Išplitusio sensibilizuoto krūties vėžio diagnostika ir gydymas

Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08406 Vilnius 2 Klaipėdos universitetas, Herkaus Manto g. 84, LT-92294, Klaipėda El. paštas: [email protected] Tikslas Nustatyti sensibilizuotų navikų terapijos galimybes gydant išplitusį krūties vėžį. Ligoniai ir metodai Nuo 2001 m. 54 ligonėms išplitusiam krūties vėžiui gydyti taikyta sensibilizuotų navikų terapija (SNT). 53 ligonėms rastos dauginės metastazės. Metastazės smegenyse diagnozuotos 19 ligonių, kauluose – 29, kepenyse – 15, plaučiuose – 12, limfmazgiuose – 16, minkštuosiuose audiniuose – 13 ir odoje – 15 ligonių. Taikydami SNT į veną suleisdavome 2,5 mg/kg hematoporfirino darinio (HpD) ir jis po 24 val. selektyviai susikaupdavo navikiniame audinyje. Praėjus 24 val. po HpD suleidimo jam aktyvinti navikus apšviesdavome raudona 635 nm šviesa – tai vadinamoji fotosensibilizuotų navikų terapija (FDT), ir (arba) taikydavome radiosensibilizuotų navikų terapiją (RST) – praėjus 24, 48 bei 72 val. po HpD suleidimo naviką apšvitindavome 60Co skleidžiamais gama spinduliais 2 Gy doze. Suminė dozė – 6 Gy. RST taikėme visoms 54 ligonėms. FDT taikėme: 16 ligonių vietiškai krūtinės odoje ir poodyje išplitusiam vėžiui gydyti bei 1 ligonei metastazei akies tinklainėje gydyti. Visų odos ir poodžio navikų riboms patikslinti taikėme ir fotodinaminę diagnostiką. Praėjus 24–78 val. po HpD suleidimo, įtartinus odos plotus apšviesdavome violetine 405 nm šviesa. Navikinis audinys švytėdavo avietine spalva. Rezultatai Pritaikius SNT 54 ligonėms išplitusiam krūties vėžiui gydyti, 33 pacientėms per 7–10 dienų po RST labai pakilo Karnovskio indeksas, šešioms pacientėms visi navikai visiškai regresavo, 14 moterų visi gydyti navikai regresavo daugiau nei 50 %, ligos remisija truko ilgiau nei 6 mėn. Šešiolika ligonių navikų regresija buvo dalinė, 18 ligonių gydymas buvo neveiksmingas. SNT buvo ypač efektyvi krūties vėžio metastazėms smegenyse ir kauluose gydyti. Vienai ligonei po dviejų RST kursų visiškai išnyko visos trys metastazės galvos smegenyse. Šešioms ligonėms visos metastazės smegenyse regresavo daugiau nei 50 %, ligos remisija truko daugiau nei 6 mėnesius. Dauginių krūties vėžio metastazių smegenyse turinčių 19 ligonių vidutinis išgyvenamumas nuo metastazių smegenyse diagnozavimo buvo 12 mėnesių. Pritaikius RST 29 ligonėms dauginėms krūties vėžio metastazėms kauluose gydyti, 7 ligonėms gauta visiška visų dauginių kaulinių metastazių regresija. Ligos remisija (moterys buvo kliniškai sveikos) truko 95; 48; 21; 19; 12; 11 ir 4 mėn. nuo RST. Išvados Sensibilizuotų navikų terapija yra perspektyvus išplitusio krūties vėžio gydymo metodas. Šis metodas ypač veiksmingas gydant krūties vėžio metastazes galvos smegenyse ir kauluose. Tikslinga toliau tyrinėti šį gydymo metodą, siekiant jį modifikuoti pagal ligos išplitimą ir metastazių lokalizaciją. Reikšminiai žodžiai: išplitęs krūties vėžys, sensibilizuotų navikų terapija, hematoporfirino darinys. Sensitized treatment and diagnostics of advanced breast