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Background: With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs’ performance are needed. Methods: We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years. Results: 238 patients were included: 157 received first-line abiraterone acetate plus prednisone (“abiraterone” thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, pConclusion: This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This study evaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260 U/l) and GGT (≤ or >45.5 U/l) levels. Results: Improved overall survival was recorded in patients with GGT levels ≤45.5 U/l (p

Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade

Background Several progresses have been achieved for first-line chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with Gem-NabP and FOLFIRINOX extensively used as standard first line regimens. However, the best second-line chemotherapy choice after progression is still not completely defined. The aim of this study is to compare effectiveness and safety of two possible second-line therapeutic options, FOLFOX and FOLFIRI, after progression to Gem-NabP. Methods From January 2015 to December 2018, patients with metastatic PDAC, progressed to the first-line treatment with Gem-NabP, and treated with a fluoropyrimidine-based second-line chemotherapy were considered eligible for our retrospective analysis. Overall survival (OS) and progression free survival (PFS) were set as primary endpoints whereas, disease control rate (DCR) and the rate and severity of treatment-related AEs were secondary endpoints. Results Overall, 31 patients were treated with Gem-NabP in first-line regimen, 11 received second-line with FOLFOX and 20 with FOLFIRI after progression. Baseline demographic and clinic features were similar in the two groups excluding median age of 55.5 years (range: 50-73) and 68 years (range: 59-72) in FOLFIRI and FOLFOX groups, respectively (p=0.002). Median PFS was three months (95%CI: 3-4), with no significative difference between the two groups. Median OS was eight months (95%CI: 5-10) and was significantly higher in the FOLFIRI group compared with the FOLFOX group, nine months (95%CI: 7-17) vs five months (95%CI: 2-10; p

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent adverse events observed with taxane use, whose disability often required modification or treatment discontinuation. The aim of this study was to assess the value of several variables as risk factors for CIPN development. Material and Methods: Eligible patients with metastatic pancreatic cancer receiving chemotherapy with nab-paclitaxel and gemcitabine were assessed in a multicenter study. Peripheral neuropathy was categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02, and a physical/neurological examination. Univariate and multivariate regression analyses were used to identify blood-based and clinical factors associated with CIPN. Results: Data were available from 153 patients from five Italian centers. Key risk factors of CIPN in univariate regression models included age, number of chemotherapy cycles, statin assumption, and concomitant comorbidities. However, in the multivariate analysis, only for age (OR 1.0, p < 0.01, 95% CI: 1.01–1.11) and the number of cycles (OR 1.22, p < 0.01, 95% CI: 1.09–1.36), the correlation with CIPN development has been confirmed. Conclusion: Our study confirms age and the number of chemotherapy cycles as CIPN risk factors. The identification and validation of different risk factors could be advantageous to prevent or optimize management of CIPN which outstandingly affect the patient’s quality of life.

Over the years the treatment strategy of gastric cancer (GC) has been modified to improve clinical outcome. Neoadjuvant and perioperative therapies are emerging as the new standard of care in the setting of locally advanced disease, with systemic treatment performed also before surgery. At the same time, the molecular and biological aspects of disease are becoming important factors conditioning the results. Conducted studies confirm the improvement in the long-term prognosis of operable GC with neoadjuvant or perioperative strategy. To date, we have no clear data to identify the best strategy to be used, so it is necessary to design studies that integrate clinical and biological variables for GC to improve knowledge and better define treatment strategies.

