Publications by authors named "Vincenzo Bagnardi"

150 Publications

Surgical Resection vs. Percutaneous Ablation for Single Hepatocellular Carcinoma: Exploring the Impact of Li-RADS Classification on Oncological Outcomes.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, 20162 Milan, Italy.

: Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. : We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS) and local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). : Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; = 0.049) and RFS (42.5% vs. 29.8%; = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; = 0.035), RFS (45.0% vs. 27.0% RFS; < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. : Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.
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http://dx.doi.org/10.3390/cancers13071671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038048PMC
April 2021

Prognostic Impact of Baseline Immunologic Profile in Aggressive B-cell non-Hodgkin's Lymphomas.

Mediterr J Hematol Infect Dis 2021 1;13(1):e2021018. Epub 2021 Mar 1.

Division of Onco-Hematoncology, European Institute of Oncology, IRCCS, Milano, Italy.

Host immune homeostasis as an independent prognostic indicator has been inadequately evaluated in aggressive non-Hodgkin's lymphomas (NHL). The present study addresses the prognostic significance in aggressive NHLs of the immunologic profile evaluated by pretreatment serum levels of immunoglobulins (Ig) and lymphocyte-monocyte ratio (LMR). In this series of 90 patients with aggressive lymphoma, the median level for IgG was 1,024mg/dl (range 436-2236), and for LMR was 2.2 (range 0.2-13.8). CR rate was higher with IgG levels ≥1,024mg/dL (91% vs 77% p=0.059). LMR ≤ 2.2 was associated with lower 1-year PFS (73% vs. 92%, p 0.016). Patients with good/very good R-IPI showed a reduced PFS if IgG or LMR was low, while patients with poor R-IPI did better if LMR or IgG levels were high. We combined both parameters with the R-IPI and produced a four-risk prognostic score showing one-year PFS of 95% (95% CI 68%-99%), 100% (95% CI 100%-100%), 73% (95% CI 52%-86%), and 59% (95% CI 31%-79%), in patients with zero, one, two and three risk factors, respectively. The results indicate for the first time the value of baseline serum Ig levels in the prognostic assessment of aggressive lymphoma.
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http://dx.doi.org/10.4084/MJHID.2021.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938923PMC
March 2021

Wireless ultrasound-guided vacuum-assisted breast biopsy: Experience in clinical practice at European Institute of Oncology.

Breast J 2021 Mar 6. Epub 2021 Mar 6.

Department of Emergency and Organs Transplantation, Section of Anatomic Pathology, School of Medicine, University of Bari "Aldo Moro", Bari, Italy.

In the last few years, ultrasound-guided vacuum-assisted breast biopsy (US-VABB) has replaced surgical biopsy due to higher diagnostic accuracy and lower patient discomfort, and, at present, an even greater possibility is represented by the new wireless ultrasound-guided VAB device (Wi-UVAB). The purpose of our study is to determine the diagnostic accuracy of this new device in a sizeable representative number of patients. From January 2014 to June 2018, 168 biopsies were performed in our institution using the new Wi-UVAB device. We analyzed sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of biopsies obtained with the new device using surgical results as reference point, following patients for at least one year. In our cohort, we obtained a complete sensitivity of 97.5%, an absolute sensitivity of 94.3%, a complete specificity of 98%, and an absolute specificity of 98%. The positive predictive value of the procedure was 97.5% while the negative predictive value was 98%. The diagnostic accuracy was 98%. The Wi-UVAB is a safe procedure with high diagnostic accuracy, comparable to that of the traditional vacuum-assisted breast biopsy and even higher than that of core needle biopsy (CNB). Moreover, the Wi-UVAB is easy to use and shows low costs as core needle biopsy (CNB).
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http://dx.doi.org/10.1111/tbj.14216DOI Listing
March 2021

Is BMI a Factor in Compliance to Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