cancer Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilnius University, Institute of Oncology, Santariškių Str. 1, LT-08406 Vilnius, Lithuania 2 Klaipėda University, Herkaus Manto Str. 84, LT-92294, Klaipėda, Lithuania E-mail: [email protected] Background / objective The current methodologies used in oncology are of quite limited possibilities. Therefore, there is a constant search for the new perspective treatment methods that could prolong the life of cancer patients and improve its qualitaty. One of such methods is sensitized tumour therapy based on quite selective porphyrin accumulation in tumours. This study presents our primary results in radiosensitized advanced breast cancer therapy using hematoporphyrin derivatives as photo-and radiosensitizers. Patients and methods In 2001–2010, a total of 54 female patients with advanced breast cancer underwent radiosensitized treatment (RST). All patients had undergone chemotherapy and / or radiotherapy and surgical treatment before RST. In all cases, any radical method of treatment was impossible. Multiplex metastatic lesions were established in 53 patients. Brain multiplex metastases were diagnosed in 19 patients and multiplex bone metastases in 29 patients. Lung metastatic lesions were found in 12 patients, liver in 15 patients, lymph node metastases in 16 patients. The hematoporphyrin derivative was injected intravenously; 24, 48 and 72 hours after injection of the sensitizer, the tumorus were irradiated with gamma rays from radioactive 60Co, 2 Gy at a time (6 Gy per course). In all cases when it was possible, patients undervent also photodynamic therapy. Tumours were irradiated with red 630 nm laser light. Results As a result of RST, complete regression of all treated tumours was observed in 6 patients after two or more RST courses. A significant response – regression of more than 50% of all brain metastases and remission of the disease for over 6 months – was established in 14 patients. Partial response was observed in 16 patients with malignant brain tumours. For the rest of 18 patients the treatment was ineffective. The Karnofsky performance scale index increased immediately in 33 patients following RST treatment. RST was especially effective in the treatment of brain and bone metastatic lesions. As regards brain metastazes, in one patient all three brain metastatic lesions completely disappeared and there were no evidence of any recurrence in brain for 8 months. In 6 patients, regression of more than 50% of all brain metastases and remission of the disease for over 6 months was established. The median survival of 19 patients with multiplex brain metastases was 12 months from the moment of brain metastases detection. As regards bone metastazes, as a result of RST, all metastatic bone lesions completely disappeared in 7 patients. Conclusion Radiosensitized advanced metastatic breast cancer treatment is a hopeful method, especially when lesions involve the brain and bones. Keywords: advanced breast cancer, radiosensitized treatment, hematoporphyrin derivative

