Main principles of the organization of cancer control in USSR and selected data on cancer incidence.

The main principles and the structure of the cancer control organization in the USSR are described. The trends in the incidence of selected forms of malignant tumors and regional differences in USSR are documented with statistical data.

Stage I melanoma of the limbs. Immediate versus delayed node dissection.

553 patients with stage I malignant melanoma of the limbs entered a prospective randomized clinical trial carried out by the W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to January 1974. 286 patients were submitted to wide excision of primary and node dissection at the time as appearance of regional lymph node metastases and 267 to wide excision and immediate node dissection. Survival was identical in the 2 groups. Different subsets of patients were evaluated to assess whether some groups of patients may benefit from immediate node dissection. As regards sex, females and a significantly higher survival rate than males (p < 0.05), but results were not improved by immediate node dissection. Maximum diameter and elevation of primary melanoma were significantly related to survival but also in these cases immediate node dissection did not achieve better results. 63 patients had an excisional biopsy of their melanoma within 4 weeks before final treatment. This procedure did not worsen survival and also in this case immediate node dissection did not improve survival. 273 cases were classified according to histologic type: survival of superficial spreading and nodular melanoma was not different at a statistically significant level after the 2 treatment modalities. 325 cases were considered classifiable according to Clark's levels, out of these 165 were submitted to immediate node dissection. Neither level III nor level IV cases showed higher survival rate after immediate node dissection. Maximum tumor thickness according to Breslow was evaluated in 338 cases: 188 were submitted to wide excision and immediate node dissection. In no clusters of thickness did the enlarged surgical procedure achieve better results. The authors conclude that there is good evidence that in stage I melanoma of the extremities delayed dissection.

[Expression of the apoptosis inhibitor soluble Fas antigen in patients with malignant and benign bone neoplasms]. / Ekspressiia ingibitora apoptoza--rastvorimogo Fas-antigena u bol'nykh so zlokachestvennymi i dobrokachestvennymi novoobrazovaniiami kostei.

This paper presents results of comparative enzyme immunoassay of soluble serum Fas antigen (sFas) in 98 patients with benign and malignant bone tumors, 15 patients with mechanical bone traumas, and 60 normal individuals of compatible age. The prevalence and concentration of sFas were significantly greater in patients with bone tumors than in normal donors and patients with mechanical bone traumas. The association of sFas with the pathogenesis of primary bone tumors is discussed in the paper.

[Osteosarcoma: biochemical and endocrinological studies as a basis for its pathogenetic treatments]. / Biokhimicheskie i éndokrinologicheskie issledovaniia pri osteosarkome -- osnova patogeneticheskikh metodov lecheniia opukholi.

The paper considers data of the long-term studies of androgen metabolism, baseline serum levels of reproductive steroid hormones and their receptors in the tumor, in the blood concentrations of sex steroid-binding globulin and pituitary hormones, the expression of epidermal growth factor, its receptors and ligands, soluble Fas-antigen, vascular endothelial growth factor, angiogenin, and the content of calmodulin, cAMP in the osteosarcoma in 300 patients aged 14 to 56 years, which were made at the N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. Analyzing the findings identified some lines in the study of new pathogenetic treatments for osteosarcoma, aimed at regulating androgen metabolism, correcting the cyclooxygenase pathway of arachidonic acid, the expression of receptors of epidermal growth factor and its ligands, the processes of neoangiogenesis in the tumor. A role of the above parameters in the pathogenesis of osteosarcoma is discussed.

[Treatment of limb osteosarcoma at the turn of the century (half century of experience in research)]. / Lechenie osteosarkomy konechnostei na rubezhe stoletii (poluvekovoi opyt issledovanii).

The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.

[Bone tumors and androgen metabolism]. / Opukholi kostei i metabolizm androgenov.

The paper provides data of comparative assessment of activity of the key enzymes in metabolism of androgens in various morphological variants of sarcomas and benign bone tumors in 46 patients within the age range from 15 to 61, which were under treatment in the ORC named after N. N. Blokhin, RAMS, from 1996 to 1997. On the basis on publications and our own research results we can suggest that malignant human bone tumors of various histogenesis are subject to metabolic processes of testosterone (T), the principal androgen regulator in the bone tissue, as well as formation in bones of 5 alpha-dihydrotestosterone (DHT). One cannot exclude a possibility that metabolism of androgen in bone tissues is directed towards formation of other androgens (in addition to DHT), which may participate in the bone tissue regulation, for instance, 3 alpha- and 3 beta-diols; specific activity of the latter has recently been intensively scrutinized. One can expect that further research shall disclose the clinical significance of metabolism of androgens and of individual androgens in human bone formations.

[Metabolism of androgens in various histological variants of bone tumors]. / Osobennosti metabolizma androgenov v razlichnykh gistologicheskikh variantakh opukholei kostei.