Chirurgia (Bucur) 2021 Jan-Feb;116(1):51-59

AIMS Academy Clinical Research Network

Compliance to adjuvant chemotherapy (AC) for patients undergoing rectal surgery ranges from 43% to 73.6%. Reasons reported for not initiating or completing AC include onset of postoperative complications, drug toxicity, disease progression and/or patient preferences. Little is known regarding the impact of obesity on the compliance to AC in this setting. This multicenter, retrospective study analyzed compliance to AC and treatment-related morbidity in 511 patients having undergone surgery with curative intent for rectal cancer in six Italian colorectal centers between January 2013 and December 2017. 70 patients were obese (BMI 30 kg/m2). The proportion of open procedures (22.9% vs. 13.4%) and conversions (14.3% vs. 4.8%) was greater in obese compared to non-obese patients (p 0.001). Median hospital stay was one day longer for obese patients (9 days vs. 10 days, p=0.038) while there was no statistically significant difference in the complication rate, whether overall (58.6% in obese vs. 52.3% in non-obese) or with a Clavien-Dindo score 3 (17.1% vs 10.9%). AC was offered to 49/70 (70%) patients in the obese group and 306/441 (69.4%) in the non-obese group (p=0.43). There was no statistically significant difference in AC compliance: 18.4% and 22.9% did not start AC, while 36.7% and 34.6%, started AC but did not complete the scheduled treatment (p=0.79) in the obese and non-obese group, respectively. Overall, 55% of patients who started AC successfully completed their adjuvant treatment. Obesity did not impact compliance to AC for locally advanced rectal cancer: compliance was poor in obese and non-obese patients with no statistically significant difference between the two groups. Major complication rate was not statistically significantly affected by increased BMI.
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http://dx.doi.org/10.21614/chirurgia.116.1.51DOI Listing
April 2021

Intra- inter-observer repeatability in liver computed tomography volumetry in patients undergoing radioembolization simulation.

Abdom Radiol (NY) 2021 Feb 25. Epub 2021 Feb 25.

Division of Interventional Radiology, IEO European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, Milan, 20141, Italy.

Purpose: The careful evaluation of MDCT is an essential step for the treatment planning in pre-treatment imaging work-up for Trans-Arterial Radio Embolization (TARE). It may provide unique volumetric data (CTVs), which are information useful for an effective and safe TARE. The purpose of this study is to demonstrate that the radiographer is able to calculate CTVs of TARE simulation with the same precision as the interventional radiologist.

Methods: This study retrospectively considers 17 consecutive patients (8 males, 9 females; mean age 66.3 ± 13.2 years) who underwent pre-treatment work-up for TARE, between May 2019 and February 2020 (trial ID:2234 - protocol). For each patient, four specific parameters are evaluated from MDCT achieved during treatment simulation: healthy liver volume (HLV), the whole hepatic parenchyma (THV = healthy liver and TTV = tumour) involved by TARE, and whole liver volume (WLV). Four independent observers-R1 (expert interventional radiologist), T1, T2, and T3 (radiographers, with different experiences in the field of interventional radiology)-are involved in the imaging analysed.

Results: All the 4 observers detected the same number of hepatic lesion(s) per patient. Regarding the three radiographers, the intra-observer reliability for CTVs is very high 0.997 to 1.000 (95%CI). Also inter-observer reproducibility between radiographers is excellent regarding CTVs, 0.965 to 0.999 (95%CI). The accuracy of radiographer evaluation is very high 0.964 to 0.999 (95%CI).

Conclusions And Implications For Practice: The high intra- and inter-observer reproducibility shows that a properly trained radiographers might have the same accuracy as interventional radiologists, in assessing liver CTV data for planning TARE.
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http://dx.doi.org/10.1007/s00261-021-02980-6DOI Listing
February 2021

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion.

Transplantation 2021 Jan 7. Epub 2021 Jan 7.

1. Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 2. Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 5. UO Chirurgia Generale e dei Trapianti, AOU Sant'Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. 6. Division of Liver Transplantation, AO Papa Giovanni XXIII, Bergamo, Italy. 7. General Surgery 2U, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. 8. Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplant Unit, Padua University, Padua, Italy. 9. Abdominal Surgery and Organ Transplantation Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS - ISMETT), Palermo, Italy 10. Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy 11. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

Background: Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE).

