Tumors In Europe Research Articles

Does solitary- and organ-confined metastasectomy really improve survival in advanced urologic malignancies?

The role of metastasectomy on survival in advanced/urologic malignancies still remains unclear. Renal cell carcinoma (RCC) is the most common solid tumor within the kidney. 25-30 % of patients have metastases at manifestation. Urothelial carcinoma (UC) consists of bladder carcinoma, upper urinary tract urothelial cell carcinoma and urethral carcinoma. Bladder cancer is the ninth most common cancer worldwide. Half of patients with muscle invasive bladder cancer have lymph node or distant metastases. In metastatic disease first-line treatment is multi-agent platinum-based systemic chemotherapy. Testicular cancer is the most common cancer in men between the age of 15 and 35. Testicular tumors represent excellent oncologic outcomes. Prostate cancer is the most common solid tumor in Europe. Surgical resection of metastases can be considered as a treatment choice in advanced/metastatic urologic malignancies to improve survival rates, particularly in RCC and UC. Metastasectomy can be suggested in conjunction with effective chemotherapy if complete resection is possible. Solitary metastasectomy can represent better survival rates compared to multiple metastasectomy even if multiple metastases confined to single organ. Site of metastases is one of the main determinants of successful metastasectomy such as lung metastasectomy in urothelial cell carcinoma and liver metastasectomy in RCC may lead to better oncologic outcomes. Due to the lack of the relevant data it is not possible to make an evidence-based recommendation on the role of metastasectomy for solitary-/organ-confined metastases of prostate cancer, testicular cancer and penile cancer.

Complete Response to Radiotherapy in a Pineal Parenchymal Tumor of Intermediate Differentiation

Background and Importance: Approximately 20 percent of parenchymal pineal tumors (PPT) arise from the epithelial cells and are extremely rare, especially in adults, accounting for less than 1 percent of all primary brain tumors in Europe and North America. PPT of intermediate differentiation (PPTID) was recognized as a new entity and introduced in the 2007 WHO classification, corresponding to grades II (GII) or III (GIII). Previous studies had suggested its potentially aggressive behavior and tendency for cerebrospinal fluid seeding. A standard treatment for these tumors has not yet been defined. The gross total surgical resection is indicated whenever technically feasible and the impact of adjuvant radiotherapy and chemotherapy is not established. In fact, little is known about the radiation and chemotherapy sensitivity of these tumors. Clinical Presentation: We describe a case of a recurrent PPTID (G II, Ki67:10%) which underwent to an endoscopic third ventriculostomy, biopsy and a two conformal radiation therapy course (25 fractions of 180 cGy over 4 weeks and, 3 fractions of 180 cGy, total of 5400cGy). After that, the patient was completely asymptomatic and an MRI revealed no residual mass. There was no sign of relapse by the 27-months follow-up. Conclusion: Given the paucity of good clinical evidence for a standard therapy and the fact that the currently PPTID treatment is experience-based, we conclude that radiotherapy can be considered as suitable possibility of primary treatment. Due to its rarity, prospective multi-institutional studies should be arranged to establish the optimal PPTID management.

Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study

BackgroundPrimary malignant brain tumours are rare but represent a serious health burden due to their poor survival. This manuscript describes the survival of malignant brain tumours in adults diagnosed 2000–2007 in Europe. MethodsFor this study we analysed patients archived in 86 European population-based cancer registries, followed up to 31st December 2008. Only primary malignant neuroepithelial brain tumours (with pathological confirmation) and primary malignant unspecified brain tumours without pathological confirmation were included. We estimated 1-year and 5-year relative survival (RS) weighted by age group and country. We also estimated country-specific and age-specific survival, together with survival differences between time periods (for 1999–2001, 2002–2004 and 2005–2007). ResultsGlioblastoma represents 49% of all brain tumours, followed by other/unspecified astrocytoma (18%), oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours (1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for ependymoma to only 6% for glioblastoma and sharply decreased with increasing age.Differences between countries were relatively small, but generally RS in Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase in 1-year RS (up to 10–12%) was noted over time, being largest in Central and Northern Europe in patients between 45 and 74years of age. ConclusionsDespite an increase in 1-year RS in most European regions, the survival of primary malignant brain tumours is still poor. Disparities between countries were evident, being even larger at the end of the study period than at the beginning, suggesting differences in availability of the latest treatment modalities.