The role of androgens in human normal and neoplastic bone tissues is still unclear. The paper presents data on metabolism of androgens in homogenates of malignant (osteosarcoma, chondrosarcoma, Ewing and giant cell) and benign primary tumors from 46 male and female patients aged 14-58 years. Using two substrates (testosterone and 5 alpha-dihydrotestosterone) for the first time are shown activities of main enzymes of androgen metabolism in all tumor types. 5 alpha-reductase activity was similar in all tumors, 3 alpha-hydroxysteroid dehydrogenase activity was the highest while that of 17 beta-hydroxysteroid dehydrogenase was the lowest. Unknown metabolite(s) of 5 alpha-dehydrotestosterone was discovered which may be hydroxy-metabolites of 5 alpha-androstane-3 beta, 17 beta-diol. A principal scheme of androgen metabolism in human neoplastic tissue is proposed.

[Prognostic significance of p53, HER-2/neu, Ki-67 and VEGF expression in chondrosarcomas]. / Prognosticheskoe znachenie ékspressii p53, HER2/neu, Ki-67 i VEGF v khondrosarkomakh.

Expression of the mutant protein-suppressor of tumor growth p53 and the receptor of epidermal growth factor of type II--HER-2/neu may serve as prognostic factors for patients with chondrosarcoma of malignancy grade II. Combined expression of these proteins in the tumor tissue correlates with shorter 5-year survival of recurrence-free patients. The data obtained may be used for prognosis of chondrosarcoma course and choice of adequate therapy.

[Risk factors for cancer of the oral cavity and esophagus in a high incidence region]. / Faktory riska raka polosti rta i pishchevoda v regione s vysokoi zabolevaemost'iu.

Relative risk of precancerous changes development in the oral cavity is much higher in nas chewers and cigarette smokers. It is particularly higher in users of both. Insufficient levels of riboflavin, carotin and vitamin A were found in some of those examined.

[Melanoma of the skin and pregnancy]. / Melanoma kozhi i beremennost'.

Out of 2018 patients, skin melanoma occurred in IO2 (5%) cases during pregnancy. Three-, five- and ten year survival was analysed in the latter cases versus term of pregnancy, abortion and the stage of the disease. Also comparison was made between the said group, another 42 females who developed tumors during lactation period and 599 normally-cycling females of reproductive age who were not pregnant when melanoma appeared (controls). Significantly lower 10-year survival was observed in pregnant patients, as compared with those who were not pregnant (p less than 0.05). Five- and ten-year survivals were significantly lower in cases of stage I tumor during the latter half of pregnancy than in skin melanoma patients who were not pregnant (p less than 0.05). Abortion during the first half of pregnancy was found to produce an adverse effect on prognosis in stage I tumor patients while this effect was reversed in stage II tumor. No significant differences were found between 3-, 5- and 10-year survival in melanoma patients who had pregnancies before the disease and those who had not (p greater than 0.05).

[Late results of the combined treatment of locally disseminated soft tissue sarcomas]. / Otdalennye rezul'taty kombinirovannogo lecheniia mestnorasprostranennykh sarkom miagkikh tkanei.

Radical surgery was performed in 69 cases of primary and recurrent localized soft-tissue sarcomas (extended dissection of tumor--53, exarticulation or amputation--16) after a course of non-uniform irradiation, when other methods of specific treatment had failed. Areas of exposed tumors were irradiated with focal doses of 90-120 Gy, screened areas--with 40-60 Gy. Radiation was delivered through a latticed diaphragm from the same field. Postoperative complications due to intensive irradiation and radiation injury were comparable to those involved in standard radiation procedures. A 5-year survival rate was 50% (primary tumor--16 and relapse--77%).

[Prognostic factors in parosteal sarcoma]. / Faktory prognoza pri parostal'noi sarkome.

Principles of evaluating prognosis in parosteal sarcoma were developed with respect to clinical and morphological pattern of disease and type of treatment. A mathematical model for making prognosis and a procedure for its multifactorial analysis were suggested.

[The diagnosis and treatment of primary malignant tumors of the sternum]. / Diagnostika i lechenie pervichnykh zlokachestvennykh opukholei grudiny.

Results of examination and treatment of 24 patients with primary neoplasms of the sternum including chondrosarcoma (18 cases), solitary plasmacytoma (5) and osteogenic sarcoma (1) were analysed. The diagnosis was based mainly on X-ray procedures and was further improved by computed tomography which allowed to precisely evaluate the extent of intrathoracic mass and its relation to adjacent mediastinal structures. Surgery was the main procedure used for the treatment of primary tumors of the sternum. Sixteen patients were operated on, and not a single case showed involvement of the mediastinum. Closure of defect was the major difficulty involved in the surgical treatment. Adequate resection of the sternum followed by autoplasty yielded good results.

[Experience with and outlook for the use of cisplatin in the combined therapy of osteogenic sarcoma]. / Opy primeneniia i perspektivy ispol'zovaniia tsis-platina v kombinirovannoi terapii osteogennoi sarkomy.

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.

[Results of examining the population in a region with high morbidity for oral mucosal cancer: precancerous changes]. / Rezul'taty obsledovaniia naseleniia v regione s vysokoi zabolevaemost'iu rakom slizistoi obolochki rta: predrakovye izmeneniia.

