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Here we report a case of 50-mm lump within the left breast in a 56-year-old man. The patient underwent left total mastectomy and sentinel node biopsy. The pathology report showed low-grade intracystic papillary breast carcinoma surrounded by ductal carcinoma in situ. Sentinel node biopsy was negative. The patient was prescribed five years tamoxifen.

PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy-related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue.

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

Aim The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. ( NCT00412022 )

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Purpose To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m 2 ; raltitrexed (RTX), 2.5 mg/m 2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m 2 (31 patients) or 800 mg/m 2 (32 patients); levo-folinic acid (LFA), 250 mg/m 2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results Overall, neutropenia (40%) and diarrhea (13%) were the most common grade ≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%–92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

e12654Background: Standard preoperative systemic therapy for HER2+ breast cancer (BC) patients (pts) includes chemotherapy (CT) and Trastuzumab (T). Two randomized phase II trials, NeoSphere and TR...

Virtual reality (VR) during chemotherapy has resulted in an elapsed time compression effect, validating the use of VR in the treatment of some stressful conditions. In the past literature the framework of the pacemaker–accumulator cognitive model of time perception resulted very reliable to explain this effect. This pilot-study explored the efficacy of Virtual Reality in reducing the perception of time during receipt of intravenous chemotherapy. Patient’s retrospective estimates of time elapsed during this treatment were evaluated versus patient’s treated with Music-Therapy. Materials and methods 47 breast cancer patients were randomly assigned to 20 min of VR treatment (N = 24) or 20 min of Music-therapy (N = 23) during chemotherapy infusion. Difference between actual and perceived elapsed time during chemotherapy with VR and with MT were evaluated with ANOVA analysis. Results: The VR group underestimated the time spent with VR treatment, instead MT treatment group overestimated it. In one step anova model, the VR versus MT treatment showed a significant difference in terms of altered time perception (F = 5.06, p = 0.0008). Further analysis on the same panel of patients will be conducted to explain also the role of some possible mediator of this effect.

Data from eight randomised trials on high-dose chemotherapy (HDC) for metastatic breast cancer (MBC) have been published, but only seven studies are evaluable after the Bezwoda trial was discredited. Moreover, overall survival (OS) has been evaluated in only four out of seven studies since three had a crossover design. OS was similar for the HDC and standard-dose chemotherapy (SDC) group in the four evaluable trials, while disease-free survival (DFS) was improved in the HDC group in six of the seven trials. The delay in relapse for patients with metastatic disease represents an important clinical outcome; furthermore, since none of the reported studies randomised more than 220 patients, their statistical power may have been too limited to detect meaningful survival differences. Finally, preliminary experiences have shown that HDC seems to be the ideal platform upon which to build novel therapies. In conclusion, HDC remains an important field of clinical research for breast cancer patients with stage IV disease and, from the studies reported in this article, there is some evidence for offering this therapeutic modality to selected patients who are interested in a medically aggressive approach.

Evidence on adjuvant chemotherapy for elderly early breast cancer patients is poor, due to the low number of phase 3 trials. ELDA shows that weekly docetaxel does not prolong DFS compared with standard CMF and worsens quality of life. Non-hematological toxicity is worse with weekly docetaxel. Age, comorbidities and functioning geriatric scales may be predictive of non-hematological side effects. Background Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. Patients and methods We carried out a multicenter, randomized phase III study. Women aged 65–79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m2 days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. Results From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83–1.76,P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80–2.22,P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. Conclusions Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. ClinicalTrials.gov NCT00331097.

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease. Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC. Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3–4 toxicities were neutropaenia and neurotoxicity. Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC.

High-dose chemotherapy followed by autologous bone marrow or peripheral blood progenitor cell transplantation represents a recognized option in the treatment of solid tumors and hematologic diseases. Patients receiving high-dose chemotherapy are traditionally supported with parenteral nutrition with the aim to prevent malnutrition secondary to gastrointestinal toxicity and metabolic alterations induced by the conditioning regimens. Nevertheless, well-defined guidelines for its use in this clinical setting are lacking and there are several areas of controversy.