Uncovering the roles of miRNAs and their relationship with androgen receptor in prostate cancer.

Prostate cancer (PCa) is the second most commonly occurring malignant tumor in Europe and America. Normal and neoplastic growth of prostate gland are dependent on androgen receptor (AR) expression and function. PCa is driven by androgen and its receptor, and they continue to be the key drivers of castration-resistant prostate cancer (CRPC). CRPC is the terminal stage of PCa and seriously jeopardizes the patient's quality of life and lifespan. miRNAs are small noncoding RNAs, 18–25 nt in length that destabilize mRNA or repress protein synthesis by interacting with the 3′-untranslated regions (3'-UTR) of target mRNAs. miRNAs can regulate AR or be regulated by AR and then affect various signaling pathways related to cellular functions and tumor processes. In this review, we focus on the relationship between miRNAs and AR in PCa and elucidate their roles in the induction of malignant changes in PCa. © 2014 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 66(6):379–386, 2014

Liver Transplantation for Neuroendocrine Tumors in Europe—Results and Trends in Patient Selection

The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

PCN35 Survival Estimates of Six Major Advanced and Metastatic Solid Tumors in Europe: A Cancer Registry and Literature Review

PCN35 Survival Estimates of Six Major Advanced and Metastatic Solid Tumors in Europe: A Cancer Registry and Literature Review

1156O - Ramsete: A Single-Arm, Multicenter, Single-Stage Phase II Trial of Rad001 (EVEROLIMUS) in Advanced and Metastatic Silent Neuro-Endocrine Tumours in Europe: Analysis by Tumor Origin

Ramsete : a single-arm, multicenter, single-stage phase ii trial of rad001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in europe: analysis by tumor origin

RAMSETE: A single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe.

4122 Background: The mammalian target of rapamycin (mTOR) signaling pathway is involved in the pathogenesis of neuroendocrine tumors (NET). Everolimus (RAD001), an oral mTOR inhibitor, has antitumor activity in patients (pts) with advanced NET. In this open-label, multicenter, phase II study (RAMSETE), the safety and efficacy of everolimus monotherapy was evaluated in pts with advanced nonsyndromic, nonpancreatic NET. Methods: Pts with advanced (unresectable or metastatic), progressive, nonsyndromic, nonpancreatic NET received everolimus (10 mg/day) as monotherapy. The primary endpoint was objective response rate (proportion of pts with best overall complete response [CR] or partial response [PR] per RECIST v1.0) by central radiologic review. A secondary endpoint included progression-free survival (PFS). Results: By database soft lock (December 1, 2011), 73 pts from 16 European clinics received everolimus (median duration of treatment: 193 days). Fifty-five (75%) pts discontinued; reasons included disease progression (n=23), adverse events (AEs [n=23]), withdrawal of consent (n=4), death (n=3), and protocol deviation (n=2). In the per protocol population (N=60), 32 (53%) pts received prior antineoplastic therapy. The best response by central review was stable disease in 55%. By local review, 3 (5%) pts had a PR, with SD in 39 (65%) pts. Median PFS by central review was 185 days (95% CI: 158-255). Median PFS by local investigator review was 285 days (95% CI: 231-not estimable). 69 (95%) pts reported treatment-related AEs of any grade, including rash (n=28; 38%), diarrhea (n=20; 27%), mucosal inflammation (n=18; 25%), and decreased appetite (n=17; 23%). Treatment-related grades 3 and 4 AEs and serious AEs were reported by 27 (37%) and 18 (25%) pts, respectively. Conclusions: In this open-label trial of everolimus in pts with advanced, nonsyndromic, extrapancreatic NET, a high rate of disease stabilization was achieved after prior tumor progression with favorable median PFS. This study further supports efficacy of everolimus in types of NET other than those studied in RADIANT-3 (pancreatic NET) and RADIANT-2 (NET associated with carcinoid syndrome).

