Journal of thrombosis and haemostasis : JTH, Jan 15, 2015
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan no... more Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major haemorrhage and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization and management were performed. In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major haemorrhage and mortality were 5.8% (95%CI 3.7-8.3), 4.7% (95%CI 3.0-6.8) and 37% (95%CI 28-47). VTE recurrence risk was comparable under low molecular weight hepar...
Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity ... more Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity with about 50 cases described by the literature. Given the rarity of this pathology, the sharing of accurate available informations is important to improve its knowledge. We reported a case of a woman diagnosed with PRMC who received different lines of chemotherapy and radiotherapy and we also performed a review of the literature on the issue. (www.actabiomedica.it).
Journal of thrombosis and haemostasis : JTH, Jan 15, 2015
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan no... more Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major haemorrhage and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization and management were performed. In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major haemorrhage and mortality were 5.8% (95%CI 3.7-8.3), 4.7% (95%CI 3.0-6.8) and 37% (95%CI 28-47). VTE recurrence risk was comparable under low molecular weight hepar...
Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, includi... more Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI). We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment. Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction. The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.
Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity ... more Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity with about 50 cases described by the literature. Given the rarity of this pathology, the sharing of accurate available informations is important to improve its knowledge. We reported a case of a woman diagnosed with PRMC who received different lines of chemotherapy and radiotherapy and we also performed a review of the literature on the issue. (www.actabiomedica.it).
The female genital tract is an infrequent site of metastasis, in particular from extragenital pri... more The female genital tract is an infrequent site of metastasis, in particular from extragenital primary tumors such as non-small cell lung cancer. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in adnexa, cervix and vagina were also observed in the literature, but none of these had endometrial involvement. We report the first case, to our knowledge, of non-small cell lung cancer with metastatic spread to the endometrium.
Renal failure in cancer patients is not a rare clinical condition and often contraindicates antic... more Renal failure in cancer patients is not a rare clinical condition and often contraindicates anticancer drug treatment; moreover, chemotherapeutic drugs are frequently identified as possible iatrogenic cause of renal failure. Molecular therapies, when appropriate, could represent a therapeutic option for cancer patients with severe renal disease, but the lack of knowledge in this field, at present, limits their use in patients undergoing dialysis. Herein we describe a case, at our knowledge the first reported, of a patient with advanced lung adenocarcinoma on maintenance hemodialysis treated with gefitinib and then with afatinib; we also reviewed the literature on epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) used in NSCLC patients with concomitant renal impairment.
We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 inser... more We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 insertion with concomitant PIK3CA mutation showing dramatic and persisting improvement upon erlotinib therapy, after progression during PI3K inhibitor.
The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in... more The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib.
Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unkno... more Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unknown and strictly related to the imaging used for tumor assessment. Recent findings suggest a similar clinical outcome of asymptomatic pulmonary embolism events compared to symptomatic events with a significant impact on survival. The aim of the present study was to determine the prevalence of asymptomatic pulmonary embolism in a population of lung cancer outpatients and to investigate its clinical features. Methods. Outpatients with a diagnosis of lung carcinoma undergoing chemotherapy were selected from October 2006 to June 2009. Disease and patient characteristics, risk factors and treatment modalities were collected. All the computed tomography images performed for each patient during the study period were retrospectively reviewed to identify pulmonary embolism. Results. A total of 141 consecutive patients were included and 657 computed tomography scans were completely reviewed (from two to six consecutive scans for each patient). Asymptomatic pulmonary embolism in the study population had a prevalence of 14.9% (21 patients). Most of the events occurred in patients with adenocarcinoma, advanced stage and poor performance status, during the early phases of first-line chemotherapy or at the same time of the cancer diagnosis. Compared with the symptomatic pulmonary embolism events (5 patients), asymptomatic events occurred earlier (time from cancer diagnosis to pulmonary embolism of 3.5 [95% CI, 2.0-4.9] versus 12.1 months [95% CI, 6.3-17.9; P = 0.02]) and had a better prognosis (survival from PE of 7.5 [95% CI, 3.4-11.6] versus 1.9 months [95% CI, 0-3.9; P = 0.04]). Conclusions. Our findings indicate an underestimation of embolic events among lung cancer outpatients due to their frequent asymptomatic natur. Such a high prevalence suggests the importance to pay more attention to pulmonary embolism prevention in this population.
