Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1 / The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients

Introducción y objetivos: El objetivo de este estudio fue analizar el impacto del grado histológico del tumor en la predicción de supervivencia de los tumores primarios T1 G2 y G3 OMS 1973, que han sido clasificados como HG (alto grado) en el sistema de clasificación OMS 2004. Materiales y métodos: Se revisaron retrospectivamente los datos de 481 pacientes con cáncer de vejiga T1HG primario, tratados entre 1986 y 2016 en 2 centros universitarios. Para comparar los grupos se realizaron pruebas de log-rank y análisis de regresión de Cox. Resultados: Noventa y cinco (19,8%) tumores fueron clasificados como G2 y 386 (80,2%) como G3. La mediana de seguimiento fue de 68 meses. Las tasas de recurrencia y progresión fueron 228 (47,5%) y 109 (22,7%) pacientes, respectivamente. Se realizó cistectomía radical en 114 pacientes (23,7%) y hubo 64 (13,3%) casos de muerte cáncer-específica. La tasa de supervivencia libre de recurrencia para G2, G3 y el total de los pacientes fue del 68,7, el 51,2 y el 56,3%, respectivamente, y la para tasa libre de progresión, se obtuvieron unos valores del 89,3, el 73,2 y el 78,1%. Durante todo el período de seguimiento, los pacientes con tumores G3 obtuvieron peores tasas de supervivencia libre de progresión y de recurrencia que los pacientes con tumores G2. En el análisis multivariante, después del ajuste de las características clínicas, el riesgo de recurrencia y progresión para los tumores G3 fue 1,65 y 2,42 veces mayor que para los tumores G2. Conclusiones: Se demostró que los tumores T1G3 se caracterizan por peores tasas de supervivencia libre de progresión y recurrencia en comparación con los cánceres G2

Introduction and objectives: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. Materials and methods: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2 university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. Results: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. Conclusions: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers

Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3 / Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder

Introducción y objetivos: Existen varios estudios con el objetivo de validar las tablas del Club Urológico Español de Tratamiento Oncológico (CUETO). Sin embargo, ninguno de estos estudios se ha centrado en el cáncer de vejiga de alto y muy alto riesgo. El objetivo del presente estudio fue validar externamente el modelo CUETO para predecir la recidiva y la progresión de la enfermedad en el grupo de tumores T1G3 tratados con bacilo Calmette-Guérin (BCG). Pacientes o materiales y métodos: Se analizaron los datos de 414 pacientes con cáncer de vejiga T1G3 primario. Para evaluar la discriminación del modelo se usaron modelos de riesgos proporcionales de Cox y se calcularon los índices de concordancia. Resultados: La mediana de seguimiento fue de 68 meses. Se observó recidiva en 212 (51,2%) y 64 pacientes (15,5%) experimentaron más de un episodio de recurrencia durante el periodo de seguimiento. La progresión del cáncer se observó en 106 pacientes (25,6%), 115 pacientes (27,8%) fueron tratados con cistectomía radical, y hubo 64 (15,5%) muertes por tumor. Para la probabilidad de recidiva y progresión, el índice de concordancia de los modelos CUETO fue de 0,633 y 0,697, respectivamente. Las tablas de CUETO subestimaron significativamente el riesgo de recidiva y marginalmente el riesgo de progresión en el primer año de observación. Durante los 5 años de observación, la tendencia de la recidiva fue mucho menos clara. Por el contrario, hubo una ligera sobreestimación en el riesgo de progresión. El estudio está limitado por su naturaleza retrospectiva. Conclusiones: Se demostró que las tablas de riesgo del grupo CUETO logran una discriminación correcta, tanto para la recidiva de la enfermedad como para la progresión, en pacientes con T1G3 tratados con BCG. El modelo de puntuación (CUETO) subestima el riesgo de recidiva del tumor, pero acierta al predecir el riesgo de progresión

Introduction and objectives: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. Patients or materials and methods: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. Results: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. Conclusions: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression

The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients. / Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. MATERIALS AND METHODS: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. RESULTS: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. CONCLUSIONS: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder. / Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3.

