[Show abstract][Hide abstract] ABSTRACT: Background:
Survival differences across Europe for patients with cancers of breast, uterus, cervix, ovary, vagina and vulva have been documented by previous EUROCARE studies. In the present EUROCARE-5 study we update survival estimates and investigate changes in country-specific and over time survival, discussing their relationship with incidence and mortality dynamics for cancers for which organised screening programs are ongoing.
We analysed cases archived in over 80 population-based cancer registries in 29 countries grouped into five European regions. We used the cohort approach to estimate 5-year relative survival (RS) for adult (⩾15years) women diagnosed 2000-2007, by age, country and region; and the period approach to estimate time trends (1999-2007) in RS for breast and cervical cancers.
In 2000-2007, 5-year RS was 57% overall, 82% for women diagnosed with breast, 76% with corpus uteri, 62% with cervical, 38% with ovarian, 40% with vaginal and 62% with vulvar cancer. Survival was low for patients resident in Eastern Europe (34% ovary-74% breast) and Ireland and the United Kingdom [Ireland/UK] (31-79%) and high for those resident in Northern Europe (41-85%) except Denmark. Survival decreased with advancing age: markedly for women with ovarian (71% 15-44years; 20% ⩾75years) and breast (86%; 72%) cancers. Survival for patients with breast and cervical cancers increased from 1999-2001 to 2005-2007, remarkably for those resident in countries with initially low survival.
Despite increases over time, survival for women's cancers remained poor in Eastern Europe, likely due to advanced stage at diagnosis and/or suboptimum access to adequate care. Low survival for women living in Ireland/UK and Denmark could indicate late detection, possibly related also to referral delay. Poor survival for ovarian cancer across the continent and over time suggests the need for a major research effort to improve prognosis for this common cancer.
Full-text · Article · Oct 2015 · European Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Background:
During the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC). The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.
HCCs diagnosed in 1996-2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan-Meier method by calendar period: 1996-2000, 2001-2005 and 2006-2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.
619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p < 0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p < 0.0001), diagnosis period (p < 0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p < 0.0001), treatment (p < 0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996-2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001-2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006-2009 (reference group).
The current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.
No preview · Article · Dec 2014 · Cancer Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Summary
Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007.
We analysed survival data for 157 499 children (age 0—14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers.
We analysed 59 579 cases. For all cancers combined for children diagnosed in 2000—07, 1-year survival was 90·6% (95% CI 90·2—90·9), 3-year survival was 81·0 % (95% CI 80·5—81·4), and 5-year survival was 77·9% (95% CI 77·4—78·3). For all cancers combined, 5-year survival rose from 76·1% (74·4—77·7) for 1999—2001, to 79·1% (77·3—80·7) for 2005—07 (hazard ratio 0·973, 95% CI 0·965—0·982, p<0·0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65·2% (95% CI 63·1—67·3) in 1999—2001, to 70·2% (67·9—72·3) in 2005—07. Europe-wide average yearly change in mortality (hazard ratio) was 0·939 (95% CI 0·919—0·960) for acute lymphoid leukaemia, 0·959 (0·933—0·986) for acute myeloid leukaemia, and 0·940 (0·897—0·984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005—07).
Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe.
Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.
Full-text · Article · Dec 2013 · The Lancet Oncology
[Show abstract][Hide abstract] ABSTRACT: Background
Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE—the largest cooperative study of population-based cancer survival in Europe—has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries.
In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000–07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999–2001, 2002–04, and 2005–07).
5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999–2001 to 2005–07 were for prostate cancer (73·4% [95% CI 72·9–73·9] vs 81·7% [81·3–82·1]), non-Hodgkin lymphoma (53·8% [53·3–54·4] vs 60·4% [60·0–60·9]), and rectal cancer (52·1% [51·6–52·6] vs 57·6% [57·1–58·1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type.
The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities.
Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.
