Papers by Alberto Zaniboni
Background: Previous meta-analyses have yielded conflicting results on the optimal surgical treat... more Background: Previous meta-analyses have yielded conflicting results on the optimal surgical treatment strategy in patients with synchronous colorectal liver metastases (sCRLM). This network meta-analysis aims to provide an overview on colorectal-, liver first and simultaneous resections to treat sCRLM. Methods: A search was conducted in MEDLINE, Embase and Cochrane CENTRAL (inception-July 11,2023). Pairwise and network meta-analyses were conducted to compare the three strategies, using colorectal-first resections as reference group. Results: Overall, 46 studies with a total of 20,991 patients were included, a significant portion at a high risk of bias. Simultaneous resections were associated with less blood loss (MD-145.44 ml, 95%CI-239.40 to −51.48) and shorter hospital stays (MD-6.39 days, 95%CI-7.78 to −4.99). Liver-first resections were associated with more transfusions (OR 1.89, 95%CI 1.04 to 3.42) and shorter hospital stays (MD-4.53 days, 95%CI-7.99 to −1.06). Simultaneous resections were associated with less incomplete macroscopic disease clearances (OR 0.33, 95%CI 0.12 to 0.92), while liver-first resections were associated with more incomplete macroscopic disease clearances (OR 2.80, 95%CI 1.16 to 6.73) and less microscopically radical (R0) resections (OR 0.64, 95%CI 0.45 to 0.90). There were no significant differences in morbidity, mortality, disease-free or overall survival. Conclusion: Based on meta-analysis of mainly observational studies, simultaneous resections were associated with less blood loss, shorter length of stay and more complete macroscopic disease clearances.
Background: Ascites is common in advanced gastrointestinal cancers with peritoneal metastases (PM... more Background: Ascites is common in advanced gastrointestinal cancers with peritoneal metastases (PM) and negatively impacts patient survival. No study to date has specifically evaluated the relationship between ascites, PM and survival outcomes in metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC). Objectives: This study aims to investigate and elucidate the relationship between malignant ascites, PM and survival outcomes in both mCRC and mGC patients. Design: This is a retrospective analysis of prospectively collected clinical trial data of mCRC and mGC patients with PM. Methods: We performed two pooled analyses, firstly of two Italian randomized trials enrolling patients with mCRC eligible for systemic therapy (TRIBE2; VALENTINO), and secondly of gastric cancer and peritoneal metastasis (GCPM) patients who underwent bi-directional therapeutic treatment comprising systemic and peritoneal-directed therapies. Results: Of 900 mCRC patients, 39 (4.3%) had PM with malignant ascites. Compared to the group without PM, median progression-free and overall survival were significantly inferior in the ascites group (hazard ratio (HR) for progression-free survival (PFS) 1.68, 95% confidence interval (CI): 1.21-2.35, p = 0.007; HR for overall survival (OS) 2.14, 95% CI: 1.57-3.01, p < 0.001), but not in the group of PM without ascites (HR for PFS 1.10, 95% CI: 0.91-1.34; HR for OS 1.04, 95% CI: 0.84-1.30). Of 170 patients with GCPM, those with ascites had higher median Peritoneal Cancer Index scores (23 vs 9, p < 0.001). Median OS was significantly inferior among those with ascites compared to those without (13.0 vs 21.0 months, HR 1.71, 95% CI: 1.16-2.52, p = 0.007). Conclusion: Ascites identifies a subgroup of patients with PM and poor outcomes, for whom tailored research are needed.
The incidence of biliary tract cancer is increasing in developed countries and is generating rene... more The incidence of biliary tract cancer is increasing in developed countries and is generating renewed interest in the scientific community due to the evidence of a high percentage (approximately 40%) of potentially targetable molecular alterations. However, to date, patient selection and the development of therapeutic approaches remain challenging due to the need for accurate diagnosis, adequate sampling, a specialized team for molecular analysis, centralization of patients in high-volume centers capable of supporting the high cost of these methods, and the feasibility of clinical studies on diseases with aggressive onset and poor prognosis. In this article, we would like to provide a detailed overview of the necessary tools for diagnostic framing and the various therapeutic scenarios being investigated concerning the most frequently detected molecular alterations.