INTRODUCTION AND OBJECTIVES: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. PATIENTS OR MATERIALS AND METHODS: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. RESULTS: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. CONCLUSIONS: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

The efficacy of stereotactic radiotherapy for metastases from renal cell carcinoma.

Our purpose was to evaluate the efficacy of stereotactic radiotherapy (SRT) for intracranial and extracranial metastases in patients with renal cell carcinoma. The retrospective analysis of 85 patients (151 tumors) treated with SRT was performed. SRT was the sole treatment in 35% of tumors, the other 65% had received additional treatment such as surgery, palliative radiotherapy, immunotherapy or chemotherapy. In 60% and 40% of patients SRT was delivered to brain and extracranial lesions, respectively. The assessment of the efficacy of SRT was based on a radiological imaging (Computed Tomography or Magnetic Resonance Imaging) and estimation of Local Control (LC) as well as Overall Survival (OS). Single fraction was used for 104 tumors and fractionated treatment for 47 tumors. The crude LC for evaluable lesions was 81%, stratified by tumor location: brain LC=94%, extracranial tumors LC=70% (p=0.049). The median OS was 9.4 months; 1-year and 2-year OS were 40% and 29%, respectively. The additional treatment did not lead to a better local response (p=0,543), but resulted in a benefit in OS (7 vs 13 months, p=0,01). A positive relationship between the biologically effective dose (BED) and local response was noted, but the BED was influenced by a tumor volume (R=-0,38; p<0,00001). The presence of multi-organ metastases reduced the OS rate (8.7 vs 19.1 months; p=0,01). The interval between the diagnosis of the metastasis and its treatment with SRT was inversely related to OS (P=0.0001). SRT results in a good local response, which is more beneficial for brain than extracranial lesions. The local efficacy of the SRT depends on the radiation dose. Multidisciplinary treatment and earlier application of SRT improves the prognosis of patients.

Influence of interfraction motion on margins for radiotherapy of gastric cancer.

OBJECTIVE: The aim of this study was to evaluate interfraction uncertainties using kilovoltage (kV) radiographs for patients with gastric cancer during chemoradiotherapy and to calculate the planning target volume (PTV) margins. METHODS: 1284 measurements of set-up errors were analysed for treated patients. The measurements of craniocaudal (axis y), laterolateral (axis x) and anteroposterior (axis z) shifts in kV radiographs were performed. Interfraction clinical target volume (CTV)-PTV margins for all directions were calculated using the van Herk formula. RESULTS: The main shift for the y-axis was 0.7 mm [standard deviation (SD), ±7.6], for the x-axis was 0.4 mm (SD, ±3.7) and for the z-axis was 0.6 mm (SD, ±3.5). The CTV-PTV margin in the x, y and z directions was 8.3, 15.5 and 8.0 mm, respectively. We observed that the interfractional motion for patients increased approximately 0.0034 cm along the x direction with each subsequent fraction, whereas a 0.0058-cm reduction in length along the y-axis was observed. No time effects for the z direction were noticed. CONCLUSION: According to our experience, a PTV margin of 9 mm along the x-axis, 16 mm along the y-axis and 8 mm along the z direction should be considered in the absence of image-guided radiotherapy. ADVANCES IN KNOWLEDGE: This knowledge concerning PTV set-up margins could be particularly useful for centres without a kV on-board imaging system.

Daily image-guidance in prostate cancer radiotherapy - implications for treatment margins.

UNLABELLED: Our purpose was to evaluate interfractional organ and patient movement during radiotherapy of prostate cancer and to calculate the necessary CTV to PTV margins. Fifty patients irradiated between 2009 and 2011were included into the prospective study. The 2D-2D KV system combined with the intraprostatic fiducial marker were used for daily position verification. Based on the 8629 measurements of isocentre displacement an interfractional motion of pelvis and prostate was evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed. Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are necessary in case of no IGRT.There was no clinically relevant changes in patient/target mobility throughout the whole treatment. The IGRT is essential for state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are much bigger in case of no IGRT performed. Changing of margins size throughout regular treatment is not necessary. KEYWORDS: IGRT, prostate cancer, fiducial marker.

