Intraoperative Radiotherapy Versus Whole-Breast External Beam Radiotherapy in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis

There has not been a clear answer about the efficacy of intraoperative radiotherapy (IORT) for women with early-stage breast cancer.The aim of this meta-analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy (EBRT) for women with early-stage breast cancer.MEDLINE, EMBASE, the Web of Science, and the Cochrane Library were searched up to October 2014. Two authors independently conducted the literature selection and data extraction.Studies that compared IORT with whole-breast EBRT were included in the systematic review. IORT was defined as a single dose of irradiation to the tumor bed during breast-conserving surgery rather than whole-breast irradiation.Qualities of RCTs were evaluated according to the PEDro scale. Qualities of non-RCTs were evaluated according to the Methodological Index for Non-Randomized Studies (MINORS). The risk ratios (RRs) of ipsilateral breast tumor recurrence, overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were pooled using a random-effects model.Four studies with 5415 patients were included in this meta-analysis, including 2 randomized controlled trials (RCTs) and 2 non-RCTs. Ipsilateral breast tumor recurrence was significantly higher in patients with IORT compared to those with whole-breast EBRT (RR 2.83, 95% CI 1.23–6.51), but with significant heterogeneity (I² = 58.5%, P = 0.065). Comparing IORT with whole-breast EBRT, the pooled RRs for overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were 0.88 (95% CI: 0.66–1.17), 1.20 (95% CI: 0.77–1.86), 0.76 (95% CI: 0.44–1.31), and 0.95 (95% CI: 0.61–1.49), respectively.IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT. Overall mortality did not differ significantly. IORT should be used in conjunction with the prudent selection of suitable patients. It is imperative to identify women with a low risk of local recurrence.     

Acute Myeloid Leukaemia Complicating a Breast Cancer after Mastectomy and Radiotherapy

The author reports a patient treated three years ago for a breast carcinoma. High doses of X-ray had been delivered after radical mastectomy. The possible relationship between this exposure and a rapidly fatal acute myeloid leukaemia is emphasized.     

乳腺癌放化疗引起心脏毒性的一级预防进展

女性乳腺癌发病率和死亡率分别位居中国女性恶性肿瘤的第1位和第5位。早期诊断和规范治疗显著减少乳腺癌患者的死亡率,但乳腺癌放化疗的心脏毒性成为其死亡的主要原因之一。早期预防心脏毒性至关重要。现从以下几方面论述:评估心血管疾病风险、放射治疗策略、预防蒽环类药物心脏毒性以及β受体阻滞剂和/或血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体阻滞剂和他汀类药物的心脏保护作用。     

Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review

Cardiovascular toxicity is a potential short- or long-term complication of anticancer therapy. Exposure to chemotherapy medications, primarily the anthracycline class, can lead to potentially irreversible clinically significant cardiac dysfunction. The advent of novel biologic agents, including monoclonal antibodies and tyrosine kinase inhibitors, has revolutionized the treatment of several types of malignancies. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare serious complications have been observed; and longer-term follow-up is needed to determine the exact profile of related cardiac adverse effects. Cardiac toxicity associated with cancer therapies can range from asymptomatic subclinical abnormalities, including electrocardiographic changes and temporary left ventricular ejection fraction decline, to life-threatening events such as congestive heart failure or acute coronary syndromes. Assessment of the prevalence, type, and severity of cardiac toxicity caused by various cancer treatments is a critical topic for patient management and specifically for new drug development. Guidelines for monitoring cardiac adverse effects have been formulated; however, appropriate supportive evidence remains limited. Given the rate of new drug development designed to fulfill unmet oncologic needs, efforts are needed to promote strategies for cardiac risk detection and management and to avoid unintended consequences potentially impeding development of, regulatory approval for, and patient access to novel therapies. These advances require ongoing research to assess and manage the cardiovascular safety of patients treated with anticancer agents, as well as a well-organized collaboration between oncologists and cardiologists. The aim of this review is to summarize potential cardiovascular toxicities for a range of cancer chemotherapeutics and to review general mechanisms of cardiovascular toxicity for each agent.     

Absorption of Wheat Starch in Patients Resected for Left-Sided Colonic Cancer

Bacterial fermentation of carbohydrate in the colon, producing short-chain fatty acids (SCFA)–and especially butyrate–has been shown possibly to impede cell proliferation and regulate cell differentiation of colonocytes. In patients with diverticular disease or benign polyps in the colon a hyperabsorption of potato starch in the small intestine has been found. We have investigated the absorption of wheat starch in 15 patients radically resected for cancer in the descending or sigmoid colon, and the results were compared with those of 15 healthy controls. The starch malabsorption was quantified by the hydrogen breath test. The patients malabsorbed 2-14 g (median, 8g) of 100 g wheat starch ingested, and the control group malabsorbed 3-11 g (median, 6 g) (P > 0.1). Mouth-to-cecum transit time for wheat starch and lactulose and the hydrogen production capacity after the lactulose standards were also similar in patients and controls. The results do not support the theory that hyperabsorption of starch is characteristic of patients with malignant disease in the large intestine     

Moderate Alcohol Consumption and Breast Cancer in Women: From Epidemiology to Mechanisms and Interventions

Epidemiologic studies indicate that moderate alcohol consumption increases breast cancer risk in women. Understanding the mechanistic basis of this relationship has important implications for women's health and breast cancer prevention. In this commentary, we focus on some recent epidemiologic studies linking moderate alcohol consumption to breast cancer risk and place the results of those studies within the framework of our current understanding of the temporal and mechanistic basis of human carcinogenesis. This analysis supports the hypothesis that alcohol acts as a weak cumulative breast carcinogen and may also be a tumor promoter. We discuss the implications of these mechanisms for the prevention and treatment of alcohol‐related breast cancer and present some considerations for future studies. Moderate alcohol consumption has been shown to benefit cardiovascular health and recently been associated with healthy aging. Therefore, a better understanding of how moderate alcohol consumption impacts breast cancer risk will allow women to make better informed decisions about the risks and benefits of alcohol consumption in the context of their overall health and at different stages of their life. Such mechanistic information is also important for the development of rational clinical interventions to reduce ethanol‐related breast cancer mortality.     

