Preoperative stereotactic ablative body radiotherapy with postoperative conventional irradiation of soft tissue sarcomas: Protocol overview with a preliminary safety report.

Preoperative radiotherapy in patients with soft tissue sarcomas is characterized by important advantages: high precision of dose delivery, reduction of tumor volume and implantation potential, induction of immunologic response. Postoperative irradiation is associated with a reduced risk of complication, and a comprehensive radiotherapy planning in accordance with the pathologic report. Combination of pre- and postoperative irradiation gives the opportunity to use the best of both methods. OBJECTIVE: To analyze feasibility and safety of radiotherapy protocol that combined pre- and postoperative radiotherapy in patients with soft tissues sarcomas of extremities. MATERIALS AND METHODS: From 06.2018 to 01.2021, 23 patients with soft tissue sarcomas of extremities were included in the protocol (NCT04330456) and 14 cases with at least 12 months follow-up were eligible for analysis. Preoperative stereotactic ablative body radiotherapy (SBRT) was performed as 5 fraction of 7 Gy with dose reduction (5 fractions of 5 Gy) on the margins of the tumor. Postoperative radiotherapy started 5-8 weeks after the surgery and was performed as standard compartmental irradiation in 25 fractions of 2 Gy. Complications were determined according to CTCAE and wound complication scales. RESULTS: Preoperative SBRT and subsequent radical resection with tumor free surgical margins were performed in all 14 cases. Primary wound closure was mentioned in all patients. Postoperative radiotherapy started 51.8 days (range 33-99 days) days after the surgery. With a relatively short follow-up of 21.5 (13-30) months, we recorded 2 cases (14%) of severe complications (Canadian sarcoma group criteria), and there were no local recurrences. CONCLUSION: Our preliminary results demonstrate that the combination of preoperative SBRT and postoperative conventional radiotherapy is feasible and does not increase the risk of postoperative complications.

[The use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in prostate cancer patients].

There was studied the use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in 35 patients with localized prostate cancer (cT1-T2 N0 M0). Sentinel lymph nodes were imaged in 31 (89%) patients. There were advantageously detected drainage pathways to exterior (77%) and internal iliac (58%) lymph nodes. Visceral (29%) lymph nodes (paraprostatic, paravesical and mesorectal) were less determined. There was established high informative value of SPECT-CT for imaging sentinel lymph nodes, determining their location as well as identification of lymph drainage pathways in patients with prostate cancer.

[Clinical value of transperineal saturation biopsy in patients with suspicious for prostate cancer].

The aim of the study was to evaluate clinical value of transperineal saturation biopsy (TPSB) in 52 patients with suspicious for prostate cancer (PCa): 31 - primary patients and 17 - men with non-effective transrectal biopsy. PCa was diagnosed in 31 of 52 (59,6%) patients. Focal lesions revealed in 6 (19,4%), multifocal - in another 25 (80,6%) cases. TPSB is very helpful in primary diagnosis and for therapy planning.

[Use of SPECT-CT for visualization of sentinel lymph nodes in breast cancer patients].

This study was performed in order to determine individual variability of axillary sentinel lymph nodes (SLN) localization in patient with breast cancer (BC). Individual topography of axillary SLN was determined in 182 patients with early BC. All women were candidates for conservative surgical treatment with postoperative radiotherapy. SPECT-CT visualization of SLN started 120-240 min after intratumoral injection of 74-150MBq of 99mTc-radiocolloids. Distribution of axillary SLN was allocated to following subregions: central (C), pectoral (P), apical (AP), lateral (L), subscapular (SSc). SLN visualization by SPECT-CT was successful in 153 cases (84%). AP nodes were detected in 7 patients (5%). SLN were localized on thoracic wall in 34 cases (22%), in the intrapectoral region--in 3 (2%) women. According to axillary levels they were detected on level I--in 149 (97%), level II--15 (10%), level III-- (7.5%) cases.

[Changes in Properties of Water during Germination of Zucchini Seed in Water Used].

