Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial.

INTRODUCTION: The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment Of the Axilla - Surgery Or Radiotherapy) trial compares completion of axillary lymph node dissection (cALND) to regional nodal irradiation (RNI) in patients with sentinel lymph node metastasis (pN1sn) in stage I-II breast cancer. PATIENTS AND METHODS: Patients with primary invasive breast cancer (cN0 and cT ≤ 3 cm) were randomized before surgery for cALND (standard treatment) or RNI (investigational treatment). Sentinel lymph nodes (SN) were investigated with serial sectioning at 0.5 mm levels by hematoxylin-eosin staining. Investigational treatment arm patients received 50 Gy RNI instead of cALND. Adjuvant treatment and follow up were performed according to the actual guidelines. Between August 2002 and June 2009, 1054 patients were randomized for cALND and 1052 patients for RNI. SN was evaluated in 2073 patients and was positive in 526 patients (25.4%). 474 cases were evaluable (244 in the cALND and 230 in the RNI arm), and in the cALND group 94 of 244 patients (38.5%) who underwent completion axillary surgery has additional positive nodes. The two arms were well balanced according to the majority of main prognostic factors. Primary endpoint was axillary recurrence and secondary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Mean follow-up was 97 months (Q1-Q3: 80-120). Axillary recurrence was 2.0% in cALND arm vs. 1.7% in RNI arm (p = 1.00). OS at 8 years was 77.9% vs. 84.8% (p = 0.060), and DFS was 72.1% in cALND arm and 77.4% after RNI (p = 0.51). The results show that RNI is statistically not inferior to cALND treatment. CONCLUSIONS: The long term follow-up results of this prospective-randomized trial suggest that RNI without cALND does not increase the risk of axillary failure in selected patients with early-stage invasive breast cancer (cT ≤ 3 cm, cN0) and pN1(sn). Axillary radiotherapy should be an alternative treatment for selected patients with sentinel lymph node metastases.

Clinical experiences with the use of ULTRAPRO® mesh in single-stage direct-to-implant immediate postmastectomy breast reconstruction in 102 patients: A retrospective cohort study.

BACKGROUND: Acellular dermal matrices have been used for direct-to-implant (DTI) breast reconstruction (BR), eliminating the load of the lower pole skin envelope. However, the available allograft matrices add considerable health care costs. This study examined the long-term follow-up of synthetic ULTRAPRO® mesh as a low-cost potential alternative to biological matrices. PATIENTS AND METHODS: A retrospective cohort study was performed between January 2013 and January 2016, involved 112 early-stage breast cancer and/or BRCA 1/2 patients, and evaluated 189 immediate DTI BRs following skin-, areola- or nipple-sparing mastectomy using ULTRAPRO® mesh. Patient characteristics and postoperative complications were recorded, and quality of life was rated by the patients using the EORTC-QLQ-C30-BR23 questionnaire. Aesthetic outcomes and palpability of the implants were evaluated by four breast surgeons on a 5-point Likert scale. All recorded parameters were statistically analysed. RESULTS: Ten patients were lost-to-follow-up, resulting in 102 patients and 174 breast surgery cases analysed. The mean age was 43 years, with 23.4 months of follow-up on average. Forty-six patients (45.1%) had previous radiotherapy with pre-existing scars. In total, 32 complications (18.3%) were recorded, including 12 minor (6.9%) and 20 major (11.4%) complications requiring revision. All median quality of life scores were above 83 points, representing a high score, with an average 4-point rating for the aesthetic outcome and natural consistency of the breast. CONCLUSION: Partially absorbable ULTRAPRO® mesh could be used successfully in DTI BR, offering a safe, less expensive alternative to biological matrices. Adequate indications and patient selection are necessary.

Objective decision making between conventional and oncoplastic breast-conserving surgery or mastectomy: An aesthetic and functional prospective cohort study.

