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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. 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. 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). 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.

La cardiotossicità da farmaci antitumorali è diventata un importante problema clinico per i cardiologi e per gli oncologi. La disfunzione ventricolare sinistra e lo scompenso sono i quadri più rilevanti ed i meglio conosciuti, ma non bisogna dimenticare altre forme di tossicità come l’ipertensione, il tromboembolismo, le pericarditi, le aritmie e l’ischemia mio-cardica. Il loro trattamento non è sempre identico a quello usato nei pazienti non oncologici poiché la patogenesi ed il quadro clinico sono diversi, ma soprattutto perché la gravità del tumore e la prospettiva di vita richiedono di non so-spendere il trattamento antiblastico. Da qui nasce la necessità di una stretta collaborazione tra cardiologo e oncologo per preservare la qualità di vita del paziente, bilanciando il rischio di cardiotossicità e il beneficio della terapia oncologica.

Purpose Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. Methods We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. Results The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). Conclusions This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.

OBJECTIVES Although it has been postulated that patients might benefit from the centralization of high-volume specialized centres, conflicting results have been reported on the relationship between the number of lung resections performed and the long-term, all-cause mortality rates among patients who underwent surgery for lung cancer. A population-based observational study was performed to contribute to the ongoing debate. METHODS The 2613 patients, all residents of the Lombardy region (Italy), who underwent lung resection for lung cancer from 2012 to 2014 were entered into the cohort and were followed until 2018. The hospitals were classified according to the annual number of pulmonary resections performed. Three categories of lung resection cases were identified: low (≤30), intermediate (31–95) and high (>95). The outcome of interest was all-cause death. A frailty model was used to estimate the death risk associated with the categories of numbers of lung resections performed, taking into account the multilevel structure of the data. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS The 1-year and 5-year survival rates of cohort members were 90% and 63%. Patients operated on in high-volume centres were on average younger and more often women. Compared to patients operated on in a low-volume centre, the mortality risk exhibited a significant, progressive reduction as the numbers of lung resections performed increased to intermediate (−13%; 95% confidence interval +10% to −31%) and high (−26%; 0% to −45%). Sensitivity analyses revealed that the association was consistent. CONCLUSIONS Further evidence that the volume of lung resection cases performed strongly affects the long-term survival of lung cancer patients has been supplied.

EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens.Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events.At the cut-off date of interim analysis, median PFS was 6.3 months [95% confidence interval (CI) 5.0-8.1] in arm A vs 6.3 months (95% CI 5.0-7.8) in arm B, without statistical difference. OS was comparable in the two arms: 12.4 in arm A (95% CI 9.1-19.2) vs 11.5 months in arm B (95% CI 8.6-15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%, P = 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B.A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC.

Background: Breast cancer is the most prevalent cancer affecting women and it represents an important economic burden. The aim of this study was to estimate the socio-economic burden of breast cancer (BC) in Italy both from the National Health Service (NHS) and the government perspectives (costs borne by the social security system). Methods: The economic analysis was based on the costs incurred by the NHS from 2008 to 2016 (direct costs related to hospitalizations) and by the National Social Security Institute (INPS) from 2009 to 2015 (costs of social security benefits) for patients with breast cancer. The analysis was based on the Hospital Information System (HIS) and Disability Insurance Awards databases. For both databases, patients affected by a malignant neoplasm of the female breast, carcinoma in situ, or secondary malignant neoplasm of the breast were considered. Results: Results show that more than 75,000 women were hospitalized for breast cancer every year, with an overall cost for hospitalization of about €300 million per year. From the Social Security analysis, a number of 29,000 beneficiaries each year was estimated. Considering per patient social costs, breast cancer at the primary stage cost €8828 per year, while secondary neoplasms cost €9780, with an average total economic burden of €257 million per year. Conclusions: This analysis focused on the economic impact of breast cancer in Italy, showing that an advanced stage of the disease was associated with a higher cost.