The first-line combination therapies utilizing cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6... more The first-line combination therapies utilizing cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) have significantly impacted the course of hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 negative (HER2-) advanced breast cancer (ABC). However, resistance often emerges, leading to a molecularly different disease. Estrogen receptor one (ESR1) gene mutations, driving resistance to aromatase inhibitors (AIs), may guide the use of fulvestrant or emerging oral selective estrogen receptor degraders (SERDs) like elacestrant. The dynamic nature of ESR1 mutations suggests potential guidance for continuing CDK4/6i therapy beyond progression. Targeting mutations like breast cancer gene 1 and 2 (BRCA 1/2) with Poly (ADP-ribose) polymerase (PARP) inhibitors or the PI3K/AKT/mTOR pathway provides therapeutic options. The advent of antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-DXd) and novel agents targeting Trophoblast cell surface antigen-2 (Trop-2) introduces further complexity, underscoring the need for early intervention targeting specific genomic alterations in metastatic BC.
Cancer Treatment Reviews, Feb 1, 2022
Retrospective series suggest that bevacizumab-induced hypertension (HTN) is a prognostic and pote... more Retrospective series suggest that bevacizumab-induced hypertension (HTN) is a prognostic and potentially predictive biomarker of efficacy of the antiangiogenic drug in the upfront treatment of metastatic colorectal cancer (mCRC) patients. The immortal-time bias and the effect of pre-existing HTN might affect these findings. We conducted a pooled, post hoc analysis of 2 prospective randomized trials of chemotherapy plus bevacizumab in mCRC, and performed a systematic review of the available literature focusing on how the immortal-time bias was taken into account and how pre-existing HTN potentially requiring the use of antihypertensive drugs was managed. The pooled-analysis included patients enrolled in the phase III TRIBE and TRIBE-2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively. Association between HTN and survival outcomes was assessed by incorporating a time-dependent Cox regression model to consider the time-dependency of the probability of HTN onset during the treatment. The systematic review was conducted according to PRISMA guidelines. The systematic review retrieved 14 eligible and highly heterogeneous studies. A positive prognostic impact of bevacizumab-induced HTN was reported in the 58% of the analyses reporting Progression Free Survival (PFS) and in the 54% of the analyses reporting Overall Survival (OS) data. Immortal-time bias was incorporated in 4 studies (28%). In TRIBE and TRIBE-2 study populations (N = 1175), patients experiencing ≥ G2 HTN during first-line bevacizumab administration showed longer PFS (median: 14.7 versus 10.3 months, p < 0.001) and OS (median: 31.7 versus 24.2 months, p < 0.001). The association with OS retained statistical significance after correction for time-dependency (p = 0.003) and was confirmed in the multivariable model including HTN as a time-dependent variable (p = 0.02). Moreover, in patients with pre-existing HTN, no difference in terms of PFS and OS was observed compared with the subgroup of patients who never experienced ≥G2 HTN (HR 1.01, p = 0.86 and HR 1.02, p = 0.78 respectively. Bevacizumab-induced HTN during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction. Toxicity should be interpreted as a time-dependent variable when exploring its association with clinical outcome.
Diagnostics, Jun 8, 2020
Prostate cancer with extensive dural metastases is very rare, with only few cases described in th... more Prostate cancer with extensive dural metastases is very rare, with only few cases described in the literature. We report one such case of a 74-year-old man with advanced prostate cancer, and in relatively good clinical condition. The patient returned with complaints of headache and diplopia. Fluorocholine (18 F) chloride (18 F-FCH) is an analog of choline in which a hydrogen atom has been replaced by fluorine (18 F). After crossing the cell membrane by a carrier-mediated mechanism, choline is phosphorylated by choline kinase to produce phosphorylcholine. 18 F-FCH positron emission tomography-computed tomography (PET/CT) is widely used to stage and restage patients affected by prostate cancer with good sensitivity. 18 F-FCH PET/CT showed disease progression with the onset of multiple skull lesions. Numerous suspicious dural hypermetabolic lesions indicating neoplastic involvement were detected along the fronto-parietal convexities, in the left fronto-orbital region and right lateral wall of the orbit, concerning for metastases in these regions. A contrast-enhanced computed tomography (CECT) scan was performed which showed corresponding enhancing tissue which correlated with the PET findings. The final imaging diagnosis was osteo-dural metastases from prostate cancer associated with poor outcome. Awareness of this pattern of metastases may be of clinical relevance in order to avoid unnecessary invasive diagnostic procedures in groups of patients with a dismal prognosis.
