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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.

A votive offering or ex-voto includes a variety of usually non-professional artworks offered to divinities and placed in religious sites to fulfill a vow or in gratitude for recovery from an illness or injury. Unfortunately, the ancient period lacks a scientifically verifiable understanding of the true nature of cancer and its natural history and, consequently, a lack of effective treatment. This paper discusses two ex-votos potentially related to breast cancer distant more than 2000 years, one from the other. The ex-votos convey the complex relationship of humans with illness through an art expression stemming from the heart and minds of ordinary people.

Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p 0.001). Younger patients (i.e. 65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.

Background/Aim: Abemaciclib is a cyclin-dependent kinase 4/6 inhibitor approved in combination with endocrine therapy for treating hormone receptor-positive and human epidermal growth factor receptor 2-negative early and advanced breast cancer patients. The safety profile of abemaciclib is characterized by frequent gastrointestinal toxicity, especially diarrhea. Therefore, we performed an exploratory analysis of clinical factors that may be potentially associated with diarrhea in patients treated with abemaciclib plus endocrine therapy. Patients and Methods: Factors potentially predisposing to diarrhea were selected, such as age ≥70 years, concomitant medications and diseases, diet, and use of laxatives. These variables were correlated with the onset of grade 2/3 diarrhea in a cohort of patients treated with abemaciclib from advanced breast cancer. Univariate and multivariate analysis was performed. Sensitivity and specificity were tested using the ROC curve. Results: Eighty women with advanced breast cancer were included in the study. The univariate analysis found a statistically significant correlation between grade 2/3 diarrhea and age ≥70 years, polypharmacy, and concomitant gastrointestinal diseases (p

Introduction: Bone metastases (BMs) are the common cause of cancer-related pain, as approximately 45% of cancer patients suffer from bone pain (BP). Radiotherapy (RT) is well established as BP treatment strategy; also, other approaches have been shown to be effective in this setting. Radiofrequency thermoablation (RFA) in a combined strategy with RT appears to be feasible and effective in the treatment of metastatic BP ensuring a better quality of life. Aim of this retrospective study was to describe a case series of patients with painful osteolytic lesions at risk of fracture treated with the RFA-RT combined approach, analyzing local control and pain control as outcomes. Methods: Data of all patients with BM treated with combined approach in our center from April 2016 to June 2020 were retrospectively analyzed. Patients underwent RFA followed by cementoplasty on the same day and RT in a second phase. RT dose ranged between 30 and 37.5 Gy in 5/10 fractions. BP was evaluated according to the numeric rating scale (NRS), at the beginning of treatment and at 1, 2, 3, 6, 9, and 12 months from the end of combined treatment. Results: A total of 27 patients were treated from April 2016 to June 2020 with RFA-RT combined approach. The large majority of patients underwent stereotactic body radiotherapy (SBRT) (23/27). All patients experienced an NRS value decrease >2 at 1 month and between the first and second months. NRS mean value reached 0 at 3, 6, 9, and 12 months’ evaluations. Discussion/Conclusion: The results of this retrospective analysis of patients treated with RFA-RT combined approach for BP support its safety and efficacy in terms of pain reduction. SBRT role in this combined approach has to be investigated in randomized trials.

