memo - Magazine of European Medical Oncology

Kahán, Z.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0286-z

The proportion of breast cancers detected in the very early stages (in situ and invasive breast cancers <15 mm) in daily practice has significantly increased, thanks to breast screening, breast awareness and improved detection methods. Most of these tumours show less aggressive biological phenotype than their more advanced counterparts, and have an excellent long-term prognosis without applying oncological treatments. The identification of the minority of cancers with a poor prognosis and their appropriate therapy is the real challenge. In fact, neither the first-generation prognostic factors (the tumour size, the lymph node status and the histology grade), nor the usual additional parameters (the receptor status and proliferation markers) are reliable enough for the estimation of the outcome. Likewise, the conventional predictive factors such as the ER, PR and HER2 status are not sufficient for the individualization of therapy in those cases that need oncological therapy. This overview points to the pressing need and the emerging elements of a potential new classification system of early breast cancer including the consideration of the mammographic appearance, the extent of the disease instead of just the largest dimension of the main invasive focus and the mode of detection or the use of molecular tests.

Starý, J.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0276-1

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0291-2

Zielinski, C. C.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0277-0

Cserni, G.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0280-5

The TNM is the most widely used staging system for malignant disease. Its seventh edition has been updated in several respects, but there still remain controversial issues requiring further improvement. The current review highlights the items related to early breast cancer. It deals separately with contradictions found in the online resources, those related to the different categories, the stages, grade and finally it places the TNM in the milieu of biological markers often used to tailor individual patient treatment. Although TNM has lost its nearly unique role in assessing patient risk and in selecting systemic therapy for breast cancer, it is still of importance in reflecting the anatomic extent of disease in a categorical way, selecting surgical treatment and comparing similar tumours of different extent.

Tabár, L.; Tucker, L.; Davenport, R. R.; Mullet, J. G.; Hsiu-Hsi Chen, A. T.; Ming-Fang Yen, A.; Yueh-Hsia Chiu, S.; Gladwell, J.; Olinger, K.; Dean, P. B.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0287-y

BACKGROUND: The efficacy and reproducibility of mammographic tumour feature use for predicting patient outcome were tested in consecutive in situ and 1–14 mm invasive breast cancer cases from two breast centres in two different health care systems. METHODS: All in situ and 1–14 mm invasive cancers detected in Falun from 1996–2006 (n = 971), in Roanoke from 2002–2007 (n = 555), and in women aged 40–69 (age limits for invitation to screening) in Falun from 1977–1995 (n = 844) were included; of these the mammograms, pathology slides and follow-up information were available in 95%, 97% and 91% of the cases, respectively. The cancers were classified according to their mammographic appearance: stellate or circular without associated calcifications, or malignant type calcifications with or without an associated tumour mass. The mammographic tumour features and the disease specific survival were correlated. Terminal digit preference of tumour size measurements was examined. RESULTS: Mammographic tumour features were similarly represented in both centres. A significant preference was observed for tumour size measurements divisible by 5 mm. Outcome was significantly poorer for cases having casting type calcifications on the mammogram and excellent for the remaining cases. CONCLUSIONS: Outcome prediction of patients with 1–14 mm invasive breast cancer is significantly improved by the addition of mammographic tumour features to the currently used prognostic factors. The integration of imaging morphology into the TNM classification of invasive breast cancers smaller than 15 mm facilitates specifically targeted therapy and may curtail overtreatment. The significant digit preference found in this study may justify using the terminal digits of "4" and/or "9" as upper size limits for tumour size categories.

