Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials.

BACKGROUND & AIMS: The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This meta-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment. METHODS: Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods. RESULTS: Six studies met the inclusion criteria. Globally, 5121 patients were included in this meta-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56-0.81, p < 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78-0.92, p = 0.001). There is no statistical increase in adverse events. CONCLUSIONS: Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.

A Systematic Review and a Meta-analysis of Randomized Controlled Trials' Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

PURPOSE OF REVIEW: Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes. RECENT FINDINGS: Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

BACKGROUND: Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). MATERIALS AND METHODS: We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. RESULTS: One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. CONCLUSION: We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. IMPLICATIONS FOR PRACTICE: This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Psychological impact of Covid-19 pandemic on oncological patients: A survey in Northern Italy.

The psychological impact of the Covid 19 pandemic on cancer patients, a population at higher risk of fatal consequences if infected, has been only rarely evaluated. This study was conducted at the Departments of Oncology of four hospitals located in the Verona area in Italy to investigate the psychological consequences of the pandemic on cancer patients under active anticancer treatments. A 13-item ad hoc questionnaire to evaluate the psychological status of patients before and during the pandemic was administered to 474 consecutive subjects in the time frame between April 27th and June 7th 2020. Among the 13 questions, 7 were considered appropriate to elaborate an Emotional Vulnerability Index (EVI) that allows to separate the population in two groups (low versus high emotional vulnerability) according to observed median values. During the emergency period, the feeling of high vulnerability was found in 246 patients (53%) and was significantly associated with the following clinical variables: female gender, being under chemotherapy treatment, age ≤ 65 years. Compared to the pre-pandemic phase, the feeling of vulnerability was increased in 41 patients (9%), remained stably high in 196 (42%) and, surprisingly, was reduced in 10 patients (2%). Overall, in a population characterized by an high level of emotional vulnerability the pandemic had a marginal impact and only a small proportion of patients reported an increase of their emotional vulnerability.

The pharmacological costs of complete liver resections in unselected advanced colorectal cancer patients: a review of published Phase II and III trials.

The pharmacological costs of regimens used as front-line therapy in advanced colorectal cancer patients and their impact on the liver resection rates have not been considered. In this paper, we made a review of published randomized Phase II and III trials that reported the liver resection rates following upfront chemotherapy and linked this outcome to the pharmacological costs of drugs used. The costs are calculated based on the price at Pharmacy of our Hospital in Legnago (Italy), and as a measure of activity, we used the number of patients needed to treat to get one complete liver resection. Number needed to treat is highly variable among the different trials according to patient's characteristics, tumor biology and the efficacy of chemotherapy administered. The range of activity is greatly amplified when the costs are compared.

Carboplatin-containing regimens as front-line treatment for advanced non-small-cell lung cancer in two groups of elderly.

OBJECTIVES: We evaluated the impact of a carboplatin-based doublet in two groups of elderly patients with advanced non-small cell lung cancers (NSCLC). MATERIALS AND METHODS: A retrospective analysis of all consecutive elderly patients (≧70 year old) with advanced NSCLC who received a carboplatin-based doublet as front-line therapy at our medical oncology unit was performed. RESULTS: In the study, 57 consecutive elderly patients with advanced NSCLC were included. Carboplatin was combined with vinorelbine in 41 patients (71·9%) and with gemcitabine in 16 patients (28·1%). Overall, a total of 227 cycles were administered to 57 patients - 142 cycles were administered to patients in group 1 and 85 cycles were given to patients in group 2 - median number of administered cycles per patient was 4 (range 1-6). Of the patients, 35 (62%, group 1) were 'young-old' (70-74-year old) and 20 (38%, group 2) were 'old-old' (75-82-year old). Toxicity was mild in both subgroups (grade 3-4 neutropenia in 17·1% of group 1 and in 9·1% of group 2). At the univariate analysis, the median overall survival (OS) was 10·07 months (P = 0·789, 95% CI: 8·49-11·64), 10·1 months in group 1 and 9·8 months in group 2. CONCLUSIONS: This evaluation shows the safety and efficacy of a carboplatin-based doublet given as first-line chemotherapy in elderly advanced NSCLC patients. The combination with vinorelbine or gemcitabine is associated with a very good toxicity profile that does not seem to have a detrimental effect on efficacy.