Purpose In this prospective observational study, we sought to compare the efficacy and safety of docetaxel + oxaliplatin + capecitabine (DOC) with epirubicin + oxaliplatin + 5-fluouracil (EOF) as neoadjuvant chemotherapy (NAC) for clinical T3 or T4 non-metastatic gastric cancer (GC) patients. Methods The DOC NAC consisted of docetaxel 35 mg/m2 (days 1–8), oxaliplatin 85 mg/m2 (day 1), and capecitabine 750 mg/m2 twice daily (days 1–14), every 3 weeks. The EOF NAC consisted of intravenous (IV) epirubicin 50 mg/m2 combined with IV oxaliplatin 130 mg/m2 on day 1 and continuous infusion 5-fluouracil 750 mg/m2 on days 1–5, every 3 weeks. After 4 cycles of NAC or upon progression during chemotherapy, patients underwent gastrectomy with standard D2 or D3 lymphadenectomy. Pathological complete response rate per Becker tumor regression grading system was the primary endpoint and the secondary endpoints included progression-free survival (2-yr PFS) and 2-year overall survival (2-yr OS) and tolerability. Results Overall, we identified 63 patients with T3-4 non-metastatic GC starting either NAC regimen between January 2010 and December 2017 at our Institution: 34 in the DOC group and 29 in EOF group. Thirty patients (88%) in the DOC group and 22 (76%) in the EOF group completed the 4 planned cycles of NAC. Fifty-seven patients received surgery. Results indicated no statistical significant differences between the two groups, and only a trend for some better data in favour of the DOC group. The R0 resection rate was 90.6% and 88.0% for the DOC and EOF cohorts, respectively. The pathological complete response rate was 6.2% in the DOC group and 4.0% in the EOF group. Becker 1–2 pathological response was found in 46.8% of the DOC cohort and 28.0% of the EOF cohort (p = .14). The 2-yr PFS rate was 54.1% for DOC vs. 41.4% for EOF (p = .14) and the 2-yr OS rate was 80.8% for DOC vs. 58.6% for EOF (p = .05). Neutropenia was the most common grade ≥3 toxicity and occurred in 8 (23.5%) patients of the DOC group and 10 (34.4%) patients of the EOF group (p = .33). Conclusions These findings seem to confirm the feasibility of NAC for clinically T3 and T4 non-metastatic GC and, despite no statistical significant difference was documented, suggest a trend for better activity and tolerability for the docetaxel-based regimen (DOC) compared to the epirubicin-based combination (EOF).

Key Points Question Do patients receiving abiraterone acetate with prednisone as first-line therapy for the treatment of metastatic castration-resistant prostate cancer with bone metastases benefit from the addition of bone resorption inhibitors? Findings In this cohort study of 745 patients receiving first-line abiraterone acetate with prednisone for the treatment of metastatic castration-resistant prostate cancer with bone metastases, the use of concomitant bone resorption inhibitors was associated with improvements in overall survival, particularly among those with a high volume of disease. Meaning These findings suggest that the addition of bone resorption inhibitors to abiraterone acetate with prednisone as first-line therapy could be beneficial for the treatment of patients with metastatic castration-resistant prostate cancer with bone metastases., Importance Bone resorption inhibitors (BRIs) are recommended by international guidelines to prevent skeletal-related events (SREs) among patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. Abiraterone acetate with prednisone is currently the most common first-line therapy for the treatment of patients with mCRPC; however, the clinical impact of the addition of BRIs to abiraterone acetate with prednisone in this disease setting is unknown. Objective To evaluate the association of the use of concomitant BRIs with overall survival (OS) and time to first SRE among patients with mCRPC and bone metastases receiving abiraterone acetate with prednisone as first-line therapy. Design, Setting, and Participants This retrospective cohort study collected data from 745 consecutive patients who began receiving abiraterone acetate with prednisone as first-line therapy for mCRPC with bone metastases between January 1, 2013, and December 31, 2016. Data were collected from 8 hospitals in Canada, Europe, and the US from June 15 to September 15, 2019. Exposures Patients were classified by receipt vs nonreceipt of concomitant BRIs and subclassified by volume of disease (high volume or low volume, using definitions from the Chemohormonal Therapy Vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer [CHAARTED] E3805 study) at the initiation of abiraterone acetate with prednisone therapy. Main Outcomes and Measures The primary end point was OS. The secondary end point was time to first SRE. The Kaplan-Meier method and Cox proportional hazards models were used. Results Of the 745 men (median age, 77.6 years [interquartile range, 68.1-83.6 years]; 699 White individuals [93.8%]) included in the analysis, 529 men (71.0%) received abiraterone acetate with prednisone alone (abiraterone acetate cohort), and 216 men (29.0%) received abiraterone acetate with prednisone plus BRIs (BRI cohort). A total of 420 men (56.4%) had high-volume disease, and 276 men (37.0%) had low-volume disease. The median follow-up was 23.5 months (95% CI, 19.8-24.9 months). Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone acetate cohort (31.8 vs 23.0 months; hazard ratio [HR], 0.65; 95% CI, 0.54-0.79; P, This cohort study examines whether the addition of bone resorption inhibitors is associated with improvements in overall survival and skeletal-related events among patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate with prednisone as first-line therapy.

