Publications by authors named "Chiara Alessandra Cella"

14 Publications

  • Page 1 of 1

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

Cancers (Basel) 2021 Feb 7;13(4). Epub 2021 Feb 7.

Department of Surgery, European Institute of Oncology IRCCS, 20141 Milan, Italy.

After the results reported by the "Chemoradiotherapy for esophageal Cancer Followed by Surgery Study" (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively ( ≦ 0.001). Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.
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http://dx.doi.org/10.3390/cancers13040666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915215PMC
February 2021

Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients.

Oncol Res Treat 2020 24;43(9):414-427. Epub 2020 Jun 24.

University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany.

Background: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs).

Methods: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy. Baseline RAMs included the Khorana-, Vienna Cancer, Thrombosis-, Protecht-, ONKOTEV-, and Catscore. IPF, MPV, P-selectin, D-dimer, and TG were analysed at baseline and 3-month follow-up.

Results: We enrolled 100 patients, of whom 89 completed the follow-up. Frequent tumour types were breast (30%), gastric (14%), gynaecological (14%), and colorectal (14%) cancer. Ten of the 89 patients (11.2%) developed VTE. The highest VTE rate was observed in patients with cholangiocarcinoma (3/5; 60%). Baseline D-dimer levels but not IPF, MPV, or P-selectin were associated with the risk of developing VTE (HR 6.9; p = 0.021). None of the RAMs showed statistical significance in predicting VTE. Peak thrombin and endogenous thrombin potential were lower in patients who developed VTE. Biomarker changes between baseline and follow-up were not associated with VTE risk.

Conclusions: VTE risk was well predicted by baseline D-dimer levels. Adding D-dimer could improve existing RAMs to better identify patients who may benefit from primary VTE prophylaxis. The VTE risk among patients with cholangiocarcinoma should be further evaluated.
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http://dx.doi.org/10.1159/000508271DOI Listing
February 2021

The Italian Rare Pancreatic Exocrine Cancer Initiative.

Tumori 2019 Aug 9;105(4):353-358. Epub 2019 Apr 9.

1 Medical Oncology Unit, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, Bari, Italy.

Introduction: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available.

Methods: A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays.

Conclusions: We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.
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http://dx.doi.org/10.1177/0300891619839461DOI Listing
August 2019

Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis.

Cancer Treat Rev 2018 Dec 13;71:39-46. Epub 2018 Oct 13.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address:

Introduction: Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice.

Materials And Methods: We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP). Tumor downsizing of ≥10% was considered as objective response.

Results: We selected 17 out of 2758 studies, comprising 1118 patients with tumor response reported as WP. Proliferation index, tumor burden and anti-tumor therapies were heterogeneous. Chemotherapy alone (mainly, capecitabine/temozolomide) or in combination showed the best results, with ≥10% TS ranging from 65% to 93%. Peptide receptor radionuclide therapy combined with chemotherapy (Chemo-PRRT) and sunitinib appeared promising by inducing objective response in a significant proportion of patients (93% and 60%, respectively). Time to tumor response was reported in only two trials. No clear clinical and/or biological predictive factors emerged.

Conclusion: Based on response criteria used in our retrospective analysis, systemic chemotherapy alone or in combination appeared to have the main cytoreductive impact. However no conclusions regarding either a specific regimen or combination can be drawn. Furthermore, tumor population selection and/or choice of regimen may have a significant influence. Further analysis should be also conducted to identify potential predictive biomarkers of responses, in order to design future prospective interventional clinical trials enrolling more homogenous populations of advanced well-differentiated PanNETs.
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http://dx.doi.org/10.1016/j.ctrv.2018.10.008DOI Listing
December 2018

Systemic Chemotherapy for Advanced Rare Pancreatic Histotype Tumors: A Retrospective Multicenter Analysis.