Methods: We coordinated a multicenter retrospective Italian cohort study with 44 controlled DCD donors, who underwent NRP, to present transplant characteristics and results. To rank our results according to the high donor risk, we matched and compared a subgroup of 37 controlled DCD livers, preserved with NRP and D-HOPE, with static-preserved controlled DCD transplants from an established European program.

Results: In the Italian cohort, D-HOPE was used in 84% of cases, and the primary nonfunction rate was 5%. Compared to the matched comparator group, the NRP+D-HOPE-group showed a lower incidence of moderate and severe acute kidney injury (stage 2: 8% vs 27% and stage 3: 3% vs 27%, P=0.001). Ischemic cholangiopathy remained low (2-year proportion free: 97% vs 92%, P=0.317), despite the high-risk profile resulting from the longer donor warm ischemia in Italy (40 vs 18min, P<0.001).

Conclusions: These data suggest that NRP and D-HOPE yield good results in DCD livers with prolonged warm ischemia.
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http://dx.doi.org/10.1097/TP.0000000000003595DOI Listing
January 2021

Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis.

Eur J Cancer 2021 Mar 22;145:197-209. Epub 2021 Jan 22.

Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milano, Milan, Italy. Electronic address:

Background: We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials.

Material And Methods: All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method and Cox proportional-hazards model were used for survival analyses.

Results: At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74-1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55-1.14, P = 0.21). Interestingly, patients diagnosed with 'immunogenic' tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78-1.00, P = 0.047).

Conclusion: Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.
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http://dx.doi.org/10.1016/j.ejca.2020.12.028DOI Listing
March 2021

EGFR-TKI Plus Anti-Angiogenic Drugs in EGFR-Mutated Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Clinical Trials.

JNCI Cancer Spectr 2020 Dec 29;4(6):pkaa064. Epub 2020 Jul 29.

Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, Istituto Europeo di Oncologia, IRCCS, Milan, Italy.

Background: Results of several randomized clinical trials (RCTs) testing the combination of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) plus an anti-angiogenic drug in advanced EGFR-mutated non-small cell lung cancer were reported.

Methods: We first report a systematic review and meta-analysis of all RCTs to estimate effectiveness and toxicity of this new therapeutic approach compared with first-generation EGFR-TKI monotherapy. Subsequently, we present a network meta-analysis comparing the combination of an EGFR-TKI plus an anti-angiogenic drug with 2 new treatment options: combination of an EGFR-TKI plus chemotherapy or new EGFR-TKIs of second or third generation as monotherapy.

Results: Five RCTs were included in the first meta-analysis. The progression-free survival (PFS) was statistically significantly larger in patients treated with an EGFR-TKI plus an anti-angiogenic drug compared with EGFR-TKI monotherapy: the pooled PFS-hazard ratio (HR) was 0.59 (95% confidence interval [CI] = 0.51 to 0.69). The pooled median-PFS was 17.8 months (95% CI = 16.5 to 19.3 months) for the combination vs 11.7 months (95% CI = 11.1 to 12.7 months) for EGFR-TKI as monotherapy. No statistically significant differences between the 2 treatment arms were observed in overall survival or objective response rate. The rate of grade equal or higher than 3 adverse events was statistically significantly higher in patients treated with EGFR-TKI plus an anti-angiogenic drug: the pooled-relative risk was 1.72 (95% CI = 1.43 to 2.06). Ten RCTs were included in the network meta-analysis. All 3 experimental treatments were associated with a statistically significant improvement in PFS compared with first-generation EGFR-TKIs. When compared to each other, none of the 3 experimental treatments were statistically significantly associated with larger PFS or lower rate of grade 3 or higher adverse events.

Conclusion: Patients with EGFR-mutated non small-cell lung cancer derived clinically meaningful larger PFS benefit from the addition of an anti-angiogenic drug to a first-generation EGFR-TKI at the cost of an increase of toxicities.
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http://dx.doi.org/10.1093/jncics/pkaa064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737478PMC
December 2020

The COVID-19 second wave risk and liver transplantation: lesson from the recent past and the unavoidable need of living donors.

Transpl Int 2021 03 9;34(3):585-587. Epub 2021 Feb 9.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1111/tri.13803DOI Listing
March 2021

Robotic Liver Resection Versus Percutaneous Ablation for Early HCC: Short- and Long-Term Results.