Background and objectives Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA. Methods We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: “pure” SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC–NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing 10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared. Results Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as “pure” SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5–7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival. Conclusions The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival.

The combination of nab-paclitaxel and gemcitabine demonstrated greater efficacy than gemcitabine alone but resulted in higher rates of chemotherapy-induced peripheral neuropathy (CINP) in patients with metastatic pancreatic cancer (mPC). We aimed to evaluate the correlation between the development of treatment-related peripheral neuropathy and the efficacy of nab-P/Gem combination in these patients. mPC patients treated with nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 as a first-line therapy were included. Treatment-related adverse events, mainly peripheral neuropathy, were categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02. Efficacy outcomes, including overall survival (OS), progression-free survival (PSF), and disease control rate (DCR), were estimated by the Kaplan–Meier model. A total of 153 patients were analyzed, of these, 47 patients (30.7%) developed grade 1–2 neuropathy. PFS was 7 months (95% CI (6–7 months)) for patients with grade 1–2 neuropathy and 6 months (95% CI (5–6 months)) for patients without peripheral neuropathy (p = 0.42). Median OS was 13 months (95% CI (10–18 months)) and 10 months (95% CI (8–13 months)) in patients with and without peripheral neuropathy, respectively (p = 0.04). DCR was achieved by 83% of patients with grade 1–2 neuropathy and by 58% of patients without neuropathy (p = 0.03). In the multivariate analysis, grade 1–2 neuropathy was independently associated with OS (HR 0.65, 95% CI, 0.45–0.98, p = 0.03). nab-P/Gem represents an optimal first-line treatment for mPC patients. Among possible treatment-related adverse events, peripheral neuropathy is the most frequent, with different grades and incidence. Our study suggests that patients experiencing CINP may have a more favorable outcome, with a higher disease control rate and prolonged median survival compared to those without neuropathy.

Objectives: Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. Methods: Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three “CT report sections” depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). Results: In the final round, 23 out of 24 items obtained agreement (≥ 8) and consensus (≤ 2) and 19 out 24 items obtained a good stability (p > 0.05). Conclusions: The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making. Key Points: • Imaging represents the cornerstone for tailored treatment in GC patients. • CT-structured radiology report in GC patients is useful for multidisciplinary decision making.

Highlights • Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. • CD3+ TILs rate was not prognostic for patients with stage II colon cancer who had adjuvant therapy. • Low CD3+ TILs rate may be an additional risk factor for stage II colon cancer patients who did not have adjuvant therapy yet., Background High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not. Methods Patients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ. Results Of the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P

The second line treatment of hepatocellular carcinoma (HCC) has recently become an exciting area of interest since new emerging options have demonstrated survival benefits versus placebo. Unfortunately, predictive biomarkers are unavailable for these treatments. Ramucirumab, a monoclonal antibody against VEGFR-2, has demonstrated overall survival superiority against placebo as a second line therapy for patients with AFP > 400 ng/ml in the recent REACH-2 trial. This review will provide the current updated knowledge regarding the HCC cancerogenesis and angiogenic VEGF/VEGFR-2 pathways and the clinical development of ramucirumab in advanced HCC. This study will also critically assess the gaps in a previous negative phase III trial that tested other potentially useful treatments and suggest ways to modernise clinical trials and personalise therapy for advanced HCC.

