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Giulia Veronesi

Publications and source records attributed to Giulia Veronesi.

At least 19 recordsLinked to original sources
PubMed2026

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥ 50%; however, up to 30% of patients experience early progression or death, including cases of hyperprogressive disease (HPD). High baseline levels (≥ 30.5%) of circulating CD10- low-density neutrophils (LDNs) have been associated with increased HPD occurrence. Emerging evidence suggests that combining ICI with platinum-based chemotherapy (PCT) may mitigate the risk of HPD. Currently, no prospective studies have addressed HPD prevention in this context. PATIENTS AND METHODS: HYPERBOLIC (NCT07274384) is a phase 2, randomized, open-label, multicenter, international trial evaluating whether adding 3 cycles of PCT to first-line cemiplimab reduces HPD rate in stage IV NSCLC with PD-L1 ≥ 50% and CD10- LDNs (identified by flow cytometry as CD15⁺CD11b⁺ within the PBMC fraction, with immature cells defined by loss of CD10) ≥ 30.5%. Seventy-four patients will be randomized (1:1 ratio) to receive cemiplimab alone or cemiplimab plus 3 PCT cycles, followed by cemiplimab maintenance. Randomization will be stratified by Lung Immune Prognostic Index. The first computed tomography scan at week 7 after treatment start will assess HPD occurrence, defined as RECIST v 1.1. disease progression with a delta tumor growth rate (ΔTGR) ≥ 50% and/or TGR ratio ≥ 2. The primary endpoint will be the combined rate of HPD and early death (death within 12 weeks with no radiological evaluation). Secondary endpoints will be HPD rate according to alternative definitions, overall survival, progression free survival, objective response rate, and safety. An extensive translational research platform will include spatial transcriptomics of tumor tissue, single-cell RNA sequencing of PBMCs, circulating-free DNA and plasma factors profiling, and saliva/stool microbiome genomics and metabolomics, to longitudinally explore tumor-host dynamic interactions during treatment. CONCLUSION: to our knowledge, HYPERBOLIC is the first prospective, biomarker-driven trial investigating early treatment escalation based on HPD risk in PD-L1-high NSCLC.

CD10↗
PubMed2007

Superior vena cava resection for lung and mediastinal malignancies: a single-center experience with 70 cases.

BACKGROUND: The oncologic value of superior vena cava (SVC) resection for lung and mediastinal malignancies remains controversial. In this context, we have reviewed our experience in the treatment of locally advanced lung and mediastinal tumor invading the SVC system, analyzing postoperative outcome and long-term oncologic results. METHODS: The clinical data of patients who underwent SVC resection were retrospectively analyzed to assess postoperative mortality, and overall and procedure-specific morbidity. Overall survival was calculated for mediastinal and lung tumor groups. RESULTS: From 1998 to 2004, 70 consecutive patients (52 with lung cancer and 18 with mediastinal tumors) underwent SVC system resection. There were 25 replacements (36%) of the SVC system by prosthesis, whereas the remaining underwent partial resection. Major postoperative morbidity and mortality rates in lung cancer patients were 23% and 7.7%, respectively (50% and 5.6% in mediastinal tumors). In the lung cancer group, 5-year survival probability was 31%, and it was affected by mediastinal nodal status (5-year survival in N0-N1 patients 52%, 21% in N2 patients, 0 in N3 patients). Median survival for mediastinal tumors was 49 months. CONCLUSIONS: In conclusion, SVC resection may achieve permanent cure in patients who would have been defined as inoperable 10 years ago. In the case of mediastinal tumors, the need for SVC resection alone should not be considered a contraindication for surgery when prosthetic replacement is feasible. In the case of lung tumors, infiltration of SVC can achieve satisfactory long-term results after neoadjuvant chemotherapy, only when pathologic N2 disease is excluded by preoperative mediastinoscopy.

Aged↗
PubMed2007

Oligometastatic non-small cell lung cancer: a multidisciplinary approach in the positron emission tomographic scan era.

