Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

[INTRAOPERATIVE RADIOTHERAPY (IORT) IN EARLY BREAST CANCER - 500 PATIENTS, ONE CENTER'S EXPERIENCE].

AIMS: To present our Institute's experience with intraoperative radiotherapy in this selected population by collecting and analyzing clinical data, including long-term follow-up. BACKGROUND: Breast-conserving therapy is the standard treatment for early-stage breast cancer. The treatment includes tumor resection and a whole breast irradiation. Intraoperative radiotherapy is a single dose of irradiation given to the tumor bed immediately after it is removed. This treatment is suitable for a selected population of patients with early stage breast cancer, which constitutes about 20% of all breast cancer patients and is supposed to replace the standard whole breast radiation treatment. METHODS: Between the years 2006-2017, 737 women with early breast cancer were treated in Carmel Medical Center with intraoperative radiotherapy. We herein report the results of the first 500 patients who were treated until 2015. RESULTS: In 13.8% of the patients, additional breast treatment was recommended due to poor pathological characteristics of the disease in final pathological examination. During a median follow-up period of 74 months (1-136), recurrence was observed in 22 patients (4.4%), and in 7 patients (1.4%) recurrence was observed in regional lymph nodes; 13 patients (2.6%) developed metastatic disease. Risk factors for regional recurrence were identified: tumor size greater than 2 cm, lack of adjuvant therapy and poor genetic profile of the disease. CONCLUSIONS: Intraoperative radiotherapy is feasible and may offer an alternative to the standard whole breast radiotherapy, in low risk early breast cancer patients. The patients should be selected according to known risk factors.

Sidedness Matters: Surrogate Biomarkers Prognosticate Colorectal Cancer upon Anatomic Location.

BACKGROUND: Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors are associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these two validated prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. MATERIALS AND METHODS: We retrospectively analyzed patients with T3 mismatch repair-proficient (MMR-P) stage II CRC for whom RS assay was performed. Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. RS and CDX2 expression were correlated with primary tumor location. RESULTS: The analysis included 1,147 patients with MMR-P stage II CRC (median age 69 years [range 29-93]). Tumor distribution across the colon was as follows: 46% (n = 551) were right-sided and 54% (n = 596) were left-sided. RS was higher in right-sided tumors (p = .01). The RS results gradually decreased across the colon (cecum, highest score; sigmoid, lowest score; p = .04). Right-sided tumors exhibited more CDX2-negative tumors (p = .07). CONCLUSION: Our study indicates that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be taken into account for recurrence risk assessment and consideration of adjuvant treatment. IMPLICATIONS FOR PRACTICE: Sidedness matters, even in stage II colorectal cancer (CRC). Using two previously established prognostic tools, the Oncotype DX assay and CDX2 expression, this study found that right-sided tumors may display worse prognosis compared with left-sided tumors in mismatch repair-proficient stage II CRC. Therefore, primary tumor location should be taken into account for recurrence risk assessment and consideration of adjuvant treatment.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Oral Bisphosphonates and Improved Survival of Breast Cancer.

Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. ©2016 AACR.

Impact of the 12-Gene Colon Cancer Assay on Clinical Decision Making for Adjuvant Therapy in Stage II Colon Cancer Patients.

OBJECTIVES: To evaluate the impact of the 12-gene Colon Cancer Recurrence Score Assay-a clinically validated prognosticator in stage II colon cancer after surgical resection-on adjuvant treatment decisions in T3 mismatch repair proficient (MMR-P) stage II colon cancer in clinical practice. METHODS: This retrospective analysis included all patients with T3 MMR-P stage II colon cancer (Clalit Health Services members) with Recurrence Score results (time frame January 2011 to May 2012). Treatment recommendations pretesting were compared with the treatments received. Changes were categorized as decreased (to observation alone/removing oxaliplatin from the therapy) or increased (from observation alone/adding oxaliplatin to the therapy) intensity. RESULTS: The analysis included 269 patients; 58%, 32%, and 10% of the values were in the low (<30), intermediate (30-40), and high (≥41) score groups, respectively. In 102 patients (38%), treatment changed post-testing (decreased/increased intensity 76/26 patients). The overall impact was decreased chemotherapy use (45.0% to 27.9%; P < 0.001). Treatment changes occurred in all score groups, but more frequently in the high (change rate 63.0%; 95% confidence interval [CI] 42.3%-80.6%) than in the intermediate (30.6%; 95% CI 21.0%-41.5%) and low (37.6%; 95% CI 30.0%-45.7%) score groups. The direction of the change was consistent with the assay result, with increased intensity more common in higher score values and decreased intensity more common in lower score values. CONCLUSIONS: Testing significantly affected adjuvant treatment in T3 MMR-P stage II colon cancer in clinical practice. The study is limited by its design, which compared treatment recommendations pretesting to actual treatments received post-testing, lack of a control group, and nonassessment of confounding factors that may have affected treatment decisions.