Background Several progresses have been achieved for first-line chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with Gem-NabP and FOLFIRINOX extensively used as standard first line regimens. However, the best second-line chemotherapy choice after progression is still not completely defined. The aim of this study is to compare effectiveness and safety of two possible second-line therapeutic options, FOLFOX and FOLFIRI, after progression to Gem-NabP. Methods From January 2015 to December 2018, patients with metastatic PDAC, progressed to the first-line treatment with Gem-NabP, and treated with a fluoropyrimidine-based second-line chemotherapy were considered eligible for our retrospective analysis. Overall survival (OS) and progression free survival (PFS) were set as primary endpoints whereas, disease control rate (DCR) and the rate and severity of treatment-related AEs were secondary endpoints. Results Overall, 31 patients were treated with Gem-NabP in first-line regimen, 11 received second-line with FOLFOX and 20 with FOLFIRI after progression. Baseline demographic and clinic features were similar in the two groups excluding median age of 55.5 years (range: 50–73) and 68 years (range: 59–72) in FOLFIRI and FOLFOX groups, respectively (p=0.002). Median PFS was three months (95%CI: 3–4), with no significative difference between the two groups. Median OS was eight months (95%CI: 5–10) and was significantly higher in the FOLFIRI group compared with the FOLFOX group, nine months (95%CI: 7–17) vs five months (95%CI: 2–10; p

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1-2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1-2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42-74), and the median overall survival was 117 days (95% CI: 94-154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.

The aim of this retrospective study is to evaluate the activity and safety of a steroidal switch from prednisone to dexamethasone in patients with advanced, heavily pre-treated, castration-resistant prostate cancer (CRPC) who progressed on abiraterone acetate. Treatment consisted of oral daily abiraterone plus dexamethasone (0.5 mg once daily) administered until disease progression or unacceptable toxicity. Thirty-six patients were evaluated: all men underwent a prior treatment with enzalutamide. A PSA decrease ≥50% was observed in 11% of patients; median progression-free survival was 10.8 weeks (95% CI: 9.2–16), and median survival was 17.6 weeks (95% CI: 15.8–28.8). Better efficacy and survival were observed in the subgroup of patients treated with abiraterone acetate prior for a period >3 months; treatment was well tolerated, and no grade 3–4 toxicities were observed. Our findings did not suggest the use of steroid switch in all CRPC who were heavily pre-treated. However, the switch could be an option for patients who responded well to prior abiraterone acetate treatment.

Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous reports suggested that circulating tumor cell (CTC) AR-V7 detection is a poor prognostic indicator for the clinical efficacy of secondary hormone therapies, we conducted a prospective multicenter validation study.PROPHECY ( ClinicalTrials.gov identifier: NCT02269982) is a multicenter, prospective-blinded study of men with high-risk mCRPC starting abiraterone acetate or enzalutamide treatment. The primary objective was to validate the prognostic significance of baseline CTC AR-V7 on the basis of radiographic or clinical progression free-survival (PFS) by using the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay. Overall survival (OS) and prostate-specific antigen responses were secondary end points.We enrolled 118 men with mCRPC who were starting abiraterone or enzalutamide treatment. AR-V7 detection by both the Johns Hopkins and Epic AR-V7 assays was independently associated with shorter PFS (hazard ratio, 1.9 [95% CI, 1.1 to 3.3;Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, and such men with mCRPC should be offered alternative treatments.

PURPOSE: The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer.METHODS: This is a retrospective study of patients treated with ramucirumab plus paclitaxel.RESULTS: Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events.CONCLUSION: Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.

Visceral metastasis is widely considered a prognostic factor for overall survival of men with metastatic castration-sensitive prostate cancer (mCSPC) and has been historically managed with androgen deprivation therapy (ADT). More recently, this therapeutic scenario has been enriched by the possibility to integrate ADT with chemotherapy or novel androgen-signaling-targeted inhibitors. In order to define the effect of chemotherapy/androgen-signaling-targeted inhibitors plus ADT, we performed a pooled analysis on patients with mCSPC and visceral metastases, revealing that survival was significantly improved in patients without visceral metastasis (hazard ratio, 0.64; 95% confidence interval, 0.56-0.74; P .01) compared to men with visceral metastases (hazard ratio, 0.68; 95% confidence interval, 0.51-0.91; P .01). Although several limitations do not allow us to draw definitive conclusions, our analysis confirms the efficacy of chemotherapy/androgen-signaling-targeted inhibitors in combination with ADT in mCSPC with visceral metastases as well. In the absence of specific randomized controlled trials, symptoms, toxicity, cost, patient preference, and clinical experience should guide the decision to add chemotherapy or androgen receptor-targeted therapy to ADT in patients with visceral metastases from mCSPC.

