Introduction
The 21-gene Oncotype DX Breast Recurrence Score® test, (Genomic Health, Redwood City CA) has not been formally evaluated in an older cohort with estrogen receptor (ER)-positive breast ...cancer (BC) in term of physicians’ treatment decisions. We determine the utility of Recurrence Score® (RS) result on adjuvant therapy prescription in elderly patients with resected early BC.
Material and methods
PONDx was a multicenter, prospective, observational study, and which investigated the real-life use of the Oncotype DX® test by physicians treating early BC patients in clinical practice.
Results
Data from the elderly extracted from 1724 BC patients who underwent Oncotype DX testing were available from 27 reference centers located in 6 regions of Italy (Lombardia, Lazio, Emilia Romagna, Campania, Abruzzo, and Marche). A total of 230 patients (13% of the total population) aged > 70 years were analyzed. The study primarily evaluated the impact of the Oncotype DX test on adjuvant treatment decisions. Physicians chosen chemotherapy plus endocrine therapy in 36% of elderly patients and 46% of those 50–70 years before the Oncotype DX test. After knowing the RS data, these rates fell to 23 and 33% (38 and 28% relative reduction, respectively).
Conclusions
21-gene test may be helpful even in a relatively low-risk group as elderly patients and may avoid the toxicity of adjuvant chemotherapy in a significant amount. If the Oncotype DX test is currently adopted on a large scale among the elderly and may impact the general prognosis of elderly BC patients, it is challenging and still unproven.
A proliferative marker, expressed as the percentage of cells in a cell cycle, has been developed and used as a discriminant of more aggressive malignant phenotypes in early breast cancer (BC). The ...marker is usually expressed by the immunohistochemical staining of the cell cycle antigen Ki-67. It has not, however, yet been definitely evaluated, due to methodological concerns, which specific Ki-67 cut-off provide the strongest prognostic information in resected BC. We conducted a meta-analysis to explore the prognostic value of different cut-off levels of Ki-67 in terms of overall survival (OS) and disease-free survival (DFS) in early BC. The databases of PubMed, the ISI Web of Science, EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, and CINHAL were used to identify the relevant literature. Data from studies reporting a hazard ratio (HR) and a 95 % confidence interval (CI) calculated as a multivariate analysis were pooled in a meta-analysis, with metaregression used to test for trends in predefined subgroups. All the statistical tests were 2-sided. Forty-one studies encompassing 64,196 BC patients were included in the analysis. Overall,
n
= 25 studies were available for the OS analysis. The pooled HR for high versus low Ki-67 was 1.57 (95 % CI 1.33–1.87,
P
< 0.00001). Twenty-nine studies were available for the DFS analysis. The pooled HR for high versus low Ki-67 was 1.50 (95 % CI 1.34–1.69,
P
< 0.00001). When a cut-off of Ki-67 staining ≥ 25 % was used, the pooled HR for OS was 2.05 (95 % CI 1.66–2.53,
P
< 0.00001), which was significantly different to studies where the cut-offs chosen were <25 %. In ER+ tumors, the HR for high versus low Ki-67 was similar and significant (HR = 1.51, 95 % CI 1.25–1.81,
P
< 0.0001). We conclude that Ki-67 has an independent prognostic value in terms of OS in BC patients. The Ki-67 threshold with the greatest prognostic significance is as yet unknown, but a cut-off >25 % is associated with a greater risk of death compared with lower expression rates.
