Breast density assessment in adolescent girls using dual-energy X-ray absorptiometry: a feasibility study

Breast density, the radiographically opaque fraction of the breast in a mammogram, is one of the strongest biomarkers of breast cancer risk. However, younger populations do not typically have mammograms due to radiation concerns. This study explored a commercially available dual-energy X-ray absorptiometer (DXA) system as a low-dose method to measure breast fibroglandular density in adolescent girls. Eighteen girls (13-14 years old) indicated their breast development according to Tanner and underwent three dedicated DXA scans, two of their left and one of their right breasts. Total projected breast area was manually delineated on each image and percent fibroglandular volume density (%FGV), absolute fibroglandular volume (FGV), total breast area, and volume were computed. It was possible to image breasts representing all five Tanner stages; %FGV ranged from 31.9% to 92.2% with a mean of 71.1 +/- 14.8%, whereas FGV ranged from 80 to 270 cm(3) with a mean of 168 +/- 54 cm(3). Left and right breast %FGV were highly correlated (r(p) = 0.97, P < 0.0001) and of the same magnitude (P = 0.18). However, left total volume and FGV were larger than the right by 38 cm(3) (P = 0.04) and 19 cm(3) (P = 0.02), respectively. Total volume and FGV increased by Tanner stage, whereas %FGV did not. Our method had excellent precision for %FGV and moderate precision for FGV (root mean square SDs of 2.4% and 16.6 cm(3)). These pilot data indicate that dedicated DXA breast scans may be useful in studies exploring breast density in girls.     

双膦酸盐治疗恶性肿瘤骨转移的研究进展

骨转移是恶性肿瘤常见的并发症,在发生骨转移的肿瘤患者中,晚期乳腺癌和前列腺癌患者约占80%,肺癌、结肠癌、胃癌、膀胱癌、子宫癌、直肠癌、甲状腺癌和肾癌患者约占15%～30%。全世界每     

Developments in the systemic treatment of metastatic cervical cancer

Despite the available prevention and early detection strategies, advanced squamous-cell carcinoma of the uterine cervix remains a major concern for public health. Systemic treatment with cisplatin, either in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metastatic disease has been the cornerstone of treatment for more than two decades. Cisplatin has been also combined with a number of agents including paclitaxel, topotecan, gemcitabine, vinorelbine and ifosfamide, leading to encouraging response rates and increases in progression-free survival in a series of randomized phase III trials. Platinum-based triplets have been also tested, albeit at the cost of substantial toxicity. More recently, combinations with molecular agents targeting critical pathways in cervical malignant transformation are being assessed in clinical trials. In the current review, we discuss all recent advances in the systemic treatment of metastatic cervical cancer with emphasis on the results of large randomized phase III trials. Concerns regarding treatment-related toxicity in the context of co-morbidities and the need for potent predictive biomarkers for individualized treatment are also addressed.     

Facts and controversies in systemic treatment of metastatic breast cancer

The management of metastatic breast cancer remains an important and controversial issue. The systemic therapy, comprising endocrine, cytotoxic and biological agents, can be administered sequentially or in combination. Few drugs or combinations provide a significant improvement in survival and, therefore, in the great majority of cases, treatment is given with a palliative intent. With the exception of first-line therapy, for which general agreement exists, currently there is no consensual standard of care. This review will summarize the current knowledge and outline the controversial issues related to systemic therapy of metastatic breast cancer, with emphasis on treatment tailoring. The potential role of tumor molecular profile(s) in the selection of patients that could benefit the most from each strategy/agent will be discussed.     

Future directions in non-endocrine systemic treatment of metastatic prostate cancer

The management of prostate cancer that has become resistant to androgen deprivation is becoming more complex. Chemotherapy using docetaxel is now an established therapy for such patients with metastatic disease. Other agents including the epothilones are being evaluated and combination regimens have shown significant activity in the phase 2 setting. Other approaches for instance bisphosphonates and small molecule targeted agents are being investigated although their place in therapy is still to be determined. The use of hormones post-chemotherapy may also be useful for a subset of patients. Determining endpoints in phase 2 studies remain a problem as PSA on its own may be unreliable – new guidelines for reporting such studies have just been released which should allow some standardisation in approach. Combining various approaches is likely to depend on the pattern and speed of progression following failure of androgen deprivation.     