In this research the changes in the supramolecular structure of distilled water during germination of the seed in this water were studied. We used three methods: gravimetry, precision thermal analysis, electron work function measurements. In the first stage of seed germination--seed swelling--the seed extracts coherent domains in the water, herewith due to the transition of coherent domains adsorbed in nanofields into a stable state the flow of electromagnetic energy appears. In the second stage of the experiment--germ growing--the flow of biophotons occurs. This is evidenced by the increased water electron work function. A hypothetical model of the process of zucchini seed germination is suggested.

[METHODOLOGIC PROBLEMS OF SENTINEL LYMPH NODE BIOPSY IN PATIENTS WITH BREAST CANCER].

The study included data on 168 patients with breast cancer, surgical treatment of whom was supplemented by axillary dissection (133 patients or 79.2%) or biopsy of sentinel lymph nodes (35 patients or 20.8%). The examination included ultrasound, planar scintigraphy of the breast and zones of regional lymph drainage. In 122 patients with primary breast cancer stage cT1-2N0M0 retrospective analysis of radionuclide imaging sentinel lymph node was performed. In 89 patients the introduction of colloidal radiopharmaceutical was carried out using a particle diameter of not more than 80-100 nm, in 33 patients study was conducted after administration of radiocolloid with a particle diameter of 200 to 1000 nm. Based on the data obtained by scintigraphy and ultrasonography of zones of regional lymph drainage there were offered two diagnostics models: the first, in which the presence of metastatic axillary lymph nodes was established when there were changes according to at least one of the diagnostic methods--scintigraphy or ultrasound; the second, in which the defeat of lymph nodes was determined only in the case of simultaneous detection of ultrasound and scintigraphic evidence of axillary lymph nodes. Sensitivity, specificity, and overall accuracy of the combination of ultrasound and planar scintigraphy axillary lymph nodes using the first model accounted for 82.7%, 67.7% and 74.4%, respectively. In the second model, the specificity was 94.6%, sensitivity--56%. Rapid transport of radiopharmaceuticals from the injection site, a high gradient of radiopharmaceuticals accumulation in sentinel lymph nodes, effective their visualization, approaching to 100%, were undoubted advantages of radiocolloids having a particle diameter up to 100 nm.

[The role of scintimammography with 99mTs-technetril to predict the pathologic status of regional lymph nodes in patients with locally advanced breast cancer after neoadjuvant chemotherapy].

The purpose of this study was to establish the role of scintimammography with 99mTs-technetril for predicting pathological status of regional lymph nodes after neoadjuvant chemotherapy. In 123 primary patients with locally advanced breast cancer stage cT1-4N0-3M0 there was performed scintimammography: before treatment and after 2-3 cycles of neoadjuvant chemotherapy 63 patients; after 2-3 cycles of neoadjuvant chemotherapy and before surgery--in 5 patients; after 4-6 cycles of neoadjuvant chemotherapy--55 women. All patients were divided into 2 groups: the first included 68 patients whom scintimammography was performed before and after 2-3 cycles of neoadjuvant chemotherapy; the second--60 women whom scintimammography was performed before treatment and before surgery. In patients of the first group positive results were obtained in 16 (23.5%), negative--26 (38.3%), false positive--16 (23.5%) and false negative--10 (14.7%) cases. Sensitivity, specificity, overall accuracy, positive predictive value and negative results were 61.5%, 61.9%, 61.7%, 50% and 72.2%, respectively. During the scintimammography after 4-6 cycles of neoadjuvant chemotherapy positive results were observed in 17 (28.3%) negative--18 (30%), false positive--19 (31.7%) and false negative--6 (10%) of patients. Thus, the sensitivity, specificity, overall accuracy, positive predictive value and negative results amounted to 73.9%, 48.6%, 58.3%, 47.2%, 75% respectively.

[High-dose brachytherapy for prostate cancer in real time using 192-IR (specifics of dosimetric planning)].