We report the case of a heavily pretreated male subject affected by left funiculus liposarcoma and successfully treated with eribulin mesylate. After three surgical interventions, radiotherapy on the lesion of the penile bulb for satellite nodules and an epirubicin + ifosfamide chemotherapy treatment for six cycles, eribulin was administered at the dose of 1.1 mg/m2 on days 1 and 8, every 3 weeks for a total of nine cycles. A significant reduction of the lesions was achieved after four cycles of therapy, with a good profile of tolerability.

Objectives The aim of this study was to evaluate the efficacy and safety of the combination Gemcitabine (Gem) plus nab-Paclitaxel (NabP) (Gem/NabP), followed by maintenance Gem in older adults with locally advanced or metastatic pancreatic cancer (PC). Materials and methods In this prospective observational study, the induction chemotherapy consisted of NabP 125 mg/m2 followed by Gem 1000 mg/m2 on days 1, 8, and 15 of a 4-week cycle. After a maximum of 3 cycles, patients without evidence of progressive disease (PD) were administered Gem 1000 mg/m2 weekly for 3 of 4 weeks as maintenance therapy until documentation of PD or unacceptable toxicity. The primary endpoint was six-month disease-control rate (DCR). Results Overall, 36 patients >70 years with metastatic or locally advanced PC were enrolled at participating Institutions. After completion of Gem/NabP, 18 (50%) patients achieved partial response, 13 (36%) had stable disease, and 5 (14%) had PD. Thirty-one patients (86%) received Gem monotherapy as maintenance treatment for a median of 3 cycles (range, 2–9 cycles). Six-month DCR was 61% (95% CI, 45–77), median PFS was 6.4 months (95% CI, 5.4–8.3), and median OS was 13.4 months (95% CI, 11.1–16.7). During Gem/NabP regimen, the most common grade 3 toxicity included neutropenia (22%), anemia (19%) and thrombocytopenia (8%). Grade 3 neuropathy was not observed. During Gem maintenance therapy, grade 3 hematological toxicity was described in 6 patients (19%). Conclusion Gem/NabP followed by maintenance Gem appears to be safe and effective for older patients with locally advanced or metastatic PC.

The aim of this retrospective study was to detail the main clinicopathological characteristics of advanced cancer patients exhibiting hyperprogressive disease (HPD) during immune checkpoint inhibitor (ICI) nivolumab as second- or third-line treatment. A cohort of patients starting second or third-line nivolumab for advanced cancer from 2016 to 2018 was identified from our institution IRB approved and prospectively collected registry. HPD was defined as at least two-fold increase in the tumor growth rate (TGR) during immunotherapy compared to TGR during the preimmunotherapy period. Overall, 47 patients were eligible for this analysis. HPD was observed in three patients (6%) with metastatic lung adenocarcinoma, metastatic urothelial transitional carcinoma, and metastatic hepatocellular carcinoma, respectively. These three patients showed a rapid clinical deterioration and survived less than 3.5 months from immunotherapy onset. Their chief preimmunotherapy characteristics were: age75 years, ≥2 metastatic sites, programmed death-ligand 150%, neutrophil-to-lymphocyte ratio3, and elevated lactate dehydrogenase. The results of the current study seem to reinforce the hypothesis that in some cases immunotherapy promotes a dramatic increase of TGR and may suggest possible clinical predictors of HPD during nivolumab.