Platinum doublets as first-line treatment for elderly patients with advanced non-small cell lung cancer.

AIMS AND BACKGROUND: More than 50% of patients with advanced non-small cell lung cancer are diagnosed in the elderly. Few prospective clinical data with cisplatin-based chemotherapy are available, and some authors have suggested that a non-platinum single agent should be the preferred form of cure in these patients. The aim of the study was to evaluate the efficacy and safety of first-line chemotherapy based on platinums (carboplatin or cisplatin) plus a third generation compound (vinorelbine or gemcitabine) in elderly patients with advanced non-small cell lung cancer in daily clinical practice. METHODS: A retrospective analysis of consecutive elderly (≥70 years of age) patients with advanced non-small cell lung cancer treated at our Medical Oncology Unit from February 2005 to September 2011 was performed. RESULTS: A total of 249 cycles of chemotherapy was administered to 62 patients (median age, 72 years; range, 70-81) presenting a median Charlson comorbidity index of 1 and a good ECOG PS (0-1, 52 patients; 2, 10 patients). The median number of cycles/patient was 4, and all 62 patients received a platinum-based doublet as first-line chemotherapy: 57 with carboplatin (92%) and 5 with cisplatin (8%). As best response to the treatment, 19 (31%) partial responses and 20 (32%) stable diseases were observed. Median overall survival was 9.8 months. Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect in 19 administered cycles (8%). CONCLUSIONS: Advanced non-small cell lung cancer in elderly patients can be safely treated with a platinum-based doublet. Observed toxicity is manageable, and overall survival is in keeping with data from the literature.

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience.

The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991-7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m(2) and cisplatin 25 mg/m(2) on day 1, followed by 5-FU 180 mg/m(2)/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week's rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40-78 years). The median number of cycles per patient was 4 (range 2-6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16-51], a median time to progression of 6.4 months (95% CI 5.4-7.4), and a median overall survival of 10.7 months (95% CI 6.6-14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III-IV toxicities observed in >5% of patients were anemia and mucositis.

Informal caregiving burden in advanced non-small cell lung cancer: the HABIT study.

INTRODUCTION: This study's aim was to assess economic data regarding the home assistance burden for advanced non-small cell lung cancer (NSCLC) patients in Italy. PATIENTS AND METHODS: One hundred four NSCLC patients in second-line chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian oncology departments and were observed for 3 months. The main caregiver's workload was assessed monthly by a task scale; other caregivers' activities were also registered. Eastern Cooperative Oncology Group performance status was assessed by physicians, and patients completed the Lung Cancer Symptoms (LCS) subscale. Formal caregiving time was valued according to market prices; informal caregiving hours were valued using the wage rate for an equivalent service. Covariance analysis was performed to check for influential factors in assistance costs. RESULTS: The mean age of the total sample was 65.5 years, and prevalence of males was over 80%. In over 70% of cases, the principal caregiver was patient's spouse, living with the patient and not working. Principal caregiver support was the main cost item: 2.368 euros in 2LC and 2.805 euros in ST, representing 74% of total trimonthly assistance costs. Regression analysis showed a positive correlation between the severity of symptoms and the costs of assistance. The caregiving burden was higher in patients with bone and/or cerebral metastases; other metastasis sites seemed to have no impact on assistance costs. CONCLUSION: Considering quality of life as the ultimate health outcome, clinicians are challenged to contribute to a research and policy agenda that holds burden of care in due consideration.

Multiple-target chemotherapy (LV-modulated 5-FU bolus and continuous infusion, oxaliplatin, CPT- 11) in advanced 5-FU-refractory colorectal cancer: MTD definition and efficacy evaluation. A phase I-II study.