Short-term complications of intra-operative radiotherapy for early breast cancer.

INTRODUCTION: IORT is becoming an accepted radiotherapy technique for treatment of early breast cancer. Data regarding the early complications of breast IORT are lacking. OBJECTIVES: Assess the nature and risk factors for early complications of breast conserving surgery (BCS) and intraoperative radiotherapy (IORT) with INTRABEAM®. METHODS: IORT with INTRABEAM® was administered to breast cancer patients in Carmel Medical Center as part of an institutional clinical registry project. Three hundred and ninety five patients treated during 2006-2013 were included. Clinical and treatment data and data regarding complications documented within 1 year of surgery were collected. The association between clinical and treatment variables and risk of complications was assessed. RESULTS: Complications were documented in 108 (27.3%) of patients. Grade III or IV complications were found in 5% of patients. Infections were diagnosed in 43 (10.8%) patients, seroma in 40 (10.1%), wound dehiscence in 32 (8.1%), and bleeding and hematomas in 11(2.8%). Two patients had a small size skin necrosis. Sixteen patients with a seroma had a secondary complication. All complications resolved. Diabetes mellitus and use of anticoagulants were associated with an increased risk of wound dehiscence and bleeding, respectively. CONCLUSIONS: IORT for breast cancer is safe in appropriately selected patients. Careful surgical technique and postoperative care is prudent. J. Surg. Oncol. 2016;113:370-373. © 2016 Wiley Periodicals, Inc.

[OUTCOMES OF HEPATIC, PANCREATIC AND GASTRIC SURGERY IN THE ELDERLY POPULATION: MORBIDITY, MORTALITY AND RESPONSE TO ONCOLOGIC TREATMENT].

INTRODUCTION: There is a continuous rise in the proportion of elderly people in the general population. Previously, old age was a contraindication for numerous medical procedures. AIM: To assess the postoperative outcome of elderly patients who underwent major surgery of the liver, pancreas and stomach. MATERIALS AND METHODS: A retrospective analysis of patients aged 75 and older who underwent elective operations for malignant tumors of the stomach, pancreas and liver between January 2005 and December 2009 in the Department of Surgery A, at Carmel Medical Center. RESULTS: Of 258 operations, 80 (31%) were performed on patients older than 75 years; 46 (57.5%) were for males and 34 (42.5%) for females, with a mean age of 79 years. One patient was operated on twice. In 68 Patients (85%) the disease was primary and in 12 (15%) it was metastatic; 28 (35.4%) tumors were in the distal stomach, 13 (16.5%) in the proximal stomach; in the pancreas 13 tumors (16.5%) were in the head and 8 (10.1%) in the body/tail; 17 patients had liver metastases (21.5%1; 68 operations (85%) were performed in an open approach and 12 (15%) laparoscopically. Median hospital stay was 12 (±7.48) days and median ICU stay was 2 (±3.53) days. Median followup was 23 (±23) months. Complete records of 76 patients showed that 33 (43.4%) are alive with no evidence of disease; 12 (15.8%) were alive with stable disease; 25 (32.89%) died of cancer and 6 (7.8%) of other causes. DISCUSSION: These favorable results allow us to offer elderly patients the entire spectrum of surgical and medical procedures without considering advanced age as an absolute contraindication. CONCLUSIONS: Chronological age as a single parameter should not be a contraindication for radical medical treatment.

[Modeling integrative oncology care program for Arab patients in north Israel: towards quality of life improvement during chemotherapy].