Interviewing and examination of a population characterized by a high level of morbidity of oral cavity cancer, supposedly induced by the use of nas, established a high incidence of leukoplakia and preleukoplakia at this site which are identified as precancerous lesions. The highest relative risk of oral cavity leukoplakia was found in persons who both chew nas and smoke tobacco (12.4). Relative risk of leukoplakia is also elevated in those who either chew nas (5.6) or smoke cigarettes (7.7). This risk increases in step with the quantity of nas consumed per day as well as the number of cigarettes. The scrapings obtained from the oral cavity mucosa of nas chewers and cigarette smokers were shown to contain relatively higher levels of micronuclear cells. The results of this and previous investigations suggest that tests for the frequency of micronuclear cell occurrence may prove instrumental in identifying the early signs of carcinogenesis as well as in evaluating the efficacy of prophylactic measures.

[Immunological reactions of skin melanoma patients to nonspecific and adaptive immunotherapy]. / Immunologicheskie reaktsii bol'nykh melanomoi kozhi pri nespetsificheskoi i adoptivnoi immunoterapii.

Patients with malignant skin melanoma were given different kinds of immunotherapy; nonspecific immunotherapy with BCG vaccine, adaptive immunotherapy with methotrexate or phytohemagglutinin activated autolymphocytes, and also a combination of polychemotherapy with BCG. The state of cell immunity was determined prior to, during and at the end of the therapy, in accordance with the courses. As a result of the conducted therapy an increased level of cell immunity was observed, that usually corresponded to clinical development of the disease. At the same time, the increase in immune response indices due to continuous administration of BCG vaccine is not related with the clinical course, while the persistent anergy or reduced level of cell immunity during this kind of therapy is a poor prognostic sign.

[Current approaches to the combination therapy of osteogenic sarcoma]. / Sovremennye podkhody k kompleksnoi terapii osteogennoi sarkomy.

The results of treatment of 315 cases of osteogenic sarcoma are presented. Available methods of primary tumor therapy fail to prevent dissemination of neoplastic disease by blood circulation. However, following a prophylactic course of chemotherapy (adriamycin, vincristine, cyclophosphamide, sarcolysine), 3- and 5-year survival rates in 45 cases of limb amputation for osteosarcoma increased to 38.1% and 30.5%, respectively. No recurrences were observed in 39 patients with extensive segmental resection of bone who preoperatively received intra-arterial infusions and radiation therapy; the 3-year survival rates were a high as 43.9% and patients showed good performance. The method offers good advantages in the treatment of patients with osteogenic sarcoma.

[Role and place of radio- and chemotherapy in treating bone sarcomas]. / Rol' i mesto luchevoi i khimioterapii v lechenii sarkom kostei.

The results of combination therapy of 510 patients with osteosarcoma were analysed. It was established that most advantage is offered by this therapy in cases of osteogenic sarcoma and Ewing's sarcoma supplemented with surgery whenever required. A 33.9 and 30.1% increases in 3- and 6-year survival, respectively, were registered in 50 cases of osteogenic sarcoma, following amputation and a course of polychemotherapy (adriamycin, vincristin, sarcolysin and cyclophosphamide). There were no relapses in 40 cases of extensive segmental resection of the site of bone lesion with preoperative intra-arterial infusion of adriamycin, radiation therapy and adjuvant polychemotherapy. This scheme resulted in 4-year survival in 55.7% and good performance. A 5-year survival rose to 40.8% in 45 cases of Ewing's sarcoma, following adjuvant therapy with sarcolysin or cyclophosphamide administered after a course of radiation therapy in the dose of 50-60 Gy.

[Survival and prognosis in adjuvant chemotherapy for osteogenic sarcoma patients]. / Vyzhivaemost' i prognoz v usloviiakh ad"iuvantnoi khimioterapii u bol'nykh osteogennoi sarkomoi.

The effect of adjuvant chemotherapy on survival and prognosis in osteogenic sarcoma versus basic clinico-roentgenomorphological characteristics of tumor was studied in 108 cases. Prognosis was found to depend on patient's age, site and size of tumor, but mainly on the roentgeno-morphological pattern of the latter. Osteolytic form appeared to have a better course in cases of adjuvant chemotherapy. This was matched by osteoplastic form requiring surgical treatment only. The results suggest a strictly differentiated approach to selection of treatment modality, particularly in cases of post-operative chemotherapy.

[Results of a phase I clinical trial of "theraphthal + ascorbic acid" catalytic system]. / Rezul'taty I fazy klinicheskogo izucheniia kataliticheskoi sistemy "teraftal + askorbinovaia kislota".

Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic system have been completed. The dose-limiting toxicity and maximum tolerable dose were not reached even at the end of maximal dose trials. No side-effects characteristic of antitumor cytostatic drugs were registered. The gravest side-effect ever recorded was a collapse which could not be linked to teraphtal dosage and was probably caused by hypersensitivity to the drug. The drug was recommended for phase II trials.