In this paper, possibilities of laser fluorescence spectroscopy to predict the reactions of the oral cavity cancer to radiation treatment are considered. A theoretically substantiated assumption about the link between the tumor’s consumption of an exogenous photosensitizer and its radioresistance is proposed. The first experience with the use of the Radahlorin photosensitizer is described; preliminary results of the 5 patients study are presented. As a result different photosensitizer consumptions versus different treatment outcomes are discussed.

Background: Cancer of the parotid salivary gland (PSG) accounts for more than a half of all cases of salivary gland malignancies. Its treatment strategy remains a matter of debate. Aim : To identify factors significantly associated with the 3-year survival of patients with PSG cancer after combination treatment. Materials and methods : Thirty nine patients with morphologically confirmed PSG cancer (T1-4N0) were recruited into the study. Surgery (partial or total parotidectomy without the cervical lymphatic node dissection) was performed in 32 patients. The most frequent diagnosis (n = 10; 25.6% of all cases) was adenocarcinoma. Radiation to PSG and the regional lymphatic nodes was used in 15 patients as neoadjuvant and in 24 as adjuvant regimen. Three-year survival rates were analyzed in 36 patients by the Kaplan-Meier method, with consideration of their sex, age and the sequence of surgical and radiation treatment. Results : The 3-year survival after combination treatment of PSG cancer patients was 82.7%. Women, patients above 60 years of age and those who received adjuvant radiation therapy demonstrated a trend towards better 3-year survival, although it was non-significant (p > 0.05). Conclusion : Combination strategy remains an effective approach to PSG cancer irrespective of age and sex of patients. The use of radiation therapy as a single modality is possible only in exceptional cases.

Background: Cancer of the parotid salivary gland (PSG) accounts for more than a half of all cases of salivary gland malignancies. Its treatment strategy remains a matter of debate.Aim: To identify factors significantly associated with the 3-year survival of patients with PSG cancer after combination treatment.Materials and methods: Thirty nine patients with morphologically confirmed PSG cancer (T1-4N0) were recruited into the study. Surgery (partial or total parotidectomy without the cervical lymphatic node dissection) was performed in 32 patients. The most frequent diagnosis (n = 10; 25.6% of all cases) was adenocarcinoma. Radiation to PSG and the regional lymphatic nodes was used in 15 patients as neoadjuvant and in 24 as adjuvant regimen. Three-year survival rates were analyzed in 36 patients by the Kaplan-Meier method, with consideration of their sex, age and the sequence of surgical and radiation treatment.Results: The 3-year survival after combination treatment of PSG cancer patients was 82.7%. Women, patients above 60 years of age and those who received adjuvant radiation therapy demonstrated a trend towards better 3-year survival, although it was non-significant (p > 0.05).Conclusion: Combination strategy remains an effective approach to PSG cancer irrespective of age and sex of patients. The use of radiation therapy as a single modality is possible only in exceptional cases.

Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells. Materials and methods: The study was performed in 517 patients with basal cell (n = 361) and squamous cell (n = 156) skin cancer, 274 (53%) of whom had T2 and 243 (47%), T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm²). The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation) from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05). In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was equally effective, irrespective of the use of metronidazole: the immediate cure rate was 94.8 ± 2.2% (92/97 patients) in the metronidazole group and 89.8 ± 3.9% (53/59) in the control group. With the combined radiation therapy of T2 basal skin cancer patients with the tumor size of 4–5 cm, the immediate cure rate was increased significantly from 73.2 ± 6.9% (30/42) in the control group to 88.2 ± 3.7% in the metronidazole group (67/76) (р < 0.05). With distant gamma-therapy of T3 basal cell skin cancer, this parameter was increased from 70.5 ± 6.8% (31/44) in the control group to 88.4 ± 4.8% (38/43) in the metronidazole group (р < 0.05). The radiation-sensitizing effect of metronidazole and low intensity laser combined with the distant gamma-therapy of T3 basal cell skin cancer was significant and similar: the immediate cure rate with the use of metronidazole was 85.9 ± 4.6% (49/57), and with the use of low intensity laser, 84.6 ± 5.0% (44/52), compared to 66.0 ± 6.9% (31/47) in the control group (р < 0.05). Although the relapse rate after radiation therapy with metronidazole or low intensity laser was lower by 5–11%, compared to that after the radiation without modifiers, there was no statistically significant difference after a 3-year follow-up. Conclusion: A significant benefit of radiation therapy combined with radiation sensitizers on the immediate cure rate of locally-advanced basal cell skin cancers was confirmed. It seems that radiation sensitizers of hypoxic cells do improve immediate results of cure without any significant effect on tumor relapse rate in the future.