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Background: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting.

Methods: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short- and long-term outcomes to define the best approach in this specific cohort.

Results: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively.

Conclusions: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.
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http://dx.doi.org/10.3390/cancers12123578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761404PMC
November 2020

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.

Eur J Surg Oncol 2021 Apr 15;47(4):804-812. Epub 2020 Oct 15.

Division of Breast Cancer Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy.

Introduction: In patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6-14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs).

Methods: This study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory.

Results: Axillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3-12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8-93.2) and 81.0% (95% CI, 77.2-84.2) in the whole cohort, 92.0% (95% CI, 89.0-94.2) and 81.5% (95% CI, 76.9-85.2) in those initially cN0, 89.8% (95% CI, 85.0-93.2) and 80.1% (95% CI, 72.8-85.7) in those initially cN1/2.

Conclusion: The 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.
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http://dx.doi.org/10.1016/j.ejso.2020.10.014DOI Listing
April 2021

Metaplastic breast cancer: Prognostic and therapeutic considerations.

J Surg Oncol 2021 Jan 12;123(1):61-70. Epub 2020 Oct 12.

Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy.

Introduction: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting.

Methods: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS).

Results: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting.

Conclusion: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.
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http://dx.doi.org/10.1002/jso.26248DOI Listing
January 2021

Liver transplantation from brain-dead donors on mechanical circulatory support: a systematic review of the literature.

Transpl Int 2021 Jan 28;34(1):5-15. Epub 2020 Oct 28.

Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.
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http://dx.doi.org/10.1111/tri.13766DOI Listing
January 2021

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy.

Breast 2020 Oct 24;53:138-142. Epub 2020 Jul 24.

Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Background: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment.

Patients And Methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy.

Results: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11).

Conclusions: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.
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http://dx.doi.org/10.1016/j.breast.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424227PMC
October 2020

Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis.

Am J Gastroenterol 2020 12;115(12):1940-1949

Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Introduction: The aim of this study was to provide the most comprehensive and up-to-date evidence on the association between cigarette smoking and colorectal cancer (CRC) risk.

Methods: We conducted a systematic review and meta-analysis of epidemiological studies on the association between cigarette smoking and CRC risk published up to September 2018. We calculated relative risk (RR) of CRC according to smoking status, intensity, duration, pack-years, and time since quitting, with a focus on molecular subtypes of CRC.

Results: The meta-analysis summarizes the evidence from 188 original studies. Compared with never smokers, the pooled RR for CRC was 1.14 (95% confidence interval [CI] 1.10-1.18) for current smokers and 1.17 (95% CI 1.15-1.20) for former smokers. CRC risk increased linearly with smoking intensity and duration. Former smokers who had quit smoking for more than 25 years had significantly decreased risk of CRC compared with current smokers. Smoking was strongly associated with the risk of CRC, characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20-1.67; number of studies [n] = 4), BRAF mutation (RR 1.63; 95% CI 1.23-2.16; n = 4), or high microsatellite instability (RR 1.56; 95% CI 1.32-1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90-1.20; n = 5) or TP53 (RR 1.13; 95% CI 0.99-1.29; n = 5) mutations.

Discussion: Cigarette smoking increases the risk of CRC in a dose-dependent manner with intensity and duration, and quitting smoking reduces CRC risk. Smoking greatly increases the risk of CRC that develops through the microsatellite instability pathway, characterized by microsatellite instability-high, CpG island methylator phenotype positive, and BRAF mutation.
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http://dx.doi.org/10.14309/ajg.0000000000000803DOI Listing
December 2020

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center.

Ther Adv Med Oncol 2020 15;12:1758835920940945. Epub 2020 Jul 15.

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

Background And Aims: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1-2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT).

Patients And Methods: We carried out a retrospective study on 67 patients affected by stage I-III ASCC, treated with CDDP (60-70 mg/m every 21 days for two courses) plus C (825 mg/m twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent.

Results: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively.Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3-4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%).

Conclusion: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.
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http://dx.doi.org/10.1177/1758835920940945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364808PMC
July 2020

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

Oncology 2020 9;98(10):714-718. Epub 2020 Jun 9.

Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy.

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT.

Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases.

Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5-43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0-108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4-10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9-30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA.

Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.
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http://dx.doi.org/10.1159/000507707DOI Listing
October 2020

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

Breast J 2020 07 7;26(7):1330-1336. Epub 2020 Jun 7.

Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.
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http://dx.doi.org/10.1111/tbj.13851DOI Listing
July 2020

Association of a CT-Based Clinical and Radiomics Score of Non-Small Cell Lung Cancer (NSCLC) with Lymph Node Status and Overall Survival.

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, 40126 Bologna, Italy.

Background: To evaluate whether a model based on radiomic and clinical features may be associated with lymph node (LN) status and overall survival (OS) in lung cancer (LC) patients; to evaluate whether CT reconstruction algorithms may influence the model performance.

Methods: patients operated on for LC with a pathological stage up to T3N1 were retrospectively selected and divided into training and validation sets. For the prediction of positive LNs and OS, the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was used; univariable and multivariable logistic regression analysis assessed the association of clinical-radiomic variables and endpoints. All tests were repeated after dividing the groups according to the CT reconstruction algorithm. -values < 0.05 were considered significant.

Results: 270 patients were included and divided into training (n = 180) and validation sets (n = 90). Transfissural extension was significantly associated with positive LNs. For OS prediction, high- and low-risk groups were different according to the radiomics score, also after dividing the two groups according to reconstruction algorithms.

Conclusions: a combined clinical-radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance.
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http://dx.doi.org/10.3390/cancers12061432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352293PMC
May 2020

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

J Am Coll Cardiol 2020 04;75(15):1772-1784

Department of Cardiology and Electrotherapy, Medical University of Gdansk, Gdansk, Poland.

Background: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported.

Objectives: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1.

Methods: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis.

Results: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00).

Conclusions: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.
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http://dx.doi.org/10.1016/j.jacc.2020.02.033DOI Listing
April 2020

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

BJU Int 2020 07 1;126(1):104-113. Epub 2020 Apr 1.

Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy.

Objectives: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification.

Patients And Methods: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used.

Results: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%).

Conclusion: The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.
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http://dx.doi.org/10.1111/bju.15048DOI Listing
July 2020

Modified-BEP Chemotherapy in Patients With Germ-Cell Tumors Treated at a Comprehensive Cancer Center.

Am J Clin Oncol 2020 06;43(6):381-387

Medical Division of Urogenital and Head and Neck Cancer.

Objectives: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen.

Materials And Methods: Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring.

Results: Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity.

Conclusion: In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.
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http://dx.doi.org/10.1097/COC.0000000000000679DOI Listing
June 2020

Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy.

Int J Colorectal Dis 2020 Apr 8;35(4):685-694. Epub 2020 Feb 8.

Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

Purpose: To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response.

Methods: Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1.

Results: Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6 months and 92% (95% CI 83-96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD.

Conclusion: Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.
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http://dx.doi.org/10.1007/s00384-020-03517-xDOI Listing
April 2020

High precision radiotherapy including intensity-modulated radiation therapy and pulsed-dose-rate brachytherapy for cervical cancer: a retrospective monoinstitutional study.

J Contemp Brachytherapy 2019 Dec 8;11(6):516-526. Epub 2019 Dec 8.

Department of Radiotherapy, IEO European Institute of Oncology IRCCS, Milan, Italy.

Purpose: To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution.

Material And Methods: Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria.

Results: Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy.

Conclusions: Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.
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http://dx.doi.org/10.5114/jcb.2019.90478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964350PMC
December 2019

The Impact of Sarcopenia on Postoperative Course following Pancreatoduodenectomy: Single-Center Experience of 110 Consecutive Cases.

Dig Surg 2020 20;37(4):312-320. Epub 2020 Jan 20.

Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy.

Background: Despite that mortality following pancreatoduodenectomy (PD) has gradually dropped during the past few decades, the incidence of postoperative complications remains high, ranging from 30-60%. Many studies have been focused on identification of perioperative risk factors for morbidity, and in recent years, sarcopenia has been pointed out as a valid predictor of postoperative complication.