At present, multidisciplinary tumor boards (MDTB) are considered best practice in oncology. However, web-based virtualization of MDTB may increase participation in meetings, the number of cases discussed, and adherence to guidelines, deliver better treatment, and eventually improve outcomes for patients with prostate cancer.This is an observational study focused on exploring the structuring process and implementing a multi-institutional virtual MDTB in Sicily, Italy. Other endpoints included the analysis of cooperation between participants, adherence to guidelines, patient outcomes, and patient satisfaction.Overall, 126 patients were referred to the virtual MDTB for a total of 302 cases discussed in an 18-month period. Nearly 45% of cases were referred from general hospitals or tertiary centers, 38% from comprehensive cancer centers, and only 17% from academic ones. Most health professional participants (95%) reported eliminating geographical barriers and consequently reducing costs and saving time as key advantages of virtual meetings over face-to-face ones. Using a specifically designed platform for virtual MDTBs was another excellent point, especially to geolocate clinical trials and time-lapse data storage. The majority of referred patients had stage T 3-4 prostate cancer (79%). Overall, 71% of proposals discussed were approved unchanged, while 19% changed after the virtual MDTB discussion. Debated points were mostly radiologic, surgical, medical, or radiation treatment-related issues. In particular, the prescriptive appropriateness of positron emission tomography with 68Ga-prostatic specific membrane antigen, newer drugs, radiation versus surgical approach, stage T3-4 cases, and adjuvant therapy represented the most debated issues. The proposed diagnostic and/or therapeutic options were controlled for adherence to the guidelines and/or updated scientific evidence. Overall, 98% of approved proposals and changes were in line with the guidelines. Overall, most participants felt virtual MDTB was very useful and case discussions led to a major change of strategy in 19% of cases.Virtual MDTBs are a very useful way to achieve best management of prostate cancer while saving time and fostering cooperation.

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients’ privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5–8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals.Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in apatient-centeredapproach.

Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.

The use of opioids in cancer survivors with chronic pain raises concerns as it occurs with chronic non-malignant pain .Thus, in some circumstances advanced therapeuthic strategies should be performed to allow pain control for prolonged periods of time We describe a case of a long-survivor patient receiving prolonged opioid therapy. She received multiple opioid rotations or some more complex treatments, including burst of ketamine and midazolam, which allowed to maintain an acceptable pain control for 12 years, despite her poor compliance. Different opioids in different phases were given. A high level of knowledge, experience, and assessment is mandatory to implement of pain management among survivors.

Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with initial low response rate, with a significant proportion of patients not responding to these agents. Hence, novel appealing predictive biomarkers, such as those related to tumor cell signaling pathways, metabolism or the tumor microenvironment, have emerged as potentially useful to select those patients most likely to benefit from immunotherapy. Moreover, most patients ultimately develop acquired resistance to ICI treatment over time and novel therapeutic strategies are urgently needed to overcome or delay resistance. Herein, we provide an overview on recent advances in immunotherapy in NSCLC, focusing on updated results from studies on ICIs in different disease settings and at different lines of treatment. We further describe currently emerging predictive biomarkers, beyond PD-L1, to optimize patient selection and novel strategies to improve clinical outcomes.

Background This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. Methods 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. Results PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. Conclusions Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT – Napoli – 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it

The spread of instant messenger systems provides an excellent opportunity and a helpful tool to healthcare professionals. WhatsApp instant messenger use is widely prevalent among health professionals, cancer patients, caregivers and the general population. It is a quick and easy communication tool that may also be used on personal computers and business purposes. WhatsApp instant messenger and other similar tools may be a very useful complement for e-medicine. Instant messaging systems may be helpful, especially in rural areas, in medium- or low-income countries, or to avoid unnecessary travels, improve knowledge and awareness of cancer, monitor home care and support the delivery of home care. The unregulated use of WhatsApp instant messenger requires sound and shared guidelines to assure impeccable professional service. Although a significant number of papers have investigated the roles of social networks in connecting patients to health professionals, there is still a lack of information and scientific data about their uses, benefits and limitations in connecting health providers only for professional communication. The role of instant messenger systems in cancer practice and research needs to be clarified. In this paper, we report a focus on available data, pros and contras of the unregulated use of WhatsApp instant messaging, in the context of e-medicine, as an interprofessional and doctor/patient communication tool in oncology.