BRAFV600-mutated colorectal cancer (CRC) accounts for 8% to 12% of all CRC diagnoses. These tumors are often associated with specific patient features, including right-sided primary tumor location, peritoneal and non-regional lymph node involvement, and poor prognosis. In approximately 30% of cases, a simultaneous mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) phenotype is identified. The prognostic impact of the BRAF mutation appears to be less marked in patients with MSI-H CRC than in patients with microsatellite stable (MSS) tumor. The treatment of BRAFV600-mutated CRC is still a challenge for the clinicians, mainly due to the poor survival outcomes obtained with traditional chemotherapy regimens. In recent years, two novel treatment strategies have offered remarkable changes in the treatment of this specific patient subgroup. The first approach has included targeted therapies directed against BRAF and MEK, with support from the epidermal growth factor receptor (EGFR) blockade. The second approach has included immunotherapeutic agents that have been shown to be particularly promising for patients with simultaneous dMMR/MSI-H phenotype. Here we review the clinical trials that specifically enrolled patients with BRAF-mutated CRC, from the phase I/II studies to the phase III trial BEACON CRC. We also examine the future directions towards a molecularly guided therapy for patients with BRAF-mutated CRC and the crucial role of a molecularly and clinically based algorithm in order to offer the best choice of treatment for these patients.

The aim of this study was to evaluate the efficacy and safety of modified docetaxel, oxaliplatin, capecitabine (DOC) combination chemotherapy, followed by maintenance capecitabine as first-line therapy for patients with metastatic gastric or gastroesophageal junction (GEJ) cancer. Treatment consisted of docetaxel 35 mg/m (days 1-8), l-OHP 85 mg/m (day 1), and capecitabine 750 mg/m twice daily (days 1-14), every 3 weeks. After six cycles of DOC, patients who did not progress received maintenance treatment with three-weekly capecitabine 1000 mg/m twice daily (days 1-14), until disease progression or unacceptable toxicity. Six-month disease control rate (DCR) was the primary endpoint and overall survival (OS), progression-free survival (PFS) and safety were the secondary endpoints. The Kaplan-Meier method was applied to estimate OS and PFS. Between July 2014 and September 2017, 37 patients with metastatic gastric or GEJ cancer were enrolled at our institution. Upon completion of the DOC regimen, 35 patients (94.5%) received capecitabine as maintenance chemotherapy for a median of 7 cycles (range, 3-14 cycles). The six-month DCR was 83.7% [95% confidence interval (CI), 71.8-95.6%], median PFS was 8.2 months (95% CI, 6.3-9.8 months), and median OS was 14.4 months (95% CI, 11.7-18.6 months). During DOC chemotherapy, the most common grade 3-4 adverse events were neutropenia (29.7%), anemia (10.8%), and diarrhea (10.8%). During maintenance treatment, toxicity was sporadic and mainly of grade 1-2. Modified DOC followed by capecitabine as maintenance chemotherapy seems to be an active and well tolerated first-line treatment strategy for patients with metastatic gastric and GEJ cancer.

The aim of this report is to investigate the activity of ramucirumab in combination with paclitaxel in patients with metastatic gastric cancer (GC) and lung metastases. We retrospectively reviewed clinical data from patients with GC treated in second line with ramucirumab and paclitaxel according to the presence or not of lung metastases. Thirty-one patients were eligible. Five (16.1%) patients had lung metastases. The median progression-free survival was 156 days in patients without lung metastases compared with 54 days in patients with lung metastases. The median survival also showed a trend in favour of patients without lung metastases. Despite the small number of patients and the retrospective nature of the data, our analysis showed relatively poor efficacy of ramucirumab plus paclitaxel as a second-line treatment in patients with lung metastases from GC. Further studies are required to evaluate novel treatments in this subset of patients.

Background Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31). Materials and methods Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC. Results A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors. Conclusions A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18&ndash, 1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2&ndash, 65.8) in arm A and 40.3% (95% CI: 28.9&ndash, 55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3&ndash, 72.2) and 53.9% (95% CI: 35.5&ndash, 69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.

Metastatic gastric cancer is still a disease with a poor prognosis. Recently, different novel agents (e.g., apatinib, nivolumab, TAS-102) have demonstrated a survival advantage compared with placebo for patients with heavily pretreated metastatic gastric cancer. Although the possible availability of active agents may be a desirable option in a very poor therapeutic scenario, clinical data from the recent studies with these drugs raise yet controversial issues. The purpose of this review is to briefly summarize the results of these novel drugs focusing on the limitations that bring some shadows on their positive therapeutic results.

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.