Split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck cancer patients-final results of a randomized clinical trial.

OBJECTIVE: Evaluation of the efficacy and toxicity of split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck (H&N) cancer patients. METHODS: We enrolled 101 patients (39 in CHA-CHA and 37 in conventional (Conv.) arm completed the treatment). The CHA-CHA arm patients were irradiated twice a day, 7 days a week, using a fraction dose (fd) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm. Patients in the control (Conv.) arm group were irradiated with a fd of 2 Gy, five times a week to a total dose of 72-74 Gy in the overall treatment time of 50-53 days. Quality of life (QOL) and acute mucosal reaction were evaluated during radiotherapy (RT). After RT, we followed the effect of treatment, QOL, performance status and adverse effects of radiation. For statistical analysis mainly a hierarchical multilevel modelling was used. RESULTS: QOL was most deteriorated in the CHA-CHA arm; the CHA-CHA scheme also caused a relatively stronger acute injury. There were no significant differences in late adverse effects. In the CHA-CHA arm in 35% and in Conv. arm in 30% of patients, disease was controlled during follow-up. Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm. However, the overall survival rate analysis did not show significant difference between both arms. CONCLUSION: Despite differences in treatment results, we cannot conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients. ADVANCES IN KNOWLEDGE: Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients.

Linac based radical radioablation of liver tumors.

Due to the low percentage of resectable liver tumors, new alternative treatment modalities are used. Among them, radioablation, that is, by using a limited number of high dose radiation. The aim of this study was to evaluate the effectiveness of liver tumor radioablation at 36 Gy delivered in three fractions. The analyzed material comprised of 65 liver tumors. In 61 cases, we irradiated metastases (20 rectal cancers) and in 4 primary liver tumors. Radioablation, was done using 6 and 20 MV photons with a fraction dose of 12 Gy once a week up to a total dose of 36 Gy. During the follow-up we measured tumor diameters, and for our statistics we used a classical linear regression and the Bayesian approach. Mild and moderate late toxicity was observed. We found a significant absolute and relative decrease in tumor size during the first 6 months from the whole analyzed group. In subgroups with adenocarcinomas, metastases of gastrointestinal tract (GI) cancers, metastases of cancers other than GI cancers, and in the subgroup in which 2D-2D kV system (IGRT) and respiratory gating was used. The percentage of tumors with local control (lack of "in field" progression) after 6 months was 89%. The obtained results permit us to conclude that gated SBRT of liver tumors is an effective and safe treatment modality resulting in a significant regression of liver tumors and that the highest degree of tumor size reduction can be expected for metastases of non-gastro intestinal tract cancers.

Armeria maritima from a calamine heap--initial studies on physiologic-metabolic adaptations to metal-enriched soil.

Plants of Armeria maritima are found both on unpolluted sites and on soils strongly polluted with heavy metals. Seedlings of A. maritima from a zinc-lead calamine heap in ore-mining region (Boleslaw population) and from unpolluted area (Manasterz population) were tested to determine the zinc, cadmium and lead tolerance. In hydroponic experiments Boleslaw population was more tolerant to zinc, cadmium and lead. Localization of heavy metals in roots was determined using the histochemical method for detecting metal-complexes with dithizone. Their accumulation was found in root hairs, rhizoderma and at the surface of the central cylinder. Glutathione level in plants increased after metal treatment of both populations. However, its high level was not correlated with phytochelatin production. These metal-binding complexes were not detected in plants exposed to zinc, cadmium or lead. Changes of organic acids concentrations in Armeria treated with metals may suggest their role in metal translocation from roots to shoots. The content of organic acids, especially malate, decreased in the roots and increased in the leaves. These changes may be important in Pb-tolerance of Manasterz population and in Zn-, Cd-tolerance of calamine population from Boleslaw.