Stoddard, F. R.; Szasz, A. M.; Szekely, B.; Tokes, A.-M.; Kulka, J.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0285-0

Breast cancer is a heterogeneous disease concerning its morphology and behaviour. Until a few years ago, the prognosis of a given breast cancer case was mainly defined based on several parameters included in the pathology report: pTNM, grade, type, lymphovascular invasion, hormone receptor status and HER-2 status. The risk categories defined in the most recent St. Gallen consensus documents were complemented by the addition of the Ki67 index provisionally as a good marker for prognosis and for the risk of progressive disease. Newer assays are being developed to help augment these standard pathologic markers. The application of emerging molecular techniques in oncology is giving way to a variety of new prognostic and predictive tests designed to help tailor patient-specific treatment algorithms. While a few of these have accumulated sufficient validation to merit their use in the routine work-up of certain cancers, most still need additional studies to validate their roles in patient management. This review gives an overview of the major molecular pathology tests that are currently available for routine diagnostics. We provide information about their development, technical issues, and current and emerging utility as prognostic and/or predictive studies. Additionally, we discuss tests that are currently under investigation requiring additional validation.

Tot, T.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0288-x

The radiological – surgical parameters (tumour size, lesion distribution, disease extent and surgical margins) and the oncological morphologic parameters (tumour type and grade, hormone receptor status, proliferative activity and TNM stage) are equally important for adequate characterisation of early breast carcinomas. Conventional histopathology methods may be sufficient in determining oncological parameters while large-format histopathology used in context of systematic radiological – pathological correlation is the only adequate approach in determining the radiological – surgical parameters in modern breast pathology. This is particularly valid for the parameters of lesion distribution and disease extent, which prognostic power has recently been evidenced and which are often underestimated if conventional histology methods are used. This review will focus on the radiological – surgical parameters in early breast carcinomas, their clinical significance and the optimal methods of their assessment.

Emmanuel, K.; Augschöll, C.; Öfner, D.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0284-1

Multidisciplinary strategies are commonly used to treat liver metastases of various origins, especially colorectal cancer. Progress in surgical techniques and the use of appropriate devices have opened the fields for a laparoscopic approach to increasingly complex procedures, like liver resection. Patients benefit from shorter hospital stay, less postoperative pain, reduced postoperative morbidity and better cosmetic results. According to a meta-analysis, delaying initiation of adjuvant chemotherapy after curative surgery for stage III colorectal cancer was associated with a statistically significant decrease in overall survival. It is tempting to assume that these results may be assignable to metastatic disease. Therefore, laparoscopic liver resection offers a substantial contribution to multimodal treatment of liver metastases.

Bellmann, R.; Weiler, S.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0290-3

Invasive fungal infections are a major threat for haemato-oncologic patients. The diagnosis is challenging, but an early and adequate therapy is crucial for survival. Echinocandins are suggested for initial treatment of critically ill patients with invasive candidiasis. Fluconazole is justified when the condition is stable and resistance is infrequent i. e. the incidence for Candida glabrata and Candida krusei is low. For invasive aspergillosis voriconazole is usually the drug of choice. Amphotericin B preparations, particularly the lipid formulations are adequate alternatives for invasive aspergillosis and for invasive candidiasis. First-line treatment of zygomycosis is performed with an amphotericin B preparation, whereas posaconazole is licensed for salvage therapy or oral step down treatment. Liposomal amphotericin B, amphotericin B colloidal dispersion and caspofungin are licensed for empirical anti-fungal treatment in persistent fever and neutropenia.

Micic, D.; Slavkovic, B.; Rasovic Gvozdenovic, N.; Kuzmanovic, M.; Dokmanovic, L.; Krstovski, N.; Skoric, D.; Konstantinidis, N.; Kostic, G.; Predojevic, J.; Janic, D.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0282-3

We present the results of a retrospective study of ALL treatment from 1995 to 2002 according to the modified SR arm of ALL BFM 90 protocol in Serbia. Treatment was performed in five centres, two of them located in Belgrade, one in Nis, one in Novi Sad and one in neighbouring Republic of Srpska. Modification was necessary due to inadequate supply of medications and diagnostic reagents at the time and was mainly related to reduction of treatment intensity and the differences of patient stratification in comparison to the original BFM protocol. There were 462 patients, 188 of whom were girls (40.7%) and 274 boys (59.3%); median age was 5.5 years (range 1–17.9 years). In total, 98.4% patients achieved complete remission after induction treatment. Twenty patients (4.3%) died before achieving complete remission during induction treatment; additionally, there were 34 remission deaths (7.4%) and 88 relapses (19%). Median time of follow-up was 87.1 months. Ninety four patients (20.3%) were lost to follow-up (LFU). Five-year event-free survival (EFS) was 73.1% and 10-year EFS 70.5%.