There were analyzed dosimetric plans obtained during the first session of HDR brachytherapy in 70 primary prostate cancer patients. Assessments were subjected to dosimetric parameters (V100, D90, D2cc, D10) obtained after implantation in the prostate needle-intrastats estimated before and after adjustment of contours of the prostate and surrounding organs at risk. It was showed that in most cases they were matched to the intended dosimetric parameters: V100 average--94,1% (V100 more than 90% in 97.2% of cases), D90 average--104,3% (D90 100% achieved in 95.7% of cases). In contrast, when using primary plan dosimetry without estimation of changing the geometry of the prostate and organs at risk in 38.6% patients V100 value was below 80%, in 41.4% patients--was in the range from 80% to 90%. In 24.3% patients index D90 did not exceed 80%, in 31.4% patients determined in the range from 80% to 90% and in 24.3% patients was close to 100%. In the absence of correction of contours of the urethra and the prostate in 18% patients the value of D10 for the urethra was higher border 115% and could increase to critical 189%.

[The use of SPECT-CT in the diagnosis of cancerous lesions of axillary lymph nodes in patients with breast cancer].

The purpose of the study was to explore the possibilities of a new hybrid technology of SPECT-CT in the diagnosis of metastatic regional lymph nodes (LN) in patients with breast cancer (BC). There were examined 57 primary patients. All patients underwent axillary lymph node dissection and /or biopsy of sentinel LN followed by histological examination of the material. Metastases in LN were verified in 20 (35%) of 57 examined patients. Sensitivity, specificity and overall accuracy of SPECT-CT in the combined use of anatomical and functional criteria for assessing the state of LN accounted for 75%, 89% and 84%, respectively. Sensitivity of SPECT-CT in the diagnosis of massive axillary LN lesion (more than two) in breast cancer patients was 95%. Thus, the new hybrid technology of SPECT-CT, combining functional and anatomical techniques for assessing of pathological changes, is highly informative in the diagnosis of metastatic lesions of regional LN in patients with breast cancer.

[SPECT-CT in the diagnosis of metastatic skeletal lesion].

The aim of this study was to compare the diagnostic capabilities of SPECT-CT and planar osteoscintigraphy with 99m-Tc-labeled phosphates in cancer patients. There were examined 227 patients with various primary malignancies (mean age 57 years). Depending on the identified changes in the planar study patients were divided into four groups: I--no abnormalities (n = 62), II--benign changes (n = 67), III--suspected metastatic lesion (n = 41), IV--metastatic lesion (n = 57). The use of SPECT-CT in group I revealed metastatic lesion in 7 (11%) patients, in 15 (24%) patients there were additionally found benign focal changes in the skeleton. In group II metastases were found in 4 (6%) patients; it was not possible to exclude secondary lesion in 3 (4%) patients. In group III suspected metastatic lesion was excluded in 29 (71%) and confirmed in 7 (17%) patients. In group IV in 14 (25%) patients there were found non-tumor changes, the nature of the changes has not been found in 2 (4%) patients. As a result, SPECT-CT with 99m-Tc-labeled phosphates is more informative method of diagnosis of metastatic skeletal lesion than planar osteoscintigraphy. SPECT-CT application resulted in changes of conclusions of the planar scintigraphy about the nature of bone pathology in 67 (30%) cancer patients. However, in 4% the recognition of the nature of changes in the skeleton has failed.

[Role of single-photon emission-computed tomography and x-ray computed tomography in diagnosing lymphatic metastases in patients with non-small cell lung cancer].