Annals of Oncology, Oct 1, 2018
European Journal of Cancer, 1994
Cellular proliferation rate has been investigated in 84 primttive carcinomas, 4 carcinoid tlllllo... more Cellular proliferation rate has been investigated in 84 primttive carcinomas, 4 carcinoid tlllllors and IO non neoplastic lesions of the lung. Ki-57 (Dako) and PCNA (Dako) by means of immuttohistochemical methods, Ag NOR count and area by means of a silver staining technique and SPF by flow-cytometry were performed. Moreover, p53 (DBA) oncosuppressor gate-related protein expression and DNA-I&X were also detected. RI-67. PCNA. AeNOR and 053 were automaticallv counted bv an imaze analvzer. Lute c&nom& w& set accorhing to WHO (I 981), heyberg (I 476) end ciinical ,@ttall ceii and non small cell carcinoma) c1awfication.s. Patxnts were followed up over three years. Statistical analysis was pet%omed using ANOVA, Student's T and &-square tests. Clinical course does seem to closelv correlate both with stane CD< 0.0001) and era& f~< 0.00s) of the neoplasm. On the co&aty prolifaatmn mark& & not se& to c&elate'to clinical course, even though advanced tumors exhibit higher AgNOR count (p< 0.03), as well as poorly differentiated hnors show higher PCNA (p< O.OOl), IO-67 (p< 0.02) and SPF (p< 0.02) values. Moreover, higher mean AgNoR area values (p< 0.005) were recorded m seaming hunors, while higher SPF values (p< 0.005) were counted in small cell caranomas. In conclusion, our study underlutes the prognostic signiticance of grading and staging in lung carcinoma and, moreover, It suggests a role for proliferation markers as prognostic indicators.
British Journal of Cancer, Feb 9, 2023
BACKGROUND: Trop-2 and Nectin-4 are transmembrane proteins overexpressed in many tumours and targ... more BACKGROUND: Trop-2 and Nectin-4 are transmembrane proteins overexpressed in many tumours and targets of antibody-drug conjugates (ADC). In metastatic colorectal cancer (mCRC), the role of Trop-2 and Nectin-4 has been poorly investigated. METHODS: Tumour samples of patients randomised in the phase III TRIBE2 were assessed for Trop-2 and Nectin-4 expression. RESULTS: Three hundred eighty-six tumours were assessed for Trop-2 expression. 90 (23%), 115 (30%) and 181 (47%) were Trop-2 high, medium and low, respectively. Patients with low Trop-2 tumours achieved longer PFS (12 versus 9.9 months, p = 0.047) and OS (27.3 versus 21.3 months, p = 0.015) than those with high/medium Trop-2 tumours. These findings were confirmed in multivariate analysis (p = 0.022 and p = 0.023, respectively). A greater OS benefit from treatment intensification with FOLFOXIRI/ bevacizumab was observed in patients with high/medium Trop-2 tumours (p-for-interaction = 0.041).Two hundred fifty-one tumours were assessed for Nectin-4 expression. Fourteen (5%), 67 (27%) and 170 (68%) were high, medium and low, respectively. No prognostic impact was observed based on Nectin-4 expression and no interaction effect was reported between Nectin-4 expression groups and treatment arm. CONCLUSIONS: In mCRC, expression levels of Trop-2 and Nectin-4 are heterogeneous, suggesting a target-driven development of anti-Trop2 and anti-Nectin-4 ADCs. Medium/high Trop-2 expression is associated with worse prognosis and higher benefit from chemotherapy intensification.