Photodynamic (fluorescence) diagnostics of skin lesions.

The diagnostic value and methodological features of photodynamic (fluorescence) diagnostics in skin lesions were analysed during the study. In addition, fluorescence induced by different photosensitizer precursors (5-aminolevulinic acid and methyl aminolevulinate) was compared. The possibilities of photodynamic diagnostics in skin lesions using light sources with different wavelength were investigated in this study. The optimal wavelength of light for inducing fluorescence in skin lesions was determined in order to diagnose tumours of different histological types (i.e. squamous cell carcinoma, basal cell carcinoma and premalignant lesions). The differences of fluorescence in malignant and premalignant skin lesions were evaluated. Photodynamic diagnostics furthermore was used as method of visualisation helping to delineate exact margins of skin tumour before and during the treatment and to achieve thoroughness of treatment in patients with malignant epithelial skin tumours

Fluorescence diagnostics of skin tumors using 5-aminolevulinic acid and its methyl ester

Objective. The incidence of malignant skin tumors is rapidly increasing. Early diagnosis, determining the margins of the tumor, is extremely important to achieve good treatment results. We investigated fluorescence of protoporphyrin IX in skin carcinomas. The study aimed to compare the effectiveness of topical 5-aminolevulinic acid and methyl-aminolevulinate in determining the exact margins of skin tumors. Materials and methods. Fluorescence measurements were performed in 126 patients with malignant, premalignant, and benign skin lesions for detection of the margins of squamous cell carcinoma and basal cell carcinoma. 5-Aminolevulinic acid or its methyl ester was applied to the skin lesion for 2–4 h, and the data of evaluated protoporphyrin IX fluorescence were correlated with the data of morphological tissue examination. Results. Malignant tissue shows a specific red fluorescence when illuminated with blue-violet light, whereas no fluorescence was observed in normal skin. In 30% of cases, the delineation of neoplastic lesions excited by 5-aminolevulinic acid was slightly weaker than using methyl-aminolevulinate. A sensitivity of 95.4% and a specificity of 88.6% as well as positive and negative predictive values of 86.1% and 96.3%, respectively, were obtained. Conclusions. Fluorescence diagnostics can be used for complete visualization of malignant skin lesions after topical application of 5-aminolevulinic acid or methyl aminolevulinate. It has been shown to be highly effective in the diagnostics of malignant superficial skin lesion. This method is applicable for detecting early superficial tumors, margins of tumors, and follow-up after therapy. Topical application of methyl aminolevulinate is slightly superior to 5-aminolevulinic acid in detection of lesion margins

Žiurkių C6 gliomos ląstelių įjautrinimas porfirinais prieš jonizuojančiąją spinduliuotę

Background. Radiosensitizers are used in order to increase the efficacy of radiotherapy. Most of the presently known radiosensitizing agents have a poor selectivity and are not tumour-specific. Porphyrins have a selective uptake in tumour relative to the surrounding normal tissue. The aim of the present work was to test the capability of two photosensitizers - hematoporphyrin derivative (HpD) or temoporfin (mTHPC) - and gamma rays to produce some kind of selective inhibition of tumour cell proliferation. Materials and methods. Dark toxicity experiments were carried out using a sensitizer concentration range 0-50 μg/ml for HpD, or 0-5 μg/ml for mTHPC. For the radiosensitized treatment of rat C6 glioma cells, HpD was added at a final concentration of 1 μg/ml and mTHPC at a final concentration of 0.1 μg/ml. The irradiation with gamma rays was performed using doses ranging from 0 to 8 Gy. Cell survival was determined using the colony forming assay. Results. HpD (1 μg/ml) and mTHPC (0.1 μg/ml) were found to have no toxic effects on C6 glioma cells. A cytotoxic dose without drugs, inducing a reduction in colony survival by 20%, was achieved at 2 Gy and by 50% at 4 Gy. The radiosensitized treatment of cells with HpD resulted in a significant (p ≤ 0.05) decline in cell survival as compared with irradiation alone. For C6 treated with mTHPC, the results did not differ between the two groups (with and without the drug). Conclusions. The results of this study have shown that mTHPC (0.1 μg/ml) does not act as a radiosensitizer, whereas HpD can act, under certain conditions, as a tumour radiosensitizer. These findings suggest that HpD is a potential agent in combination with radiation therapy of malignant gliomas

Sensitization of rat C6 glioma cells to ionizing radiation by porphyrins

Background. Radiosensitizers are used in order to increase the efficacy of radiotherapy. Most of the presently known radiosensitizing agents have a poor selectivity and are not tumour-specific. Porphyrins have a selective uptake in tumour relative to the surrounding normal tissue. The aim of the present work was to test the capability of two photosensitizers - hematoporphyrin derivative (HpD) or temoporfin (mTHPC) - and gamma rays to produce some kind of selective inhibition of tumour cell proliferation. Materials and methods. Dark toxicity experiments were carried out using a sensitizer concentration range 0-50 μg/ml for HpD, or 0-5 μg/ml for mTHPC. For the radiosensitized treatment of rat C6 glioma cells, HpD was added at a final concentration of 1 μg/ml and mTHPC at a final concentration of 0.1 μg/ml. The irradiation with gamma rays was performed using doses ranging from 0 to 8 Gy. Cell survival was determined using the colony forming assay. Results. HpD (1 μg/ml) and mTHPC (0.1 μg/ml) were found to have no toxic effects on C6 glioma cells. A cytotoxic dose without drugs, inducing a reduction in colony survival by 20%, was achieved at 2 Gy and by 50% at 4 Gy. The radiosensitized treatment of cells with HpD resulted in a significant (p ≤ 0.05) decline in cell survival as compared with irradiation alone. For C6 treated with mTHPC, the results did not differ between the two groups (with and without the drug). Conclusions. The results of this study have shown that mTHPC (0.1 μg/ml) does not act as a radiosensitizer, whereas HpD can act, under certain conditions, as a tumour radiosensitizer. These findings suggest that HpD is a potential agent in combination with radiation therapy of malignant gliomas