Materials And Methods: Perioperative data from 110 consecutive patients who underwent PD were retrieved, and the presence of sarcopenia was assessed by the measurement of Hounsfield unit average calculation on preoperative CT scans. Postoperative complications were graded according to Clavien-Dindo classification, and the morbidity burden was assessed by comprehensive complication index (CCI) calculation.

Results: Sarcopenia was associated with advanced age (72 vs. 66 years; p = 0.014) and lower preoperative albumin levels (3.5 vs. 3.7 g/dL; p = 0.010); it represented an independent risk factor for clinically relevant complications (relative risk: 1.71; p = 0.015) and was related to a higher rate of Grade C postoperative pancreatic fistula (50.0 vs. 11.4%; p = 0.005) and a higher CCI (47.6 vs. 29.6; p = 0.001).

Conclusions: Sarcopenia represents a valid indicator of increased morbidity risk and may play a central role in preoperative risk stratification, allowing the selection of patients who may benefit from prehabilitation programs.
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http://dx.doi.org/10.1159/000504703DOI Listing
April 2021

Prognostic and predictive value of cell cycle progression (CCP) score in ductal carcinoma in situ of the breast.

Mod Pathol 2020 06 10;33(6):1065-1077. Epub 2020 Jan 10.

Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.

The natural history of ductal carcinoma in situ (DCIS) is highly variable and difficult to predict. Biomarkers are needed to stratify patients with DCIS for adjuvant therapy. We investigated the prognostic and predictive relevance of cell cycle progression (CCP) score in women with DCIS. We measured the expression of 23 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumor samples, and assessed the correlation of a predefined score with histopathologic features and recurrence. The signature was analyzed in a cohort of 909 consecutive DCIS with full histopathological features treated in a single institution. The main outcome measure was ipsilateral breast event (IBE) as first event observed, be it in situ or invasive. Median follow-up time was 8.7 years (IQR 6.5-10.5 years). There were 150 ipsilateral IBEs, 84 (56%) of which were invasive. In the first 5 years of follow-up, the score provided statistically different findings (p = 0.009), with IBE rates of 14.7% (95% CI, 10.4-19.7) for the highest quartile of CCP score (Q4) and 8.7% (95% CI, 6.7-11.0) for the lowest quartiles (Q1-3). The prognostic value for IBEs approached significance also in women treated with mastectomy (adjusted hazard ratio [HR] Q4 vs. Q1-3 = 2.60; 95% CI: 0.96-7.08; P = 0.06). Radiotherapy provided a greater benefit in women with higher CCP score. In addition, Q4 predicted a different risk after tamoxifen depending on menopausal status, with a beneficial trend on IBEs in postmenopausal women (HR 0.30; 95% CI, 0.07-1.39), and an opposite trend in premenopausal women (HR 1.68; 95% CI, 0.38-7.44) (P-interaction = 0.03). The results of this study provide for the first time the evidence that CCP score is a prognostic marker, which, after additional validation, could have an important role in personalizing the management of DCIS.
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http://dx.doi.org/10.1038/s41379-020-0452-0DOI Listing
June 2020

Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

BMC Med 2020 01 10;18(1). Epub 2020 Jan 10.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.

Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs.

Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles.

Conclusion: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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http://dx.doi.org/10.1186/s12916-019-1474-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953215PMC
January 2020

Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence.

Breast Cancer Res 2019 12 30;21(1):153. Epub 2019 Dec 30.

Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

Background: Invasive lobular carcinomas (ILCs) account for 10-15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs.

Patients And Methods: We retrospectively analyzed all consecutive patients with hormone receptor-positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5 years of endocrine treatment. The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5 years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5 years after surgery was the prospectively defined primary endpoint.

Results: One thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7 years. Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06-5.01) as compared with the first 5 years of follow-up (DM-HR, 9.55; 95% CI, 5.64-16.2; heterogeneity p value 0.002). Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5 years from surgery (DM-HR, 1.81; 95% CI 1.19-2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status. A combined score, obtained integrating the previously validated Clinical Treatment Score post 5 years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs.