BACKGROUND: Breast-conserving surgery (BCS) is considered the standard treatment for early-stage breast cancer. However, fair to poor cosmetic outcomes following conventional BCS have been observed in as many as one-third of cases. The aim of this study was to determine the critical tumor-to-breast volume ratio for each quadrant of the breast beyond which conventional BCS would no longer offer acceptable cosmetic and functional results or satisfactory quality of life for the patient. METHODS: A prospective cohort study was performed between December 2011 and December 2013 involving 350 patients younger than 70 years with early-stage unifocal (T ≤ 30 mm) breast cancer who underwent wide excision and axillary sentinel lymph node biopsy followed by whole-breast irradiation. Using validated panels and software (the Breast Cancer Treatment Outcome Scale [BCTOS], EORTC Cancer Quality of Life Questionnaire number C30-BR23, and Breast Cancer Conservative Treatment - cosmetic results [BCCT.core] software), quality of life and aesthetic and functional parameters and their changes in correlation to the percentage of breast volume excised were statistically analyzed. RESULTS: The maximum percentages of breast volume that were resectable by conventional BCS without resulting in unacceptable aesthetic and functional outcomes or decreased quality of life were 18-19% in the upper-outer quadrant (p < 0.0001), 14-15% in the lower-outer quadrant (p < 0.0001), 8-9% in the upper-inner quadrant (p < 0.0001), and 9-10% in the lower-inner quadrant (p < 0.0001). CONCLUSION: Aided by the calculated cut-off values for each breast quadrant, breast surgeons might render more objective decisions regarding performing conventional BCS, using oncoplastic techniques or choosing mastectomy with immediate reconstruction.

Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

Bilateral juvenile fibroadenosis of the breast: management with subcutaneous mastectomy and silicone implant placement.

Bilateral fibroadenosis is a rare, benign disorder, affecting adolescents or women of childbearing age. Choosing the most optimal therapy that manages both the physical and psychological aspects of the disease is a challenge. The goals of the treatment are complete resection of the lesions with optimal cosmesis. Options range from cryoablation, ultrasound-guided vacuum-assisted eradication and simple excision of the lesions to subcutaneous mastectomy with reconstruction. We present a case of a 25-year-old woman with 37 complex fibroadenomas affecting both breasts who was treated with nipple-sparing subcutaneous mastectomy and silicone implant reconstruction to both the surgeons' and patient's satisfaction.

Patient positioning variations to reduce dose to normal tissues during 3D conformal radiotherapy for high-risk prostate cancer.

BACKGROUND AND PURPOSE: The goal of this work was to assess optimal treatment positioning of 3D conformal radiotherapy (3DCRT) for high-risk prostate cancer patients. PATIENTS AND METHODS: Treatment plans of 25 patients in different patient positions were evaluated: with knee and ankle support (KAS) in the supine position and with a belly board (BB) in the prone position both with full (FB) and empty bladder (EB). Planning target volumes (PTVs) for pelvis, prostate and vesicles, prostate, and organs at risk (OARs) were delineated. Dose and overlapping volumes were evaluated. RESULTS: Overlapping volumes were significantly smaller with a FB than with an EB. No significant differences were found in overlapping volumes with respect to patient fixation systems, but the percentage values of dose to the OARs showed significantly better results employing KAS than a BB. A FB reduced the dose volumes to the OARs. Comparison with respect to circumference of abdomen (CA) showed significantly smaller overlapping at large CA in most of the cases. CONCLUSION: Supine position is suggested with KAS combined with a FB (especially in cases of larger CA) when using 3DCRT with planning technique modification for high-risk prostate cancer patients to reduce the dose of OARs, based on our results.

Prognosis of patients with local recurrence after mastectomy or conservative surgery for early-stage invasive breast cancer.

Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124 developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68. The 10-year actuarial rate of cause-specific survival after treatment for ILR was 52%. On multivariate analysis three independent prognostic factors for the risk of death after ILR were identified: operability of recurrence (operable vs. inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40 years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph node stage (negative vs. positive) showed borderline significance (p=0.06), and type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3) were not independent predictors of survival. In the mastectomy group, single surgical scar recurrence with initial node negative stage predicted good prognosis, and the 10-year survival was 85%. In the CS group, the 10-year survival rate was 88% with new primary tumor and 54% with true recurrence (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete excision) had no significant impact on survival (p=0.2). The majority (n=44) of CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified unfavorable prognostic factors are pointers of the forthcoming systemic progression. Patients with < or = 2 cm in-breast recurrence might receive a second CS.

Molecular identification, expression and prognostic role of estrogen- and progesterone receptors in head and neck cancer.

