Indirect control of tumor growth in radiological clinic: “competitive” therapy

In order to verify the principle of indirect control a tumor on the base of morphogenic cells distraction from it, the 114 patients with advanced ovarian carcinoma were treated with subtotal halfbody (low part) irradiation at low doses (0,1 Gy x 10 during 3 weeks or 3Gy x 3 daily), and obtained data were compared with that for 190 patients received conventional local irradiation of the tumor (2 Gy x 23 daily). The surgery and chemotherapy components were equalized in both groups. The 34 and 11% of 5-years survival was obtained at low dose half body irradiation for primary and relapsed patients in comparison with conventional local radiotherapy (3% and 0%). It is concluded, that reparation /regeneration processes being provoked artificially in normal tissues of cancer host are capable to compete remotely with tumor for the morphogenic/feeding cells originated from bone marrow and circulating with the blood.

Conventional medicine recognizes a selective killing of tumor cells as only way of fighting with cancer. This way has brought some doubtless benefits in the past, but in the last decades the effectiveness of traditional treatment progresses more slowly, than it would be desirable. The life span of mammals at normal conditions and chronic irradiation as well depends on limit of proliferative capacity of bone marrow given at the birth [9]. Despite this, a strong hematodepression follows inevitably palliative chemo- and radiotherapy of cancer. As we argued earlier, the therapeutic mielosuppression restricts temporarily a morphogenic cells activity inside a tumor [8]. The morphogenic cells (trophocytes / feeding cells) is presented in the blood by hematopoietic stem cells, prolymphocytes, angiogenic T-cells and some others [7]. There are two ways to restrict the tumor growth’s support by them: 1) either to provoke a repopulation stem cells in bone marrow by its injuring with relatively high “hematotoxic” doses of “curative” factor, or 2) to redirect the circulating morphogen-ic cells from tumor toward a reparation/regeneration of numerous but nonlethal injuries of different normal cells, induced by relatively low doses of “curative” toxicants [8]. In both cases the mechanism of expected benefit has to be not direct but the mediated by rearrangement of the tissues re-newing’s balance between the cancer and host body. The purpose our presentation is to demonstrate the reliability of described “competitive” approach of cancer therapy at real clinical conditions.

Methods. Taking into account a presence of expected invisible metastases at advanced stages of ovarian cancer patients, the half -body (low part) irradiation (HBI) were performed for 114 patients, and they were compared then with 190 of those received conventional local radiotherapy (CLR). All patients have received the surgery before HBI and chemotherapy after it. The surgery and chemotherapy were identical in HBI and CLR groups. All patients in HBI group were divided before irradiation onto 2 subgroups according individual ratio of lymphocytes number to CD34+ ctem cells numbers in the blood [4]. The patients with quasinormal / forced or exhausted ratios formed subgroups HBIa and HBIb respectively. The regime 3Gy x 3 daily (NSD = 5,5Gy; D_eff = 2,8 Sv) was chosen for HBIa paients, regime 0,1Gy x 10 during 3weeks (NSD = 0,4Gy; D eff = 0,2-0,25 Sv) -for HBIb patients.

Results. Obtained average results (Table 1 ) prove very clearly the possibility to get best survival without traditional local irradiation of tumor at high, so-called “tumoricydic” total dose 40-50 Gy.

These results are quite comparable with modern data published already by National Cancer Institute, USA and some others for chemotherapy [1, 2].

Discussion. The found distinction of results arose due to features of a radiation component of combined therapy. In 2002 we proposed indirect mechanism of diminishing the lung cancer incidence in areas with slightly increased natural radiation background. It was based on the redistribution of circulating morphogenic cells [6] and was confirmed later at large [8].

Table 1

The comparison of the direct (noncalculated) 5-years survival after conventional and “competitive” therapies of advanced ovarian carcinoma (n=301 patients)

As a proliferative resource of bone marrow is limited and associated very closely with the life span and the level of lymphopenia [7, 9], we employ two regimes (HBIa or HBIb), chosen according lymphocytes number in the blood before treatment with special correction on the stem cells presence. It was made for modeling of two mechanisms of realization of an indirect tumor control. The HBIa regime (D_eff. = 2,8 Sv) was employed mostly as myelosuppressive one. The HBIb (D_eff. = 0,2-0,25 Sv) was just capable to divert the morpho-genic sells from tumor, but did not diminish their number. It is obviously, the both regimes cannot provide the tumor growth control by direct killing of malignant cells. They were rather similar with non-selective cytotoxic chemotherapy of cancer, which cannot damage the tumor cells lethally, as the conventional local radiotherapy does. Otherwise, non-selective chemotherapy would be fatal to the organism as a whole. Beside this, a myelosuppressive action of modern combined chemotherapy is not the rare, random event, as the 85% of main anti-cancer drugs are myelodepressants. Hence, the mechanism of nonselective chemotherapy supposed to be an indirect one also, causing temporary disturbances of cellular reproduction in distant normal tissues [3]. The bone marrow is a main target among them, being the most damaged from the systems responsible for preservation of life.

Conclusion:

We do not find of any principal objections to start comprehensive investigation of “competitive” low doseradiotherapy as an alternative to nonselective cytotoxic chemotherapy of cancer.