Abstract Introduction The prognosis of advanced/recurrent cervical cancer patients is generally poor with 1-year survival ranging between 15 and 20%. Cisplatin (CDDP) based treatments are considered ...the most effective regimens; unfortunately toxicity is an issue in a population in which the treatment remains palliative in the finality. Carboplatin (CBDCA), with its more favorable non toxicity profile and the convenience of outpatient administration, may be a suitable alternative to CDDP in combination regimens. Materials and methods We performed a systematic review of the literature comparing CDDP and CBDCA based chemotherapy for advanced cervical cancer (recurrent, persistent or metastatic disease). Only studies that met the following criteria were considered for the present review: 1) patients treated with CDDP/paclitaxel or CBDCA/paclitaxel combinations as first line chemotherapy for metastatic disease; 2) one or more of the following data available: overall response rate (RR), progression free survival (PFS) or time to progression (TTP), overall survival (OS); 3) single-arm retrospective or prospective study; and 4) at least 20 patients enrolled. Results 17 eligible studies comprehensive of 1181 patients were included in the final analysis. The objective RR was 48.5% for CBDCA and 49.3% for CDDP-based chemotherapy. Median PFS for CDDP and CBDCA-based treatments was 6.9 months and 5 months respectively (p = 0.03); the corresponding figures for median OS were 12.87 and 10 months respectively (p = 0.17). Discussion Our study indicates that CBDCA may represent an attractive and valid alternative to the more toxic and equally effective CDDP in the treatment of advanced or recurrent cervical cancer.
Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. ...Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality.
We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate.
A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions.
The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.
While surgery is the preferred option for isolated, operable liver metastases from colorectal cancer (CRC), ablative techniques are endorsed for medically or technically inoperable lesions. ...Stereotactic body radiotherapy (SBRT) is an alternative ablative local therapy that delivers high RT doses in a few fractions to the cancer, sparing surrounding critical tissue. We have performed a systematic review of published trials to evaluate the efficacy of SBRT as a primary modality therapy for CRC liver oligometastases.
We searched the Cochrane Central Register of Controlled Trials, Pubmed, and EMBASE for publications regarding SBRT for CRC liver metastases. Overall survival (OS: median, 1- and 2-year OS %) was the primary endpoint, and median PFS and one- and two-year local control (LC) were the secondary endpoints. A random-effect model pooled-analysis was performed to calculate the aggregated OS rates at 1 and 2 years as well as the one- and two-year LC.
A total of 18 studies, encompassing 656 patients, were included in the analysis. The pooled one- and two-year OS were 67.18% (95% CI, 42.1–92.2) and 56.5% (95% CI, 36.7–76.2), respectively. Median PFS and OS were 11.5 and 31.5 months. The pooled one-year LC was 67% (95% CI, 43.8–90.2), while the pooled two-year LC was 59.3% (95% CI, 37.2–81.5). Correlation analysis revealed a moderate/poor linear relationship between the SBRT (BED10) dose and LC (p = 0.001, R = 0.47)/OS (p = 0.001, R = 0.29) at 2 years. Mild-moderate and severe liver toxicity were 30.7% and 8.7%.
SBRT for liver oligometastases is an effective option for patients with advanced CRC, with encouraging local control and survival. However, a definitive validation in large randomised studies is required, due to the retrospective or non-randomised nature of the included studies and the limitations of series with different doses/schedules of treatment.
Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil ...(5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26-0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45-1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role.
Introduction
Immune checkpoint inhibitors (ICIs) represent a cornerstone for the treatment of many advanced tumors. When 65 is considered as a cut-off age, ICIs are equally effective in younger and ...older patients. However, the efficacy of ICIs among patients aged ≥ 75 remains uncertain, since those patients were generally under-represented in clinical trials. We performed a pooled analysis of major randomized trials including data of outcome in very older population.
Material and methods
We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from the inception of each database to November 22th, 2019. We only included (1) randomized studies comparing ICIs alone or in combinations with no ICIs, (2) studies reporting data of patients older than 75 years, (3) studies for solid tumors, and (4) studies with HR and 95% confidence interval (CI) available for OS based on 75 years as cut-off age. All data were expressed as the combination of HR and 95% CI, and
P
< 0.05 was considered to be statistically significant.
Results
A total of
n
= 8 publications for a total of
n
= 12 randomized studies were aggregated in the quantitative analysis. Overall, the pooled analysis showed a borderline significant OS benefit for ICIs compared to no ICIs arms (HR = 0.84, 95% CI 0.7–1;
P
= 0.05) in particular in first-line trials with HR = 0.77 (95%CI 0.61–0.96;
P
= 0.02).
