High rate of clinical fractures was reported during adjuvant HT trials (9-14% in BIG 1-98, ATAC, IES). Since 2015, in Italy, bisphosphonates and denosumab are reimbursed for prevention of bone fractures in EBC HR+ postmenopausal pts receiving HT, regardless of T-score values (Note 79 of AIFA-Agenzia Italiana del Farmaco). In 2019, these drugs were administered only in 25% of potentially beneficiary pts. The P&P is a nationwide Bone Health (BH) management project designed to improve adherence to recommendations regarding fracture risk assessment and risk prevention measures in pts receiving HT for HR+ EBC. The BH management model P&P was developed in 10 Italian cancer centres and includes: 1- training of multidisciplinary team and presentation of a BH management model by the oncologist (with referral to the Bone Specialist if osteoporosis); 2- implementation of this model in every centre; 3- evaluation, after 12 months, of rate of EBC HR+ pts in postmenopausal status (natural, surgical, secondary to chemotherapy or hormonal blockage) assessed for BH within 30 days from the start of adjuvant HT; 4- evaluation, after 12 months, of rate of EBC HR+ pts receiving therapy within 90 days from the start of adjuvant HT, according to the criteria for reimbursement by AIFA. At 12 months after implementation of P&P, data are available from 6 centres (IRCCS Negrar, Ancona Hospital, IRCCS San Martino Genova, Poliambulanza Brescia, Cardarelli Napoli, Papa Giovanni XXIII Bergamo) in 1,551 postmenopausal EBC HR+ pts. The first analysis reports that 83% of EBC HR+ patients who started adjuvant HT were assessed for BH within 30 days compared to 43% in the 2019 national survey and 68% of pts started bisphosphonates/denosumab compared to 25% in the 2019 national survey. Implementation of the P&P model has been shown to increase the rate of postmenopausal EBC HR+ pts on adjuvant HT assessed for BH and treated with bisphosphonate/denosumab to reduce the risk of bone fractures. A new project is ongoing to assess the rate of fractures in Italian pts after the approval of Note 79 by AIFA.

Introduction: In the last years the use of autologous fat grafting (lipofilling) has become a widely used procedure in breast reconstruction after surgery for breast cancer but experimental and clinical studies reported conflicting results about the risk of local recurrence. In fact adipocyte, preadipocyte and progenitor cell can stimulate angiogenesis and cell growth. Among breast cancer population the BRCA carriers are about 5-10% but have higher risk of relapse. We investigated the safety of lipofilling in this subgroup. Materials and methods: We performed a monocentric retrospective review of clinical data of all women BRCA1-2 mutated underwent surgery for primary breast cancer from March 2011 to June 2017. We then selected those patients (pts) who underwent reconstruction with lipofilling. Following we analyzed pts and tumour characteristics, treatment administered, number of lipofilling, BRCA mutation type and tumour relapse. Discussion: Our research identified 12 cases. The median age was 48 (range 34-61). Every cancer was invasive, 50% were triple negative, 25% overexpressed human epidermal growth factor receptor-2 (Her2). The pathological stages were I (42%) and II (58%). Every patient received chemotherapy, 66% radiotherapy, 50% (pts who had estrogen receptor positive cancer) the hormonal one and the 25% (those overexpressed Her2) trastuzumab. The median follow up from primary surgery was quite long: 60 months (range 20-93) whereas from lipofilling was 27 (range 10-64). The median number of lipofilling was 3 (range 1-6). 50% had a BRCA1 mutation, 42% a BRCA2 and 8% a variant of uncertain significance in BRCA2. We reported 3 cancer related events: two local relapse (one contralateral) and one systemic. Conclusion: To our knowledge this is the first study to investigate the safety of lipofilling in BRCA carriers. Given the small sample size and the data prematurity we can only suppose that this technique can be possible in this subtype of patients too.