Full-text · Article · Dec 2013 · The Lancet Oncology
[Show abstract][Hide abstract] ABSTRACT: Assessing the quality of cancer care (QoCC) has become increasingly important to providers, regulators and purchasers of care worldwide. The aim of this study was to develop evidence-based quality indicators (QIs) for colorectal cancer (CRC) to be applied in a population-based setting.
A comprehensive evidence-based literature search was performed to identify the initial list of QIs, which were then selected and developed using a two-step-modified Delphi process involving two multidisciplinary expert panels with expertise in CRC care, quality of care and epidemiology.
The QIs of the clinical cancer care (QC3) population-based project, which involves all the public and private hospitals and clinics present on the territory of Canton Ticino (South Switzerland).
Ticino Cancer Registry, The Colorectal Cancer Working Group (CRC-WG) and the external academic Advisory Board (AB).
Set of QIs which encompass the whole diagnostic-treatment process of CRC.
Of the 149 QIs that emerged from 181 sources of literature, 104 were selected during the in-person meeting of CRC-WG. During the Delphi process, CRC-WG shortened the list to 89 QI. AB finally validated 27 QIs according to the phase of care: diagnosis (N=6), pathology (N=3), treatment (N=16) and outcome (N=2).
Using the validated Delphi methodology, including a literature review of the evidence and integration of expert opinions from local clinicians and international experts, we were able to develop a list of QIs to assess QoCC for CRC. This will hopefully guarantee feasibility of data retrieval, as well as acceptance and translation of QIs into the daily clinical practice to improve QoCC. Moreover, evidence-based selected QIs allow one to assess immediate changes and improvements in the diagnostic-therapeutic process that could be translated into a short-term benefit for patients with a possible gain both in overall and disease-free survival.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present population-based descriptive study was to evaluate the incidence and mortality trends for melanoma to gain insights on the effectiveness of opportunistic secondary prevention strategies. Data on all invasive cutaneous melanoma cases occurring between 1996 and 2011 were retrieved from the Ticino Cancer Registry, southern Switzerland. The European age-standardized incidence rates were computed by the period of diagnosis, Breslow thickness and histological types. Trends in incidence and mortality rates were measured as the annual per cent change (APC). A total of 1230 patients had a diagnosis of invasive cutaneous melanoma. Cases were categorized as follows: superficial spreading melanoma (55.7%), nodular melanoma (10.0%), lentigo maligna melanoma (5.5%), melanoma not otherwise specified (25.2%) and other types (3.6%). The incidence rate of invasive melanoma rose from 17.4 per 100 000 inhabitants in 1996-2003 to 20.6 in 2004-2011, with an overall APC of +2.1% [95% confidence interval (CI): -0.8%, +5.1%]. An increase in incidence was observed for superficial spreading melanoma (APC=+2.9%; 95% CI: -1.1%, +7.0%) and thin melanomas (i.e. ≤1.00 mm) (APC=+3.4%; 95% CI: +0.2%, +6.7%), whereas we detected a descriptive growing incidence of thick melanomas (APC=+2.1%; 95% CI: -1.4%, +5.8%). Mortality trend analysis revealed constant rates throughout the study period (APC=-1.0%; 95% CI: -5.5%, +3.7%). This population-based study confirms that in a country with the highest incidence of cutaneous melanomas, that is, Switzerland, the opportunistic screening strategy does not change the incidence of thick melanomas nor the overall mortality. This study suggests there is still a need for public health efforts in primary and secondary prevention.
No preview · Article · Jul 2013 · Melanoma research
[Show abstract][Hide abstract] ABSTRACT: CDX2 expression has been recently found to be almost restricted to the columnar cell variant (CCV) of papillary thyroid carcinoma (PTC). We analyzed CDX2 expression and BRAF molecular status in a series of different variants of PTC comprising 6 cases of the columnar cell variant (1 of the aggressive subtype and 5 of the non-aggressive subtype), 18 cases of the classic variant, 7 cases of the follicular variant, 4 cases of the tall cell variant, and 1 case of the diffuse sclerosing variant. CDX2 expression was not found in any of the 30 PTC samples analyzed but in 4 out of 6 (66%) of the CCV-PTC. BRAF was mutated in only one case (17%) of CCV-PTC and in 21 cases (70%) of the remaining PTC variants. These data fully confirm the finding that CDX2 expression is strictly associated with the columnar cell morphology of PTC, whereas no correlation was found between the loss of CDX2 expression and the occurrence of BRAF mutation, as shown in colorectal carcinoma.