Conclusion
We conclude that ICIs may be offered in patients older than 75 years, providing a complete geriatric and clinical evaluation is performed in all subjects before starting therapy.
Objective
The preferred neoadjuvant treatment for gastroesophageal junction (GEJ) adenocarcinoma is still matter of debate. We conducted a meta-analysis to assess the different impact of neoadjuvant ...combined chemotherapy and radiotherapy (CTRT) versus chemotherapy (CT) alone.
Methods
A comprehensive search was performed in EMBASE, PubMed, and Cochrane Library databases from inception to 30th June 2018. Studies comparing survival of patients who underwent CTRT or CT alone before surgery for GEJ adenocarcinoma were included. Hazard ratio (HR) for overall survival (OS) was extracted, and a random-effects model was used for pooled analysis. Median OS, 5-year OS, complete pathologic response (pCR), locoregional and distant failure rates were also calculated.
Results
22 studies including 18,260 patients were considered for the final analysis. The pooled results demonstrated that combined CTRT do not significantly reduce the risk of death (HR 0.95, 95% CI 0.84–1.07;
P
= 0.41) but has a positive impact on the risk of relapse (HR 0.85, 95% CI 0.75–0.97;
P
= 0.01) compared to CT alone. Addition of RT to CT alone significantly increased the odds of pCR by 2.8 (95% CI 2.27–3.47;
P
< 0.001) and reduced the risk of locoregional failure (OR 0.6, 95% CI 0.39–0.91;
P
= 0.01) but not the risk of distant metastases (OR 0.81, 95% CI 0.59–1.11;
P
= 0.19).
Conclusions
In this systematic review and meta-analysis comparing neoadjuvant CTRT with CT for adenocarcinoma of GEJ, we found no difference in terms of median OS, despite a higher pCR rate and a reduced risk of locoregional recurrences for the combined approach. Further studies, preferably large randomized clinical trials, are needed to confirm these results.
Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We ...performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies,
= 16; patients,
= 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24-1.91;
= 0.01 and HR = 1.34, 95% CI: 1.02-1.76;
= 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41-4.43;
< 0.01) or brain metastases (HR = 1.51, 95% CI 1.22-1.87;
< 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
Background
Current guidelines support the use of adjuvant chemotherapy (CT) following neoadjuvant chemoradiotherapy (CTRT) and surgery to treat rectal cancer, although clinical trials have provided ...little evidence that it is effective. We performed a systematic review of published studies to assess whether adjuvant CT improves outcome after neoadjuvant therapy and radical surgery in cases of rectal cancer.
Materials and methods
We conducted an electronic database search for randomized and nonrandomized studies in PubMed, EMBASE, Web of Science, Scopus and the Cochrane Register of Controlled Trials. We then carried out a meta-analysis by using the fixed- or random-effects models. The primary endpoint was 5-year overall survival (OS) reported as odds ratios (ORs) and 95 % confidence intervals (CIs).
Results
Two randomized controlled trials (RCTs), one pooled analysis of five RCTs and 10 retrospective studies that included a total of 5,457 patients matched our selection criteria. Meta-analysis showed that for rectal cancer patients treated with surgery and neoadjuvant CTRT, adjuvant CT improves 5-year OS (OR, 0.64; 95 % CI, 0.46–0.88;
p
= 0.006) and 5-year disease-free survival (DFS) (OR, 0.71; 95 % CI, 0.6–0.83;
p
< 0.0001). The 5-year OS benefit was significantly larger in downstaged patients and in retrospective series. A better DFS was instead noted in all studies due to a reduced risk of local relapse.
Conclusions
Amongst rectal cancer patients treated with neoadjuvant therapy and surgery, adjuvant CT seems to improve the 5-year DFS and OS rates and may be discussed with patients. However, the benefit derives mainly from retrospective evidence.
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