Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.

Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms.

Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors.

The levels of sPD-1 and sPD-L1 were analyzed in blood serum of 132 patients (age 14-70 years) with primary bone tumors: osteosarcoma (N=39), chondrosarcoma (N=42), Ewing sarcoma (N=9), chordoma (N=12), giant-cell bone tumor (GCBT) (N=16), benign neoplasms (N=14) and in and practically healthy subjects (age 19-58 years; N=27). sPD-L1 levels in all studied bone neoplasms were significantly higher than in the control. Serum sPD-1 level in GCBT patients was significantly higher than in the control, benign neoplasms, chondrosarcoma, and chordoma patients, but did not differ from osteosarcoma group. sPD-1 concentration in Ewing sarcoma was significantly higher than in chordoma and chondrosarcoma, but did not differ from the control. sPD-1 level in chondrosarcoma patients was also lower than in osteosarcoma, Ewing sarcoma, and in the control. Both sPD-1 and sPD-L1 concentrations were not significantly associated with the type of affected bone, process localization, disease stage, tumor histological grade, patients' age and sex. These results suggest the possibility of using these biological markers for preliminary assessment of the character of the process in the bone.

[The possibilities of treatment of recurrent colorectal cancer with sacral invasion]. / Vozmozhnosti lecheniya retsidiva raka pryamoi kishki s invaziei v krestets (s kommentariem).

AIM: To describe current methods of surgical treatment of rare form of recurrent rectal cancer with sacral invasion. MATERIAL AND METHODS: The article presents the methodology for the treatment of patients with recurrent colorectal cancer and sacral invasion using preoperative chemoradiotherapy followed by high-tech surgery of recurrent tumor removal with sacral resection at various levels (including high intersection at S1 level). CONCLUSION: It was concluded that chemoradiotherapy is indicated in patients with recurrent colorectal cancer if it was not made at the first stage of treatment. Additional radiotherapy up to optimum overall focal dose prior to surgery is advisable in those patients who previously underwent radiotherapy with partial dose. This type of operations has high risk of complications and requires a personalized approach to the selection of patients. However, R0-resection is associated with favorable long-term prognosis, significantly increased survival and overall quality of life. Combined surgery for recurrent tumors with sacral invasion should be performed by multidisciplinary surgical team in specialized centers using current possibilities of anesthesiology and intensive care.

[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.