BACKGROUND: In the last decade, a number of integrative oncology programs have been established within leading oncology departments in Israel aiming to provide consultations that address patients' concerns and improve their quality of life (QOL). OBJECTIVE: To identify Arab cancer patients' attitudes, needs and expectations concerning integration of complementary and traditional medicine (CTM) in their supportive oncology care. METHODS: This article presents studies based on both qualitative (including interviews with patients, oncologists and CTM practitioners) and quantitative studies which were designed to evaluate patients' attitudes, needs and expectations regarding CTM integration in supportive oncology care. RESULTS: Of the 313 Arab respondents, 109 reported on the use of herbal medicine for cancer-associated outcomes. Over 78% of respondents considered QOL improvement as their main expectation of integrated CM consultation. Similar expectations were expressed in studies exploring 155 cancer care practitioners in Israel and Arab countries, 27 CTM-trained Arab practitioners, and a sample of 15 Arab patients referred to integrative medicine consultation. CONCLUSIONS: Arab cancer patients support QOL-oriented integrated medicine programs provided in oncology settings. Integrative medicine consultation should provide patients with an evidence-based recommendation on efficacy and safety of herbs commonly used concomitant with chemotherapy. We recommend designing integrative oncology training courses for physicians who will provide evidence-based consultation attuned with Arab patients' needs, concerns and cultural-sensitive orientation.

Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.

PURPOSE: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. PATIENTS AND METHODS: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. RESULTS: A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). CONCLUSION: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.

[Intraoperative radiotherapy (IORT) in early breast cancer].

BACKGROUND: Breast-conservation therapy is widely accepted as an effective treatment option for patients with early stage carcinoma of the breast. The proportion of patients with recurrence after receiving partial breast irradiation is the same as that seen in patients treated with whole breast irradiation. Therefore, the necessity of whole breast irradiation has been questioned, and partial breast irradiation has emerged as a reasonable alternative. METHODS: Since 2006, 468 women with early breast cancer (age > 60 years, T1, infiltrative duct carcinoma and with no clinical or sonographic suspicion of involved axillary lymph nodes) were treated in the Carmel Medical Center with intraoperative radiotherapy, using the INTRABEAM System giving 20 Gy at the tumor bed. We report the cohort of the first 100 patients who have had a follow up period of more than 3 years. RESULTS: The median age was 70 years (range 56-87 years). Twenty four patients had mild to moderate local complications, while nine patients experienced major local complications. Eighteen patients had metastatic involvement of the axillary lymph nodes, and in 16 of them, only one node was involved. Five patients had additional local therapy (one patient underwent mastectomy and four patients received whole breast irradiation). During the follow up period, four ipsilateral breast failures were observed: two new primary tumors (by location and histology) and two local recurrences. CONCLUSIONS: Intraoperative radiotherapy using the INTRABEAM system is feasible and may offer an alternative to whole breast radiotherapy, in low risk early breast cancer patients with a low rate of local recurrence and morbidity. Longer follow up is required in order to evaluate long term results and late toxicity.

Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone: A Randomized Controlled Study.

OBJECTIVE: To examine the role of intratympanic Dexamethasone (ITD) in the prevention of Cisplatin-induced hearing loss. STUDY DESIGN: Prospective randomized controlled clinical trial. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Twenty-six patients suffering from a neoplastic disease for which the treatment protocol included Cisplatin were recruited. Prior to each Cisplatin treatment session ITD was injected to the baseline randomly assigned ear while the other ear of the same patient served as the control. Audiometry and Distortion Product Otoacoustic Emissions (DPOAEs) test results of the baseline and follow-up examinations were compared within and between the study and control ears. RESULTS: The cumulative dose of Cisplatin was greater than 400 mg for the 15 subjects who completed the study. The pure tone threshold at 8000 Hz and pure tone average threshold at 4000 to 8000 Hz significantly increased in both the study (P < .005, P < .03, respectively) and control ears (P < .01, P < .005, respectively). Significant increase in the pure tone threshold for 6000 Hz was observed in the control (P < .02) but not in the study group. Within the groups comparison also revealed significant decrease in the DPOAE average signal-to-noise ratio (SNR) for the f2 frequencies 7031 (P < .04) and 8391 Hz (P < .04) and SNR average for 4000 to 8000 Hz in the control (P < .04) but not in the study ears. CONCLUSIONS: ITD significantly attenuated hearing loss at 6000 Hz and decreased the outer hair dysfunction in the DPOAE f2 range of 4000 to 8000 Hz. ITD might have potential in the reduction of Cisplatin-induced hearing loss.

Statins, aspirin and risk of venous thromboembolic events in breast cancer patients.

Venous thromboembolic events (VTE's) are associated with decreased survival in breast cancer patients. Studies suggested that statins reduce the risk of VTE's in the general population. Low dose Aspirin reduces risk of VTE's in high risk populations. The Breast Cancer in Northern Israel Study is a case-control study of consecutive breast cancer cases diagnosed in northern Israel and matched controls. The present analysis was limited to cases with breast cancer enrolled in the study. Data was extracted from Clalit Health Services (CHS) database and from computerized pharmacy records. Out of 3,585 patients enrolled, 261 (7.3%) had a VTE during median follow up of 4.2 years. The 1 and 2 year cumulative incidence was 2.64 and 3.65%. 55.7% of patients used statins, predominantly simvastatin (75.8%). 44.5% used aspirin. In multivariate analysis neither statins nor aspirin use was associated with a reduced risk for a VTE. Unadjusted HR for statin and aspirin was 1.461 (1.018-2.096) and 1.293 (0.846-1.976), respectively, and the adjusted HR were 0.86 (0.648-1.14) and 1.013 (0.737-1.392). Results were similar when only simvastatin use was assessed. Metastatic disease, chemotherapy, age, BMI and presence of comorbidities were significantly associated with risk of VTE's. Our study is the first to look at the effect of statins and aspirin on the incidence of VTE's in patients with breast cancer. In our cohort, statin and aspirin use did not decrease the risk for a VTE. Our results might be explained by use of low potency statins (simvastatin and pravastatin) and by alternate mechanisms for VTE formation in patients with cancer.

The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients.

Oncotype DX testing is reimbursed in Israel for node-negative and node-positive (N1+; up to 3 positive nodes including micrometastases), estrogen receptor positive (ER+), breast cancer patients. This retrospective study evaluated the impact of Oncotype DX testing on treatment decisions in N1+/ER+ breast cancer patients. To this end, we compared treatments for all N+ patients for whom testing had been ordered with treatments for patients with similar characteristics where the test had not been available. The retrospective analysis included 951 patients (282 Oncotype DX, 669 controls), all of whom received endocrine therapy with or without chemotherapy. In Oncotype DX patients, 7.1, 37.0, and 100 % of those with low, intermediate, and high Recurrence Score results (Oncotype DX summary score) received chemotherapy, respectively (P < 0.0001, all comparisons). Chemotherapy use was lower in Oncotype DX patients versus controls (24.5 vs. 70.1 %). In a multivariate logistic regression analysis in which the probability of receiving chemotherapy was modeled as a function of Oncotype DX testing, age, tumor size, tumor grade, nodal status, and the interactions between Oncotype DX testing and the other covariates, Oncotype DX testing was associated with significantly lower odds of receiving chemotherapy (odds ratio 0.16; 95 % CI 0.11-0.24; P < 0.0001). In summary, our findings suggest that Oncotype DX testing has a significant impact on reducing chemotherapy use in N1+/ER+ breast cancer patients in Israel.

Integrating complementary medicine and supportive care: patients' perspectives toward complementary medicine and spirituality.

