•The clinical course of advanced cancer for many patients with bone metastases can be transformed through optimum multidisciplinary management.•Bone-targeted agents significantly reduce skeletal ...morbidity in patients with bone metastases across tumour types and should be part of standard treatment.•Treatment-induced bone loss increases fracture risk and may require use of a bone-targeted agent in addition to lifestyle modifications.•The addition of a bisphosphonate to standard adjuvant therapies for postmenopausal early breast cancer reduces bone recurrence and improves survival.
Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a ...few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial.
Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR<3) versus high (NLR≥3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution.
NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) hazard ratio (HR) 1.27 (95% CI 1.05–1.55), P=0.017 and overall survival (OS) HR 1.56 (95% CI 1.25–1.95), P<0.001 than patients with low NLR. In the multivariable model, NLR retained a significant association with OS HR 1.44 (95% CI 1.14–1.82), P=0.014 but not with PFS HR 1.18 (95% CI 0.95–1.46), P=0.375. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction=0.536) or OS (P for interaction=0.831). Patients with low HR 0.84 (95% CI 0.64–1.08) and high HR 0.73 (95% CI 0.54–0.97) NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS HR 0.83 (95% CI 0.62–1.12) for low NLR; HR 0.82 (95% CI 0.59–1.12) for high NLR.
This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.
•This ESMO Guideline provides key recommendations on the role of PROMs during the care of patients with cancer.•It covers the use of PROMs in patients with cancer from the start of active treatment ...during follow-up and at the end of life.•Recommendations are based on available scientific evidence and the authors’ collective expert consensus.•Authorship includes a multidisciplinary group of experts from Europe, North America, Asia and Australia.
Highlights • Evasion of immune surveillance, a process defined immune-editing, leads to RCC malignant progression. • The PD-1/PD-L1 axis inhibition by targeted-antibodies, increases T-cell ...proliferation and anti-tumor activity. • PD-1 and PD-L1 inhibitors have been tested in RCC, alone or combined with anti-VEGF/VEGFR drugs or other immunotherapies. • We discuss the role of PD-1/PD-L1 in RCC, focusing on current clinical studies and future perspectives.
KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. ...Additional KRAS mutations are described in CRC.
We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients.
Among 87 KRAS codons 12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1 case, respectively. None of mutated patients responded vs 22 of 68 wild type (P=0.096). Eleven patients were not evaluable. KRAS mutations were associated with shorter progression-free survival (PFS, HR: 0.46, P=0.028). None of 13 BRAF-mutated patients responded vs 24 of 74 BRAF wild type (P=0.016). BRAF mutation was associated with a trend towards shorter PFS (HR: 0.59, P=0.073). In the subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a lower response rate (0 vs 37%, P=0.047) and worse PFS (HR: 0.45, P=0.023). Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%, P=0.0005) and PFS (HR: 0.51, P=0.006) compared with KRAS and BRAF wild-type patients.
Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs.
•This ESMO Clinical Practice Guideline provides recommendations on the prevention/management of dermatological toxicities.•Authorship includes a multidisciplinary group of experts from different ...institutions and countries in Europe and abroad.•Recommendations for prevention/therapy of acneiform rash, hand-foot syndrome, alopecia, pruritus, paronychia, and onycholysis.•Recommendations are provided, including levels of evidence and grades of recommendation where applicable.
Abstract Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to ...distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei , Albatrellus confluens , Cordyceps militaris , Ganoderma lucidum , Poria cocos and Silybum marianum , together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.
Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II ...prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy.
We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy.
Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P=0.01).
Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options.
Osteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, ...therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.
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