Therapeutic Advances in Medical Oncology, 2020
Journal of Chemotherapy, Aug 1, 1989
In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidin... more In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidine salvage pathway, 15 patients with refractory metastatic breast cancer (MBC) were treated with oral dipyridamole (D): 75 mg p.o. q.i.d. and 5-FU: 400 mg/m2 i.v. by bolus for 5 consecutive days, every 28 days. All the patients were pretreated with 5-FU and an anthracycline-based regimen. Toxicity was minimal, with 8 patients experiencing a D-related moderate headache. Although no objective responses were seen, two patients with 5-FU refractory disease showed tumor shrinkage. A different D schedule and the addition of folinic acid (FA) to 5-FU might provide better results and deserves further evaluation.
Clinical Colorectal Cancer, Jun 1, 2023
European Journal of Nuclear Medicine and Molecular Imaging, Mar 26, 2021
A 79-year-old man with clinical history of advanced prostate cancer was referred to our instituti... more A 79-year-old man with clinical history of advanced prostate cancer was referred to our institution for worsening dyspnea. Cardiac ultrasound imaging showed enlarged right ventricle and severe pulmonary hypertension. Suspecting pulmonary embolism, a thorax/abdomen contrast-enhanced CT scan was performed with no evidence of thromboembolism (a, b) neither lung parenchymal alterations (c, d). Since this patient was affected by end-stage prostate cancer, pulmonary tumor thrombotic microangiopathy (PTTM) was hypothesized as the cause of the severe pulmonary hypertension. PTTM is characterized bymultiple microthrombi of cancer cells surrounded by fibrotic intimal cell proliferation and by vascular remodeling mediated by tumoral growth factors. It is more frequently associated with gastric adenocarcinoma and also with other neoplasms [1, 2]. It can cause severe pulmonary hypertension and right ventricular failure. The diagnosis is challenging as computed tomography (CT) findings are often unspecific [3], whereas conventional lung scintigraphy may reveal perfusion defects [4–6]. For this reason, our patient underwent a lung scintigraphy but planar images (e) showed irregular radiotracer distribution on both lungs without significant defects clearly referable to embolism. Conversely, SPECT-CT scan revealed multiple perfusion defects compatible with pulmonary embolism (f, g). It is wellestablished that SPECT-CT lung scintigraphy has higher diagnostic accuracy for detecting pulmonary embolism than traditional planar images. Moreover, the accompanying low-dose CT scan yields clinically relevant information [7, 8]. This is the first case of PTTM where SPECT-CT added diagnostic value detecting multiple defects not revealed by planar images due to intrinsic poor spatial resolution. Therefore, in this clinical setting, SPECT-CT imaging must be recommended to unmask small perfusion defects.