Treatment of advanced non-small cell lung cancer (NSCLC) has radically improved in the last years due to development and clinical approval of highly effective agents including immune checkpoint inhibitors (ICIs) and oncogene-directed therapies. Molecular profiling of lung cancer samples for activated oncogenes, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF, is routinely performed to select the most appropriate up-front treatment. However, the identification of new therapeutic targets remains a high priority. Recently, MET exon 14 skipping mutations have emerged as novel actionable oncogenic alterations in NSCLC, sensitive to MET inhibition. In this review we discuss: (I) MET gene and MET receptor structure and signaling pathway; (II) MET exon 14 alterations; (III) current data on MET inhibitors, mainly focusing on selective MET tyrosine kinase inhibitors (TKIs), in the treatment of NSCLC with MET exon 14 skipping mutations. We identified the references for this review through a literature search of papers about MET, MET exon 14 skipping mutations, and MET inhibitors, published up to September 2020, by using PubMed, Scopus and Web of Science databases. We also searched on websites of main international cancer congresses (ASCO, ESMO, IASLC) for ongoing studies presented as abstracts. MET exon 14 skipping mutations have been associated with clinical activity of selective MET inhibitors, including capmatinib, that has recently received approval by FDA for clinical use in this subgroup of NSCLC patients. A large number of trials are testing MET inhibitors, also in combinatorial therapeutic strategies, in MET exon 14-altered NSCLC. Results from these trials are eagerly awaited to definitively establish the role and setting for use of these agents in NSCLC patients.

Background/aim Upper limb breast cancer-related lymphedema (BCRL) is a chronic and severe condition affecting a significant percentage of breast cancer survivors. Even though its physiopathology is well-known, there is no worldwide consensus on BCRL evaluation and a gold-standard treatment. This narrative review aims at providing a brief descriptive overview with regard to BCRL treatment modalities. Materials and methods We conducted a literature search within the PubMed database, and 33 articles out of 56 were selected, including reviews, systematic reviews, and meta-analyses aiming find the most updated evidence regarding BCRL treatment modalities. Results Physical exercise (aerobic exercise, resistance exercise, aquatic therapy), bandages, and intermittent pneumatic compression were shown to be most effective in BCRL patients, in terms of swelling reduction in the acute-intensive phase. Furthermore, physical exercise was beneficial also as a maintenance tool. Manual lymphatic drainage demonstrated efficacy in preventing secondary lymphedema if applied immediately after breast cancer surgery or in early phases of BCRL or as a maintenance tool. Complementary procedures such as acupuncture, reflexology, yoga and photo-biomodulation therapy did not show conclusive results in BCRL treatment. Surgery was shown effective in managing symptoms (liposuction), preventing (lymphaticovenular anastomosis) and treating BCRL (vascularized lymph node transfer). Conclusion BCRL is still a challenging condition either for breast cancer survivors and clinicians, deeply impacting patient functioning and quality of life. Due to the lack of globally accepted criteria in evaluating BCRL, to date a gold standard treatment for this widespread issue is still needed.

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.

A retrospective analysis of 70 patients with triple-negative or hormone-resistant advanced breast carcinoma who had not previously received chemotherapy was carried out. Patients received oral vinorelbine 60 mg/m2 on day 1 and 8, plus capecitabine 1000 mg/m2 bid for 14 consecutive days every 3 weeks. Overall response rate was 53% with a 9% complete response rate. Stable disease was recorded in 27% of the cases. Median progression-free survival was 7.9 months and median overall survival was 29.2 months. Toxicity was generally mild and easily manageable. These data demonstrate that this combination is feasible, safe and active as first-line treatment of triple-negative fully hormone-resistant advanced breast carcinoma patients., Lay abstract The adoption of metronomic chemotherapy in the treatment of breast cancer is an important step forward in the management of this disease. The fluoropyrimidine capecitabine and the vinca alkaloid vinorelbine have been shown to be at least as active. Our data confirm the activity and safety of this all-oral regimen as first-line metronomic therapy being response rate.

Purpose Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. Methods We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). Results Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines. Conclusion This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Objective Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer. Materials and methods The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported. Results In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months. Conclusions This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.