In cancer patients, hypercoagulability is a common finding. It has been associated with an increased risk of venous thromboembolism, but also to tumor proliferation and progression. In this prospective study of a large cohort of breast cancer patients, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: (i) are associated with breast cancer-specific clinico-pathological features; and (ii) can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and pro-thrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years of follow up, 71 patients experienced a recurrence. Cox multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-negative or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs. 20.7%; Hazard Ratio=3.5; P

Polymorphisms contribute to inter-individual differences and show a promising predictive role for chemotherapy-related toxicity in colon cancer (CC). TOSCA is a multicentre, randomized, non-inferiority, phase III study conducted in high-risk stage II/stage III CC patients treated with 6 vs 3 months of FOLFOX-4 or XELOX adjuvant chemotherapy. During this post-hoc analysis, 218 women and 294 men were genotyped for 17 polymorphisms: TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/−), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386). The aim was to assess the interaction between these polymorphisms and sex, on safety in terms of time to grade ≥3 haematological (TTH), grade ≥3 gastrointestinal (TTG) and grade ≥2 neurological (TTN) toxicity. Interactions were detected on TTH for rs1801133 and rs1799793, on TTG for rs13181 and on TTN for rs11615. Rs1799793 GA genotype (p = 0.006) and A allele (p = 0.009) shortened TTH in men. In women, the rs11615 CC genotype worsened TTN (co-dominant model p = 0.008, recessive model p = 0.003) and rs13181 G allele improved the TTG (p = 0.039). Differences between the two sexes in genotype distribution of rs1885301 (p = 0.020) and rs4148386 (p = 0.005) were found. We highlight that polymorphisms could be sex-specific biomarkers. These results, however, need to be confirmed in additional series.

There is no sufficient evidence to establish a standard of care for patients with brain metastases (BM) from HER2Data of 154 patients were retrospectively collected at 14 Italian institutions through a specifically designed database.Median overall survival (OS) was 24.5 months. Patients receiving surgery/stereotactic radiosurgery experienced longer OS compared to those receiving whole-brain radiotherapy or no treatment (33.5 vs. 11.4 months; hazard ratio = 0.34; 95% confidence interval, 0.22-0.52; P .001). Interestingly, whole-brain radiotherapy did not improve OS compared to no treatment (11.4 vs. 9.8 months; hazard ratio = 0.99; 95% confidence interval, 0.62-1.62; P = .99). HER2-targeted therapy was associated with better OS compared to systemic therapy without HER2-targeted therapy or no systemic therapy (27.5 vs. 5.4 months; hazard ratio = 0.26; 95% confidence interval, 0.17-0.41; P .001). At multivariate analysis stratified by local treatments, systemic therapy, Karnofsky performance status, and neurologic symptoms significantly affected OS. Age, number of BM, steroid therapy, number of previous lines of systemic therapy, status of extracranial disease, and period of diagnosis had no significant impact on OS.Patients with BM from HER2

Introduction:Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available.Methods:A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway–oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays.Conclusions:We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.

Levels of serum lactate dehydrogenase (LDH) are a recognized prognostic factor in malignant melanoma (MM). It is relevant to confirm its prognostic role in patients treated with targeted therapies [BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi)] and immunotherapy (IT). Furthermore, its role as a predictive marker in patients treated with these drugs had still not been investigated. We performed an electronic search for studies reporting information on overall survival (OS) or progression-free survival (PFS) according to LDH levels and on their predictive effect in patients treated with targeted therapies (BRAFi and MEKi) and IT. Data were pooled using hazard ratios (HRs) for OS and HRs for PFS according to a fixed-effect or a random-effect model. For predictive analysys, effect of new agents versus standard therapy was evaluated in LDH high population. A total of 71 publications were retrieved for a total of 16 159 patients. Overall, elevated LDH levels were associated with an HR for OS of 1.72 [95% confidence interval (CI): 1.6-1.85; P0.0001]. Similarly, HR for PFS was 1.83 (95% CI: 1.53-2.2; P0.0001). In the LDH elevated subgroup, new agents improved OS significantly (HR: 0.71; 95% CI: 0.62-0.82; P0.0001) and PFS (HR: 0.63; 95% CI: 0.55-0.72; P0.0001). In advanced MM treated with IT or BRAFi±MEKi, elevated LDH level at baseline represents a poor prognostic factor. However, patients with increased LDH levels and treated with these drugs gain significant benefits in terms of PFS and OS.

Introduction 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. Materials and methods 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. Results 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%. Conclusion 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.