OBJECTIVES: The association of spirituality and complementary and alternative medicine (CAM) in oncology is unfolding as a research theme that may have practical implications in supportive care. The purpose of this study was to explore patients' perspectives regarding CAM and spirituality in order to address their needs in an integrative oncology program. METHODS: A 27-item questionnaire was developed that was administered by research assistants to a convenience sample of patients attending a community-based oncology service in northern Israel. RESULTS: Of the 509 respondents, 302 (67.4%) were undergoing active oncological treatment and 146 (32.6%) were doing follow-up surveillance. Current and/or previous year CAM use for oncology treatment was reported by 244 of 495 respondents (49%). A logistic regression model indicated that CAM use was associated with younger age, Jewish religion, and higher cancer-related spiritual quest [EXP(B)=2.102, 95% confidence interval for EXP(B) 1.236-3.575, p=0.006]. Compared with patients with lower spiritual quest, CAM users with higher spiritual quest expressed more expectations of CAM counseling in the following themes: improving daily functioning and coping with disease, lessening chemotherapy side-effects, and supporting the patient and family emotionally and spiritually. In addition, they expected their social worker to be more involved in building the CAM treatment plan compared to patients with average spiritual quest (35.3% versus 16.3%, p=0.038). CONCLUSIONS: Higher degree of spiritual quest is associated with increased CAM use, and higher expectations from CAM providers and social workers in the context of CAM integration within cancer care.

Chemotherapy-related cognitive impairment: does integrating complementary medicine have something to add? Review of the literature.

Chemotherapy-related cognitive impairment is a phenomenon of cognitive decline that some patients experience during and after chemotherapy. The prevalence of chemotherapy-related cognitive impairment in cancer survivors ranges from 14 to 85 %. Memory loss and lack of concentration are the most frequent symptoms, often resulting in deterioration of daily functioning and a decreased quality of life. Despite ongoing research on chemotherapy-related cognitive impairment, a clear understanding of the underlying mechanisms of the neurotoxicity induced by chemotherapy and the factors that determine a patient's vulnerability are still lacking. We review current knowledge regarding the etiology of chemotherapy-related cognitive impairment, risk factors, conventional therapy, coping strategies, and potential complementary and integrative medicine treatments. Complementary and integrative medicine modalities that may improve chemotherapy-related cognitive impairment include mind-body techniques and acupuncture, as well as nutrition and herbal therapies. Studies on these modalities have not directly tested the hypothesis of modifying chemotherapy-related cognitive impairment and were done on different disorders of memory loss and lack of concentration. We recommend conducting further research on the potential role of complementary and integrative medicine modalities in the treatment and prevention of chemotherapy-related cognitive impairment.

Modeling an integrative oncology program within a community-centered oncology service in Israel.

OBJECTIVE: Describing the processes that preceded the opening of an integrative oncology program (IOP) within the oncology service (OS) of the largest health maintenance organization in northern Israel. METHODS: The groundwork towards initiation of the IOP was based on three key elements (1) Interviews with patients, practitioners and directors were performed in order to explore perspectives regarding complementary medicine integration (CM) within the OS; (2) review of research data on CM efficacy and safety in cancer care; (3) critical comparative analysis of seven models of IOPs in Israel, Europe, and the U.S. RESULTS: Ninety-three interviews included 24 patients, 34 conventional practitioners, 9 medical directors, and 26 CM-trained practitioners. The interviews revealed that there is a need for CM in the OS, aimed towards improving patients' well-being during chemotherapy and advanced disease. An integrative oncology score (IOS) was formulated based on 6 themes considered promoters of successful integration. CONCLUSIONS: Integration of CM within an oncology service should address patients' needs and research knowledge and be built upon mandatory practitioners' communication. PRACTICE IMPLICATIONS: IOP modeling necessitates in-depth study aimed at revealing the OS needs and expectations, adjusting research data to the OS clinical challenges, and tailoring an appropriate model of integrative care.

Barriers to integration of traditional and complementary medicine in supportive cancer care of arab patients in northern Israel.

In 2008, an Integrative Oncology Program (IOP), aiming to improve patients' quality of life during chemotherapy and advanced cancer, was launched within the Clalit Health Organization's oncology service at the Lin Medical Center, Haifa, Israel. The IOP clinical activity is documented using a research-based registry protocol. In this study, we present an analysis of the registry protocol of 15 Arab patients with cancer who were referred to the IOP. Analysis of patients' reported outcomes using the Edmonton Symptom Assessment Scale suggests that integrative medicine care improves fatigue (P = 0.024), nausea (P = 0.043), depression (P = 0.012), anxiety (P = 0.044), appetite (P = 0.012), and general well-being (P = 0.031). Barriers to integration of traditional and complementary medicine in supportive care of Arab patients are discussed followed by six practical recommendations aimed at improving accessibility of patients to integrative supportive care, as well as compliance with treatments.