BACKGROUND Multidisciplinary tumor boards play a pivotal role in the patient-centered clinical management and in the decision-making process to provide best evidence-based, diagnostic, and therapeutic care to patients with cancer. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore, the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key point to successfully obtain an oncology team and implement a network among health professionals and institutions. This need is stronger than ever during the COVID-19 pandemic. OBJECTIVE This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily, Italy. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patient satisfaction. METHODS This protocol encompasses a pragmatic, observational, multicenter, noninterventional, prospective trial. The study’s programmed duration is 5 years, with a half-yearly analysis of the primary and secondary objectives’ measurements. Oncology care health professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a nonhierarchic manner. VMTB employs an innovative, virtual, cloud-based platform to share anonymized medical data that are discussed via a videoconferencing system both satisfying security criteria and compliance with the Health Insurance Portability and Accountability Act. RESULTS The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region. The results of this study will particularly focus on the organization of VMTBs, involving oncology units present in different hospitals spread in the area, and creating a network to allow best patient care pathways and a hub-and-spoke relationship. The present results will also include data concerning organization skills and pitfalls, barriers, efficiency, number, and types with respect to clinical cases and customer satisfaction. CONCLUSIONS VMTB represents a unique opportunity to optimize patient management through a patient-centered approach. An efficient virtualization and data-banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully be useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/26220

Background Multidisciplinary tumor boards play a pivotal role in the patient-centered clinical management and in the decision-making process to provide best evidence-based, diagnostic, and therapeutic care to patients with cancer. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore, the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key point to successfully obtain an oncology team and implement a network among health professionals and institutions. This need is stronger than ever during the COVID-19 pandemic. Objective This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily, Italy. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patient satisfaction. Methods This protocol encompasses a pragmatic, observational, multicenter, noninterventional, prospective trial. The study’s programmed duration is 5 years, with a half-yearly analysis of the primary and secondary objectives’ measurements. Oncology care health professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a nonhierarchic manner. VMTB employs an innovative, virtual, cloud-based platform to share anonymized medical data that are discussed via a videoconferencing system both satisfying security criteria and compliance with the Health Insurance Portability and Accountability Act. Results The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region. The results of this study will particularly focus on the organization of VMTBs, involving oncology units present in different hospitals spread in the area, and creating a network to allow best patient care pathways and a hub-and-spoke relationship. The present results will also include data concerning organization skills and pitfalls, barriers, efficiency, number, and types with respect to clinical cases and customer satisfaction. Conclusions VMTB represents a unique opportunity to optimize patient management through a patient-centered approach. An efficient virtualization and data-banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully be useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology. International Registered Report Identifier (IRRID) DERR1-10.2196/26220

Highlights • To contain COVID-19 spread, Italy is under a global lockdown except for health services and food supply. • In this scenario, growing apprehension concerning legal consequences is rising among health professionals. • Hospitals and health professionals are highly exposed to liability. • More articulated legal regulations are strongly needed., To contain COVID-19 spread, Italy is under a global lockdown since February 21, 2020, except for health services and food supply. In this scenario, growing apprehension concerning legal consequences is rising among health professionals due to several ethical and legal questions. Even if medical ethicists may approve patients’ prioritization protocols, hospitals and health professionals remain highly exposed to liability. The so-called smart-working may be very useful, but it may harbor potential legal harms for health personnel and patients and safety. Moreover, personal umbrella policies also often exclude liability arising out of the transmission of a communicable disease, especially a pandemic state, is declared. Under the pressure of medical associations, Italian Government political forces have very recently presented an amendment to the recently released ordinances for the COVID-19 emergency aimed to reduce medical liability. Presumably, similar epidemics or other wide-scale similar events may happen again in an unpredictable future. Therefore, more articulated legal regulations are strongly needed starting from lessons learned from this epidemic.

Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients' quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NKEligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastatic non-small cell lung cancer (NSCLC), ovarian cancer or urothelial cancer and experienced nausea and/or vomiting after the first cycle of chemotherapy, despite an antiemetic prophylaxis with a 5HTDuring the first cycle of chemotherapy, 15 out of 30 (50%) patients did not properly control CINV with a 5HTOur experience showed that NEPA has proven to be very effective and well tolerated in the prophylaxis of CINV induced by carboplatin-based chemotherapy.

Aim This retrospective observational study evaluated the role of hypo-fractionated stereotactic radiotherapy (SRT) in patients with oligo-progressive metastatic renal cell carcinoma (mRCC) treated with first-line oral tyrosine kinase inhibitors (TKI). Data on local control, delay of further progression, and safety are reported. Patients and methods Between January 2010 and December 2016, 28 patients with mRCC who showed oligo-progressive disease while receiving first-line pazopanib were treated with hypofractionated SRT to progressive metastatic sites to delay the change of systemic therapy. First and second progression-free survival (PFS-1 and PFS-2) were recorded, as well as objective response and toxicity. Results After pazopanib therapy, nine partial remissions (32%), 12 stable disease (43%) and seven progressions (25%) were recorded. The median time to progression from first-line pazopanib until oligo-progression was 9.45 months (PFS-1 range=2-30 months). Seventeen patients (61%) showed progression at pre-existing tumor sites, and 11 patients (39%) showed the appearance of new metastases. Progression-free survival after radiation therapy was 4.55 months (PFS-2 range=1-11 months). PFS-1 plus PFS-2 was 14.0 months (range=3-41 months). Severe grade 3-4 toxicities were seen only occasionally. Conclusion Patients with oligo-progressive mRCC treated with first-line pazopanib may benefit from hypo-fractionated high-dose SRT at progressing sites achieving a further increase in median progression-free survival. Further studies and prospective validation are required to establish if this minimally invasive approach may have a positive impact on overall survival and reported outcomes.

Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on efficacy and tolerability, abemaciclib is a potentially convenient, safe, and effective agent for the treatment of patients with advanced hormone receptor-positive patients. Orally administered abemaciclib in combination with aromatase inhibitors or fulvestrant has the potential to allow significant improvement in survival outcomes, quality of life, response rate, and duration of response even in poor prognosis subgroups. Adequate patients’ information, clinical selection, and prompt, proactive management of side effects are mandatory.

Aim This paper aims to analyze the usefulness of the G8 geriatric oncology questionnaire in patients with advanced/metastatic pancreatic adenocarcinoma (aPAC) and its possible association with different clinical outcomes. Methods Patients age > 70 years were screened with the G8 tool and treated with intravenous nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 for 3 consecutive weeks followed by one-week rest as prescribed after clinical evaluation by treating oncologists. Patient’s charts were evaluated for type and severity of toxicity, 2 cycle rate of completion, discontinuation rate, delays, dose reductions, and other outcomes response rates, progression-free, and overall survival. Sensitivity, specificity, and possible correlations were analyzed. Results Sensitivity and specificity of the G8 score for severe toxicity were respectively 55.9% and 50%. No association between all types of severe grade 3-4 toxicity, delays, or dose reductions, and the G8 score was present (p=0.622). ORR was 32.5% with no complete responses. Median PFS and OS were 4.5 months and 8.1 months, respectively. Correlation between G8 score and PFS was not statistically significant (p=0.0652). Correlation between G8 score and OS was statistically significant (p=0.0251). Although median survival of G8 fit patients was superior to that of G8 vulnerable patients (6.5 versus 4 months), the difference was not statistically different (p=0.1975). Conclusion Clinical results in terms of response rate, survival outcomes, and side-effects were in the range reported by others. However, the G8 questionnaire is not a reliable diagnostic tool to predict the risk of severe toxicity, and clinical outcomes in older patients with aPAC.