CA 19-9 is a marker correlated to the clinical evolution of pancreatic adenocarcinoma. To analyze the clinical value of pre- and postoperative CA 19-9 serum levels in stage I and II pancreatic cancer. We analyzed 61 patients resected for pancreatic cancer. Patients were evaluated about the pre-operative CA 19-9 values and then divided into 3 groups: high, high-low and low, on the basis of pre- and postoperative CA 19-9 levels. The correlations between these groups and age, sex, pT, pN, tumor stage, jaundice, surgical radicality, tumor size, number of harvested and positive lymph nodes, grading, overall and major morbidities and post-operative mortality together with survival rates were analyzed. Higher values of pre-operative CA 19-9 were significantly correlated to the presence of jaundice, high pT, pN, stage and higher number of metastatic lymph nodes. In 49 patients (80.3 %) an R0 resection was performed. Five-year overall survival (OS) and disease free survival (DFS) were significantly better in patients with high levels of pre-operative CA 19-9, even in R0 cases. After stratification, 30 patients were included in the high group, 13 in the high-low group and 18 in the low group. A statistically significant correlation was found between the CA 19-9 groups and the lymph nodal positivity, not between CA 19-9 and pT. OS and DFS were significantly better in low group patients. We confirm the prognostic value of preoperative CA 19-9 serum levels. We do not support early postoperative modifications of CA19-9 as an adjunctive prognostic variable.

Both abiraterone acetate (AA) and cabazitaxel (Cbz) have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel (D). Although no standard sequencing has been established as yet, Cbz has recently been proven to be active after AA. However, to date, few data are available on its safety in this setting. Therefore, the primary endpoint of this study was to investigate Cbz tolerability in mCRPC patients treated previously with D and AA. From April 2011 to the present, 43 mCRPC patients received AA after D at our institution. Of these, 22 patients were subsequently treated with Cbz and were evaluable for toxicity in the present retrospective study. Cbz was administered at a dose of 25 mg/m plus 10 mg oral prednisone every 3 weeks. Adverse events (AEs) were reported using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. Despite the advanced stage of disease and frailty of our study population, there were no unexpected side effects. The most common AEs were hematologic. Neutropenia was observed in nine (40.9%) patients and of grade≥3 in six (27.2%). No febrile neutropenia occurred. The most common nonhematologic AEs were diarrhea and asthenia, reported in eight (36.3%) and in five (22.7%) patients, respectively. In this setting, Cbz toxicity seems to be manageable and comparable with second-line Cbz. Therefore, our results seem to support the safety of Cbz as a third-line treatment for mCRPC patients.

New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include cabaziataxel (Cbz), abiraterone acetate (AA) and enzalutamide (E). In this review, the results of clinical studies in which one of these drugs is included as the third line of treatment are discussed. Our review suggests that AA and E have limited activity, while Cbz seems to retain its efficacy. Prospective studies that further examine sequential treatments are warranted.

Aim: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. Patients & methods: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1–14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. Results: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. Conclusion: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

The primary objective of this study was to determine the activity and safety of 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine in the first-line treatment of advanced biliary tract cancer. Treatment consisted of intravenous oxaliplatin 100 mg/m every 3 weeks combined with intravenous gemcitabine 1000 mg/m on days 1 and 8 and oral capecitabine 1500 mg/m 14 days on 21 in two divided doses. Treatment was administered until progressive disease, unacceptable toxicity, or patient refusal. Thirty-seven patients were enrolled: eight patients had Eastern Cooperative Oncology Group 2 performance status at presentation. The overall response rate was 35.1% [95% confidence interval (CI): 20.2-52.5%] and the disease control rate was 72.9%. The median progression-free survival was 9.4 months (95% CI: 4.1-12.2 months) and the median overall survival was 13.8 months (95% CI: 7.7-17.1 months). There were no grade 4 toxicities. Grade 3 neutropenia occurred in 13.5% of patients and grade 3 thrombocytopenia in 10.8%. The present study suggests that 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine is an active and well-tolerated chemotherapy regimen in the first-line treatment of metastatic biliary tract cancer.

Background In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. Patients and Methods Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. Results Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. Conclusion Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS.