Showing papers by "Salomon M. Stemmer published in 2016"

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer

Abstract: BackgroundThe inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). MethodsIn this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on Januar...

Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy

Abstract: STUDY QUESTION Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? SUMMARY ANSWER Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. WHAT IS KNOWN ALREADY Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. STUDY DESIGN, SIZE, DURATION A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. MAIN RESULTS AND ROLE OF CHANCE Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group). LIMITATIONS, REASONS FOR CAUTION There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. WIDER IMPLICATIONS OF THE FINDINGS Although more oocytes were collected and matured from chemotherapy-naive paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. STUDY FUNDING/COMPETING INTERESTS The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. TRIAL REGISTRATION NUMBER N/A.

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial

Abstract: Summary Background The randomised phase 3 TURANDOT trial compared two approved bevacizumab-containing regimens for HER2-negative metastatic breast cancer in terms of efficacy, safety, and quality of life. The interim analysis did not confirm non-inferior overall survival (stratified hazard ratio [HR] 1·04; 97·5% repeated CI [RCI] –∞ to 1·69). Here we report final results of our study aiming to show non-inferior overall survival with first-line bevacizumab plus capecitabine versus bevacizumab plus paclitaxel for locally recurrent or metastatic breast cancer. Methods In this multinational, open-label, randomised phase 3 TURANDOT trial, patients aged 18 years or older who had an Eastern Cooperative Oncology Group performance status 0–2 and measurable or non-measurable HER2-negative locally recurrent or metastatic breast cancer who had received no previous chemotherapy for locally recurrent or metastatic breast cancer were stratified and randomly assigned (1:1) using permuted blocks of size six to either bevacizumab plus paclitaxel (bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m 2 on days 1, 8, and 15 every 4 weeks) or bevacizumab plus capecitabine (bevacizumab 15 mg/kg on day 1 plus capecitabine 1000 mg/m 2 twice daily on days 1–14 every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification factors were oestrogen or progesterone receptor status, country, and menopausal status. The primary objective was to show non-inferior overall survival with bevacizumab plus capecitabine versus bevacizumab plus paclitaxel in the per-protocol population by rejecting the null hypothesis of inferiority (HR ≥1·33) using a stratified Cox proportional hazard model. This trial is registered with ClinicalTrials.gov, number NCT00600340. Findings Between Sept 10, 2008, and Aug 30, 2010, 564 patients were randomised, representing the intent-to-treat population. The per-protocol population comprised 531 patients (266 in the bevacizumab plus paclitaxel group and 265 in the bevacizumab plus capecitabine group). At the final overall survival analysis after 183 deaths (69%) in 266 patients receiving bevacizumab plus paclitaxel and 201 (76%) in 265 receiving bevacizumab plus capecitabine in the per-protocol population, median overall survival was 30·2 months (95% CI 25·6–32·6 months) versus 26·1 months (22·3–29·0), respectively. The stratified HR was 1·02 (97·5% RCI –∞ to 1·26; repeated p=0·0070), indicating non-inferiority. The unstratified Cox model (HR 1·13 [97·5% RCI –∞ to 1·39]; repeated p=0·061) did not support the primary analysis. Intent-to-treat analyses were consistent with the per-protocol results. The most common grade 3 or worse adverse events were neutropenia (54 [19%] of 284 patients in the bevacizumab plus paclitaxel group vs 5 [2%] of 277 patients in the bevacizumab plus capecitabine group), hand–foot syndrome (1 [ vs 43 [16%]), peripheral neuropathy (39 [14%] vs 1 [ vs 1 [ vs 16 [6%]). Serious adverse events were reported in 65 (23%) of 284 patients receiving bevacizumab plus paclitaxel and 68 (25%) of 277 receiving bevacizumab plus capecitabine. Deaths in two (1%) of 284 patients in the bevacizumab plus paclitaxel group were deemed by the investigator to be treatment-related. No treatment-related deaths occurred in the bevacizumab plus capecitabine group. Interpretation Bevacizumab plus capecitabine represents a valid first-line treatment option for HER2-negative locally recurrent or metastatic breast cancer, offering good tolerability without compromising overall survival compared with bevacizumab plus paclitaxel. Although progression-free survival with the bevacizumab plus capecitabine combination is inferior to that noted with bevacizumab plus paclitaxel, we suggest that physicians should consider possible predictive risk factors for overall survival, individual's treatment priorities, and the differing safety profiles. Funding Roche.

Optimizing the process of fertility preservation in pediatric female cancer patients – a multidisciplinary program

Abstract: Current evidence indicates sub-optimal incidence of fertility preservation (FP) in eligible patients. We present herein our designated multidisciplinary program for FP in pediatric and adolescent population and present our data on FP in female patients. Pediatric patients (age 0–18) who were candidate for highly gonadotoxic treatments were referred to FP program for a multidisciplinary discussion and gonadal risk-assessment followed by either oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients, and sperm banking for male patients. The OCP protocol consists of aspiration of oocytes from small antral follicles and in-vitro maturation followed by cryopreservation, as well as ovarian tissue cryopreservation. The establishment of a designated FP program resulted in a significant increase in referral and subsequent FP procedures of all eligible patients. Sixty-two female patients were referred for FP discussion during a period of 36 months; 41 underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two (51.6 %) were chemotherapy-naive. Seventeen patients (27 %) had sarcoma, 16 patients (26 %) had acute leukemia. The mean number of mature oocytes that were eventually vitrified was significantly higher in chemotherapy-naive patients compared with chemotherapy-exposed patients (mean 12 oocytes (1–42) versus 2 (0–7)). Multidisciplinary programs that encompass experts of all relevant fields, skilled laboratory resources and a facilitated path appear to maximize the yield. We observed a considerable higher referral rates following launching a designated program and earlier OCP in chemo-naive patients that culminated in a better fertility preservation procedure.

The Role of 18F-FDG PET/CT on Staging and Prognosis in Patients with Small Cell Lung Cancer

Abstract: We evaluated 18F-FDG PET/CT in small cell lung cancer (SCLC) staging and assessed metabolic (SUVmax, MTV and TLG) and morphologic (CTvol) variables as predictors for overall survival (OS) and progression-free survival (PFS). Patients with newly diagnosed, histopathology-confirmed SCLC, who underwent 18F-FDG PET/CT were evaluated. A Cox proportional hazard model was used to determine the association between the primary tumour SUVmax, MTV, TLG and CTvol with OS and PFS. Similar evaluations were performed when hilar/mediastinal lymphadenopathy was included [total SUVmax (TSUVmax), total MTV (TMTV) and total TLG (TTLG)]. 55 patients were included. 18F-FDG PET/CT changed staging in 6/55 (10.9%) patients who were upstaged to extensive disease. TTLG (>443.8) was a significant variable for OS with HR=2.1 (CI 1.14–3.871, p=0.017). Patients with TTLG>443.8 had a median OS of 13.4 months compared to 25.7 months in patients with TTLG 72.4) was significant for PFS with HR=2.3 (CI 1.11-4.8, p=0.025). A median PFS of 12.1 and 26.2 months was found with TMTV greater and less than 72.4, respectively (p=0.005). 18F-FDG PET/CT improved staging of patients with SCLC, and TTLG and TMTV can be used as prognostic variables for OS and PFS, respectively. • Identifying variables that predict the prognosis of patients with SCLC is important. • 18F-FDG PET/CT influences staging of patients with SCLC. • Metabolic parameters could be used as predictors for PFS and OS.

Stability and Transitions in Posttraumatic Growth Trajectories Among Cancer Patients: LCA and LTA Analyses.

Abstract: OBJECTIVES The objectives of the current study were to identify (a) different post cancer treatment adaptation profiles; (b) factors that predict these adaptation profiles; and (c) transitions in post cancer-treatment adaptation profiles and trajectories in a sample (N = 198) of female breast cancer patients over a 2-year period. METHOD Latent class analysis (LCA) was used to idenitfy profiles of post cancer treatment adaptation, based on a combined pattern of responses to observable indicators of distress, coping strategies, and posttraumatic growth. latent transition analysis (LTA) was used to track trajectories, based on the probabilities of transitions among latent classes. RESULTS Four postcancer treatment adaptation profiles were found: (a) distressed, (b) resistant, (c) constructive growth, and (d) struggling growth. CONCLUSIONS The majority of transitions between different adaptation profiles occurred between 6 and 12 months after treatment. These findings offer theoretical and practice implications regarding posttraumatic growth in breast-cancer patients by distinguishing between profiles of adaptation and highlights a previously unidentified profile-struggling growth. These results contribute to the theoretical understanding of the complex relationship between growth, distress, and coping. (PsycINFO Database Record