Oligometastatic non-small cell lung cancer (NSCLC) has a discrete number of distant lesions (5) that can be amenable to radical treatment. The treatment of the primary lung tumour in such stage IV cases is still debated. We conducted a systematic review and meta-analysis to evaluate the outcome of these patients and the added benefit in terms of overall survival (OS) and progression-free survival (PFS) when radical treatment of the primary tumour with radiotherapy (RT) was delivered. PubMed, EMBASE and Cochrane Library were systematically searched to identify relevant studies published up to July 2018. Prospective trials and retrospective series comparing RT vs no RT to the primary NSCLC in the presence of oligometastases were included. Hazard ratios (HRs) for OS and PFS were aggregated according to a fixed or random effect model. Twenty-one studies for a total of 924 synchronous oligometastatic NSCLC were analysed. Median OS and PFS were 20.4 and 12 months. Pooled 1-2-3 and 5-year OS were 70.3%, 43.5%, 29.3% and 20.2% respectively. Overall survival was improved with the addition of thoracic RT (HR = 0.44, 95%CI 0.32-0.6; P 0.001). Similarly, RT added to the primary tumour increased PFS (HR = 0.42, 95%CI 0.33-0.55; P 0.001). The only variable associated with the median OS was the year of publication with most recent series associated with a better outcome. In patients with oligometastatic NSCLC and disease controlled with ablative therapy of distant metastases, a consolidation with radical RT to the primary tumour is associated with better survival and could be considered as a treatment modality in selected cases.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians’ treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2− early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

Simple Summary Community care activity in the oncology field does not exist. This unmet need contrasts with the increasing number of patients with a previous diagnosis of cancer. Abstract Over the last few decades, thanks to early detection, effective drugs, and personalized treatments, the natural history of cancer has radically changed. Thanks to these advances, we have observed how survival of cancer patients has increased, becoming an ever more important goal in cancer care. Effective clinical governance of survivorship care is essential to ensure a successful transition between active and post-treatment life, identifying optimization of healthcare outcomes and quality of life for patients as the primary objectives. For these reasons, potential intervention models must consider these differences to rationalize the available resources, including economic aspects. In this perspective, analyzing the different models proposed in the literature to manage this type of patients, we focus on the possible role of the so-called “community oncologist”. As a trained health professional, also focused on longevity, he could represent the right management solution in all those “intermediate” clinical conditions that arise between the hospital specialist, frequently overworked, and the general practitioner, often biased by the lack of specific expertise.

BACKGROUND Hypertension is usually associated with increased cardiovascular mortality. Uncertainty exists about the possible role of hypertension as a poor prognostic factor for cancer-specific mortality (CSM). To assess the association between pre-existing hypertension and the risk of mortality and relapse after a diagnosis of cancer, we performed a systematic review and meta-analysis of published studies. METHODS PubMed, Scopus, Web of Science, the Cochrane Library and EMBASE were searched from inception until May 2020, without language restrictions, for observational studies reporting the prognosis of patients with hypertension and cancer. The primary outcome of the study refers to CSM in hypertensive vs nonhypertensive patients, and secondary endpoints were overall mortality (OM) and progression- or relapse-free survival. The effect size was reported as hazard ratios (HRs) with 95% CIs. RESULTS Mortality and relapse associated with hypertension in patients with various cancers were evaluated among 1 603 437 participants (n = 66 studies). Overall, diagnosis of cancer and hypertension was associated with an increased independent risk of OM (HR = 1.2 [95% CI, 1.13-1.27], P

The increased efficacy of cancer therapy has resulted in greater cancer survival and increasing number of people with cancer and cardiovascular diseases. The sharing of risk factors, the bidirectional relationship between cancer and cardiovascular diseases and the cardiotoxic effect of chemotherapy and radiotherapy, are the cause of the rapid expansion of cardio-oncology. All strategies to preserve cardiovascular health and mitigate the negative effect of cancer therapy, by reducing the cardiovascular risk, must be pursued to enable the timely and complete delivery of anticancer therapy and to achieve the longest remission of the disease. Comprehensive cardiac rehabilitation is an easy-to-use model, even in cancer care, and is the basis of Cardio-Oncology REhabilitation (CORE), an exercise-based multi-component intervention. In addition, CORE, besides using the rationale and knowledge of cardiac rehabilitation, can leverage the network of cardiac rehabilitation services to offer to cancer patients exercise programs, control of risk factors, psychological support, and nutrition counseling. The core components of CORE will be discussed, describing the beneficial effect on cardiorespiratory fitness, quality of life, psychological and physical well-being, and weight management. Furthermore, particular attention will be paid to how CORE can counterbalance the negative effect of therapies in those at heightened cardiovascular risk after a cancer diagnosis. Barriers for implementation, including personal, family, social and of the health care system barriers for a widespread diffusion of the CORE will also be discussed. Finally, there will be a call-to-action, for randomized clinical trials that can test the impact of CORE, on morbidity and mortality.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, either symptomatic or incidental, is a common complication in the history of cancer disease. The risk of VTE is 4-7-fold higher in oncology patients, and it represents the second leading cause of death, after cancer itself. In cancer patients, compared with the general population, VTE therapy is associated with higher rates of recurrent thrombosis and/or major bleeding. The need for treatment of VTE in patients with cancer is a challenge for the clinician because of the multiplicity of types of cancer, the disease stage and the imbricated cancer treatment. Historically, in cancer patients, low molecular weight heparins have been preferred for treatment of VTE. More recently, in large randomized clinical trials, direct oral anticoagulants (DOACs) demonstrated to reduce the risk of VTE. However, in the "real life", uncertainties remain on the use of DOACs, especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-to-drug interactions with specific anticancer therapies.In cancer patients, atrial fibrillation can arise as a perioperative complication or for the side effect of some chemotherapy agents, as well as a consequence of some associated risk factors, including cancer itself. The current clinical scores for predicting thrombotic events (CHA2DS2-VASc) or for predicting bleeding (HAS-BLED), used to guide antithrombotic therapy in the general population, have not yet been validated in cancer patients. Encouraging data for DOAC prescription in patients with atrial fibrillation and cancer are emerging: recent post-hoc analysis showed safety and efficacy of DOACs for the prevention of embolic events compared to warfarin in cancer patients. Currently, anticoagulant therapy of cancer patients should be individualized with multidisciplinary follow-up and frequent reassessment. This consensus document represents an advanced state of the art on the subject and provides useful notes on clinical practice.