Full-text · Article · Jun 2013 · Thyroid: official journal of the American Thyroid Association
[Show abstract][Hide abstract] ABSTRACT: Background:
In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease.
We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab.
Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17⩾2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH−). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH− profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively).
HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.
Full-text · Article · Jan 2013 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis.
All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated.
The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively.
The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology.
[Show abstract][Hide abstract] ABSTRACT: At present, thyroid fine-needle aspiration (FNA) specimens are diagnosed using a tiered classification scheme, with the most popular of these being the 5-tiered and 6-tiered systems. In this study, the authors present their institutional experiences using these 2 different systems and evaluate their efficacy based on the surgical follow-up.
Thyroid FNA specimens and their corresponding surgical resection specimens were collected between 2007 and 2009. The following diagnostic categories are used in both systems: unsatisfactory/nondiagnostic, benign, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant. An additional category termed atypia of undetermined significance/follicular lesion of undetermined significance was used for atypical cases in the 6-tiered system. Statistical analysis was performed by comparing the different diagnostic categories.
The case cohort included a total of 7686 thyroid FNA specimens representing 3962 nodules and 3724 nodules, respectively, in the 5-tiered and 6-tiered systems. Negative predictive values for the benign categories (96.9% vs 97.5%; P = 1) and positive predictive values for both the follicular neoplasm categories (26.5% vs 32.1%; P = .2531) and the malignant categories (99.1% vs 99.4%; P = 1) were similar. The most significant differences between the 5-tiered and 6-tiered systems were the percentage of cases classified as benign (83.9% vs 55.4%; P < .0001) and as follicular neoplasms (4.6% vs 23.8%; P < .0001). It is interesting to note that fewer patients were referred for surgery in the 5-tiered system compared with the 6-tiered one (9.1% vs 36.5%; P < .0001).
Use of either the 5-tiered or 6-tiered reporting systems for thyroid FNA specimens can potentially affect the clinical management of patients with thyroid nodules.
Full-text · Article · Apr 2012 · Cancer Cytopathology
[Show abstract][Hide abstract] ABSTRACT: Preoperative radiotherapy (RT) followed by surgery is widely accepted in the treatment of locally advanced rectal cancer (LARC). This study aimed to estimate at the population-based level the impact of preoperative RT on overall survival (OS) and cancer-specific survival (CSS) in LARCs diagnosed in Southern Switzerland between 1996 and 2007. All patients with LARC were selected from the Ticino Cancer Registry database. Patients were categorized according to the first administered treatment: preoperative radiotherapy (RT) followed by surgery (RT+) versus surgery (RT-). Clinical-pathological characteristics and 5-year OS and CSS were analysed. Among 384 patients with LARC, 54% underwent preoperative RT, occurring more frequently in the mid-distal part of the rectum compared with the RT- group (74.8 vs. 29.8%, respectively). Both 5-year OS and CSS significantly improved in RT+ patients (OS: 68 vs. 54%, respectively; CSS: 71 vs. 63%, respectively). The adjusted hazard ratio for all death was equal to 0.66 (95% confidence interval: 0.46; 0.97); similarly, the hazard ratio for cancer-specific death was 0.63 (95% confidence interval: 0.39; 0.99). These observational population-based results, after controlling for most important diagnostic and clinical prognostic factors, confirm the benefit of preoperative RT of LARC, even if the magnitude seems greater than expected in clinical trials results. Additional studies are needed, particularly with regard to the possible effect of standardized staging procedure and multidisciplinary discussion on patient outcome.
No preview · Article · Mar 2012 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the impact of immunohistochemical- (IHC-) studies on incidence and survival of lung cancer histotypes.