Abstract P5-08-02: Real-life analysis evaluating 1594 N0/Nmic breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score result: 5-year KM estimate for breast cancer specific survival with recurrence score results ≤30 is >98%

Abstract: Background: The 21-Gene Recurrence Score® Assay (Oncotype DX®) has been validated as a prognostic and predictive tool in estrogen receptor (ER)+ breast cancer in multiple studies using archival specimens of clinical trials with long term follow up. Prospective outcome data from patients where treatment decisions incorporated the Recurrence Score results have not been reported. We evaluated treatments and clinical outcomes in patients undergoing Recurrence Score testing in 9 medical centers within Clalit Health Services (CHS), the largest HMO in Israel. Methods: Medical records of patients with N0/Nmic ER+ HER2-negative disease undergoing testing from 12/2004 to 12/2010 in 9 medical centers (Rabin, Lin, Soroka, Meir, Kaplan, Hadassah, Ha9emek, Rambam, and Shaare Zedek) within CHS were individually reviewed to verify treatments given, recurrence, and survival status. 5-year Kaplan-Meier (KM) and standard error estimates for distant recurrence and breast cancer specific survival were determined. Results: 1594 patients were evaluated with 5.9 years median follow-up. Median age, 61 (25-85) years; N0/Nmic (90%/10%); Grade I (16%), II (48%), III (16%), N/A (19%); histology, IDC (80%), lobular (13%), other (7%). Distribution of Recurrence Score risk groups (Recurrence Score results of Conclusions: These are the first prospective long term clinical outcome data from approximately 1600 patients for whom the 21-gene Recurrence Score assay has been incorporated in real-life clinical decision making. The documented use of CT was appropriately based on the Recurrence Score result, and the outcomes for recurrence and survival are consistent with previously reported prospective-retrospective studies of the 21-gene assay. The 5 year KM estimates for distant recurrence rate in patients with low and intermediate Recurrence Score results who were treated based upon their Recurrence Score results were very low (0.5% and 1.2%, respectively). Citation Format: Stemmer SM, Steiner M, Rizel S, Soussan-Gutman L, Geffen DB, Nisenbaum B, Ben-Baruch N, Isaacs K, Fried G, Rosengarten O, Uziely B, Svedman C, Rothney M, Klang SH, Ryvo L, Kaufman B, Evron E, Zidan J, Shak S, Liebermann N. Real-life analysis evaluating 1594 N0/Nmic breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score result: 5-year KM estimate for breast cancer specific survival with recurrence score results ≤30 is >98%. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-02.

Young patients and gastrointestinal (GI) tract malignancies - are we addressing the unmet needs?

Abstract: Recent epidemiological studies indicate the rate of gastrointestinal (GI) malignancies among younger patients is increasing, mainly due to colorectal cancer. There is a paucity of data regarding the magnitude of treatment-related symptoms, psychosocial issues and potential unmet needs in this population. We aimed to characterize the needs of this population to evaluate whether unmet needs could be targeted by potential intervention. Female and male patients diagnosed with cancer of the gastrointestinal tract <40y retrospectively completed a questionnaire to evaluate symptoms, daily function and unmet needs at pre-treatment, during and post-treatment. Comparisons were made by gender, disease stage and treatment modality. Multiple linear regression models evaluated effects of demographics, symptoms and needs on multiple domains of health-related-quality-of-life (using Short-Form Health Survey-12 and CARES). Fifty patients were enrolled (52 % female) to a pilot study. Median age at diagnosis was 35.5y (range, 21-40y). The symptoms that significantly increased from baseline to during and post-treatment were: diarrhea (37 %), sleeping disorder (32 %) and sexual dysfunction (40 %). Patients also reported significant deterioration in occupational activities and coping with children compared with baseline. Female patients reported significant unmet need for nutritional counseling and psychosocial support compared to male patients (p < 0.05). Patients treated with multimodality-treatment presented higher rates of unmet needs (p = 0.03). Young patients with GI cancers represent a group with unique characteristics and needs compared with published evidence on other young-onset malignancies. The distinctive symptoms and areas of treatment-related functional impairments indicate there are unmet needs, especially in the area of psychosocial support and nutritional counseling.