The aims of this study were to assess the sex hormone receptor status of head and neck (HNC) cancers. Frozen surgical samples (n = 67) of HNC patients were analyzed. Protein expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PgR) of tumor cells was determined by immunocytochemistry. Data were confirmed at mRNA level by nested-PCR and sequencing. ER and PgR expressions confirmed by PCR analysis were frequent in HNC: 50.7 and 49.3% respectively. Concerning the ER isoforms, ERalpha expression was predominant over ERbeta in both of oral cavity- as well as laryngeal/hypopharyngeal (LH) cancers. The delta3 splice variant of ERalpha was detected at low frequency, while the delta5 splice variant of ERbeta was frequent in HNC. The incidence of functional receptor expression (coexpression of ER and PgR) was relatively frequent also in HNC (27/67, 40.3%) which was independent of the anatomical location of the tumor. Sex hormone receptor expressions did not affect survival of HNC patients, however, in the LH cancer subgroup ER expression was associated with a trend of shortened survival (p = 0.0636, Mantel-Cox generalized savage). ERalpha,beta and PgR expressions are frequent in HNC and may affect the prognosis of the disease, at least in case of LH cancers.

Buccal mucosal transposition flap for reconstruction of oropharyngeal-oral cavity defects: an analysis of six cases.

BACKGROUND: Operation on tumors situated in the posterior part of the oral cavity is a challenging aspect of head and neck surgery. Both the approach and the postablative reconstruction of the remaining defect require special procedures. An arsenal of reconstructive methods are available depending on the size and complexity of the defect. The goal should be to employ the simplest surgical reconstructive method, resulting in the best functional result and allowing for later complex oncotherapy. OBJECTIVE: To study the outcomes of patients treated using buccal mucosal transposition flaps for reconstruction of posterior oral cavity and oropharyngeal border defects. STUDY DESIGN: A total of 6 patients with defects of the posterior oral cavity and mesopharynx were treated with buccal mucosal transposition flaps. The patients were followed for up to 24 months. RESULTS: Defects ranging from 12 to 27 cm 2 were reconstructed with the buccal mucosal transposition flap. One patient developed an orocutaneous fistula and 1 had some trismus requiring a Z-plasty scar reorientation. One patient suffered from nasal regurgitation. Five of the 6 patients lived past 24 months, the time of follow-up of this study. CONCLUSIONS: The buccal mucosal transposition flap, with its random pattern of circulation, used alone proved to be a safe method to reconstruct soft tissue defects or line exposed hard tissues located in the posterior oral cavity and oropharynx.

The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.

OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

FDG PET imaging in hereditary thyroid cancer.

AIM: To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS: Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS: US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS: Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.

[Human papillomavirus and cervical cancer: genetic background of the neoplastic process]. / Humán papillomavírus és méhnyakrák: a tumoros folyamat kialakulásának genetikai háttere.

In a 2-year period, 136 HPV positive cytological samples of the cervix uteri were analyzed at the Department of Molecular Pathology, National Institute of Oncology, Hungary. Comparison with the international data obtained from the literature revealed that the Hungarian epidemiological data bore closest resemblance to the European ones except some differences. The HPV18 is rather seldom encountered in this country. Similarly low occurrence was noted only in Japan. However, the 14.1% occurrence rate of HPV58 in Hungary is by far higher than that in any other country in this analysis except Japan where this virus is of similarly high frequency. In Hungary, the incidence of HPV59 is relatively high just like in Central and South America. HPV33 and HPV66 infections occur in a significantly higher number with Hungary than in any of the countries studied. In our study The European type variant of HPV16 (E-V-350G) occurred in 2/10 CIN II-III cases. The authors also compared the various clinico-pathological grouping of HPV types published, and identified several inconsistencies. Viruses considered to have high risk occurred in intact epithelium, CIN I-II-III and carcinoma alike. The general tendency was, however, that certain viruses correlated with specific clinico-pathological entities. At present there is no reason to include the PCR-based HPV typing in the mass screening of cervical cancers. HPV typing and physical state of the virus can reasonable be determined if the cervical cytology is suspect for HPV infection or even control examination after "loop" conisation. Negative cytology completed with negative HPV-DNA test means the lack of cancer risk even in the case of a previously removed CIN or carcinoma. However, a positive HPV test detected after conisation associated with negative cytology finding indicates a risk of 70% of the development of CIN within 2 years.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level. METHODS: Thirty-six MTC patients with residual/recurrent biochemical signs (elevated basal calcitonin level) and/or characteristic general symptoms (diarrhea and/or flushing) were systematically examined by conventional radiology, whole-body 18F-deoxyglucose positron emission tomography (PET), dynamic liver computed tomography and magnetic resonance imaging, and hepatic angiography. RESULTS: Conventional diagnostic imaging revealed lymph node (LN) involvement in the cervical, mediastinal, supraclavicular, and axillary regions (16 cases), and multiple pulmonary (3 cases), bony (1 solitary and 1 multiple case), and breast (1 case) metastases. (18)F-deoxyglucose PET identified all these extralymphatic metastatic lesions (except 2 cases with multiple pulmonary metastases), and also supradiaphragmatic LN involvement in 34 (94%) patients. In 32 (89%) cases, multiple small (generally < or = 1 cm) hypervascular, hepatic metastases undetectable by other imaging methods were localized angiographically. Of the 23 original pathologic specimens investigated, 18 (78%) exhibited LN involvement. The smallest primary tumor in patients with hepatic metastases was 1 cm. CONCLUSIONS: Hepatic angiography is recommended for primary staging in MTC patients with a primary tumor measuring 1 cm or larger, and/or pathologically proven LN involvement, and also during restaging for suspected recurrences to avoid unnecessary extensive surgical LN dissection in the neck and mediastinum.