Single photon emission tomography (SPECT) with 99mTc-MIBI was performed after conventional staging in 83 operated non-small cell lung cancer (NSCLC) patients. Diagnostic results of SPECT and conventional computerized tomography (CT) staging were validated by histological examinations of operation material. According to histological verification 35 of 83 evaluated patients had lymph node (LN) invasion by NSCLC. SPECT detected LN involvement in 28 of these 35 patients and was false positive in additional 16 patients. Pneumonia or atelectasis were detected in 12 of 16 patients with false positive SPECT results. Sensitivity (Sen), specificity (Sp), accuracy (Ac), positive (PPV) and negative (NPV) predictive values of SPECT in diagnosis of LN invasion by NSCLC was as follows: 80%, 66%, 72%, 65%, 82%. Diagnostic accuracy of CT for detection of LN involvement was inferior to SPECT: Sen--71%, Sp--62%, Ac--66%, PPV--58%, NPV--75%. Combination of SPECT and CT data offer promising solutions with Sen reached 94% or high Sp which in patients without atelectasis or pneumonia can reach 96%.

[The use of SPECT-CT with 99mTc-labeled phosphates in patients with suspected skeletal metastases in planar bone scintigraphy].

We assessed the diagnostic capabilities of SPECT-CT in patients with unclear and suspicious on the secondary lesion with bone scintigraphy background in planar mode (227 patients (mean age - 57 years) with various primary malignancies). All patients underwent planar scintigraphy with 99mTc-labeled phosphates in the "whole body" mode and then - bizonal single-photon-emission computed tomography combined with X-ray computed tomography (SPECT-CT). In patients with the presence of lesions in the skeleton, suspicious on metastases, there was conducted comparison with the data of SPECT-CT. During planar investigation the suspicion on metastases was detected in 41 patients (18%). The use of SPECT-CT allowed excluding metastases in 29 (71%) and confirmed in 7 (17%) of them. In 5 (12%) cases the nature of the changes remained unclear. Thus, in cancer patients with revealed by planar bone scintigraphy unclear or suspicious for metastatic foci in the skeleton, the use of SPECT-CT allowed in most cases (88%) to clarify the nature of these changes.

[Effectiveness of mammary scintigraphy for determining the results of neoadjuvant polychemotherapy in breast cancer].

Analysis of mammoscintigraphy is presented to assess the effectiveness of neoadjuvant polychemotherapy for locally advanced breast cancer. In 90% of patients there is defined conformity of scintigraphy data on the effectiveness of performed polychemotherapy to the results of histologic examination of the postoperative material. The sensitivity of scintigraphy in assessing the effectiveness of neoadjuvant polychemoterapy was 83.3%, specificity--87.9%, accuracy--86.3%, predictive value of positive and negative results-78.9% and 90.1%, respectively. Mammoscintigraphy is an effective method to control the response of locally advanced breast cancer to neoadjuvant polychemotherapy.

[Markers of effectiveness of preoperative taxane-based chemotherapy for locally advanced breast cancer].

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

[Methodological issues of sentinel lymph nodes biopsy in patients with breast cancer].

Radionuclide imaging of sentinel lymph nodes (SLN) was performed in 122 breast cancer patients, which before the biopsy of lymph nodes it was performed intratumoral injection of colloidal radiopharmaceuticals (RFP): in 89 patients--nanocolloidal (NC) and in 33--colloidal with particle size from 200 to 1000 nm. After the introduction of NC the SLN image was obtained in 83 of 89 women. (93.3%). After the introduction of large colloids (200-1000 nm or more) SLN visualization in this group was achieved in 27 of 33 patients, i.e., in 81.8% of cases (p < 0.05). Along with the axillary SLN, in 55.8% of cases SLN image was obtained in parasternal area and/or lymph nodes of the second and higher orders in axillary as well as under-and supraclavicular regions. On the contrary while using larger colloids, RFP accumulated only in SLN of axillary region in 85.1%. These differences in the topography of the absorption of various diameters radiocolloids were reliable (p = 0.01). Using the NC RFN compared with colloidal RFP of larger diameter can reliably improve SLN visualization till 98.9% however leads to a concomitant accumulation of RFP in lymph nodes of the second order in 55.8% of patients.

[Combined use of 99mTc-MIBI scintigraphy and ultrasonography (US) in the diagnosis of axillary lymphatic metastasis in patients with breast cancer].