The cost and value of cancer drugs – are new innovations outpacing our ability to pay?

Abstract: Cancer drug expenditures have been increasing significantly in countries around the world. A recent paper in the IJHPR provides new knowledge and insights into this global phenomenon by analyzing how it is playing out in an Israeli health plan with over two million members, whose state-of-the-art information systems provide an opportunity to explore these changes in a comprehensive, detailed and reliable manner. There is a wide variation in both the cost-effectiveness and the budget impact of individual drugs. These issues also vary when analyzing drugs in other countries due to differential pricing mechanisms. In addition to drug expenditure, the overall cost of cancer care is increasing, partly due to expenditures on non-pharmacologic treatments and diagnostic testing. With the arrival of new therapies, the future of cancer care is exciting. However, there will be many challenges ahead with regard to the ability to pay for such innovations. In this commentary we discuss the current problems and anticipate the future challenges.

Predictive role of hand-foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer.

Abstract: Correlations between development of hand–foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial. Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV–CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV–CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed. Among 277 patients treated with BEV–CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively. This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV–CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.

The Effectiveness of Group Intervention on Enhancing Cognitive Emotion Regulation Strategies in Breast Cancer Patients A 2-Year Follow-up

Abstract: Purpose To evaluate the long-term effect of group intervention on enhancing cognitive emotion regulation (CER) strategies in female patients with early-stage breast cancer. Methods The sample included 174 patients who were diagnosed with early-to-mid stage breast cancer, completed adjuvant therapy, and agreed to fill out demographic and cognitive emotion regulation questionnaires (CERQ). About half of the patients (86, 49.4%) chose to participate in an 8-session group intervention (intervention group) while the others (88, 50.6%) did not (comparison group). The structured intervention for enhancing coping strategies with special emphasis on emotion regulation was conducted at the oncology unit at Rabin Medical Center by 2 experienced therapists. Preliminary effects on CER evaluated 6, 12, and 24 months postintervention were compared to the CER of a group of patients that opted not to participate in the group intervention. Results In the intervention group, the long-term effect (from baseline to 24 months) was assessed using the mix models module. Significant interaction effects were found for both the Negative CER scales (F(3, 268 ,404) = 3.66, P = .01) and for the Positive CER scales (F(3, 271 ,660) = 5.12, P = .002). No statistically significant differences in socio-demographic characteristics and medical variables were observed between the intervention and comparison groups. Conclusion Our findings indicate that a group intervention aimed at empowerment of coping strategies had positive long-term outcomes that reinforce adaptive coping strategies and improve less effective strategies of cognitive emotion regulation.

Cetuximab intensifies cisplatin-induced testicular toxicity

Abstract: Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Mullerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity.

Widespread morbilliform rash due to sorafenib or vemurafenib treatment for advanced cancer; experience of a tertiary dermato-oncology clinic

Abstract: Background In the literature, there are minimal data for the treatment of grade 2 or 3 morbilliform/atypical target lesion rashes secondary to sorafenib or vemurafenib given for patients with advanced stage cancer. This poses a dilemma for clinicians, particularly in patients with advanced neoplastic disease for whom other optional treatments are limited. Methods The cohort included data on all patients attending the dermato-oncological clinic at a tertiary medical center that presented in 2011–2014 with a widespread rash following treatment with sorafenib or vemurafenib. All patients were prospectively followed. Results Eight patients met the study criteria. Five, under sorafenib, aged 50–65 years, presented with an extensive grade 2 (involving 20–30% of the body surface area, two patients) or grade 3 (three patients) morbilliform rash, 5–10 days after onset of the drug. Two had atypical target lesions. The dosage was temporarily reduced in only two patients, and oral steroids were added in four. Under vemurafenib, three patients presented with an extensive grade 3 morbilliform rash 5–10 days after onset of treatment. Two had atypical target lesions. The dose was temporarily reduced in one, and another patient stopped the drug at her own initiative; both also received steroids. The rash subsided after 2–3 weeks in all eight patients, allowing continuation of the treatment at the regular dose. Conclusion Our cohort suggests that not all cases of widespread morbilliform rash or atypical erythema multiforme, which occur under treatment with sorafenib or vemurafenib, given for advanced cancer, require discontinuation of therapy.