BACKGROUND: We have assessed the survival rate of patients with non-small cell lung cancer and synchronous hematogenous solitary metastasis identified with complete staging workup, including total body [18F]fluorodeoxyglucose positron emission tomography scan, and treated with a multidisciplinary approach. METHODS: We examined the database of all patients who underwent surgery for primary non-small cell lung cancer in our institute. The criteria required for inclusion in this analysis were diagnosis of non-small cell lung cancer with synchronous hematogenous solitary metastasis by staging workup with total body computed tomography scan and brain magnetic resonance if indicated, total body positron emission tomography scan, radical surgery for the primary tumors, local treatment of the solitary metastasis, and systemic chemotherapy administration. RESULTS: We analyzed the data from 1,509 patients treated from January 2000 to December 2005: 10 patients (0.7%) satisfied the selection criteria. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression-free after 9, 18, 23, and 32 months from the start of their treatment. CONCLUSIONS: The presentation of non-small cell lung cancer with a synchronous hematogenous solitary metastasis identified by [18F]fluorodeoxyglucose positron emission tomography containing complete staging workup is extremely rare. This subset of patients can achieve long-term survival after a multidisciplinary treatment approach.

Adult↗
PubMed2006

Pulmonary artery reconstruction by a custom-made heterologous pericardial conduit in the treatment of lung cancer.

Lung cancer may involve the pulmonary artery (PA) either by direct extension of the primary tumor or by invasion of the hilar lymph nodes. In these instances, a radical resection is usually a pneumonectomy despite distal functioning lung tissue. To spare the lung parenchyma, angioplastic procedures requiring removal of a portion of the arterial wall or a circumferential resection with arterial reconstruction have been used. Several techniques of pulmonary arterioplasty have been explored suggesting that the incidence of postoperative complications is acceptably low and long-term local control can be achieved. Over a period of 7 years, 84 angioplastic procedures (alone or associated with bronchoplasty) were performed at our institution. Partial PA resection was performed in 80 (95.2%) patients. Reconstruction was performed by running suture in 63 (75%) patients and using a pericardial patch in 17 (20.2%) cases (16 autologous and 1 heterologous). A complete PA resection and reconstruction was performed in four (4.8%) patients by a polytetrafluoroethylene (PTFE) prosthesis (n=2) and by a custom-made bovine pericardial conduit (n=2). The latter are the topic of this report.

Aged↗
PubMed2006

Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases.

OBJECTIVE: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. PATIENTS AND METHODS: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan-Meier method, and compared by the log rank test. RESULTS: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p=0.001 log-rank test on Kaplan-Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p=0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. CONCLUSION: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease.

Adult↗
PubMed2006

Subclavicular recurrence of breast cancer: does surgery play a role?

Occasionally, breast cancer relapses in the subclavicular region. In patients with failed multimodal treatment, or in those who develop an isolated recurrence, surgical resection may be useful to remove all macroscopically evident diseases. However, the procedure may be technically demanding and there are no published data regarding its benefits. The aim of the present study was to evaluate the feasibility and safety of subclavicular resection in breast cancer and provide indications as to whether it can contribute to disease control. We used a transpectoral approach to surgically remove isolated breast cancer recurrence in the subclavicular region in seven consecutive patients presenting over 2 years; in the eighth case a transmanubrial approach was necessary. We found that the surgical approach proposed is feasible and safe, with a 75% rate of complete resection; however, the series was characterised by a high rate of local and distant relapse. We conclude that the technique may be useful, in selected cases, for palliation only.

Adult↗
PubMed2006

Video-assisted management of malignant pleural effusion in breast carcinoma.