Background: Laser fluorescence spectroscopy (LFS) is widely used in various medical areas, oncology being the most known of them. In general, the LFS is used for in vivo diagnostics of tumors. Recent studies have shown that this method could be used for diagnostics of local inflammation, induced by thermal or mechanical injury. It is of interest if LFS could be used for assessment of soft biological tissue injury caused by radiation exposure. Aim: To study fluorescence of an exogenous photosensitizer and its changes over time in the radiation injury area by LFS method in vivo. Materials and methods: The experiment was done in 12 outbred SHK mice whose right hind limbs were irradiated using a gamma-therapy device ROKUS-AM (source, 60Co, at dose of 15 Gy). Before irradiation, the photosensitizer Photosens was administered to all animals intraperitoneally at dose of 2.5 mg/kg. For 21 days fluorescence was assessed in vivo with a laser diagnostic system LAKK-M in the “fluorescence” operation mode, with an excitation wavelength of 635 nm. At days 7 and 21, tissue samples from the irradiated areas of the model animals were studied histologically and differential blood cell counts were assessed simultaneously. Results: The LFS method showed an increase in the accumulation of the photosensitizer in the affected area, compared to an intact contralateral area, with higher signal intensity from the irradiated limb. The changes in the fluorescence signal from the affected over time had two characteristic peaks at days 3 and 14, probably reflecting the stage of local radiation injury. Conclusion: The use of LFS with an exogenous photosensitizer has a potential for a personalized assessment of radiation reactions in radiology.

Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells.Materials and methods: The study was performed in 517 patients with basal cell (n = 361) and squamous cell (n = 156) skin cancer, 274 (53%) of whom had T2 and 243 (47%), T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm²). The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation) from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05). In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was equally effective, irrespective of the use of metronidazole: the immediate cure rate was 94.8 ± 2.2% (92/97 patients) in the metronidazole group and 89.8 ± 3.9% (53/59) in the control group. With the combined radiation therapy of T2 basal skin cancer patients with the tumor size of 4–5 cm, the immediate cure rate was increased significantly from 73.2 ± 6.9% (30/42) in the control group to 88.2 ± 3.7% in the metronidazole group (67/76) (р < 0.05). With distant gamma-therapy of T3 basal cell skin cancer, this parameter was increased from 70.5 ± 6.8% (31/44) in the control group to 88.4 ± 4.8% (38/43) in the metronidazole group (р < 0.05). The radiation-sensitizing effect of metronidazole and low intensity laser combined with the distant gamma-therapy of T3 basal cell skin cancer was significant and similar: the immediate cure rate with the use of metronidazole was 85.9 ± 4.6% (49/57), and with the use of low intensity laser, 84.6 ± 5.0% (44/52), compared to 66.0 ± 6.9% (31/47) in the control group (р < 0.05).Although the relapse rate after radiation therapy with metronidazole or low intensity laser was lower by 5–11%, compared to that after the radiation without modifiers, there was no statistically significant difference after a 3-year follow-up.Conclusion: A significant benefit of radiation therapy combined with radiation sensitizers on the immediate cure rate of locally-advanced basal cell skin cancers was confirmed. It seems that radiation sensitizers of hypoxic cells do improve immediate results of cure without any significant effect on tumor relapse rate in the future.

Early results of complex experimental investigations on the study of instrumental and methodological errors of diagnostics in noninvasive medical spectrophotometry are described. Physical and technical sources and factors of errors are considered for measurements using nonbiological simulation measures. It is shown that the geometric and spectral characteristics of the optical elements and photodetectors, and also selected models and data-processing algorithms in the computer software of the instruments, have the greatest effect on the diagnostic errors.

Early results of complex experimental investigations on instrumental and methodological errors of diagnostics in noninvasive medical spectrophotometry are described. Medicobiological sources and factors of errors are considered for natural measurements under clinical conditions. It is shown that the greatest contribution to the total measurement error is made by the interactive component, due to the interaction of the measurement instruments and objects.