BACKGROUNDObesity, defined as a body mass index (BMI) > 30 kg/m2, is associated with a significant increase in risk of many cancers. In last years, various studies suggested that obese cancer patients have better outcomes than non-obese patients. This phenomenon, also known as “the obesity paradox”, is not well understood and presents controversial explanations. We performed a systematic review and meta-analysis to assess the association between obesity and outcome after a diagnosis of cancer.PATIENTS AND METHODSPubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020, for studies reporting prognosis of patients with obesity and cancer. Risk of death, cancer-specific survival (CSS) and progression were pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI). The primary outcome of the study refers to overall survival (OS) in obese vs non-obese patients with malignancies. Secondary endpoints were CSS and progression- or disease-free survival (PFS or RFS).RESULTSMortality and relapse associated with obesity in patients with cancer were evaluated among n=6,320,365 participants (n=203 studies). Overall, association of obesity and cancer was associated with a reduced OS (HR =1.14, 95% CI: 1.09-1.19; PCONCLUSIONSIn many cancer patients, obesity reduces survival and increases the risk of relapse. In lung cancer, renal cell carcinoma and melanoma obesity was protective in terms of outcome. More intensive follow up, adequate dosing of oncological treatments, calories intake restrictions, physical activity and monitoring of obesity-related complications are effective measures for reducing mortality in these subjects.

Introduction Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. Patients and Methods COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. Results A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). Conclusions The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Stable chronic background pain (numeric rating scale, NRS &le, 4) during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). RESULTS: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (linear p-value = 0.1) and dyspnea (Linear p-value = 0.05). The ESAS and PSQI questionnaires confirmed these positive results (p &lt, 0.0001 and p = 0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance.

Polymorphisms contribute to inter-individual differences and show a promising predictive role for chemotherapy-related toxicity in colon cancer (CC). TOSCA is a multicentre, randomized, non-inferiority, phase III study conducted in high-risk stage II/stage III CC patients treated with 6 vs 3 months of FOLFOX-4 or XELOX adjuvant chemotherapy. During this post-hoc analysis, 218 women and 294 men were genotyped for 17 polymorphisms: TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/-), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386). The aim was to assess the interaction between these polymorphisms and sex, on safety in terms of time to grade ≥3 haematological (TTH), grade ≥3 gastrointestinal (TTG) and grade ≥2 neurological (TTN) toxicity. Interactions were detected on TTH for rs1801133 and rs1799793, on TTG for rs13181 and on TTN for rs11615. Rs1799793 GA genotype (p = 0.006) and A allele (p = 0.009) shortened TTH in men. In women, the rs11615 CC genotype worsened TTN (co-dominant model p = 0.008, recessive model p = 0.003) and rs13181 G allele improved the TTG (p = 0.039). Differences between the two sexes in genotype distribution of rs1885301 (p = 0.020) and rs4148386 (p = 0.005) were found. We highlight that polymorphisms could be sex-specific biomarkers. These results, however, need to be confirmed in additional series.

We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs‐negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T‐DM1 in second‐line after pertuzumab were significantly lower compared to pertuzumab‐naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2‐positive (mbc) patients., What's new? About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2‐directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti‐HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. Methods: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging. Results: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes. Conclusions: Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.

Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of irAEs versus no irAEs according to fixed or random-effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. A total of 30 studies that included a total of 4324 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death [HR=0.49, 95% confidence interval (CI): 0.38-0.62; P

Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab. Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC. Results: Of the more than 50 variables analyzed, five showed a significant correlation with DSS: ECOG PS, size of the biggest brain metastasis, number of metastatic sites, toxicity, and malignant pleural effusion. Three variables significantly correlated with TTF: malignant pleural effusion, number of metastatic sites, number of liver metastases. Malignant pleural effusion was the only variable showing a significant correlation with OR, as well as the only one correlating with all the endpoints of the study. Conclusions: This study identified clinical characteristics associated with survival and response during treatment with Nivolumab in NSCLC patients. The unfavorable association between malignant pleural effusion and objective response is a novel finding with important translational implications.

We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached. When comparing patients by trastuzumab-pretreatment, similar PFS were observed, although a longer OS was reached in trastuzumab-naïve patients (p = 0.02). Brain metastases at baseline and their development in course of therapy were associated with significantly shorter PFS (p = 0.0006) and shorter OS, although at a not fully statistically relevant extent (p = 0.06). The addition of maintenance endocrine therapy (ET) to pertuzumab/trastuzumab maintenance was associated with longer PFS (p = 0.0001), although no significant differences were detected in OS (p = 0.31). Results were confirmed by propensity score analysis (p = 0.003 and p = 0.46, respectively). In multivariate models, longer PFS was related to lower Performance Status (PS) (p = 0.07), metastatic stage at diagnosis (p = 0.006) and single metastatic site (p

Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are associated with immune-related adverse events. Conversely, little is known about the incidence of haematological toxicities across published trials. We have performed a systematic review and meta-analysis to evaluate the incidence of immunotherapy-related anaemia, neutropenia and thrombocytopenia among different tumour types, trials phases and anti-PD-(L)1 agents.A PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of references from relevant articles were done. Studies regarding haematological diseases were excluded. The pooled incidence rates weighted for the individual sample sizes were calculated according to fixed or random effect models. Incidence of all-grade and grade (G) III or higher anaemia were the primary end-points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end-points.Forty-seven studies of PD-(L)1 inhibitors for a total of 9324 evaluable patients were included in the meta-analysis. The overall incidence of anaemia during PD-(L)1 inhibitor was 9.8% (95% confidence interval [CI], 6-13.6%) for all-grade and 5% (95% CI, 3.3-6.7%) for G3-5 anaemia. The incidence was higher in diseases different from genitourinary, lung and melanoma, with avelumab and in phase II studies. In randomised trials, relative risk of all-grade anaemia for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25 (95% CI, 0.16-0.39; p 0.001). Incidence of all grades and G3-5 neutropenia and thrombocytopenia were 0.94%, 1.07%, 2.8% and 1.8%, respectively. Febrile neutropenia was 0.45%.The incidence of PD-(L)1 inhibitor-related anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile neutropenia were rare. These findings are useful for clinicians and suggest that blood cell count should be checked before every cycle and support should be given when severe toxicity appears.

Introduction Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. Once the disease progresses, evidence for the efficacy of palliative treatments is lacking, and platinum re-challenge or single-agent chemotherapy are commonly used. To assess the effects of cytostatic or targeted therapy for treating MPM, we performed a systematic review and meta-analysis. Material and methods PubMed, the Cochrane Library, and Embase databases were searched to identify published articles on second-line treatments for recurrent or advanced mesothelioma. Inclusion criteria were publication in the English language, describing clinical trials with 20 or more patients, and evaluability for efficacy and for receiving second-line systemic therapies. Data were pooled using number of events/number of evaluable patients, median overall survival (OS) and progression-free survival (PFS), according to a fixed or random effect model. Pooled median OS was the primary endpoint. Results A total of 49 eligible studies (n = 3938 patients; range, 12–400) were identified. Median progression-free survival (PFS) was 3.4 months (95%CI 2.87–3.93). Median pooled OS was 7.86 (95%CI 7.01–8.72). The pooled overall response rate (ORR) was 8.63% (95%CI 6–11.26), and the pooled disease control rate (DCR) was 54.8% (95%CI 48.9–60.6). Median pooled OS with platinum- and pemetrexed-based chemotherapy were 7.93 and 7.78 months, respectively. Conclusions There remains uncertainty about the ideal second-line agent for MPM. Based on this meta-analysis, palliative chemotherapy or other experimental agents can be considered for patients with MPM who desire further treatment after their disease has progressed, during or after first-line therapy.