Factors Affecting Communication Patterns between Oncology Staff and Family Members of Deceased Patients: A Cross-Sectional Study.

Abstract: Objective Perceptions of the role of oncology medical staff in supporting bereaved families have evolved with the transition to interdisciplinary cancer care. We investigated the interactions between oncology professionals and bereaved families. Methods This cross-sectional study involved all oncology medical staff at the Davidoff Center. Participants were given a questionnaire relating to bereavement follow-up. Responses were measured using a 5-point Likert scale. Results Of 155 staff members, 107 filled questionnaires with 50% of the families of their deceased patients. Contacting bereaved families was considered the responsibility of the physicians (90%), nurses (84%), or social workers (89%). The main barriers to contacting bereaved families were emotional overload (68%) and lack of time (63%); 60% indicated a need for additional communication tools for bereavement follow-up. In a multivariate analysis, profession (physician vs. nurse), primary workplace (outpatient setting vs. other), and self-defined religion were significant variables with respect to the perceived importance of contacting bereaved families and to actually contacting them. Other factors (e.g., age, gender) were non-significant. Conclusions Perspectives regarding bereavement actions differ significantly across medical professions, work settings, and self-defined religions. Additional guidance and education regarding bereavement actions is warranted.

Radiotherapy and Sorafenib in the Management of Patients with Hepatocellular Carcinoma Have Led to Improved Survival: A Single Center Experience.

Abstract: Background & Aims: Hepatocellular Carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer mortality worldwide. We aimed to assess the effect of novel treatment options on the survival of HCC patients. Methods: This retrospective study included all HCC patients diagnosed between 2000 and 2013 referred to the Davidoff center and treated by a multidisciplinary team. Results: The analysis included 321 patients (median age, 64 years; 74.8% males; 74.1% viral carriers; 76.0% cirrhosis; 56.7% diagnosis at an early stage). The estimated hazard ratio by multivariate analysis for the effect of the period of diagnosis (2007-2013 vs. 2000-2006) on survival was 0.72 (95% CI: 0.54-0.96; p=0.027). There was no difference in the distribution by CP score, by BCLC stage at diagnosis or in the proportion of patients undergoing surgical procedures (liver transplantation or resection). In the later time frame, there was a significant decrease in the proportion of patients undergoing percutaneous treatments (14.6% vs.4.2%, p=0.004) and embolization (46.9% vs.24.6%, p=0.001), and a significant increase in radiotherapy (1.5% vs. 8.4%, p=0.009) and treatment with sorafenib (6% vs. 18.3%, p=0.002). Conclusion: Technological/pharmaceutical innovations have led to advancement in HCC treatment. Since there was no significant difference in the proportion of patients undergoing surgical procedures during the evaluated timeframe, the improved survival may stem from better management of advanced stage patients by a multidisciplinary team.

ReCAP: Perspectives of Patients, Caregivers, and Medical Staff on Greetings in Oncology Practice: A Prospective Survey

Abstract: QUESTION ASKED:What is the preferred greeting process (name calling, hand shaking) in oncology practice, by patients, caregivers and medical staff?SUMMARY ANSWER:Findings suggest that patients with cancer in Israel prefer a casual environment that includes calling them by their given name and shaking hands. Yet, they prefer that physicians introduce themselves in a more formal manner, with full name and title.METHODS:A total of 186 patients and 104 caregivers visiting the outpatient clinics at the Davidoff Cancer Institute completed a questionnaire about greeting-related preferences. Similar questionnaires were completed by 93 staff members (physicians, nurses, secretaries, and psychosocial team).BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:First, our attempt to delineate the greeting process is artificial, because a human encounter is much more than just gestures. Also, this was a single-center study, and some of the subgroups were too small to analyze. Last, the answers provided by respondents were not verifi...