Background: The fear of loss of dignity is a recurring concern among oncological patients, especially in the advanced stage of illness, for those who are in advanced stage of their disease. Chochinov has made the model of Dignity Therapy (DT) used primarily with people who were terminally ill. It consists of a short-term psychotherapy intervention that includes 3 major issues: physical aspects related to the disease and symptoms; existential/spiritual based on the patient's life history; social relationships linked to the quality of the relationship between the patient, practitioners and family members. The DT is a multi-dimensional psychosocial intervention for patient-centered care and it depends on experiences of generativity and the pursuit of purpose and meaning. It invites patients to discuss issues that matter most or that they would (most) want mainly to remember. Methods: Since 2016 we applied to 4 patients the DT in the perspective of simultaneous care with metastatic disease, in psychological therapy and still in chemotherapy. We are using the Italian validate version of semi-structured interview. The intervention takes place in 3-4 meetings, lasting 1 hour each, after informed consent. The interview uses 10 core questions and the responses are used to create a written legacy document to family members. The DT session is audio-recorded, transcribed, edited and given back to the patient. Content includes lifetime events that are most significant in the life of the patient, who can later personalize adding photos, images, titles or more. Results: Because the our small sample, we do not have a statistically relevant data, but we have noticed that the common themes that emerge in patients mainly concern the attributed value to the affections and the family and the experiences that have contributed to building their identity. The introduction of topics such as dignity, searching for meaning, has proved to be a valuable tool for the development of the true meaning of one's life, despite the changes in the disease. Moreover, in some cases, it has contributed to allowing the person to find a way of self-reliance in relation to loved ones. Conclusion: In our experience, DT showed to be a new promising therapeutic intervention for suffering and distress at the end of life. The literature review finds robust evidence for DT's overwhelming acceptability, rare for any medical intervention, especially in psychosocial-spiritual care.

Introduction: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib.Patients and methods: We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival.Results: Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%.Conclusion: Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib, which is likely due to the high percentage of heavily pretreated patients (some received four or five types of therapy before regorafenib). We think that regorafenib could represent a chemotherapy resensitizing agent; however, additional studies are needed in patients who have received less pretreatment.

Background: In recent years, literature has reported an increase in the use of Complementary Alternative Medicine (CAM) by cancer patients to manage symptoms related to the disease or side effects of the treatments. Yoga is one of the most widely used complementary and alternative medicine therapies to cope with the most common symptoms of cancer as anxiety, depression, fatigue and sleep disorders. Recent studies conducted with cancer patients indicate that Yoga is associated with improvement in overall QOL, emotional well-being, physical symptoms and distress. In April 2013 we started the "Yoga project in Oncology " which involved the use of specific exercises of this discipline as a complement of cancer treatments. The aim of this study was to evaluate the impact of Yoga training on mood, fatigue and sleep quality in metastatic cancer patients. Material and methods: The Yoga intervention used the Yoga Ratna approach, consisting of pranayama (breathing exercises), gentle yoga asanas (postures) and meditation. The program includes 8 weekly group meetings lasting 1.5 hours, trained by a Yoga professional teacher with a psychologist. At the beginning (T0) and at the end (T1) of the training we administered the following tests: Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression; Fatigue Symptom Inventory (FSI) to assess fatigue symptoms; Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Results: Sample consisted of 35 patients with metastatic cancer receiving chemotherapy. The majority of the patients were women (65.7%), the mean age was 55 years, 62.8% of patients were married and 45.7% were employed with a medium-high level of education (57.1%). All patients had advanced disease: 54.3% breast cancer, 31.4% colorectal cancer; 8.6% others gastrointestinal tumors and 5.7% pancreatic cancer. The preliminary results showed a not statistically significant trend concerning anxiety and depression improvement and a better sleep quality. In addition, we found an increase of fatigue symptoms. Conclusions: These results don't show statistically significant correlations probably because the still small sample treated so far. Moreover patients continued to receive medical treatment (chemotherapy) during Yoga training and this condition could have influenced their fatigue perception. Nevertheless, every participant expressed a very positive evaluation of this experience concerning a better body awareness and anxiety control.