Temperature fields on the surface of skin and the parameters of the microcirculation of blood in the skin accompanying various procedures of low-intensity laser therapy have been investigated by means of an IRTIS-2000ME digital thermograph and a LAKK-M spectrophotometric diagnostic complex. It is shown that changes of the parameters of the microcirculation of the blood in the skin accompanying both surface laser procedures and intravenous laser irradiation of the blood, if they were observed, were always accompanied by changes of the temperature of the skin surface. (C) 2011 Optical Society of America.

This report, as a continuation of 8-years research on the problem of noninvasive clinical fluorescence diagnostics efficiency, discusses a hypothesis of influence of a chronic hypoxia state in soft alive tissues on the intensity of a laser-induced endogenous porphyrins' autofluorescence in a red region of optical spectra. Earlier this hypothesis was proposed on the basis of analysis of fluorescence activity for erosive-ulcerative impairments of the upper part of a gastrointestinal tract (SPIE Proc., vol. 4613, 2002. - p.286-294). Today the hypothesis additionally is confirmed by means of observation after patients with another illness and by means of analysis of some well-known literature data. An authors' methodology of clinical trails to verify the hypothesis using an up-to-date noninvasive fluorescence diagnostic technique is presented as well. Both theoretical reasons and all new clinical data show that the chronic hypoxia state can be one of the major factors of appearance of a large and abnormal laser-induced autofluorescent signal from biotissues in the spectrum range 600-800 nm, which is associated with abnormally high accumulation of endogenous porphyrins in the tissues. So, the noninvasive autofluorescent diagnostic technique could be a powerful tool to estimate in vivo a chronic hypoxia condition in soft biotissues. For that purpose a classification of chronic hypoxia levels versus in vivo autofluorescence contrast coefficients in tissues is proposed as well.

Paper discusses an accuracy, reliability and reproducibility of "in vivo" laser fluorescent diagnostics (LFD) in medicine. Modern equipment and calibration standards for LFD are discussed as well. It is shown, that, in spite of the fact that formal random errors of "in vivo" instantaneous fluorescent measurements have been previously evaluated on a level of 30-40%, the medical accuracy and reliability of LFD could reach a quite high and informative level. Most of the formal "random" disperses in results of the single "snapshot" measurements are associated with a changeable and alive character of the object of diagnostics.

Based on an analysis of various clinical data, the assumption was recently expressed that the often observed in vivo increased fluorescence of endogenous porphyrins in living biological tissues is a consequence of the status of chronic hypoxia in the tissues. Starting from this, this article discusses the accuracy, reproducibility, and information content of methods of in vivo laser fluorescence diagnosis (LFD) in actual clinical practice. It is shown that, despite the random error of single measurements in LFD of 30–40% established earlier, the accuracy and reliability can reach a fairly high level when the results of the diagnosis are interpreted. The formal random scatter in the results of single measurements is largely determined not by the instrumental error but by the methodological error and by the living and changeable character of the object of diagnosis, especially at the level of the blood-microcirculation system.

The laser "in vivo" autofluorescence diagnostics is now widely studied and applied in different areas of medicine, such as an oncology, dermatology, etc. Recently we have reported of created new professional multiwave laser diagnostic system (MLDS) for this, purpose under the international scientific research and development project #1001 supported by the International Scientific and Technology Center. This presentation lights some results of application of the MLDS in a real clinical practice at Moscow Regional Research and Clinical Institute "MONIKI", Department of Radiology. With the use of MLDS we investigated a skin and oral cavity cancer endogenous fluorescence before, during and after standard radiotherapy treatment. A statistical analysis showed that the best radiotherapy result was achieved for the patients with a small initial porfirines' autofluorescence and a great initial flavines' one from irradiated tumor tissues. It was shown that each radiotherapy procedure has an influence on a tissues' autofluorescence intensity. The tendencies in porfirines' fluorescence during a treatment course can be an additional prognostic factor for the prediction of the efficacy of a radiotherapy treatment. Moreover, it was estimated that a number of non-cancerous skin disease has a typical "cancer" initial autofluorescence, that makes it difficult to distinguish them one from another with the use of only the fluorescence diagnostics, but opens the way to investigate the non-cancerous tissues diseases with the help of tissues endogenous fluorescence phenomenon.