[Validity of chromosome analysis and bleomycin sensitivity assay in the prevention of head and neck cancer in Hungary]. / A kromoszómaanalízis és a bleomycin-teszt hazai alkalmazhatóságának vizsgálata a fej-nyaki laphámrák prevenciójában.

Because of unfavourable cancer mortality statistics of Hungary, the search of different biomarkers is one of the most important demands of the national primary cancer prevention programme. The aim of this study was to clarify the usefulness of bleomycin sensitivity assay elaborated in the USA, and to find whether it serves under our environmental conditions as a biomarker of individual sensitivity and risk for head and neck cancer, beside chromosomal aberration analysis. The test reflecting mutagen sensitivity is based on the mean values of chromatid breaks induced by bleomycin in vitro in a single lymphocyte (break/cell = b/c). Since cancer formation is influenced by environmental mutagens, in contrast to others, their 111 head and neck cancer patients were matched not only with 230 healthy controls (106 nonsmokers and 124 smokers), but also with 44 strong alcoholic and smoking patients with liver diseases whose lifestyle did not differ from that of the cancer patients. According to the results of conventional chromosome analysis, the aberrant cell frequency was the highest in the cancer patients (3.34%), while in the alcoholics (2.73%) and healthy smokers (2.88%) the values were similar. Thus, the genetic instability occurring in the form of elevated rate of spontaneous chromosomal aberrations was mostly expressed in head and neck cancer patients. Mutagen sensitivity measured by the b/c values of bleomycin assay was significantly higher in both the cancer (1.16 b/c) and the alcoholic patients (1.34 b/c) compared with the controls (1.0 b/c). The bleomycin sensitivity assay, therefore, seems to be the biomarker not only of cancer, but also the disease of the same etiology such as alcohol-related liver disease. However the method is not suitable for the assessment of individual cancer risk because of the high variability of b/c values in each group, and their considerable overlapping with the controls. It can also be supported with extremely high mutagen sensitivity of Hungarian controls (63 and 67%), which is three-fold of US values (23%). The bleomycin sensitivity assay is not a selective biomarker if comparing to the controls, probably due to the action of more complex exposures under Hungarian environmental conditions. When estimating cancer risk, the results of conventional chromosome analysis offer more information than bleomycin sensitivity assay.

[The effect of tumour bed boost on local control after breast conserving surgery. First results of the randomized boost trial of the National Institute of Oncology] / A tumorágy kiegészítô besugárzásának hatása a lokális daganatmentességre emlômegtartó mûtét után. First results of the randomized boost trial of the National Institute of Oncology.

PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC) after breast conserving surgery in a prospective study. METHODS: Between 1995 and 1998, 207 women with early invasive breast cancer who underwent conservative operation were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either no further radiotherapy (n=103) or a boost to the tumour bed (n=104) with either 16 Gy electron (n=52) or 12-14.25 Gy high dose rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude rate of local recurrence was 6.7% with and 13.6% without boost. The respective rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC, relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1% (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111), respectively, in favour of the boost group. Systemic treatments had no significant impact on LTC (88.9% with and 89.6% without systemic treatment, p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free survival was improved significantly with boost. However, the influence of boost treatment on breast cancer-specific survival should be tested in further studies. In spite of the higher incidence of late radiation side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. The final results of the EORTC trial and other ongoing studies will help to clarify the indication of boost dose according to prognostic subgroups.