BACKGROUND: Advanced breast carcinoma almost always leads to a malignant pleural effusion, conditioning the performance status of patients and consequently quality of life. The treatment of malignant pleural effusion should be a priority in the management of such patients. The results of video-thoracoscopic approach (VATS) chemical pleurodesis was analyzed in patients with recurrent pleural effusion from breast carcinoma. METHODS: From October 1998 to June 2004, 71 consecutive patients with breast carcinoma-related pleural effusion were treated by the same thoracic-surgeon team with intracavitary nebulization of 8 g of asbestos-free sterilized talc via VATS. Multiple pleural biopsies were performed to determine biologic characteristics of recurrent disease. RESULTS: Talc pleurodesis was performed in all cases, with no intraoperative or postoperative complications. Median length of hospital stay was 5 days (range, 5-8). The overall success rate of the surgical procedure was 89% (confidence interval [CI], 79-95%) with a mean follow-up of 22 months (range, 2-81 mos). The overall survival time was 17 months (range, 2-80). Biopsies showed a switch on receptor status and c-erB-2 status from negative (primary tumor) to positive (pleural metastasis) in 11 (15%) patients. In another 7 (9.8%) patients, we obtained completely new information that was hitherto unknown. CONCLUSION: Talc pleurodesis via VATS is an effective and safe procedure that yields a high rate of success at the first attempt and achieves long-term control of malignant pleural effusion due to breast carcinoma. Concomitant biopsies performed during the VATS procedure were a determining factor in the subsequent decision-making process.

Adult↗
PubMed2006

Anomalous right upper lobe venous drainage.

Anomalous pulmonary venous return is a rare congenital anomaly mainly involving the right lung and is often associated with congenital intracardiac malformations as atrial septal defect. We report a case of anomalous right upper lobe venous drainage resulting in two right upper lobe veins draining into the azygous vein and into the confluence between superior vena cava and azygous vein, respectively. Preoperative identification of such an aberrant venous drainage is useful for avoiding unexpected intraoperative bleeding.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Does chemotherapy increase the risk of respiratory complications after pneumonectomy?

OBJECTIVE: The impact of induction chemotherapy on postoperative complications after pneumonectomy remains unclear. The aim of the study was to test the hypothesis that chemotherapy may increase the risk of postoperative respiratory complications. METHODS: Data from 202 consecutive standard pneumonectomies performed for lung cancer were collected and analyzed. Postoperative and 90-day mortality, overall morbidity, and respiratory complication rates were evaluated in patients who had no induction treatment (group A, n = 103) as well as in those who received it (n = 99, group B). Preoperative chemotherapy was inserted as a variable together with 12 other variables (age, sex, smoking status, body mass index, previous cardiac event, American Society of Anesthesiologists score, preoperative forced expiratory volume in 1 second [percent], diffusion capacity for carbon monoxide adjusted for alveolar volume [percent], side of pneumonectomy, perfusion of the removed lung, operating time, and blood transfusion) into univariate and multivariate logistic regression. RESULTS: No difference in terms of mortality was recorded between group A (4.9%) and group B (3%, P > .05). Respiratory complications were more frequent in group B than in group A (19 cases, 19.2%, vs 7 cases, 6.8%, P = .008). Univariate logistic regression has demonstrated that pulmonary complications were more frequent in patients over the age of 70 than in those aged 70 or less (25.7% vs 10.2, P = .02), in those with a lower diffusion capacity adjusted for alveolar volume (18.3% vs 5.95%, P = .06), and in patients who received preoperative chemotherapy (19.2% vs 6.8, P = .008). Logistic regression confirmed the role of age (odds ratio = 6.3), preoperative chemotherapy (odds ratio = 4.4), and diffusion capacity adjusted for alveolar volume (odds ratio = 0.33) as risk factors of respiratory complications. CONCLUSIONS: Standard pneumonectomy is a safe procedure even after induction chemotherapy, with a mortality rate in the order of 5%, but this increases in patients over the age of 70 years. In the case of induction chemotherapy, the risk of respiratory complications is significantly increased, apparently not affecting the overall mortality rate.

Female↗
PubMed2005

Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients.