Pancreas 2018 07;47(6):759-771

Modena Cancer Center, University of Modena and Reggio Emilia, Azienda Ospedaliera-Universitaria di Modena, Modena, Italy.

Objectives: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients?

Methods: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival.

Results: Of approximately 4300 exocrine pancreatic cancer patients, 79 advanced cases affected by rare histological types were identified, with pancreatic acinar cell cancer (n = 23), pancreatic adenosquamous cancer (n = 16), and mucinous cystic neoplasm with an associated invasive mucinous cystadenocarcinoma (n = 15) most represented. Survival analyses for each subgroup in relation with the different chemotherapy regimens showed the lack of statistical significance correlations.

Conclusions: Because of the lack of clinical trials in patients affected by these rare pancreatic histotypes, only their molecular classification would help clinicians in future therapeutic choice.
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http://dx.doi.org/10.1097/MPA.0000000000001063DOI Listing
July 2018

Should cT2N0M0 be managed as a localized or locally advanced esophageal carcinoma?

J Thorac Dis 2017 Sep;9(9):2829-2834

Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy.

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http://dx.doi.org/10.21037/jtd.2017.08.82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708429PMC
September 2017

The role of multimodal treatment in patients with advanced lung neuroendocrine tumors.

J Thorac Dis 2017 Nov;9(Suppl 15):S1501-S1510

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Lung neuroendocrine tumors (NETs) comprise typical (TC) and atypical carcinoids (AC). They represent the well differentiated (WD) or low/intermediate grade forms of lung neuroendocrine neoplasms (NENs). Unlike the lung poorly differentiated NENs, that are usually treated with chemotherapy, lung NETs can be managed with several different therapies, making a multidisciplinary interaction a key point. We critically discussed the multimodal clinical management of patients with advanced lung NETs. Provided that no therapeutic algorithm has been validate so far, each clinical case should be discussed within a NEN-dedicated multidisciplinary team. Among the systemic therapies available for metastatic lung NETs everolimus is the only approved drug, on the basis of the results of the phase III RADIANT-4 trial. Another phase III trial, the SPINET, is ongoing comparing lanreotide with placebo. Peptide receptor radionuclide therapy and chemotherapy were not studied within phase III trials for lung NETs, and they have been reported to be active within retrospective or phase II prospective studies. Temozolomide and oxaliplatin are two interesting chemotherapeutic agents in lung NETs. While some European Institutions were certificated as Centers of Excellence for gastroenteropancreatic NENs by the European Neuroendocrine Tumor Society (ENETS), an equivalent ENETS certification for lung NENs does not exist yet. Ideally a lung NEN-dedicated multidisciplinary tumor board should include NEN-dedicated medical oncologists, thoracic medical oncologist, thoracic surgeons, pathologists, interventional radiologists, endocrinologists, radiotherapists, interventional pneumologists, nuclear physician.
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http://dx.doi.org/10.21037/jtd.2017.06.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690950PMC
November 2017

Preventing Venous Thromboembolism in Ambulatory Cancer Patients: The ONKOTEV Study.

Oncologist 2017 05 19;22(5):601-608. Epub 2017 Apr 19.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Background: The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis.

Materials And Methods: We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model.

Results: The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%,  = .001), 6 months (75.4% vs. 58.6%,  < .001), and 12 months (69.8% vs. 58.3%,  = .014).

Conclusion: ONKOTEV score steps into history of cancer-related-VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program. 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous thromboembolism in cancer outpatients with a risk model score will drive physicians' decision of starting thromboprophylaxis in high-risk patients.
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http://dx.doi.org/10.1634/theoncologist.2016-0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423517PMC
May 2017

Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report.

Ecancermedicalscience 2016 21;10:635. Epub 2016 Apr 21.

Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumours, European Institute of Oncology, Milan 20141, Italy.

We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient's clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma.
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http://dx.doi.org/10.3332/ecancer.2016.635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854227PMC
May 2016

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors.