Prognostic Implications of Diabetes in Patients With Left-Sided Endocarditis: Findings From a Large Cohort Study

Patients with diabetes mellitus (DM) have a higher incidence of infections, and those with bacteremia are more prone to develop sepsis and infective endocarditis (IE). Nevertheless, data concerning the impact of DM on the prognosis of patients with IE are limited and sometimes contradictory. We examined the impact of DM on the inhospital outcome of left-sided IE in a large cohort of patients. We studied 594 consecutive episodes of left-sided IE diagnosed at 3 tertiary care centers. They were divided into 2 groups: episodes in patients with DM (n = 114) and episodes in patients without DM (n = 480). We retrospectively analyzed the influence of DM therapy on patient outcome. Compared to patients without DM, patients with DM were older (67 ± 10 vs. 60 ± 15 yr; p < 0.001), less frequently male (53.5% vs. 67.9%; p = 0.004), and more commonly had chronic renal failure (23.9% vs. 6.9%; p < 0.001) and chronic obstructive pulmonary disease (14.6% vs. 7.8%; p = 0.019). Enterococcus (14.9% vs. 7.4%; p = 0.011) and Streptococcus bovis (8.8% vs. 3.8%; p = 0.024) were isolated more frequently. In the univariable analysis, septic shock (29.2% vs. 16.4%; p = 0.005) and mortality (43.5% vs. 30.0%; p = 0.008) were more common among patients with DM than in those without. Considering the different treatments for DM, septic shock (33.3%; p = 0.011) and death (50.8%; p = 0.012) were more frequent in patients receiving oral medication to treat diabetes than in patients with the other treatment modalities. However, multivariable analysis showed that DM had an independent association with development of septic shock (OR 2.282; 95% CI 1.186–4.393), but it was not a predictor of inhospital mortality.Staphylococci were the most frequently involved microorganisms in all patients; however, Enterococcus and Streptococcus bovis were more frequently isolated from individuals with DM and left-sided IE, whereas viridans group streptococci were more commonly isolated from those with left-sided IE who did not have DM. DM was independently associated with the development of septic shock, but it was not an independent predictor of inhospital mortality in patients with left-sided IE.Abbreviations: CI = confidence interval, COPD = chronic obstructive pulmonary disease, DM = diabetes mellitus, IE = infective endocarditis, OR = odds ratio     

Preoperative Radiotherapy Improves Outcome in Recurrent Rectal Cancer

PURPOSE When local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only.METHODS Between 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database. Ninety-two patients were suitable for resection with curative intent. Preoperative radiation with a median dosage of 50 Gy was performed in 59 patients; 33 patients did not receive preoperative radiotherapy. The median age of the patients was respectively 66 and 62 years.RESULTS The median follow-up of patients alive for the total group was 16 (range, 4–156) months. Tumor characteristics were comparable between the two groups. Complete resections were performed in 64 percent of the patients who received preoperative radiation and 45 percent of the nonirradiated patients. A complete response after radiotherapy was found in 10 percent of the preoperative irradiated patients (n = 6). There were no differences in morbidity and reintervention rate between the two groups. Local control after preoperative radiotherapy was statistically significantly higher after three and five years (P = 0.036). Overall survival and metastases-free survival were not different in both groups. Complete response to preoperative radiotherapy was predictive for an improved survival.CONCLUSIONS Preoperative radiotherapy for recurrent rectal cancer results in a higher number of complete resections and an improved local control compared with patients treated without radiotherapy. Preoperative radiotherapy should be standard treatment for patients with recurrent rectal cancer.     

Value of Intraoperative Radiotherapy in Locally Advanced Rectal Cancer

Purpose This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. Methods Between 1987 and 2002, 123 patients with initial unresectable and locally advanced rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathologic reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed. Results All patients were treated preoperatively with a median dose of 50 Gy radiotherapy. Surgery was performed six to ten weeks after radiotherapy. Twenty-seven patients were treated with intraoperative radiotherapy because margins were incomplete or ≤2 mm. Postoperative mortality was 2 percent. The median follow-up of all patients was 25.1 months. The overall five-year local control was 65 percent and the overall five-year survival was 50 percent. Positive lymph nodes and incomplete resections negatively influenced local control and overall survival. Intraoperative radiotherapy improved five-year local control (58 vs. 0 percent, P = 0.016) and overall survival (38 vs. 0 percent, P = 0.026) for patients with R1/2 resections. Conclusions The presented multimodality treatment is feasible with an acceptable mortality and a five-year overall survival of 50 percent. Addition of intraoperative radiotherapy for patients with a narrow or microscopic incomplete resection seems to overrule the unfavorable prognostic histologic finding.