Could socio-economic transformation and the resulting psychological stress influence cancer risk in Opole province, Poland?

The paper presents the results of a risk assessment analysis of cancer morbidity in Opole province before and after a political transformation in Poland, i.e. in the 1985-1989 quinquennium and the following two equivalent periods of: 1990-1994 and 1995-1999. Measures of morbidity are given and its growth in males and females are compared with the ageing effect as well as with unemployment. In the paper a general conclusion has been drawn suggesting that the socio-economic transformation begun after 1989 and the resulting stress could have been the one of the possible background effects influencing the health status in the region. It must be accentuated, however, that the relation has not been a subject of statistical proving due to a methodological impossibility; a divagated question is offered for scientific concern and open discussion.

Thyroid cancer morbidity in Opole province, Poland, after Czernobyl disaster.

The Czernobyl disaster caused an extensive pollution in Europe due to the release into the environment thousands of tons of radioactive isotopes affecting the elevated cancer morbidity in the continent. The authors used the data set on radiation in Opole province, Poland, to model thyroid cancer incidence in the 1994-1998 quinquennium. An increase in thyroid cancer morbidity in females was observed within the 137 + 134Cs elevated concentration areas. The changes of the cancer incidence in males were found not significant for the distinguished radiation levels in the region. The statistical modeling was performed via the BUGS software.

Cervix uteri cancer incidence in relation to ethnic situation in Opole province, Poland.

This paper presents results of a retrospective ecological analysis of cervix uteri cancer incidence in relation to the ethnic situation in the province of Opole, Poland. A few well-known methodological procedures were applied in the study. Detecting spatial disease clusters followed Tango's method. Estimates of relative risks of cancer morbidity were calculated via Clayton and Kaldor's empirical Bayes approach. To measure spatial correlation between neoplasmatic incidence and ethnic density, Moran's statistic was used. The Poisson modelling of the variables was performed using Markov Chain Monte Carlo technique--Gibbs sampling. The results presented in tables and graphs suggest a possible association between the ethnic pattern and risk of cervix uteri cancer in the analyzed province.

Magnesium in drinking water and liver cancer morbidity--a possible relation?

The paper presents results of a research on liver cancer morbidity in Opole province, Poland, in relation to magnesium exposure in drinking water. Based on the extensive empirical materials of cancer registry information and water quality, the well known statistical approach using BUGS software was applied in the study. The results support a hypothesis of a possible association between the deficiency of magnesium in drinking water and the increase of liver cancer morbidity in the population exposed. The outcomes were presented in a table and graphically in histograms, scatterplots and maps.

An ecological analysis of leukemia incidence around the highest 137Cs concentration in Poland.

Cancer has long been known to be a hazard of exposure to ionizing radiation. However, the assessment of health effects from exposure to radiation is a matter of considerable controversy. This paper presents results of a retrospective study of leukemia incidence (203-207, ICD-9) around the highest 137Cs pollution in Poland (as an effect of the Czarnobyl disaster and/or military bomb tests). The data relating to all the registered leukemias in males and females originated from the Regional Cancer Registry in Opole. The information on 137Cs concentration rates in Opole province was derived from the state monitoring provided by the Polish Geological Institute in Warsaw. The spatial analysis--based on the random-effects Poisson regression model--was carried out via the Markov Chain Monte Carlo (MCMC) technique (Gibbs sampling) using BUGS software. The model incorporated epidemiological data and an ecological covariate--isotope concentrations--and provided a framework for estimating the strength of a dose-response relationship. The differences in incidence levels were quantified by traditional standardized morbidity ratios (SMRs) and presented in thematic maps as well as in combined charts of distance-disease-dose relations. Additionally, to assess spatial disease clustering, a Tango test was adopted. The results of this ecological study suggest that the 137Cs concentrations did not have any negative influence on the exposed population.