ABSTRACT Aim: A non-negligible proportion of colorectal cancer patients receiving regorafenib does not seem to benefit from such a treatment approach and are then exposed to unnecessary toxicity. Neutrophil/lymphocyte ratio and piastrinosis (platelet number increase) may represent indirect indicator of tumour induced inflammation and angiogenesis and have been suggested to influence patients’ outcome. Our analysis investigated the role of neutrophil/lymphocyte ratio and piastrinosis in pretreated metastatic colorectal cancer patients receiving regorafenib. Methods: We collected neutrophil, lymphocyte and platelet count at the start of treatment. Cut-off values for neutrophil/lymphocyte ratio and platelets were calculated by ROC curve analysis. Other tested variables were: age, sex, performance status, k-ras status, number of metastatic sites, previous adjuvant chemotherapy, number of previous systemic anticancer therapies, Overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method, multivariate analysis was performed by Cox method. Results: 208 patients were eligible. In the global population median OS was 4.2 months whereas median PFS was 2.4 months. Ten (5%) achieved a partial response, 58 (29%) disease stabilization and the remaining 134 (66%) progressed under treatment. The cut off value for piastrinosis and neutrophil/lymphocyte ratio was determined at 0.545 ULN and 0.381 respectively. At univariate analysis neutrophil/lymphocyte ratio and piastrinosis both correlated with clinical outcome. At multivariate analysis a high platelet count and high neutrophil/lymphocyte ratio were related to a worse OS (Exp(b):1.49, 95%CI:1.0130-2.2103, p = 0.0439 and Exp(b):1.6963, 95%CI: 1.0757-2.6751, p = 0.0237 respectively) and PFS (Exp(b):1.4985, 95% CI: 1.0925-2.0556, p = 0.0126 and Exp(b): 1.9277, 95% CI: 1.3226-2.8097, p = 0,0007 respectively). Interestingly in 52 (25%) patients negative for these factors, median overall survival was 15.9 months vs. 3.1 months for patients harbouring at least one of the factors examined (HR:3.81, 95% CI:2.3260-4.8274, p Conclusions: Our analysis suggests that a high platelet count and a high neutrophil/lymphocyte ratio are predictive factors for clinical outcome in patients treated with regorafenib. Disclosure: All authors have declared no conflicts of interest.

Background: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G). Methods: A total of 433 stage IIIB–IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine–cisplatin (GP), gemcitabine–vinorelbine, gemcitabine–ifosfamide-cisplatin or gemcitabine–ifosfamide–vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets. Results: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months ( P =0.044), progression-free survival was 4.9 vs 6.4 months ( P =0.020) and response rate was 24% vs 31% ( P =0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3–4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3–4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3–4 nausea-vomiting was significantly increased in P-containing regimens. Conclusions: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

The aim of this study was to evaluate feasibility and toxicity of escalating doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the activity of the triplet in extensive disease small-cell lung cancer. Thirteen patients entered the phase I study: the maximum tolerated doses were epirubicin (EpiDX) 90 mg m-2 and paclitaxel (P) 175 mg m-2 with febrile neutropenia as dose-limiting toxicity. The recommended schedule for this regimen for the phase II study was EpiDX 75 mg m-2, P 175 mg m-2, etoposide (E) 100 mg m-2 intravenous (fixed dose) days 1-3 with courses repeated every 21 days. The prophylactic use of colony-stimulating factors (CSFs) was not allowed. Twenty patients entered the phase II trial: median age was 61 years (range 50-70), median Eastern Cooperative Oncology Group performance status 0 (0-2); nine patients had visceral disease and 17 had more than two metastatic sites. A total of 100 courses were administered with a median of 5 (range 1-6) per patients. Main toxicity (NCI-CTC) was myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses, respectively. Seven episodes of febrile neutropenia were documented and one patient required hospital admission. Nonhaematological toxicity was moderate. Seven out of 19 evaluable patients achieved a complete response (37%), nine patients (47.3%) a partial response with an overall response rate of 84.2% (95% confidence interval=60.4-96.6). In this poor prognostic population of patients the triplet epirubicin/paclitaxel/etoposide showed high antitumour activity with mild nonhaematological side effects. The use of CSFs should be able to improve the haematological profile.