Journal of thrombosis and haemostasis : JTH, Jan 15, 2015
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan no... more Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major haemorrhage and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization and management were performed. In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major haemorrhage and mortality were 5.8% (95%CI 3.7-8.3), 4.7% (95%CI 3.0-6.8) and 37% (95%CI 28-47). VTE recurrence risk was comparable under low molecular weight hepar...
Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity ... more Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity with about 50 cases described by the literature. Given the rarity of this pathology, the sharing of accurate available informations is important to improve its knowledge. We reported a case of a woman diagnosed with PRMC who received different lines of chemotherapy and radiotherapy and we also performed a review of the literature on the issue. (www.actabiomedica.it).
Journal of thrombosis and haemostasis : JTH, Jan 15, 2015
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan no... more Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on CT-scan not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major haemorrhage and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization and management were performed. In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major haemorrhage and mortality were 5.8% (95%CI 3.7-8.3), 4.7% (95%CI 3.0-6.8) and 37% (95%CI 28-47). VTE recurrence risk was comparable under low molecular weight hepar...
Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, includi... more Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI). We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment. Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction. The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.
Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity ... more Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare clinical entity with about 50 cases described by the literature. Given the rarity of this pathology, the sharing of accurate available informations is important to improve its knowledge. We reported a case of a woman diagnosed with PRMC who received different lines of chemotherapy and radiotherapy and we also performed a review of the literature on the issue. (www.actabiomedica.it).
The female genital tract is an infrequent site of metastasis, in particular from extragenital pri... more The female genital tract is an infrequent site of metastasis, in particular from extragenital primary tumors such as non-small cell lung cancer. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in adnexa, cervix and vagina were also observed in the literature, but none of these had endometrial involvement. We report the first case, to our knowledge, of non-small cell lung cancer with metastatic spread to the endometrium.
Renal failure in cancer patients is not a rare clinical condition and often contraindicates antic... more Renal failure in cancer patients is not a rare clinical condition and often contraindicates anticancer drug treatment; moreover, chemotherapeutic drugs are frequently identified as possible iatrogenic cause of renal failure. Molecular therapies, when appropriate, could represent a therapeutic option for cancer patients with severe renal disease, but the lack of knowledge in this field, at present, limits their use in patients undergoing dialysis. Herein we describe a case, at our knowledge the first reported, of a patient with advanced lung adenocarcinoma on maintenance hemodialysis treated with gefitinib and then with afatinib; we also reviewed the literature on epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) used in NSCLC patients with concomitant renal impairment.
We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 inser... more We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 insertion with concomitant PIK3CA mutation showing dramatic and persisting improvement upon erlotinib therapy, after progression during PI3K inhibitor.
The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in... more The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib.
Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unkno... more Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unknown and strictly related to the imaging used for tumor assessment. Recent findings suggest a similar clinical outcome of asymptomatic pulmonary embolism events compared to symptomatic events with a significant impact on survival. The aim of the present study was to determine the prevalence of asymptomatic pulmonary embolism in a population of lung cancer outpatients and to investigate its clinical features. Methods. Outpatients with a diagnosis of lung carcinoma undergoing chemotherapy were selected from October 2006 to June 2009. Disease and patient characteristics, risk factors and treatment modalities were collected. All the computed tomography images performed for each patient during the study period were retrospectively reviewed to identify pulmonary embolism. Results. A total of 141 consecutive patients were included and 657 computed tomography scans were completely reviewed (from two to six consecutive scans for each patient). Asymptomatic pulmonary embolism in the study population had a prevalence of 14.9% (21 patients). Most of the events occurred in patients with adenocarcinoma, advanced stage and poor performance status, during the early phases of first-line chemotherapy or at the same time of the cancer diagnosis. Compared with the symptomatic pulmonary embolism events (5 patients), asymptomatic events occurred earlier (time from cancer diagnosis to pulmonary embolism of 3.5 [95% CI, 2.0-4.9] versus 12.1 months [95% CI, 6.3-17.9; P = 0.02]) and had a better prognosis (survival from PE of 7.5 [95% CI, 3.4-11.6] versus 1.9 months [95% CI, 0-3.9; P = 0.04]). Conclusions. Our findings indicate an underestimation of embolic events among lung cancer outpatients due to their frequent asymptomatic natur. Such a high prevalence suggests the importance to pay more attention to pulmonary embolism prevention in this population.
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Papers by Melissa Bersanelli