Avcin, S.; Prelog, T.; Kavcic, M.; Kitanovski, L.; Anzic, J.; Benedik Dolnicar, M.; Rajic, V.; Zadravec Zaletel, L.; Debeljak, M.; Jazbec, J.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0278-z

Treatment and long-term outcome in Slovenian children and adolescents, treated for acute lymphoblastic leukaemia (ALL) were evaluated, mainly considering differences between treatment regimens being evolved during time. From year 1967 through 2004, 394 patients (pts) were treated and six therapeutic schemes had been used. Retrospectively 5-year overall survival ± standard error (5yOS), relapse rate (RR) and second neoplasm (SN) were estimated according to treatment regimen, age, and where recorded, also according to BFM risk group, white blood cell count and disease subtype. For treatment regimens used after year 1992, 5-year event-free survival ± standard error (5yEFS) was added to our observations. Among 75 pts enrolled in pre-POG treatment regimen, the probability of 5yOS was 25.3 ± 5.0%, while no data for RR and SN analysis were available. For 91 pts treated according to POG derived treatment, the probability of 5yOS was 61.6 ± 5.1%, with 64% RR and 5.5% occurrence of SN. Probability of 5yOS of 74.3 ± 7.4%, RR of 37% and 8.5% occurrence of SN were reached for 35 pts enrolled in ALL-BFM 83 protocol. ALL-BFM 86 protocol included 62 pts with 69.4 ± 5.9% probability of 5yOS, 33% RR and 3.2% occurrence of SN. For ALL-BFM 90 protocol the 5yEFS and 5yOS for 71 pts was 77.3 ± 5.2% and 81.8 ± 4.8%, respectively, with 17% RR and 1.5% occurrence of SN. Fifty-six patients enrolled in ALL-BFM 95 protocol reached 83.0 ± 5.2% 5yEFS and 92.6 ± 3.6% 5yOS, with 16% RR and 1.7% occurrence of SN. Stepwise rise of OS, decline in RR, reducing occurrence of SN and, for ALL-BFM 90 and ALL-BFM 95 protocol, improvements in EFS, were observed through time according to different treatment regimens. General improvement regarding OS, RR and occurrence of SN was most obvious after the application of BFM regimen with evident continuous rise in OS and decline in RR and occurrence of SN thereafter.

Derwich, K.; Wachowiak, J.; Zając-Spychała, O.; Balcerska, A.; Balwierz, W.; Chybicka, A.; Kowalczyk, J. R.; Matysiak, M.; Jackowska, T.; Sońta-Jakimczyk, D.; Szczepański, T.; Wysocki, M.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0279-y

PURPOSE: A non objective randomised, retrospective study was performed to assess and compare the efficacy of two different high doses of methotrexate (HD-MTX) in combination with intrathecal therapy in children with standard risk (SR) ALL as central nervous system (CNS) preventive therapy in a place of cranial radiation. PATIENTS AND METHODS: Between July 1993 and April 2002, in 650 children standard risk (SR) ALL were diagnosed and treated in Poland according to the modified ALL-BFM 90 protocol. Methotrexate was used in the dose of either 3.0 g/m2 (group A) or 5.0 g/m2 (group B) four times in two week intervals during consolidation (protocol M). RESULTS: Probability for 10-year event-free survival (pEFS) and relapse-free survival (pRFS) for all evaluated patients (n = 611) was 0.77 ± 0.02 and 0.82 ± 0.02, respectively. EFS probability for group A (n = 411) was 0.73 ± 0.03 and for group B (n = 200) – 0.85 ± 0.04, whilst RFS probability for group A was 0.79 ± 0.04 and for group B – 0.89 ± 0.03, and these differences proved statistically significant (P = 0.0050 and P = 0.0012). In multivariate analysis, T-cell immunophenotype (P = 0.0046) and age older than 10 years (P = 0.0250) had a significantly adverse impact on the outcome. CONCLUSIONS: HD-MTX used in dose 5.0 g/m2 has been found to be more effective in the treatment of SR ALL in children than HD-MTX in dose 3.0 g/m2.

