an apparently oncologic approach whereby as long as the marrow is safe, it does not matter whether the tumor receives an adequate or inadequate amount of therapy or whether the patient receives unnecessary radionuclide therapy? Should not we uphold the basic principles of nuclear medicine and radiation protection for radionuclide therapy?