Invasive extramammary Paget’s disease and the risk for secondary tumours in Europe

The aim of this study was to determine the incidence and survival of Extramammary Paget’s disease (EMPD) and to describe the possible increased risk of tumours after EMPD.All invasive cases diagnosed between 1990 and 2002 were selected from the RARECARE database. Incidence was expressed in European standardized rates. Relative survival was calculated for the period 1995–1999, with a follow-up until 31st December 2003. Standardized incidence ratios of second primary tumours were calculated to reveal possible increased risk after EMPD.European age standardized Incidence of EMPD within Europe is 0.6 per 1000,000 person years. Five-year relative survival for invasive EMPD was 91.2% (95%CI; 83.5–95.4), 8.6 percent of the EMPD patients developed other malignancies. The highest increased risk of developing a second primary tumour was found in the first year of follow-up (SIR:2.0 95%CI; 1.3–2.9), living in the South European region (SIR:2.3 95%CI; 1.5–3.5) or being female (SIR:1.5 95%CI; 1.1–1.9). Female genital organs displayed greatest increased risk of developing a second primary tumour after EMPD (SIR:15,1 95%CI; 0.38–84.23).Due to the increased risk of a second primary tumour after EMPD a thorough search for other tumours during their follow-up is recommended.

Epidemiology of glial and non-glial brain tumours in Europe

To the central nervous system (CNS) belong a heterogeneous group of glial and non glial rare cancers.The aim of the present study was to estimate the burden (incidence, prevalence, survival and proportion of cured) for the principal CNS cancers in Europe (EU27) and in European regions using population-based data from cancer registries participating in the RARECARE project.We analysed 44,947 rare CNS cancers diagnosed from 1995 to 2002 (with follow up at 31st December 2003): 86.0% astrocytic (24% low grade, 63% high grade and 13% glioma NOS), 6.4% oligodendroglial (74% low grade), 3.6% ependymal (85% low grade), 4.1% Embryonal tumours and 0.1% choroid plexus carcinoma. Incidence rates vary widely across European regions especially for astrocytic tumours ranging from 3/100,000 in Eastern Europe to 5/100,000 in United Kingdom and Ireland. Overall, about 27,700 new rare CNS cancers were estimated every year in EU27, for an annual incidence rate of 4.8 per 100,000 for astrocytic, 0.4 for oligodendroglial, 0.2 for ependymal and embryonal tumours and less than 0.1 for choroid plexus carcinoma.More than 154,000 persons with rare CNS were estimated alive (prevalent cases) in the EU at the beginning of 2008.Five-year relative survival was 14.5% for astrocytic tumours (42.6% for low grade, 4.9% for high grade and 17.5% for glioma NOS), 54.5% for oligodendroglial (64.9% high grade and 29.6% low grade), 74.2% for ependymal (80.4% low grade and 36.6% high grade), 62.8% for choroid plexus carcinomas and 56.8% for embryonal tumours. Survival rates for astrocytic tumours were relatively higher in Northern and Central Europe than in Eastern Europe and in UK and Ireland. The different availability of diagnostic imaging techniques and/or radiation therapy equipment across Europe may contribute to explain the reported survival differences.The estimated proportion of cured patients was 7.9% for the ‘glial’ group to which belong astrocytic tumours.Overall results are strongly influenced by astrocytic tumours that are the most common type.This is the first study to delineate the rare CNS cancer burden in Europe by age, sex and European region.

Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe

We provide updated estimates of survival, incidence, complete prevalence, and proportion cured for patients with testicular/paratesticular and extragonadal germ cell cancers in Europe, grouped according to the new list of cancer types developed by RARECARE. We collected data, archived in European cancer registries, with vital status information available to 31st December 2003.We analysed 26,000 cases of testicular, paratesticular and extragonadal germ cell cancers diagnosed 1995–2002, estimating that about 15,600 new testicular/paratesticular and 630 new extragonadal cancer cases occurred per year in EU27, with annual incidence rates of 31.5/1,000,000 and 1.27/1,000,000, respectively. Slightly more than 436,000 persons were alive at the beginning of 2008 with a diagnosis of testicular/paratesticular cancer, and about 17,000 with a diagnosis of extragonadal germ cell cancer.Five-year relative survival was 96% for testicular/paratesticular cancer and 71% for extragonadal germ cell cancer; the proportions cured were 95% and 69%, respectively. We found limited variation in survival between European regions except for non-seminomatous testicular cancer, for which five-year relative survival ranged from 86% in Eastern Europe to 96% in Northern Europe. Survival for all cancer types considered decreased with increasing age at diagnosis.Further investigation is required to establish the real reasons for the lower survival in Eastern Europe. Considering the high prevalence of these highly curable cancers, it is important to monitor patients long-term, so as to quantify treatment-related risks and develop treatments having limited impact on quality of life.