Kaiserová, E.; Bubánska, E.; Oravkinová, I.; Šubová, Z.; Kolenová, A.; Foltinová, A.; Čáp, J.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0283-2

Treatment of childhood acute lymphoblastic leukemia (ALL) according to the 1st Slovak protocol started in the Slovak Republic in 1971 in eight pediatric departments. Gradually, two other protocols were written, and 496 children were treated with these three protocols from 1971 to 1992. Since 1992, all children have been treated in three pediatric oncological departments. From 1992 to 1996, protocols for standard and high-risk ALL were developed that were used for 111 children in Bratislava, while the centres in Banska Bystrica and Košice had started to use BFM protocols. Since 1997, all patients with ALL have been treated according to ALL BFM 95, and since 2002, they have been included in the ALL IC BFM 2002 study. We evaluated treatment results in the standard arm of ALL BFM 95 and compared it with previous Slovak protocols. Rates of complete remission increased from 90.6% in the first Slovak protocol to 97.1% in BFM 95; EFS and OS increased from 0.46 and 0.50 to 0.67 and 0.72, respectively. Relapse rates decreased from 42% to 20.5%. EFS was significantly worse in children with leukocyte counts >100×109/l and in the HR group in comparison to standard- and medium-risk groups. OS was also significantly worse in T-cell ALL than in B-cell ALL. Death rates in the 1st complete remission decreased gradually in the Slovak protocols from 10.4% to 1.8%, but were high in BFM 95 (10.8%) due to more intensive therapy and initial unsatisfactory experiences with BFM protocols. All parameters improved in the ALL IC BFM 2002 study.

Starý, J.; Mihál, V.; Smíšek, P.; Blažek, B.; Jabali, Y.; Hrstková, H.; Hak, J.; Procházková, D.; Černá, Z.; Štěrba, J.; Trka, J.; Hrušák, O.; Zuna, J.; Mejstříková, E.; Janotová, I.; Sedláček, P.; Ptoszková, H.; Pospíšilová, D.; Toušovská, K.; Timr, P.; Vávra, V.; Zdráhalová, K.; Šrámková, L.; Zemanová, Z.; Jarošová, M.; Gajdoš, P.; Hrodek, O.

2011 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-011-0289-9

PURPOSE: Treatment of childhood acute lymphoblastic leukemia (ALL) was unified in the year 1986 in the Czech Republic using BFM protocols. PATIENTS AND METHODS: Children were treated in 10 and later on in 8 centers localized at the pediatric departments of the biggest hospitals. More than 1.000 children and adolescents up to the age of 18 years were treated between 1986 and 2002 on three consecutive studies ALL-BFM 83, ALL-BFM 90 and ALL-BFM 95. RESULTS: Event-free survival and overall survival improved gradually from 58/62% on ALL-BFM 83 through 70.5/76.6% on ALL-BFM 90 until 72.1/80.2% on ALL-BFM 95. At the same time the incidence of toxic deaths was decreasing and the success in the achievement of complete remission was increasing. Diagnostics in the Czech Republic improved remarkably in the 1990 with gradual introduction of centralized flow cytometry and molecular genetic analysis in one reference laboratory (CLIP = Childhood Leukemia Investigation Prague), which since then has become an internationally respected research center. CONCLUSIONS: Building up a network of closely collaborating leukemia centers covering the whole country, together with the establishment of reference and research laboratories has paved the way for the implementation of the Czech Pediatric Hematology Working Group (CPH) into the international studies Interfant 99, EsPhALL and for the active role in ALL IC-BFM 2002, the I-BFM-SG international randomized trial for treatment of children and adolescents with non-B ALL starting in 2002.