Neuroendocrinology 2016 21;103(6):806-14. Epub 2016 Jan 21.

Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy.

Purpose: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs.

Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples.

Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome.

Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.
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http://dx.doi.org/10.1159/000444087DOI Listing
May 2017

Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials.

Crit Rev Oncol Hematol 2016 Mar 30;99:1-12. Epub 2015 Nov 30.

Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.

Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.
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http://dx.doi.org/10.1016/j.critrevonc.2015.09.004DOI Listing
March 2016

Dual inhibition of mTOR pathway and VEGF signalling in neuroendocrine neoplasms: from bench to bedside.

Cancer Treat Rev 2015 Nov 28;41(9):754-60. Epub 2015 Jun 28.

Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy. Electronic address:

After years of limited progress in the treatment of neuroendocrine neoplasms (NENs), an increasing number of therapeutic targets have recently emerged as potential tools to improve disease outcome. The mammalian target of rapamycin (mTOR) pathway and vascular endothelial growth factor (VEGF) signalling are implicated in the regulation of cell growth, proliferation, neo-angiogenesis and tumour cell spread. Their combined blockade, in a simultaneous or sequential strategy, represents an intriguing biological rationale to overcome the onset of resistance mechanisms. However, is becoming increasingly imperative to find the optimal sequential strategy according to the best toxicity profile, and also to identify predictive biomarkers. We will provide an overview of the pre-clinical and clinical data relating to mTOR pathway/VEGF signalling as a potential targets of treatment in NENs.
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http://dx.doi.org/10.1016/j.ctrv.2015.06.008DOI Listing
November 2015

Bevacizumab maintenance in metastatic colorectal cancer: How long?

World J Clin Cases 2014 Nov;2(11):717-23

Alfonso De Stefano, Roberto Moretto, Chiara Alessandra Cella, Francesco Jacopo Romano, Lucia Raimondo, Giovanni Fiore, Francesca Di Pietro, Sabino De Placido, Chiara Carlomagno, Department of Clinical Medicine and Surgery, School of Medicine, University of Naples "Federico II", 80131 Napoli, Italy.

The management of patients with non-progressive metastatic colorectal cancer after six months of treatment has not yet been codified. The most relevant concerns are the effectiveness of maintenance vs discontinuation, and the tolerability of prolonged treatment. Here we report the case of a 72-year-old man affected by colorectal cancer with lung metastases who achieved a complete response after receiving capecitabine, oxaliplatin and bevacizumab for six months, and bevacizumab alone for six months. Bevacizumab was continued as maintenance regimen for more than three years. It was discontinued because of an arthroplasty. Fifty-eight months after beginning first-line treatment, the patient remains free from relapse. Adverse effects were minimal and easily controlled.
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http://dx.doi.org/10.12998/wjcc.v2.i11.717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233413PMC
November 2014

Primary hepatic lymphoma in a patient with previous rectal adenocarcinoma: a case report and discussion of etiopathogenesis and diagnostic tools.

Int J Hematol 2012 Mar 21;95(3):320-3. Epub 2012 Feb 21.

Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.

Primary hepatic lymphoma is an extremely rare malignancy accounting for 0.016% of all cases of non-Hodgkin lymphomas. Approximately 1-4% of histologies described show a follicular pattern. We report a case of primary hepatic non-Hodgkin lymphoma that developed in a middle-aged woman 3 years after radical treatment (neoadjuvant chemoradiotherapy and surgery) for a rectal adenocarcinoma. Abdomen ultrasound showed a single nodule in the liver, which raised the issue of differential diagnosis with a metastasis from rectal cancer. After surgical removal of the nodule, histology revealed a primary B cell, stage IE follicular non-Hodgkin lymphoma, confined to the liver; indeed, no foci of lymphoma were found elsewhere in the body.
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http://dx.doi.org/10.1007/s12185-012-1025-xDOI Listing
March 2012
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