Conclusion: We identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation.
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http://dx.doi.org/10.1186/s13058-019-1234-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937973PMC
December 2019

Expression of tumor-associated antigens in breast cancer subtypes.

Breast 2020 Feb 12;49:202-209. Epub 2019 Dec 12.

Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy; Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Objectives: Tumor-associated antigens (TAAs) are frequently overexpressed in several cancer types. The aim of this study was to investigate the expression of TAAs in breast cancer.

Material And Methods: A total of 250 selected invasive breast cancers including 50 estrogen receptor (ER)-positive (Luminal B like), 50 triple-negative (TN), 50 ER-positive lobular type, 50 ER- and progesterone receptor (PgR)-positive (Luminal A like) and 50 cerbB2-positive breast cancers, were assessed for New York esophageal squamous cell carcinoma-1 (NY-ESO-1), Wilms tumor antigen (WT-1) and PReferentially expressed Antigen of MElanoma (PRAME) antigen expression by immunohistochemistry (IHC).

Results: A significantly higher expression of cancer testis (CT)-antigens NY-ESO-1 and WT-1 antigen was detected in TN breast cancers compared with ER-positive tumors. NY-ESO-1 overexpression (score 2 + and 3+) assessed by monoclonal and polyclonal antibodies was detected in 9 (18%) TN cancers as compared to 2 (4%) ER-positive tumors (p = 0.002). WT1 over-expression (score 2 + and 3+) was confirmed in 27 (54%) TN tumor samples as compared to 6 (12%) ER-positive (p < 0.0001). PRAME over-expression (score 2 + and 3+) was detected in 8 (16%) HER2 positive tumor samples as compared to no TN and ER-positive cancers (p = 0.0021).

Conclusions: NY-ESO-1 and WT1 antigens are overexpressed in TN breast cancers. Because of the limited therapeutic options for this patient subgroup, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.
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http://dx.doi.org/10.1016/j.breast.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375652PMC
February 2020

Pre-operative evaluation of epithelial ovarian cancer patients: Role of whole body diffusion weighted imaging MR and CT scans in the selection of patients suitable for primary debulking surgery. A single-centre study.

Eur J Radiol 2020 Feb 13;123:108786. Epub 2019 Dec 13.

Clinica di Radiologia EOC, Istituto di Imaging della Svizzera Italiana (IIMSI), Via Tesserete, 46- 6900, Lugano, Switzerland; Department of Radiology, IEO European Institute of Oncology IRCCS, via Ripamonti 435, 20141 Milan, Italy.

Purpose: to evaluate the accuracy of Whole Body MRI including Diffusion-Weighted Imaging sequences (WB DWI MR) in the assessment of sites of disease in epithelial ovarian cancer (EOC), in comparison to CT; to evaluate whether a clinical-radiological score may predict suboptimal cytoreductive surgery.

Methods: patients with suspected EOC who underwent pre-operative WB DWI MR were included; CT scans were recorded. Data recorded included: age, staging, dates of examinations and surgery; tumour markers; sites of disease at imaging scans and at surgery. For calculation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB DWI MR and CT, surgical evaluation represented the gold standard. The accuracy of WB DWI MR and CT was compared. The association between clinical and radiological criteria with sub-optimal cytoreduction was tested to identify a final model to predict sub-optimal cytoreduction.

Results: 92 patients were included; 77/92 (83.7 %) were optimally cytoreduced. Sixty-six CT and 92 MR examinations were evaluated. WB DWI MR showed overall higher accuracy than CT in assessing all sites, but it performed significantly better than CT specifically for involvement of mesentery, lumbo-aortic lymph nodes, pelvis, large bowel, sigmoid-rectum. The predicting score for suboptimal cytoreduction included: mesenteric carcinomatosis; mesenteric retraction; large bowel carcinomatosis.

Conclusions: In pre-operative evaluation of EOC patients, WB DW MRI is accurate for assessment of multiple sites and it is significantly more accurate than CT for specific unresectable sites. In our series, significant sites of disease for suboptimal cytoreduction were mesenteric carcinomatosis, mesenteric retraction and large bowel carcinomatosis.
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http://dx.doi.org/10.1016/j.ejrad.2019.108786DOI Listing
February 2020