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.

[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.

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.

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.

[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.

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.

[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.

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.

Differences in pathological and clinical features of breast cancer in Arab as compared to Jewish women in Northern Israel.

Breast cancer (BC) does not affect ethnic groups equally. BC mortality is higher in Israeli Palestinian Arab women than among Israeli Jewish women. This study aims to compare clinical, biological and pathological characteristics of breast cancer in the two populations. Records of 1,140 women with BC treated at Northern Israel between 2002 and 2007 were reviewed: 872 Jews and 268 Arabs. Age at diagnosis, tumor stage, pathological differentiation, estrogen receptor (ER) and HER-2 expression were evaluated. The main age at diagnosis was 49.9 years for Arabs and 59.4 years for Jews (p < 0.0001). Mean tumor size was < 2 cm in 25% of Arabs and 53% of Jews (p < 0.0001). Lymph node metastases presented in 64.6% of Arabs and 37.2% of Jews (p < 0.0001). Stage I disease was 19% in Arab and 49.2% in Jewish women while Stages III and IV disease was 42% and 11.3% respectively (p < 0.001). ER was positive in 69% of Arabs and in 78.5% of Jews (p < 0.001). Poorly differentiated tumors were found in 28.8% of Arabs vs. 12.8% in Jews (p < 0.0001). Overexpression of HER-2 was present in 35.4% of Arab and 22% of Jewish women (p < 0.001). We found that race is an important predictive factor for breast cancer. Arab women are diagnosed at younger age, with more advanced stage and biologically more aggressive disease than in Jewish women. Socioeconomic factors alone are not sufficient to explain significant effects of race on tumor characteristics. Findings suggest a different genetic susceptibility in the two populations which needs further research.

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.

Attitudes of patients with gynecological and breast cancer toward integration of complementary medicine in cancer care.

OBJECTIVE: The purpose of this study was to explore prospectively the perspectives of patients with breast and gynecological cancers regarding integration of complementary and alternative medicine (CAM) in conventional oncology settings. METHODS: We developed a 27-item questionnaire that was administered to convenient sample of patients with breast cancer and another with gynecological cancer who were attending a community-based oncology service in northern Israel. RESULTS: Of the 275 respondents, 109 (39.6%) had gynecological cancers and 166 (60.4%) had breast cancer. Current and/or previous year CAM use for oncology treatment was significantly higher among the patients with gynecological cancer (73/166 [44%] vs 67/106 [63%], P = 0.03). A logistic regression model indicated that CAM use was associated with gynecological cancer (EXP [B], 2.51; 95% confidence interval for EXP [B], 1.29-4.88; P = 0.007], younger age, Jewish religion, and lesser degree of religiosity. The patients highly expected their gynecologist-oncologist and family doctor to refer them to CAM counseling. Moreover, they expected their gynecologist-oncologist to participate in building a CAM treatment plan if CAM were to be integrated into the oncology service. The patients expected the CAM consultant to inform them of the safety and efficacy of CAM treatments, emphasizing expectations to strengthen their general ability to cope with the disease, reduce chemotherapy side effects, and provide emotional and spiritual support. CONCLUSION: Although patients with gynecological malignancies use CAM significantly more than patients with breast cancer, both groups share similar conceptions regarding the active role of their gynecologist oncologists in the process of CAM integration within supportive care and expect CAM consultation to focus on improving their well-being.

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.

[Integrating complementary medicine in oncology supportive care: assessment of patients' needs and expectations during chemotherapy].

BACKGROUND: During the Last decade complementary medicine is gradually being integrated within conventional oncology care in Western countries. In 2008, an integrative oncology program was implemented within the Clalit Oncology Service (COS) of the Haifa and Western-Galilee district of Clalit Health Organization aiming to promote patients' well-being during chemotherapy and in advanced disease. OBJECTIVE: To identify needs and distress of patients with regard to combining complementary medicine with the supporting treatment for improvement of quality of life. METHODS: A study using semi-constructed interviews with 31 patients during chemotherapy was performed at two outpatient oncology centers of the Clalit HMO in northern Israel. RESULTS: Most participants reported significant deterioration in their quality of life during chemotherapy, mainly related to fatigue, work cessation and mood disorder. Interest in complementary medicine significantly correlated with the participants' awareness of the mind-body connection. Most participants reported on their interest to consult with physicians specializing in complementary medicine as an integral part of the oncology service care. The most favorable complementary therapies reported by patients were nutritional counseling, herbal medicine and traditional healing. CONCLUSIONS: Asking patients during chemotherapy on their beliefs regarding mind and body connections may be used as a screening question to identify patients interested in experiencing complementary therapies. Integrating physician counseling regarding complementary medicine within the oncology service may address patients' needs and concerns by matching therapies to specific symptoms and chemotherapy side-effects.

Hand-assisted laparoscopic surgery for liver tumors.

BACKGROUND: The surgical treatment for liver tumors, whether metastatic or hepatic in origin, traditionally used the open approach through large incisions. In recent years the laparoscopic approach became popular but few centers use this method routinely. OBJECTIVES: To assess the results of our initial experience with liver resection using the laparoscopic approach, in terms of patient safety and oncologic surgical outcome. METHODS: Between August 2007 and April 2008 we performed 10 liver resections in 9 patients using the hand-assisted laparoscopic surgery technique. RESULTS: The main indication for surgery was metastatic colorectal carcinoma in seven patients and hepatocellular carcinoma in two. The mean age was 67 +/- 11 years. The tumor was solitary in seven patients. Five patients had neoadjuvant chemotherapy. Altogether, 12 lesions with an average size of 17 +/- 9 mm were resected. The mean operative time was 180 +/- 52 minutes. Average postoperative stay was 6.5 +/- 3.5 days. There was no perioperative mortality. There was one conversion to open surgery due to bleeding from the left hepatic vein. No major perioperative complications were encountered. All resected margins were free of malignancy. CONCLUSIONS: Liver resection using HALS is safe and feasible and should be considered in selected patients.

Local recurrence following adjuvant chemotherapy without radiotherapy in completely resected stomach and gastroesophageal junction adenocarcinoma.

BACKGROUND: The gold standard of adjuvant treatment after surgical resection of adenocarcinoma of the stomach or gastroesophageal junction (GEJ) is chemoradiotherapy. We retrospectively evaluated chemotherapy without radiotherapy in stomach and GEJ adenocarcinoma, using a combination of etoposide, adriamycin and cisplatin (modified EAP). PATIENTS AND METHODS: Sixty-five patients with completely resected gastric or GEJ adenocarcinoma and positive regional lymph nodes were treated with modified EAP over an 8-year period. RESULTS: Recurrent disease was diagnosed in 38/58 (69%) patients evaluable for analysis. Only two (5%) had locoregional recurrence. The main toxicity was hematological, with 22 (34%) patients developing neutropenic fever and 12 (18%) anemia requiring blood transfusion. The median survival for the entire group was 20 months, with a median time to recurrence of 11 months. Seventeen (26%) patients are alive for a median of 7+ years, with no evidence of recurrent disease. CONCLUSION: Our data cast doubt on the benefit of radiotherapy adjuvant to chemotherapy.

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.

Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.