Diagnostic et traitement du cancer du pénis

Penile cancer is a rare tumor in Europe and is therefore associated with risks of diagnostic delay for stage Ta-T1 tumors or pre-epitheliomatous lesions and of an inadequate treatment strategy. Clinical examination by palpation is essential in primary tumors to look for infiltration in the corpus spongiosum and the tunica albuginea of the corpus cavernosa of the penis, and in the lymphatic drainage areas, in particular in the upper inner quadrant of the inguinal lymph nodes. The work-up must include: a biopsy in the case of diagnostic doubt, lymph node aspiration in the case of palpable adenopathies, and whole-body computed tomography (CT). Treatment of the primary tumor can include partial amputation for tumors infiltrating the corpus cavernosa, or conservative treatment for tumors limited to the glands if the diameter is less than 30 mm, after an initial circumcision. Groups at risk of lymph node metastases have been defined as a function of the pathology results of their primary tumors. In these groups at risk, or in the case of clinical lymph node metastasis, dissection of the lymph node has an important role, permitting 5-year survival rates greater than 80 % when the number of metastatic lymph nodes is ≤ 1-2. In the case of more extensive lymph node spread, a combination of chemotherapy and surgery must be discussed in multidisciplinary meetings, especially for younger patients.

DRAFT: RAMSETE trial of everolimus (RAD001) in the treatment of silent (nonfunctioning) advanced neuroendocrine tumors.

TPS208 Background: Nonfunctioning (nf) neuroendocrine tumors (NETs) do not hypersecrete biogenic amines and peptidic hormones in the blood, ie, they are nonsyndromic. Nf NETS represent at least 50% of gastroenteropancreatic NETs. Nf NETs may have symptoms due to tumor mass effect, such as abdominal pain and jaundice. Surgery is the only curative option but is limited to early well-differentiated disease. For inoperable advanced disease, there are currently no standard tumor control therapies. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR; a central regulator of cell growth and proliferation, cellular metabolism, and angiogenesis) and interrupts insulin-like growth factor/phosphatidylinositol 3-kinase signaling that is integral to NETs growth. Everolimus plus octreotide LAR showed promising efficacy in a phase II study in pts with pancreatic NETs (Yao 2009). Few studies have specifically focused on nf NETs at other primary sites (eg, bronchial, rectal, etc). The RAMSETE (RAD001 in Advanced and Metastatic Silent Neuro-Endocrine Tumours in Europe)clinical trial is examining the efficacy and safety of daily oral everolimus therapy for the treatment of advanced nonsyndromic NET pts, excluding pts with pancreatic NETs. Methods: RAMSETE is a single-arm, multicenter, single- stage phase II trial (target enrollment: 60 pts) of everolimus (10 mg/day) monotherapy treating pts with advanced nonsyndromic NETs, not including pancreatic NETs or poorly differentiated NETs. Pts may have received 0-3 prior systemic treatments and must have progressed within 12 months prior to enrollment. Study initiation was June 24, 2009; accrual is expected to finish in mid-2010. Everolimus will continue until tumor progression. The primary efficacy endpoint is the proportion of pts with complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) criteria. Secondary endpoints include disease control rate (CR + PR + SD [stable disease]), biochemical response rate based on the tumor marker chromogranin A, progression-free survival, overall survival, and safety. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis

CK2β Is Expressed in Endometrial Carcinoma and Has a Role in Apoptosis Resistance and Cell Proliferation

Protein kinase CK2 (CK2) is a serine/threonine kinase that participates in important cellular processes. We have recently demonstrated that CK2 plays a role in resistance to TRAIL/Fas-induced apoptosis in endometrial carcinoma (EC) by regulating FLIP. Here, we assessed the immunohistochemical expression of CK2beta in EC and checked its role in cell proliferation and anchorage-independent cell growth. CK2beta immunostaining was assessed in two tissue microarrays, one constructed from paraffin-embedded blocks of 95 ECs and another from 70 samples of normal endometrium. CK2beta expression was correlated with histological type; grade and stage; cell proliferation (Ki-67) and apoptotic index; immunostaining for cyclin D1, PTEN, AKT, beta-catenin, and FLIP. Moreover, the Ishikawa EC cell line was subjected to down-regulation of CK2 by shRNA. CK2beta expression was frequent in EC (nuclear, 100%; cytoplasmic, 87.5%). The staining was more intense in EC than in normal endometrium (P = 0.000), and statistically correlated with AKT, PTEN, beta-catenin, and FLIP. In EC, CK2beta expression correlated with cell proliferation. Knock-down of CK2beta blocked colony formation of EC in soft agar, and also resulted in decreased expression of cyclin D1 and ERK phosphorylation. The results confirm that CK2beta is widely expressed in EC, and suggest a role in cell proliferation and anchorage-independent cell growth.