Background Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC). Patients and methods The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age ≤75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. Results Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity. Conclusions Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.

We report a case of Guillain-Barre Syndrome (GBS) which appeared after mobilization therapy in a patient with B-cell chronic lymphocytic leukemia (B-CLL). After obtaining a partial remission with four cycles of fludarabine at standard dose, the patient underwent to high-dose Cytoxan in order to mobilize CD34+ hematopoietic progenitor cells. During neutropenia the patient experienced fever of unknown origin (FUO) and subsequently developed GBS with normalization of his neurologic condition after 2 months. It is possible that a viral-induced activation of an antigen-specific T and B-cell clone caused a local inflammation and toxicity of Schwann cells with demyelination and axonal damage with a self-limited course.

OBJECTIVE The balance of evidence suggests that acromegaly is a risk factor for colonic neoplasia. We have evaluated the prevalence of colonic polyps in acromegalics from Southern Italy and characterized the lymphocyte subsets in the colonic lamina propria in order to analyze differences in the colonic immunological environment. DESIGN All the patients and controls were submitted to pancolonoscopy. Ten per-endoscopic biopsies of the intestinal mucosa surrounding polyps were carried out to evaluate lymphocyte subsets. PATIENTS Fifty acromegalics and 318 sex- and age-matched controls entered this study. Colonic lamina propria lymphocyte subsets were studied in 34 patients and 34 controls. RESULTS Colonic polyps were resected in 23 acromegalics (46%) and 42 controls (13.2%; P

We report an episode of severe bradycardia that occurred in a 49-year-old woman with fever and malignant jaundice during antibiotic therapy with linezolid, a new oxazolidinone with activity against Gram-positive cocci. In our case, the strict temporal dependence between bradycardia and linezolid therapy seems to provide strong evidence for a causal relationship. To our knowledge, this is the first report of linezolid-induced bradycardia. This adverse event confirms that the new antibiotic linezolid should be administered with caution in patient with jaundice and hepatic insufficiency.

(2003). Late and Long-lasting Response in an Adult Chronic Idiopathic Thrombocytopenic Purpura after Extended Course of Rituximab. Leukemia & Lymphoma: Vol. 44, No. 3, pp. 561-562.

This paper describes the evolution of a CAD programming tool for remote video calibration of the Internal Automation & Robotics Technology Test Bed (IARTTB) available in the WKR Section at ESTEC. First the correspondence between the CAD model of the workcell in the off-line programming system and the real world is created. Then the robot is remotely calibrated with respect to the two racks present in the workcell by using a video camera on the end effector. A software package with a user-friendly interface has been developed to carry out the calibration procedure in a systematic way.

580 Background: The present study was aimed at comparing the antitumor activity of 12 weekly PET cycles with that of 6 triweekly ET cycles in MBC patients. Methods: Women with MBC, aging < 70 years...

8174 Background: Oral mucositis is a severe problem for patients (pts) undergoing high dose chemotherapy (HDC) followed by peripheral blood progenitor cells transplantation. Once mucositis has occurred, treatment consists of measures to palliate symptoms. Multiple agents have been used prophylactically to reduce this toxicity with discordant results. Oral cryotherapy, through vasoconstriction, can decrease the mucosal damage induced by agents with short half-lives, such as melphalan (L-PAM). Aim of this study was to evaluate the effect of local cryotherapy on oral mucositis in pts treated with high-dose (HD) L-PAM Methods: From December 2001, 23 pts (5 with multiple myeloma, 9 with non Hodgkin's Lymphoma, 7 with breast cancer, 1 with ovarian cancer) underwent HDC including L-PAM; in particular, 5 pts received HD L-PAM (140–160 mg/m2) alone and 17 pts a L-PAM including conditioning regimen. All these pts were asked to suck on ice chips for 30 minutes, starting 5 minutes prior to the L-PAM infusion. These p...