[Show abstract][Hide abstract] ABSTRACT: Background:
Histological transformation (HT) is a poorly understood event in patients with marginal zone lymphoma (MZL). Aim of this study was to analyze incidence and risk factors for HT in a large series of MZL patients.
Patients and methods:
The studied cohort included 340 MZL patients diagnosed and treated between 1995 and 2012: 157 extranodal MZL (MALT lymphoma, 46%), 85 splenic MZL (SMZL, 25%), and 37 nodal MZL (NMZL, 11%). Sixty-one patients (18%) had bone marrow infiltration at presentation, with or without detectable involvement of peripheral blood, but without other involved sites; they were considered clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ).
With a median follow-up of 4.8 years, the median overall and progression-free survival of the whole population were 14.5 years and 5 years. HT was observed in 13 cases (3.8%, 95%CI: 2%-6.5%). Elevated lactate dehydrogenase (LDH) at diagnosis was associated with risk of HT (P=0.019). HT occurred in 5% of SMZL, 4% of MALT lymphomas, 3% of NMZL, and 3% of CBL-MZ (P=0.974). Risk of HT was 5% (95%CI: 3%-9%) at 5 and 10 years after diagnosis and 10% (95%CI: 5%-20%) at 12 years. At the time of HT, most patients had high LDH and presence of B symptoms. At a median follow-up of 12 months after HT, four of 13 patients died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 57% (95%CI: 13%-86%).
In this large retrospective series, the risk of HT across all MZL types appeared lower than the one reported for follicular lymphoma.
Annals of Oncology 09/2015; DOI:10.1093/annonc/mdv368 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
In lung adenocarcinoma (ADC), anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements are mutually exclusive with epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. However, the existence of double-positive (DP) patients have been sporadically described. We identified DP cases in therapy-naive ALK-rearranged ADC and characterized the biology of these tumors to better understand the clinical response to tyrosine kinase inhibitors (TKIs).
Materials and methods:
We selected 42 ALK-positive ADCs from a multicentric series of 301 cases of ADCs. A mutational analysis was performed using Sanger and/or pyrosequencing to address exons 18-21 of EGFR and codons 12-13 of the KRAS gene. In addition, the KRAS and EGFR copy number was investigated using fluorescent in situ hybridization. DP patients were treated with TKIs, and their response was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria.
Eight of 42 ALK-positive ADCs (19%) demonstrated a concomitant mutation in the EGFR (3 cases) or KRAS (5 cases) genes and were classified as DP. All DP cases displayed copy number gains in the EGFR or KRAS gene because of polysomy or gene amplification. In the latter cases, a mutant allele-specific imbalance was observed. Four patients were treated with TKIs. The 2 EGFR-mutant DP patients demonstrated a better response to crizotinib compared with erlotinib. The 2 KRAS-mutant DP patients experienced opposite responses to crizotinib.
The incidence of DP ADC is not negligible. Patients with ALK/EGFR might benefit more from crizotinib compared with erlotinib administration, although the efficacy of TKIs in patients with ALK/KRAS remains unclear. An integrated target therapy should be considered for patients with DP ADC.
Clinical Lung Cancer 09/2015; DOI:10.1016/j.cllc.2015.08.001 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). A large series of patients with long-term follow-up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. Methods. Patients with biopsy-confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long-term outcomes were evaluated. Results. A total of 247 patients were evaluated; 76% presented with limited-stage disease. There was a history of autoimmune disorder in 41%, with Sjögren disease being the most common (83%). Fifty-seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression-free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first-line management. On multivariate analysis, age <60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjögren disease was associated with improved OS. Conclusion. Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjögren disease have improved survival. Risks for long-term complications must be weighed when determining initial therapy.
The Oncologist 08/2015; 20(10). DOI:10.1634/theoncologist.2015-0180 · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hodgkin lymphoma (HL) is an uncommon monoclonal lymphoid malignancy consisting of 2 main entities: classical HL and nodular lymphocyte predominant. Hodgkin lymphoma usually presents with peripheral lymphadenopathies, while extranodal involvement is rare. Prevalent osseous presentation is rare and still misdiagnosed, despite improvements in diagnostic techniques. Here we report the case of a 30-year-old man with multifocal HL bone involvement initially misdiagnosed as chronic recurrent osteomyelitis. This case emphasizes the difficulties in the diagnosis of HL presenting with bone pain and with radiologic skeletal findings not specific for lymphoma. These patients often have diagnostic delays and misdiagnosis. Repeated investigations and clinical suspicion of unusual presentations may be helpful in order to establish a correct diagnosis and start an effective treatment in this highly curable disease.