We aimed to evaluate different imaging strategies for diagnosis of axillary LNMs in patients with primary breast cancer (BC). 168 consecutive patients with primary BC were included in the study. Functional imaging by scintigraphy (AxSc) with 99mTc-MIBI was performed in static and tomography modes 15 min after i/v injection. Focal areas of tracer accumulation in axial region were considered as sings of LNMs. Ultrasound (US) examination of axillary region was performed on 7.5 kH scanner. Nodes with diameter more than 1 cm were considered abnormal. All patients were operated with axial LN dissection and subsequent histological evaluation. Scintigraphic signs of LNMs revealed in 65 patients: 48--true positive, 17--false positive. Among 103 women with normal AxSc results 27 had LNMs and 76--uninvolved nodes. Sensitivity (Sen), Specificity (Sp) and Accuracy (Ac) of AxSc were as follows: 64%, 82% and 74%. Sonography diagnosed LNMs in 74 women: 56 were metastatic on histology while other 18--uninvolved. On the contrary, 19 of 94 US normal sized nodes were metastatic on histology. US had following values when used for diagnosis of axillary LNMs: Sen--75%, Sp--81%, Ac--78%. When LNMs were diagnosed as the combination of concordantly abnormal US and AxSc examinations Sp reached 95%, Sen dropped down to 56% and Ac--to 77%. Another model was based on the assumption that LNMs must be diagnosed in all patients with abnormal US or AxSc examinations. According to this strategy Sen reached 83%, Sp--68% and Ac--74%. Thus, we found comparative accuracy of US and AxSc in diagnosis of axillary LNMs in patients with primary BC. Combination of both modalities can significantly improve sensitivity (83%) or specificity (95%) of final conclusion which is determined by established diagnostic strategy and criteria's that are used for BC diagnosis.

[Use of simultaneous double-tracer SPECT with 99m-Tc-technetril and 67-Ga-citrate for follow-up of patients with non-small cell lung cancer].

In 20 primary patients with focal abnormalities on conventional CT we evaluated diagnostic properties of simultaneous double-tracer SPECT. Scintigraphy was performed as a single examination with simultaneous registration of 67Ga and 99mTc-MIBI. Image acquisition was started 48-74 hours after IV injection of 130-175 MBq 67Ga-citrate and immediately after IV injection of 500-740 MBq of 99mTc-MIBI. All images for each agent were classified as positive and negative for primary tumor, N1 and N2 lymph-nodes (LN). According to histology 18 of 20 evaluated patients had non-small cell lung cancer (NSCLC), the other two patients had tuberculosis and nonspecific inflammation. SPECT with 99mTc-MIBI correctly visualized tumor in 18, 67Ga allowed correct visualization in 16 cases. Both tracers were truly negative in a patient with tuberculosis and false positive in a patient with nonspecific inflammation. Double-tracer SPECT was slightly more specific than CT in primary lesions. In 18 patients histological verification of LN status was obtained: NO was revealed in 9 cases, N1 in 4 and N2 in 5 cases. Both tracers correctly discriminated LN-positive and LN-negative cases with 94% specificity. On the contrary, CT was false-positive in 3 and false-negative in another 5 patients. Differentiation between N1 and N2 LN involvement is crucial for therapy planning. 99mTc MIBI and 67Ga revealed N1 in 2 cases and N2 in 4 cases, the diagnosis was later verified by postoperative morphology. In 2 patients SPECT overestimated extent of LN involvement and LN status was changed after surgery from N2 to N1. In 18 patients results of 99mTc-MIBI and 67Ga augmented each other. Accuracy of LN staging by SPECT with 99mTc-MIBI and 67Ga was 83%. CT accurately determined LN stage only in 7 patients, it was overestimated in 7 and underestimated in 4 cases. SPECT with 99mTc-MIBI and 67Ga demonstrated high overall accuracy in diagnostics of regional LN invasion for patients with NSCLC. Diagnostic value of conventional CT was significantly lower. Correct level of LN involvement was determined by SPECT in 83% of cases.