The paper presents an attempt to increase the effectiveness of radiotherapy of locally advanced skin cancer by use of radiomodifiers. With this aim the researchers used metronidozol (MZ) and low-intensive laser emission (LILE), whoes radiosensibilizing activity is based on overcoming radioresistance of tumor hypoxic cell fraction. In order to increase MZ concentration in the tumor and eleminate its toxic effect the authors developed a new radiosensibilization technique, implying local use of a drug applicator. The technique is based on use of textile materials with specifed medical qualities (the method of their production was developed by the Scientific and Practical Association "Textileprogress"). The second direction of the research consisted in use of low-intensive laser emission as a radiosensibilizer, which was considered to be possible due to theoretical and experimental data suggesting the LILE capability of activating microcirculation in tumor and surrounding tissues. According to the authors of the article, the improvement of tumor microsirculation must increase tumor cell oxygenation, thus increasing their radiosensitivity. Applying radiosensibilization of hypoxic cells with MZ and LILE in radiotherapy of T2 basal cell and squamous cell carcinomas with the tumor size 4-5 cm and T3 tumors using original dose fractioning regimens (TFD 72 to 73 Gy) allows significant improvement of immediate treatment results without increase in local radioreactions and without substantial influence of the recurrence rate.

Today the noninvasive (in vitro, in situ) and real-time methods of diagnostics are desirable for general clinical practice. One of such promising technique is the optical multi-wave diffusion and absorption spectrophotometry. It allows a doctor to measure a number of important medical and biological (M&B) parameters such as the blood microcirculation parameters into the soft tissues, contents of the hemoglobin fractions into the periphery blood, etc. The use of the new components of the microelectronics and optics and development of new approaches to the diagnostic data processing makes it possible to design a number of small and effective devices for this purpose. The basic principle of work of them in means of hardware function is the multi-wave light scanning of the tested tissue’s area and detecting a backscattered light. In means of software function the basic principle of work of them is the inverse optical task solution when the optical and corresponding M&B parameters of the tested medium are calculated from the measured backscattered spectral optical data. This report presents one of such designed portable apparatus “Spectrotest” developed in cooperation with Moscow Regional Research and Clinical Institute of “MONIKI”. This device allows a doctor to register the index of melanin pigmentation of the skin, the volume of the blood in the tested tissue and the average hemoglobin saturation of the peripheral blood. All this parameters are available for a doctor to see them on the monitor screen in real-time mode directly during any diagnostic or treatment procedure. For that a new modified light scattering theory with the analytical solution of the main equations has been developed. Analytical solution allows the software to calculate and indicate the measured M&B parameters on the computer’s monitor screen during less than one second. Today the developed diagnostic system “Spectrotest” is used in real clinical practice in “MONIKI” and in the Oncology Center of the Russian Academy of Medical Science for the medical research aims. The general hardware and software composites of this diagnostic apparatus and examples of the application of it for the functional diagnostic tests are presented in this report as well.

The efficiency of noninvasive laser fluorescent diagnostics for the real clinical practice is now widely discussed in special publications. One of the most perspective application area of this diagnostic technique is the oncology. For that the overwhelming majority of the research is concentrated now in the problem of the differential diagnostics of the "normal-tumor" case for different localizations and clinical forms of the young tumors. Meanwhile, the fluorescent diagnostics can has high possibilities also as a monitoring of the efficiency for different methods of tumors treatment, the radiotherapy for instance. In this report the examples of the use of laser noninvasive fluorescent diagnostics in a real clinical practice of the Radiological Department of MONIKI are presented. There was under our investigation the group of around 100 patients with different oral mucosal tumors, for whom a course of a radiotherapy treatment was purposed and for whom the research background fluorescent noninvasive monitoring was applied during the course of the care. In the report the efficiency of such laser fluorescent monitoring is discussed. It is shown that there were the strong differences in fluorescent spectra for both different forms of mucosal tumor and for the same one. In the number of clinical cases there were not marked any special fluorescent signal for a mucosal strong tumor before a treatment. During the radiotherapy treatment the different responses in fluorescent spectra were observed as a reaction of tissues after the single gamma-ray exposure and daily one as well. All this presented results allow us to propose a non-quite correct existed explanation of the nature of the biotissues fluorescent phenomenon in meaning of the diagnostics of soft tissue cancer cases.