Continuous versus split-course irradiation for lung cancer. Immunological implications.

The therapeutical irradiation for lung cancer causes profound disturbances of host's general immunocompetence, the cellular immunodepression being the dominant finding. It is thought that split-course technique holds certain advantage over the continuous irradiation, since the former includes an interruption of 4 week duration, thus allowing the lymphopoietic system to recover to a certain degree. In this report, we compared the radiotherapy-due alterations of several parameters of cellular immunity (the number and function of total T cells, active T cells and the cells of monocyte/macrophage lineage), immediately after the completion of therapy in either continuously (n = 13) or split-course-irradiated (n = 12) lung cancer patients. All patients had received the total dose of 60 Gy. Both therapeutical techniques caused alterations of the parameters tested: the significant decrease of the total and active T cells and their proliferative responses, while the phagocytic activity and the number of mononuclear phagocytes were increased, the latter being affected to a lesser extent in split-course-treated patients. Our results suggest that both techniques have similar immunodepressant effect on the cellular immunity of lung cancer patients.

The protective activity of Thymex L against radiotherapeutically-induced cellular immunodepression in lung cancer patients.

In order to prevent the radiotherapeutically-induced aggravation of initial immunodeficiency, a thymic preparation (Thymex L) was given to lung cancer patients simultaneously with irradiation. The parameters of both cellular and humoral nonspecific immunity were evaluated in two groups of patients: one was treated with radiotherapy only (60 Gy in 30 fractions); the other one received Thymex L (100 mg 3 times a week, total dose 1800 mg, i.m.) simultaneously with radiotherapy. The significant decrease of B and T cell number, and decreased lymphoproliferative response to PHA were found in all patients before therapy; the number and phagocyting capacity of blood monocytes, as well as the concentrations of circulating IgG, IgA and immunocomplexes, were all significantly increased. Immediately after irradiation the patients had even lower number of T and B cells, diminished reactivity to PHA and higher number of mononuclear phagocytes when compared to the values before therapy. In patients treated with Thymex L, the number of B and T cells and PHA-induced proliferative response were significantly higher than in those treated with radiotherapy only. No effect of this therapy was seen on active T cells, on high number and function of mononuclear phagocytes and on elevated concentrations of serum immunoglobulins and immune complexes. Our results indicate that Thymex L can successfully prevent the harmful effect of radiation therapy on cellular immunity in a majority of lung cancer patients.

A controversial issue: could a watch-and-wait policy for patients with non-Hodgkin's lymphoma clinical stage I or IE with no lymphoma left following diagnostic surgery be justified? Results of a single centre study.

BACKGROUND: A subset of patients with non-Hodgkin's lymphoma (NHL) with clinical stage I or IE at presentation is left without other NHL localizations following surgery performed for diagnostic histology, and thus without any target lesion to judge the immediate effectiveness of immediately applied additional treatment modalities. MATERIAL AND METHODS: Since 1988 we have adopted in this single centre, prospective non-randomized study, a watch-and-wait policy for such patients, who in addition had to have non-bulky disease, normal LDH levels, no 'B' symptoms and no Burkitt, lymphoblastic and cutaneous T-cell histology. Up to 1993 we have observed 50 consecutive cases. Patients were regularly followed with the endpoint to determine the relapse-free interval and overall survival. NHL relapses were treated, either with locoregional radiotherapy, or with chemotherapy, or both. RESULTS: The median observation time is at the moment 53.5+ months (range 6-106+). The initial NHL localizations were: a solitary cervical or auxillary lymph node in 18 patients, inguinal or scarpal lymph node in eight, tonsil in 12 and skin/subcutis in 12 (B-cell NHL only for skin/subcutis). Nine patients had low, 15 intermediate, and 26 high-grade histology. Within the observation period NHL relapses occurred in 10/50 patients (20 per cent). At the moment 46/50 patients (92 per cent) are alive and NHL free. The estimated 9-year freedom from relapse is 79 per cent and overall survival 92 per cent, and for 41 patients with intermediate/high-grade histologies 80 per cent and 95 per cent respectively. CONCLUSION: It seems that a proportion of the very selected subgroup of patients with stage I of IE NHL and absolutely no NHL left following diagnostic surgery, with additional criteria as described in this study can achieve a substantial freedom from relapse and overall survival rate without immediate additional therapeutic procedures following diagnosis of NHL, but no prognostic factors predicting this outcome seem yet available.

Enhancement of phytohemagglutinin-induced lymphoproliferative response by indomethacin, Thymex L or their combination in lung cancer patients.

Several studies showed that thymic factors and prostaglandin synthesis inhibitors enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer patients. In this study we investigated whether indomethacin and thymic extract (Thymex L), applied in combination, may in a synergistic pattern influence phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate that the use of the investigated agents enhances LPR to a similar level in hyporeactive patients before, as well as after, therapy. However, this drug combination exerts an additive effect on LPR, but only in patients who underwent cytoreductive radiation therapy, indicating the potential usefulness of this drug combination as an adjuvant treatment of these patients.