[Exposure or cancer predisposition? Cytogenetic examination of head and neck squamous cancer patients] / Expozíció vagy rákhajlam? Fej-nyaki laphámrákos betegek citogenetikai szûrése.

Search of different biomarkers is one of the most important demands of the national cancer prevention programme. We examined the usefulness of bleomycin sensitivity assay, whether it serves as a biomarker of individual sensitivity and risk for head and neck cancer under our environmental conditions. The test is based on the measurement of the means of chromatid breaks induced by bleomycin in vitro in a single lymphocyte (break/cell=b/c). 156 head and neck cancer patients were matched not only with 295 healthy controls (146 non-smokers and 149 smokers), but also with 51 strong alcoholic and smoking patients with liver disease whose lifestyle did not differ from that of the cancer patients. The aberrant cell frequency of cancer patients (2.85%), alcoholics (2.82%) and healthy smokers (2.81%) was similar and higher (p<0.03) than the values of non-smoker controls (2.25%). Thus, the results of conventional chromosome analysis indicate the effect of exposure to mutagens, derived mainly from smoking. Mutagen sensitivity measured by the bleomycin assay was significantly higher in both the cancer- (1.13 b/c) and the alcoholic patients (1.29 b/c) compared with smoker (1.04 b/c) and non-smoker controls (0.98 b/c). The bleomycin sensitivity assay, therefore, seems to be the biomarker not only for the cancer, but also for a disease of the same aetiology such as alcohol-related liver disease. However, the method is not suitable for the assessment of individual cancer risk due to overlapping of b/c values with those of controls. The proportion of mutagen sensitive persons in the group of Hungarian controls is 42-49%, which is two-fold of those in the US and Western Europe. When we estimate the cancer risk, the results of bleomycin sensitivity assay are equivocal under our experimental conditions, and they must be applied cautiously even in combination with the results of chromosome analysis.

[Genetic marker analysis in head and neck cancer] / Genetikai marker-vizsgálatok fej-nyaki daganatokban.

Prognostication of head and neck cancer (HNCC) involves molecular identification of residual tumor cells, prediction of recurrence, distant metastases or secondary tumors and prediction of the sensitvity to therapy. Biomarkers of HNCC are mutations of p53, p16 and amplification of Cyclin D and E2F4. One hundred and fifty-two HNCC cases have been evaluated for p53, hMLH1, Cyclin D and p16 gene alterations using PCR-SSCP and Western blot analysis. P53 mutations of HNCC have been found in 37.5% of cases. However, 11% of the cases showed p53 mutations in the normal peritumoral mucosa suggesting "field cancerization" process. Mismatch-repair gene mutations (MMR: hMHL1 and hMSH2) occurred with 17 and 8.6% frequency, respectively, while E2F4 mutations were even more frequent (21.4%) in HNCC. Our data suggest that E2F4 overexpression can be caused by the inactivation of the p16 gene in HNCC, while its mutations are most probably associated to the mutations of the MMR genes. These molecular informations can help to predict the biological potential of HNCC as well as the probability of the development of secondary HNCCs.

[PET scanning in head and neck cancer] / Pozitronemissziós tomográfia a fej-nyaki tumorok diagnosztikájában.

INTRODUCTION: FDG (fluorine-labeled deoxy-glucose) and 11C-methionine positron emission tomography was evaluated in the diagnostics of head and neck cancer. PET scans were applied for identifying/staging relapse after oncotherapy or searching unknown primary tumor with metastatic lymph nodes of the neck. METHODS: Retrospective analysis of 22 patients examined by 17 (18)FDG and 15 (11)C-methionine PET scan. In 9 cases indication was unknown primary tumor with positive neck, in 13 cases previously treated head and neck cancer patients were examined for recurrence/restaging. RESULTS: In searching for unknown primary tumor not detectable with conventional methods, PET was effective in 22%, however, false positivity and uncertain results were found as well. In restaging PET proved to be very effective (85%) to discover recurrences and to differentiate them from post-treatment (mainly irradiation) effects. In two cases silent distant metastase were detected. CONCLUSION: PET can provide valuable information about unknown primary tumors, recurrences after oncotherapy and distant metastases as well. Simultaneous use of FDG/methionine scans does not improve the results.