Annals of Oncology, Oct 1, 2017
Background: The histopathological response to pre-operative chemotherapy is associated with clini... more Background: The histopathological response to pre-operative chemotherapy is associated with clinical outcome in patients (pts) undergoing secondary resection of CRCLM. Triple chemotherapy regimens may be preferred options in this setting. Three different histopathological growth patterns (HGPs) of CRCLM have been described: desmoplastic (i.e. with a capsule of stroma separating tumor and normal cells), pushing (i.e. with limited infiltration of normal hepatic plates by tumor cells) and replacement (i.e. with abundant infiltration of normal hepatic plates by tumor cells and vessel cooption). Methods: Histopathological parameters of response were evaluated in specimens from 159 pts who underwent secondary resection of CRCLM, after receiving triplet (FOLFOXIRI or COI) plus bev (N ¼ 103) or anti-EGFR (N ¼ 56) in 5 first-line clinical studies (TRIBE, MOMA, MACBETH, COI-B and COI-E). The aims of this analysis were to evaluate the prognostic role of histopathologic response and to explore its association with clinical characteristics, and to investigate the prognostic role of HGPs and their potential different sensitivity to targeted agents. Results: When compared with partial (TRG 3) and no (TRG 4-5) pathologic response (N ¼ 118), major response (TRG 1-2, N ¼ 41) was associated with longer RFS (mRFS: 28.0 versus 11.0 mos, HR ¼ 0.57, 95%CI¼0.39-0.86; p¼0.007) and OS (mOS: unreached versus 42.1 mos, HR ¼ 0.54, 95%CI¼0.31-0.93; p¼0.027). No association of baseline clinical characteristics and RAS and BRAF status with major response was found. Major response was more frequent among pts treated with bev than with anti-EGFRs (OR ¼ 2.83, 95%CI¼1.20-6.65; p¼0.015) and was associated with deepness of response as a continuous variable (HR ¼ 1.02, 95% CI ¼ 1.00-1.04; p¼0.011). In the desmoplastic HGP (N ¼ 28) a higher percentage of major response was reported (57% vs 17% in pushing and 22% in replacement HGP, p<0.001) and a numerical advantage from anti-EGFR vs bev was evident in terms of both major response and RFS. Conversely, in the pushing HGP (N ¼ 66) a significant benefit from bev vs anti-EGFR in major response and RFS was observed. No difference was described in the replacement HGP (N ¼ 65). Conclusion: Achieving deep radiologic and major histopathologic response significantly affects the outcome of pts with CRCLM. The assessment of HGPs may be useful to predict benefit from available targeted agents. To this end, the possibility to recognize HGPs by means of imaging exams should be investigated.
Journal of Clinical Oncology, May 20, 2015
3582 Background: Improvements in survival have been reported in mCC with the addition of bevacizu... more 3582 Background: Improvements in survival have been reported in mCC with the addition of bevacizumab or cetuximab to chemotherapy. However, their efficacy in different therapy lines and the optimal...
Annals of Oncology, Dec 1, 2015
Tumori Journal, Mar 1, 2015
Tumori 2015; 101(2): e73-e74 CASE REPORT consistent with thymic clear cell carcinoma (cT4NxM0, Ma... more Tumori 2015; 101(2): e73-e74 CASE REPORT consistent with thymic clear cell carcinoma (cT4NxM0, Masaoka stage IVA) (Fig. 2). After multidisciplinary discussion and literature review, we treated the patient with neoadjuvant chemotherapy in an attempt to decrease tumor size. We administered 4 cycles of chemotherapy with carboplatin (AUC 6) and paclitaxel (225 mg/mq) every 3 weeks. Restaging CT scan performed after chemotherapy showed notable shrinkage of the lesion (2 × 1.8 cm), with resolution of pleural and pericardial effusions (Fig. 3). Complete resection of the mass and left superior lobectomy via median thoracotomy was performed in July 2013. The resected specimen was composed of thymus gland with residual outbreaks of thymic clear cell carcinoma focally infiltrating the surrounding adipose tissue and showed clear specimen borders (R0). Postoperative adjuvant radiotherapy consisting of a total dose of 45 Gy was administered to the tumor bed. At this time, the patient is in good clinical status with no evidence of relapsed disease.
Central nervous system agents in medicinal chemistry, Mar 1, 2011
European Journal of Cancer, Sep 1, 2015
Cancer Institute INCa. Age was not associated with delay to AC, but was a limitation in AC access... more Cancer Institute INCa. Age was not associated with delay to AC, but was a limitation in AC access. Relevance of omitting AC in older patients needs further investigations. In our study, emergency colectomy and not living in couple were associated with significant delays. To act on these factors is difficult and their consideration is useful in the evaluation of organizational measures implemented to reduce time to postoperative AC in CC. No conflict of interest. 2137 POSTER Comparison of two Phase II trials of mFOLFOX6 plus bevacizumab (KSCC0802) and SOX (S-1 and oxaliplatin) plus cetuximab (KSCC1002): First line chemotherapy in colorectal cancer patients with initially unresectable or not optimally resectable liver only metastases
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Papers by Alberto Zaniboni