[Show abstract][Hide abstract] ABSTRACT: Abstract
ALK gene rearrangement characterizes a subgroup of patients with lung adenocarcinoma who may benefit from ALK-inhibitors. FISH with a break-apart/split signal strategy is the gold standard to investigate ALK. The cut-off to define ALK positivity has been settled at ≥15%. A subset of patients has ALK borderline status, showing 15%5% positive cells. Several aspects, both biological and technical, might influence signals evaluation, making FISH interpretation a challenging task. To improve ALK evaluation, we classified the different FISH patterns on the basis of the type of the split signals, namely short, long, far away and deleted.
We investigated ALK gene status by FISH in 244 lung adenocarcinomas and in a series of ALK negative cell lines samples, collected in three Institutions.
ALK positive profile was found in 12% of patients; long, deleted and far away splits were the primary patterns observed. ALK borderline profile characterized 10% of samples; long and deleted splits were significantly more frequent in those borderline finally classified as ALK positive, whereas short split were mostly detected in those borderline patients finally classified as ALK negative (p=3.4*10). In the ALK negative control series, short split was the predominant pattern. Concordance was observed among different operators and probes for both samples and controls.
Difficulties in ALK FISH signal interpretation might be bypassed using this detailed scoring system, which is highly reproducible, helps clarify borderline samples (according to split type) and provides experimental evidence that 15% is a reasonable cut-off to overcome the assay-dependent background noise.
[Show abstract][Hide abstract] ABSTRACT: Objectives
The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears.Methods
Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively.ResultsLCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%.ConclusionsLCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.
[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.
Cancer Epidemiology 12/2014; 38(6). DOI:10.1016/j.canep.2014.09.008 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HER2 is a well-recognized mediator of the cancerogenic process. It is dysregulated in a wide range of solid tumors, mainly via protein overexpression and/or gene amplification, thus making HER2 an attractive target for tailored treatment. The anti-HER2 therapy trastuzumab was approved for the treatment of HER2-positive metastatic breast cancer patients more than 10 years ago. Since then, trastuzumab and other HER2-inhibitors have been entered into clinical practice for the treatment of breast cancer and, more recently, have been approved to treat HER2-positive metastatic gastric cancers. Currently, HER2-targeted therapies are under evaluation in other tumor types. Due to the relevance of proper patient selection, the accurate assessment of HER2 status is fundamental. This review will discuss the established knowledge and novel insights into the HER2 story, mainly focusing on breast, gastric and colorectal cancers, as well as providing a brief overview of salivary gland, bladder, ovarian and lung tumors.
[Show abstract][Hide abstract] ABSTRACT: Background:
Combined chemoradiation therapy is the gold standard in the treatment of squamous cell anal cancer (SCAC). However, even if the response rate is very high, many patients eventually relapse or experience a reccurrence, thus requiring an invasive surgical procedure that has severe side effects. Most SCAC tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated by anecdotal reports. Promising results obtained in other solid tumors, both squamous and non-squamous, have revealed that an increase in the EGFR gene copy number may predict the efficacy of anti-EGFR therapies, while the presence of mutations in downstream members of the EGFR pathway may confer resistance. These markers have been only sporadically considered in SCAC.
We investigated the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot-spots mutations using sequencing analysis in a cohort of 84 patients affected by SCAC.
Twenty-eight patients (34%) showed an increase in EGFR gene copy number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations were found in the BRAF gene.
The characterization of the EGFR pathway may help in identifying different subgroups of SCAC that have specific molecular features, which may have implications in what targeted therapies are used to treat each patient.
Histology and histopathology 10/2013; 29(4). · 2.10 Impact Factor
[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.
BMJ Open 07/2013; 3(7). DOI:10.1136/bmjopen-2013-002818 · 2.27 Impact Factor
[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.
Melanoma research 07/2013; 23(5). DOI:10.1097/CMR.0b013e328363b015 · 2.28 Impact Factor