Lung cancers occurred in southern Switzerland between 1996 and 2010 were selected by the Ticino Cancer Registry and categorised into adenocarcinoma (AC), squamous-cell-carcinoma (SqCC), small-cell-carcinoma (SmCC), and large-cell carcinoma/non-small-cell lung cancer (LCC/NSCLC). Incidence rates, annual-percentage-change (APC), and two-year overall survival (OS) (follow-up: 31.12.2010) were performed.
2467 cases were selected: 997 (40.4%) AC; 522 (21.2%) LCC/NSCLC, 378 (15.3%) SmCC, and 570 (23.1%) SqCC. Trend-analysis showed significant increase in AC (APC: 4.6; 95% CI: 3.1; 6.0) and decrease of LCC/NSCLC, with significant joinpoint in 2003 (APC: -14.7; 95% CI: -21.6; -7.1). Improved OS and decreased OS were detected in SqCC and LCC/NSCLC, respectively.
This study highlights that diagnosis with ancillary immunohistochemical studies will change incidence and survival of precisely defined lung cancer subtypes. It calls attention to the need for cautious interpretation of studies and clinical trials, where the diagnosis was based on histology unaccompanied by IHC studies, and to the need of standardised diagnostic procedures.
Preview · Article · Dec 2011 · Journal of Cancer Epidemiology
[Show abstract][Hide abstract] ABSTRACT: KRAS mutations represent the main cause of resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC). We evaluated whether highly sensitive methods for KRAS investigation improve the accuracy of predictions of anti-EGFR MoAbs efficacy.
We retrospectively evaluated objective tumor responses in mCRC patients treated with cetuximab or panitumumab. KRAS codons 12 and 13 were examined by direct sequencing, MALDI-TOF MS, mutant-enriched PCR, and engineered mutant-enriched PCR, which have a sensitivity of 20%, 10%, 0.1%, and 0.1%, respectively. In addition, we analyzed KRAS codon 61, BRAF, and PIK3CA by direct sequencing and PTEN expression by immunohistochemistry.
In total, 111 patients were considered. Direct sequencing revealed mutations in codons 12 and 13 of KRAS in 43/111 patients (39%) and BRAF mutations in 9/111 (8%), with almost all of these occurring in nonresponder patients. Using highly sensitive methods, we identified up to 13 additional KRAS mutations compared with direct sequencing, all occurring in nonresponders. By analyzing PIK3CA and PTEN, we found that of these 13 patients, 7 did not show any additional alteration in the PI3K pathway.
The application of highly sensitive methods for the detection of KRAS mutations significantly improves the identification of mCRC patients resistant to anti-EGFR MoAbs.
Full-text · Article · Jun 2011 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: Although some clinical-pathological features of breast cancers, such as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive tumours, are sensitive indicators of early detection, comprehensive population-based studies of opportunistic screening are needed.
Cases of DCIS or invasive breast cancer diagnosed in 1996-2007 were identified from the Ticino Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and mortality, as well as main clinical-pathological features, such as tumour diameter, AJCC stage and histological grade, were analysed.
A total of 3047 incident cases of female breast cancer were identified. The proportion of DCIS with respect to invasive cases increased from 5.8% in the period 1996-2001 to 6.4% in the period 2002-2007. The median tumour size of invasive cancers decreased from 20 mm in 1996-2001 to 18 mm in 2002-2007 (P<0.0001). An increase in well/moderately differentiated invasive tumours, from 67% in the period 1996-2001 to 73% in 2002-2007 (P<0.001), was detected and resulted in an Annual Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3).
An opportunistic screening strategy can lead to an improvement of prognostic features at diagnosis, but these features are still less favourable than those achieved by organised screening programmes.