Autentiška geroji patirtis

Autoriai išvardyti straipsnio pradžioje | Projektas neįgaliesiems studentams „Studijų prieinamumo didinimas“Kauno kolegijaKlaipėdos universitetasTeologijos katedraVilniaus universitetasVytauto Didžiojo universitetasŠiaulių universitetasŠvietimo akademij

Sensitized treatment and diagnostics of advanced breast cancer

Results. As a result of RST, complete regression of all treated tumours was observed in 6 patients after two or more RST courses. A significant response – regression of more than 50% of all brain metastases and remission of the disease for over 6 months – was established in 14 patients. Partial response was observed in 16 patients with malignant brain tumours. For the rest of 18 patients the treatment was ineffective. The Karnofsky performance scale index increased immediately in 33 patients following RST treatment. RST was especially effective in the treatment of brain and bone metastatic lesions. As regards brain metastazes, in one patient all three brain metastatic lesions completely disappeared and there were no evidence of any recurrence in brain for 8 months. In 6 patients, regression of more than 50% of all brain metastases and remission of the disease for over 6 months was established. The median survival of 19 patients with multiplex brain metastases was 12 months from the moment of brain metastases detection. As regards bone metastazes, as a result of RST, all metastatic bone lesions completely disappeared in 7 patients. Conclusion. Radiosensitized advanced metastatic breast cancer treatment is a hopeful method, especially when lesions involve the brain and bones

Burnaryklės navikų intraarterinė fluorescencinė diagnostika

The visual fluorescence diagnostics and spectroscopic measurements of healthy mucosa were performed for these volunteers. Results. A specific pink fluorescence of malignant tissue was noted while illuminating a tumour with violet light. The margins of fluorescence usually coincided with those of a malignant tumour. In doubtful cases, biopsy and morphological examination of the tissue were performed. All malignant tumours, except melanoma, showed a specific pink fluorescence when illuminated with violet light, and no fluorescence was noted in normal mucosa. However, in some cases glow artefacts were observed. We identified these "glow artefacts" - a nonspecific lilac fluorescence - in the healthy mucosa of 20 patients (in 6 patients from the first group and in 14 from the second group). Usually, artefactual fluorescence was noted in the gums (in 18 patients from 20) and at the basis of the tongue (in 11 patients from 20). There was no artefactual fluorescence in 7 patients who underwent I/a FD. Conclusions. Fluorescence diagnostics is useful for early detection of primary and recurrent malignant oral tumours, except melanoma. However, an artefactual fluorescence in the gums or in the basis of the tongue can appear. I/a FD allows avoiding this artefactual fluorescence

Fluorescence diagnostics of oral cancer

The visual fluorescence diagnostics and spectroscopic measurements of healthy mucosa were performed for these volunteers. Results. A specific pink fluorescence of malignant tissue was noted while illuminating a tumour with violet light. The margins of fluorescence usually coincided with those of a malignant tumour. In doubtful cases, biopsy and morphological examination of the tissue were performed. All malignant tumours, except melanoma, showed a specific pink fluorescence when illuminated with violet light, and no fluorescence was noted in normal mucosa. However, in some cases glow artefacts were observed. We identified these "glow artefacts" - a nonspecific lilac fluorescence - in the healthy mucosa of 20 patients (in 6 patients from the first group and in 14 from the second group). Usually, artefactual fluorescence was noted in the gums (in 18 patients from 20) and at the basis of the tongue (in 11 patients from 20). There was no artefactual fluorescence in 7 patients who underwent I/a FD. Conclusions. Fluorescence diagnostics is useful for early detection of primary and recurrent malignant oral tumours, except melanoma. However, an artefactual fluorescence in the gums or in the basis of the tongue can appear. I/a FD allows avoiding this artefactual fluorescence