589 Background: Risk factors such as hormone receptor status, primary tumor volume and grading often fail to identify node-negative breast cancer patients with poor prognosis. The search for new molecular risk markers is of primary importance in clinical practice. Changes in cell cycle control mechanisms are frequently described in human neoplasms and their prognostic significance need to be evaluated. Methods: We analysed the expression of Cyclin A in 75 consecutive node-negative breast cancer patients: 17 out of 75 (22.6%) relapsed within 5 years from diagnosis while the others did not. We correlate the expression of Cyclin A with Ki67, E2F1, tumor size, grading, estrogen receptor status (ER) and RFS (median follow-up 10 yrs). Cyclin A, Ki67 and E2F1 were determined by IHC. The median values of expression of each parameter were used as cut-off. Results: Cyclin A was overexpressed in 34 of 75 patients (45.3%) and it directly correlated with tumor size (p = 0.0009), high Ki67 (p = 0.0001) and high E2F1 (p = 0.036) levels. No relationship with age, ER status and tumor grade was observed. 12/17 pts (71%) with early relapse (within 5 yrs) showed Cyclin A overexpression in comparison with 22/58 pts (38%) who did not (p = 0.02). DFS curves for pts with Cyclin A overexpression vs no-overexpression were significantly different (p = 0.012). DFS was also different for low vs high Ki67 expression (p = 0.003) and low vs high E2F1levels (p = 0.019). Conclusions: Significantly poorer DFS was observed in cyclin A overexpressing patients. The strong relationship observed between Cyclin A overexpression, high proliferation index and large tumor size might identify breast cancers with more aggressive phenotypes and consequently patients at increased risk of relapse. No significant financial relationships to disclose.

The authors performed a randomized trial comprising patients with metastatic breast carcinoma (MBC). They used a noninferiority design to evaluate whether the results of sequential administration of epirubicin and paclitaxel were not markedly worse than the concomitant administration in terms of objective response rates (ORRs). Toxicity profile, quality of life (QOL), and pharmacoeconomic evaluations were evaluated as well.

The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mg m −2 plus Paclitaxel 200 mg m −2 (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mg m −2 on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mg m −2 on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel.

BACKGROUND The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate (pCR) in patients with locally advanced breast cancer (LABC) treated with combined modality therapy. PATIENTS AND METHODS Stage IIIA/IIIB patients received three courses of induction chemotherapy (ICT) with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by local therapy (total mastectomy or segmental mastectomy with axillary nodes dissection) and adjuvant chemotherapy (ACT) with three courses of CEF alternated with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Patients were randomized to receive ICT and ACT every 3 weeks (arm A, 'standard treatment') or every 2 weeks with granulocyte-macrophage colony-stimulating factor (GM-CSF) support (arm B, 'dose-dense treatment'). In both arms radiotherapy was administered after the end of chemotherapy (in selected cases) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years. RESULTS A total of 150 patients were randomized (77 arm A and 73 arm B) and demographics were well balanced between the two arms. Compliance to treatment was excellent: 95% and 93% of patients in arms A and B, respectively, completed the treatment program with no modification or delay. Median duration of treatment (ICT+local+ACT) was 183 days (range 0-265) in arm A and 139 days (0-226) in arm B. The average relative dose intensity (ARDI) of chemotherapy was 1.3 with a 30% increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [62%; 95% confidence interval (CI) 49% to 73.2%] and pathological response rates to ICT was observed between the two arms. Median follow-up was 5 years (range 1-96 months); median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in standard therapy: this figure has not yet been reached in the dose-dense treatment. CONCLUSIONS In LABC a dose-dense regimen, while allowing a 30% increase in the dose intensity of chemotherapy, did not provide significant improvement in pathological response rates. However, accelerated chemotherapy reduced the duration of the combined-modality program (6.1 versus 4.6 months) with no additional toxicities.