Human telomerase reverse transcriptase (hTERT), the catalytic subunity of telomerase, a marker of cell immortalization, is upregulated in most tumors, including nonsmall cell lung cancer (NSCLC). However, little is known about the role of assessing cell-free plasma circulating hTERT mRNA for tracing these tumors. We investigated by RT-polymerase chain reaction (PCR) and real-time quantitative PCR the prevalence and functional implications of hTERT mRNA in both tumor tissue and paired plasma samples in 34 (27 males and 7 females) stages I-IIIB NSCLC patients (21 adenocarcinomas and 13 squamous-cell carcinomas) by using intron- and exon-spanning primers. Plasma samples of ten healthy volunteers and normal lung tissue were used as negative controls. We detected hTERT mRNA in the plasma of 4 out of 34 (12%) tumor patients, but none was detected in the ten plasma samples of healthy volunteers. Normal lung tissue was completely devoid of hTERT mRNA. No association was found between hTERT plasma mRNA and clinicopathologic variables of the patients' population. We conclude that cell-free circulating hTERT mRNA is detectable in a subset of patients, whereas it is consistently absent in healthy volunteers. It can be added to the panel of multiple genetic tracers to detect lung cancer in the plasma of patients, although, per se, it is not specific for this tumor.

Adenocarcinoma↗
PubMed2005

A subset of high-grade pulmonary neuroendocrine carcinomas shows up-regulation of matrix metalloproteinase-7 associated with nuclear beta-catenin immunoreactivity, independent of EGFR and HER-2 gene amplification or expression.

Nuclear translocation of beta-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation in non-small cell lung cancer. Less is known on beta-catenin transactivation in high-grade pulmonary neuroendocrine tumors and on the status of beta-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or beta-catenin target genes cyclin D1 and matrix metalloproteinase-7 (MMP-7). beta-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for beta-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. beta-catenin was expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated with EGFR and HER-2 protein expression. beta-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These cases, however, did not show beta-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear beta-catenin and any clinicopathological variable including patients' survival. The subcellular compartmentalization of beta-catenin is profoundly altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows beta-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression.

Adult↗
PubMed2005

Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids.

BACKGROUND: To the authors' knowledge, little is known regarding the role of E-cadherin/beta-catenin system dysregulation in pulmonary neuroendocrine tumors. METHODS: E-cadherin and beta-catenin immunoreactivity was evaluated in 10 hyperplastic neuroendocrine tumorlets and 210 neuroendocrine tumors, including 96 typical carcinoids (CTs), 35 atypical carcinoids (ACTs), 49 large cell neuroendocrine carcinomas (LCNECs), and 30 small cell lung carcinomas (SCLCs). RESULTS: Normal and hyperplastic bronchial neuroendocrine cells expressed E-cadherin/beta-catenin with an orderly distribution along the cell membrane. Neuroendocrine tumors retained beta-catenin expression in all tumors and E-cadherin in most tumors, with the exception of 2% of LCNECs, 3% of SCLCs and 9% of ACTs. E-cadherin showed a prevalent membrane-associated, linear immunoreactivity in CTs, whereas membrane-disarrayed and cytoplasmic staining was seen in most ACTs, LCNECs, and SCLCs (P < 0.001). beta-Catenin exhibited similar immunoreactivity patterns according to tumor type and a close association with E-cadherin subcellular distribution (P < 0.001). Nuclear accumulation of beta-catenin was found only in seven LCNECs and in two SCLCs. In ACTs, disarrayed immunoreactivity for E-cadherin and/or beta-catenin was associated with a nontrabecular growth pattern, altered expression of the cell-motility marker fascin, and lymph node metastases. Furthermore, a disarrayed E-cadherin distribution pattern was associated with the pathologic lymph node classification and the number of involved lymph nodes. Multivariate analysis confirmed that a disarrayed E-cadherin or beta-catenin pattern was an independent predictor of lymph node metastases in patients with ACT. CONCLUSIONS: The subcellular compartmentalization of the E-cadherin/beta-catenin complex was altered in pulmonary neuroendocrine tumors. This likely affects the tumor growth pattern and cell motility of ACT and was correlated with the occurrence of lymph node metastases.

Adult↗
PubMed2005

Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung.

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.

Adenocarcinoma↗
PubMed2005

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study.

PURPOSE: To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. RESULTS: From February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). CONCLUSION: In this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC.

Antineoplastic Agents↗