Preview · Article · Oct 2009 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Immunosuppressive treatment has changed the prognosis of Lupus nephritis over time, but improvement in prognosis is difficult to analyze in different historical periods, and should be better demonstrated in comparison with life expectancy of sex-and age-matched people. Long-term patient and renal survival of 90 patients diagnosed with Lupus nephritis at our center from 1968 to 2001 with a follow-up time of 14+/-8 years was retrospectively evaluated. Patient and kidney survival significantly increased over time. Multivariate analyses show that risks of patient and renal death decreased by 8% at each year of follow-up, and increased by more than 5 time in patients aged > 30 years at diagnosis. As only 14 patients were men, relative survival as compared to that of the sex- and age-matched general population of the Piedmont Region was calculated for the 76 women. Improvement in the survival of the cohort of women was seen at any time of follow-up: in particular, it was sharply lower in the first period (relative survival at 5, 10 and 15 years = 0.784, 0.665, and 0.620, respectively) and increased in the second (relative survival at 5, 10 and 15 years = 0.939, 0.921, and 0.850, respectively) nearly approaching that expected for the general population, i.e. 0.993, 0.983 and 0.967, respectively. Taken together, our data allow us to draw the conclusion that life expectancy in women with Lupus nephritis has improved over time, paralleling an improved awareness of the disease and a significant increase in steroid pulse therapy as induction/remission phase. Improvement in survival is for the first time demonstrated to cover the gap with life expectancy of the general population for women with Lupus nephritis.
Full-text · Article · Oct 2009 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] ABSTRACT: Cetuximab and panitumumab efficacy in metastatic colorectal cancer (mCRC) may be influenced by EGFR gene status and/or deregulation of its downstream signalling proteins detected in primary tumour. However, metastasis might have different molecular patterns with respect to primary tumour, possibly affecting the prediction of EGFR-targeted therapy efficacy. We analysed primary tumour and metastasis in 38 mCRC patients. Twelve cases were cetuximab/panitumumab treated. EGFR gene status and protein expression were investigated through fluorescent in situ hybridisation and immunohistochemistry (IHC), K-Ras/BRAF mutations by sequencing and PTEN expression by IHC. We observed EGFR gene deregulation in 25 out of 36 primary tumours and 29 out of 36 metastases, K-Ras mutations in 16 out of 37 cancers and in 15 out of 37 metastases, BRAF mutations in 2 out of 36 cancers and 2 out of 36 metastases and PTEN loss in 8 out of 38 cancers and 12 out of 38 metastases. For the first time in literature, we show that primary colorectal cancer and paired metastasis may exhibit difference with respect to EGFR pathway deregulation mechanisms possibly implying a different response to cetuximab or panitumumab treatment. The investigation of treated patients confirms this hypothesis. We therefore suggest that the analysis of metastatic lesion should be considered in patient management as well as in designing future clinical trials aimed to investigate the effect of anti-EGFR monoclonal antibodies in the treatment of mCRC.
Full-text · Article · May 2009 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Introduction. Gastrointestinal stromal tumors (GISTs) are characterized at the molecular level by c-kit or PDGFRA oncogene mutations. Although GISTs raised major interest in past decades, population-based studies are still rare. Materials and Methods. All GISTs diagnosed in Southern Switzerland (1999-2005) were identified using Ticino Cancer Registry and analysed for c-kit and PDGFRA mutations. Clinical and molecular features were studied. Results. Annual incidence of GISTs was 1.47 cases/100,000 inhabitants (median age: 64 years; median size: 6.0 cm). Most GISTs arose in the stomach (60.5%). The malignancy risk was very-low/low in 47% of patients. DNA sequences showed a gene alteration in either c-kit or PDGFRA genes in 72.5% of patients. Mutations occurred mostly in c-kit exon 11 (60%). No mutations in c-kit exons 13 or 17 were found. An equal number of alterations in exons 12 and 18, and no mutations in exon 14 were observed in the PDGFRA gene. Discussion. This is the first comprehensive population-based study of GISTs incidence and molecular biology characterization in Central Europe. Our incidence data showed higher age-standardized rates compared to other European countries. The gene mutation spectrum differed when compared to the literature. This is relevant to improve the molecular profile knowledge based on Cancer Registry data.
No preview · Article · Dec 2008 · Histology and histopathology