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Background/aim: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib., Patients and Methods: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated., Results: The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss., Conclusion: Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To compare clinical outcomes following intensified total neoadjuvant therapy (TNT) and intensified neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC)., Patients and Methods: Of the 79 patients with LARC admitted to our department, 51 received intensified neoadjuvant CRT (CRT group) and 28 received intensified TNT (TNT group). Intensified TNT was defined as multi-agent chemotherapy, including FOLFOXIRI regimen plus bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) followed by oxaliplatin-5-fluorouracil-based CRT and surgery. Kaplan-Meier and Log rank test were used for survival analysis. Survival rates of the two groups were compared using propensity score matching., Results: Data from 28 TNT patients and 28 CRT patients were analyzed after a 1:1 propensity matching with replacement. Kaplan-Meier curve showed that overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates with TNT were comparable to those with CRT. The 5-year DMFS rates for TNT and CRT were 61.5% versus 63.0% (p=0.82), respectively. In the TNT group, 32.1% patients (n=9) achieved pathological complete response (pCR), whereas 21.4% patients (n=6) achieved pCR with CRT (p=0.37)., Conclusion: Intensified TNT and CRT resulted in similar survival outcomes, while intensified TNT led to higher pCR, albeit not statistically significant., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients., Materials and Methods: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry., Results: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047)., Conclusion: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To evaluate the efficacy of dynamic contrast-enhanced magnetic resonance (DCE-MR) in the response to anti-angiogenic-targeted agents in patients with metastatic renal cell cancer (mRCC)., Patients and Methods: Twenty-eight consecutive patients with sub-diaphragmatic metastases from mRCC were included in the protocol after signed informed consent. Baseline characteristics were collected and patients were first evaluated with a baseline computed tomography (CT) and DCE-MR, subsequently with a new DCE-MRI after 28 days of therapy and followed-up with CT until progression. Treatments were administered at standard doses. The changes of peak enhancement (ΔPE) and of the sum of longest tumor diameters (ΔLTD) were related to progression-free survival (PFS) and overall survival (OS)., Results: The median PFS was 11.4 months [95% Confidence Interval (CI): 7.9-14.7 months) and the parametric two-tailed Pearson's test showed a positive correlation between the median ΔPE and the median PFS (rp=0.809; p=0.015); no significant correlation was found between the median ΔLTD and the median PFS (rp=-0.446; p=0.27). The median OS was 23.3 months (95% CI: 13.6-33.0 months) and no significant correlation was found with the median ΔPE (rp=0.218; p=0.60) or with the median ΔLTD (rp=0.012; p=0.98)., Conclusion: The ΔPE but not the ΔLTD was found to be significantly related to PFS; these preliminary results suggest extending the number of patients and investigating the possible relationship with other tumor characteristics and MRI parameters.

Background: Recent evidence supports the hypothesis that the CellSearch assay, used in the enumeration of circulating tumor cells (CTCs), may underestimate the number of CTCs, especially in tumors, such as renal cell carcinoma, frequently lacking cytokeratin expression. According to the CellSearch guidelines, all objects with no clear cytokeratin staining are defined as "suspicious objects", and are not counted as CTCs. The aim of this study was to investigate the presence of CTCs and "suspicious objects" in 25 patients affected by metastatic renal cell carcinoma (mRCC)., Patients and Methods: Twenty-five patients were enrolled in the study, all with a diagnosis of metastatic clear cell RCC. The CellSearch™ system was used to count the CTC in 7.5 mL of whole blood. A further 10 ml blood obtained from each patient was used to isolate CTCs through CELLection™ Dynabeads®. The expression of cytokeratin (CK) 8, 18, 19 and CD44 were evaluated by RT-PCR., Results: Standard CTCs and suspicious objects were found in 16% and 60% of the patients, respectively. CK-8/18/19 transcripts were found in 15% and CD44 in 68% of the 19 patients with evidence of classical CTC or "suspicious objects" as assessed by Cellsearch., Conclusion: The low number of CTCs detected through CellSearch in renal cell carcinoma may be due to the presence of a CTC population with atypical characteristics and a peculiar gene expression profile, characterized by lack of cytokeratin expression and gain of CD44.

Background: Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws., Patients and Methods: The data for twelve patients, referred to either an oral and maxillofacial surgeon or to an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology, were reviewed. All had received cancer-related therapy simultaneously with bisphosphonate management., Results: The typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, the lesions initially occurred after dental extraction or other odontostomatological procedures, while five had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In nine cases, there was histological or cytological diagnosis of suspicious osteomyelitis. No correlation was observed between the intraoral lesions and myelosuppression secondary to antineoplastic therapy., Conclusion: Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate-mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.