AIMS AND BACKGROUND: To identify the maximum tolerated doses and to define the activity of a regimen incorporating leucovorin (LV)-modulated 5-fluorouracil (5-FU) bolus and continuous infusion, oxaliplatin (I-OHP) and irinotecan (CPT-11) in patients with advanced, 5-FU-refractory colorectal cancer (CRC). PATIENTS AND METHODS: Starting doses: LV 100 mg/m2 as a 2-hour infusion followed by 5-FU 300 mg/m2 bolus administration followed by 5-FU 500 mg/m2 as a 22-hour infusion on days 1 and 2; I-OHP 65 mg/m2 as a 2-hour infusion concomitantly with LV on day 1; CPT-11 90 mg/m2 concomitantly with LV on day 2. Planned cycle interval: 2 weeks. RESULTS: Two hundred twenty-six cycles were administered to 27 patients. Recommended doses were 5-FU bolus 300 mg/m2, 5-FU protracted infusion 500 mg/m2, I-OHP 75 mg/m2, and CPT-11 150 mg/m2. Among 25 patients evaluable for response we observed 13 disease stabilizations (52%; 95% CI: 33-71%), 6 instances of disease progression and 6 responses (24%; 95% CI: 7-41%). Median time to progression and overall survival were 24 and 60 weeks, respectively. A cycle delay > 3 days was observed in 134/199 cycles (67%). CONCLUSIONS: This study confirms the feasibility of triplet chemotherapy in patients with advanced 5-FU-refractory CRC.

Late events and clinical prognostic factors in stage I non small cell lung cancer.

UNLABELLED: Two hundred and forty six consecutive patients with pathological T1-2 N0 M0 non-small cell lung cancer were reviewed. Median follow-up was 79 months (range 3-144). So far, 110 patients have relapsed (45.6%). Actuarial median time to recurrence was 26 months in the 45 patients with thoracic relapses versus 12 months of the 65 metastatic (P<0.001). Disease-free survival (DFS) rates at 5 and 10-year were 62 and 49%, respectively. Fifteen percent of the patients (20) disease-free at 5 years relapsed in the following years; of them, 40% (8) underwent new surgery. Extrapulmonary malignancies other than lung cancer occurred in 27 patients (11.2%), mostly (21) after the diagnosis of lung cancer; in this subset median time to occurrence was 52 months (range 8-105) with a rate of occurrence remaining constant over the years after operation. Univariate and multivariate analysis demonstrated that large cell histology, lower performance status (PS) and presence of symptoms were unfavourable prognostic factors both for DFS and survival. IN CONCLUSION: this study found a non-negligible proportion of late events and identified some prognostic factors (PS, presence of symptoms and large cell histology) using information obtained from routine data.

Results of surgical treatment of adenocarcinoma of the gastric cardia.

BACKGROUND: Comparison among different studies regarding adenocarcinoma of the cardia has been difficult since the Siewert classification was introduced. This study analyzed the experience of a single institution in the treatment of gastric cardia cancer with the aim of assessing principal prognostic factors and long-term outcome. METHODS: The results of 96 patients who underwent resection with curative intent for gastric cardia cancer at the First Division of General Surgery, University of Verona, from January 1988 to February 2000, were analyzed statistically with special reference to Siewert type. RESULTS: Despite a high number of curative resections (85.4%), the 5-year survival rate was poor (24%) for all Siewert types (p = 0.8), and for early tumors (51%) also. Chance of cure was limited to pN0 and pN1 patients. Multivariate analysis showed that microscopic or macroscopic residual tumor and pN-positive categories had a significantly higher risk of death (risk ratio, 2.18 and 2.68, respectively) and the pN2 and pN3 category had the most negative prognostic factor (risk ratio, 7.6). CONCLUSIONS: The long-term prognosis for gastric cardia cancer remains poor and is independent of Siewert type, with cure limited to pN0 and pN1 patients.