Childhood central nervous system tumours – incidence and survival in Europe (1978–1997): Report from Automated Childhood Cancer Information System project

This paper describes the incidence and survival of childhood central nervous system (CNS) tumours in Europe for the period 1978–1997. A total of 19,531 cases, aged 0–14 years, from the ACCIS database were analysed by five regions: the British Isles, East, North, South, and West. Overall age-standardised incidence rate (ASR) of CNS tumours in Europe (1988–1997) was 29.9 per million, with the highest rates in the North. Astrocytoma (ASR = 11.8), primitive neuroectodermal tumours (PNET) (ASR = 6.5) and ependymoma (ASR = 3.4) were the most frequent types. Incidence increased significantly during 1978–1997, on average by 1.7% per year. Diagnostic methods may partially explain incidence rates and trends, although a role of variations in risk factors cannot be excluded. Overall 5-year survival was 64% and varied between 72% in the North and 53% in the East. PNET had the poorest prognosis (49%) and astrocytoma the best (75%). Survival has improved by 29% since late 1970s. The positive trends were seen in all regions, although the interregional differences persisted, as a reflection of the different healthcare systems.

Malignant renal tumours incidence and survival in European children (1978–1997): Report from the Automated Childhood Cancer Information System project

More than 5000 cases of malignant renal tumour diagnosed in children under the age of 15 years during the period 1978–1997 in Europe, were extracted from the database of the Automated Childhood Cancer Information System (ACCIS). In 1988–1997 the age-standardised incidence rate of childhood renal tumours in Europe was 8.8 per million, with significant differences between regions. Wilms’ tumour (WT, M-8960) accounted for 93% of renal tumours and about 7% were bilateral. The incidence rates of WT increased over the 20 years, by 0.7% per year. European 5-year survival for children diagnosed with WT in 1988–1997 was 85%, ranging from 73% in the East to 91% in the North. Patients in the age group 0–3 years at diagnosis had a more favourable prognosis (5-year survival 87%) than those diagnosed later (81%), P < 0.0001. Patients with unilateral WT ( n = 2085) had better 5-year survival (85%) than 154 patients with bilateral tumours (76%), P = 0.003. Five-year survival for 64 patients with clear cell sarcoma of kidney was 68%, for 43 patients with rhabdoid tumour of kidney it was 23%, and for 56 patients with renal cell carcinoma it was 87%. For combined European data, 5-year survival for WT increased from 73% in 1978–1982 to 87% in 1993–1997 and the increase was significant in three out of five regions (East, North and West). Further development and exploitation of the ACCIS database will benefit clinical management and aetiological studies.

Die systemische Therapie des Peniskarzinoms

Penile cancer is a rare tumor in Europe with an incidence of 0.1-0.9 per 100,000 men per year. The success of our therapy is mainly influenced by the presence of lymph node metastases. At first diagnosis 17-45% of patients already harbor lymph node metastases. Bilateral inguinal and pelvic lymphadenectomy is a curative measure in these patients. In cases of gross inguinal metastases neoadjuvant chemotherapy leads to a remission rate of 21-60% and improves the resectability. The influence on survival is not proven. The same holds true for adjuvant therapy following lymphadenectomy. Polychemotherapy rarely leads to long-lasting complete remission in patients with distant metastases. The protocols consist usually of cisplatin, bleomycin, methotrexate, and 5-fluorouracil. The overall remission rate is around 15-32%. Because of the low efficacy of the present chemotherapy regimens, one should follow new strategies, comparable to those initiated for squamous cell cancer of other organs.

Mistletoe extract/gemcitabine combination treatment: An interim report from the NCCAM/NCI phase I study in patients with advanced solid tumors

3098 Background: European Mistletoe (viscum album L.) extracts (ME) are used in varying doses and schedules as herbal adjunct treatment for solid tumors in Europe. Clinical efficacy remains controversial. Controlled data on safety, toxicity and drug interactions are lacking. Methods: Subjects with stage IV cancer (average age 51 years; breast 5, pancreas 4, colorectal 3, NSCLC 4) enrolled on a 2 stage dose escalation phase I trial of toxicity profile, dose limiting toxicity (DLT), MTD, and gemcitabine (GEM) pharmacokinetics (with and without ME) on s.c.qd ME (HELIXOR A, Helixor GmbH, KG, Rosenfeld, Germany) combined with GEM 750mg/m2i.v. on a weekly x 2 q 21d schedule for 3 cycles. We report on stage I (fixed dose GEM). Starting target ME dose level was 20mg (n=3), with escalations to 50 (n=3), 100 (n=3), 200 (n=5), and 250 mg (n=2). DLT for GEM is neutropenia. GEM and 2’,2’-difluorodeoxyuridine (dFdU) plasma concentrations (Cp) at baseline and week 8 (stable ME dose for 7 days) were determined by HPLC with UV detection o 12 subjects who completed 3 cycles (ME dose 20–200mg). The area under the curve (AUC) was determined using WinNonLin version 4.0. This project was approved by the Navy Clinical Investigation Program Project Number: 02–074 Results: No ME DLT was observed. Ten ME related grade 2 adverse events (AE, injection site reaction 4, flu-like syndrome 4, other local reaction 2), 30 grade 3 GEM-related AE (lymphopenia 12, neutropenia/low WBC 10, thrombocytopenia 2, nausea/vomiting 2, other 4) and 1 GEM related grade 4 lymphopenia were observed. Median baseline and week 8 AUC (664/670 min*nmol/ml, p=0.97) and Cp (47.7/49.7 nmol/ml, p=0.85) of GEM and dFdU (AUC 1038/1099 min*nmol/ml, p= 0.46, Cp 75.7/84 nmol/ml, p=0.67) were equivalent (signed rank test). 1038 of 1059 scheduled ME doses were given (compliance 98.2%). Tow subjects had partial clinical responses (PR) by RECIST (pancreas 1, NSCLC 1) and four subjects had stable disease > 18 wks (pancreas 1, NSCLC 2, rectal 1). Conclusions: The ME/GEM combination has been well tolerated. GEM Cp during infusion was unaffected by ME. Two subjects had a PR. Stage II (GEM dose escalation) will determine if addition of ME alters GEM toxicities and MTD. No significant financial relationships to disclose.

Hematopoetic stem cell transplantation for solid tumors in Europe

BackgroundHematopoetic stem cell transplants (HSCT) are discussed as treatment options for patients with solid tumors. Transplant numbers have changed substantially over the last decade, few controlled studies are available and different opinions prevail. Objective information on current practice is needed. Patients and methodsData from 27 902 HSCT for solid tumors (2% allogeneic, 98% autologous), collected by the European Group for Blood and Marrow Transplantation (EBMT) activity survey from 1991 to 2002 were used to assess trends, transplant rates and coefficient of variation of transplant rates in Europe. ResultsTransplant numbers increased from 536 in 1991 to 4154 in 1997 and decreased to 1913 in 2002. Indications were neuroblastoma (2504 HSCT; 9%), glioma (662 HSCT; 2%), soft tissue sarcoma (1253 HSCT; 4%), germ cell cancer (3291 HSCT; 12%), breast cancer (13 524 HSCT; 48%), Ewing’s sarcoma (1896 HSCT; 7%), lung cancer (387 HSCT; 1%), ovarian cancer (845 HSCT; 3%) and other solid tumors (3540 HSCT; 14%). Allogeneic cells were used in <20 cases up to 1997; since then allogeneic HSCT increased to 159 in 2002, mainly for renal cell carcinoma. Low coefficients of variation in transplant rates (<60%) are observed for Ewing’s sarcoma (<56.5%), suggesting consensus for this indication. ConclusionsThese data give an overview on current practice of HSCT for solid tumors in Europe. They provide objective information for health-care providers and patient counselling.

Survival of children with liver tumours in Europe 1978–1989

Hepatic tumours are rare in childhood. Within the frame of the EUROCARE II study, a total of 328 liver tumours in patients aged 0–14 years were reported during the period 1978–1989. The childhood cancer registries in UK and Germany contributed approximately a third of the cases each. Hepatoblastoma accounted for 71% of cases. The 5-year survival was 36% 95% confidence interval (CI) 28–46%, with no significant difference between the genders. Patients aged 10–14 years did worse, especially boys. Survival improved significantly during the study period. Survival in hepatocellular carcinoma was lower, 20% (95% CI 6–52%), and showed no improvement during the study period.