Background: Only 5-10% of colorectal cancer patients (pts) with liver metastases are eligible for surgical resection. Regional and systemic chemotherapy represents the best therapeutic options for unresectable metastases., Materials and Methods: In a randomized phase II trial 123 pts were enrolled with a minimum follow-up of 3 years. In Arm A 58 pts were submitted to intraarterial continuous infusion of cisplatin (CDDP), 24 mg/m2/day, while the other 65 were included in Arm B (bolus of CDDP, 24 mg/m2/day). All the pts were also given i.v. escalating doses of fluorouracil. Response was evaluated after a minimum of 3 cycles., Results: Toxicity > or = G3 was lower in Arm B. The objective response rate was 52% in all the series, the complete responses being 17.3% (17.6% vs. 17% in Arms A and B, respectively). The overall median survival was 18 months rising to 28 months in the responders., Conclusion: CDDP HAI provided similar results as FUdR in terms of response to treatment. Moreover, long-term survivors were unexpectedly observed.

Background: Oxaliplatin, a new DACH-platinum compound, has provided high response rates both in untreated and 5-FU-resistant patients., Aim: To define the feasibility and toxicity profile of Oxaliplatin administered as a continuous hepatic aterial infusion., Patients and Methods: Seventeen patients with pretreated metastatic liver colorectal cancer were treated with Oxaliplatin 20 mg/m2/day by HACI x 5 days every 3 weeks., Results: Toxicity grade 3 included pain (4 out of 17), asthenia (1 out of 17) and nausea (1 out of 17). Abdominal pain grade 4 (WHO) was noted in only one patient. Overall, severe abdominal pain (main dose-limiting toxicity) was observed in 41% of patients and no chemical hepatitis and sclerosing cholangitis pain-related was proven by an endoscopic retrograde cholangiography. The response rate was not a primary end-point; nonetheless among 15 evaluable patients we observed partial responses (PR) in 7 patients (46%) and stable disease (SD) in 21% of cases for an overall tumor growth control of 67%. Progression to disease (PD) was 33%. Following chemotherapy, one patient underwent surgical removal of residual metastases, with curative intent. The 1-year survival rate was 64%. The median duration of survival was 19 months. The median delay to hepatic progression was 10 months., Conclusion: Further studies are required to define the role of HACI Oxaliplatin, the schedule of administration (bolus vs continuous infusion) and the combination, also in this setting, with fluoropyrimidines.

Background: Recent studies have shown a good activity/tolerability for weekly paclitaxel and 5-fluorouracil in protracted continuous infusion (p.c.i.) in metastatic breast cancer patients pretreated with anthracyclines., Materials and Methods: To define the MTD of weekly paclitaxel (days 1-8-15-22, every 4 weeks with a starting dose of 75 mg/m2 and subsequent dose escalation: 90 mg/m2 and 105 mg/m2) in combination with a fixed dose of 5-fluorouracil in p.c.i. (250 mg/m2/day for 3 weeks + 1 week of rest)., Results: Eleven patients were enrolled; on Step III two patients experienced DLT (1 G 3 mucositis and 1 febrile neutropenia). G 3-4 toxicities were: G 3 mucositis (2 out of 11), G 3-4 neutropenia (1 out of 11)., Conclusion: The recommended schedule for phase II studies is: paclitaxel 90 mg/m2/w + 5-fluorouracil 250 mg/m2 in p.c.i. for 21 days. This is the first phase I trial with the combination of weekly paclitaxel and 5-fluorouracil p.c.i. in advanced breast cancer patients.

Background: In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC)., Patients and Methods: Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis., Results: The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed., Conclusions: Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

Background: SCLC relapsing or refractory after induction chemotherapy is a chemoresistant tumor. The outcome of salvage chemotherapy is poor, with low response rates (< 30%) and short survival times (3-4 months). The development of drug resistance is considered the major cause of failure of treatment. VM-26 is one of the most active drugs in SCLC. Lonidamine has shown to enhance in both vivo and vitro antitumor activity of several cytotoxic drugs acting on drug resistance mechanisms., Materials and Methods: VM-26 and lonidamine were employed as salvage chemotherapy in 30 small cell lung cancer patients. The doses of chemotherapy used were: VM-26 100 mg/m2, i.v., days 1 to 3; lonidamine 600 mg, p.o., days 1 to 5, recycled every 3 weeks., Results: We observed 13.3% of objective response and a median survival of 4 months. All the responses were obtained in patients relapsing after a response to induction chemotherapy. Toxicity was moderate with no toxic death., Conclusions: Our study shows that Lonidamine failed to increase the VM-26 activity in pretreated small cell lung cancer patients.