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.     

中医药治疗骨转移癌痛的进展

疼痛是肿瘤骨转移患者难以忍受的症状之一,具有顽固性、持续性、进行性加重等特点,发病机理尚不明确。西医治疗方案以三阶梯止痛药为主,联合放化疗等个性化治疗;中医治疗包括中药口服、中药外敷、针灸、穴位贴敷、中药注射、埋线等多种方式,起到活血化瘀止痛等功效。且中医治疗价廉惠民、无成瘾性、操作便捷、毒副反应少,因此成为骨转移癌痛治疗的研究热点。中西医联合用药可增强止痛效果,实现优势互补,且作用持久,明显提升患者生活质量。本文综述了骨转移癌痛的中医治疗进展,为后续研究提供参考。     

Evaluation of prognostic factors and comparison of systemic treatment modalities in patients with recurrent or metastatic endometrial carcinoma

Background Prognostic factors related to survival in patients with inoperable metastatic or recurrent endometrial carcinoma (MREC) have remained unclear due to lack of clinical trials. The management of these patients is also controversial. This study was performed to compare the efficacy and toxicity profiles of two different systemic therapies (chemotherapy vs hormonal therapy) given for the treatment of patients with MREC and to identify the impact of various prognostic factors on the survival. Methods Between 1992 and 2004, 44 patients with MREC were admitted to our oncology department. Four cases were excluded from this retrospective study because of lack of data in their charts. Age, presence of other systemic diseases (such as diabetes mellitus, hypertension), histological type, tumor grade, stage, disease-free interval, site of recurrence or metastasis, systemic treatment modality, overall response to treatment, and duration of time to progression were evaluated as prognostic factors. Cox regression analysis was performed for identification of independent prognostic factors and differences between patients characteristics of two treatment groups were calculated by the chi-square or t test. Results The median follow-up was 18 mo (range 3–113). The overall response rates for chemotherapy and hormonal therapy group were 42% and 41%, respectively (p>0.05). The median time to progression was 4 mo for the chemotherapy group and 5 mo for the hormonal therapy group (P>0.05). The median survival after metastasis or recurrence was 11 mo for the chemotherapy group and 16 mo for the hormonal therapy group (p>0.05). In the group of chemotherapy, grade 3–4 hematologic and nonhematologic toxicities were seen in eight and two, patients, respectively. No grade 3–4 toxicities were noted in patients treated with hormonal therapy. In multivariate analysis, only time to progression (p=0.001) and grade (p=0.04) were the independent prognostic factors on survival after metastasis or recurrence. Conclusion Histological differentiation and duration of time to progression are predictive factors for survival after metastasis or recurrence in the whole group. The efficacy of two different groups of treatment in these patients appears to be similar. But the chemotherapy may have some disadvantageous in terms of toxicity. This study supports a future randomized prospective trial of hormonal therapy vs chemotherapy in patients with MREC.     

Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents

The effect of in vitro treatment of serum with the alkylating agents carmustine (BCNU) and mechlorethamine on the protein binding of penbutolol, a basic agent mainly bound to alpha₁-acid glycoprotein (AAG), was investigated. The free fraction of penbutolol increased significantly (P<0.001) after the treatment of serum with BCNU (5.27%±0.47%) and with mechlorethamine (5.23% ±0.17%), being 1.98%±0.18% in serum not treated with BCNU or mechlorethamine. In addition, after incubation with BCNU (2 h), the free fraction of penbutolol continued increasing (10.96%±0.70% vs 5.27%±0.47% at time 0;P<0.001), whereas it remained unchanged after incubation with mechlorethamine. Moreover, dialysis against saline for 24 h did not restore the free fraction of penbutolol, which increased after treatment with carmustine (9.05%±1.24% vs. 11.04%±1.55%, nondialyzed). We concluded that the treatment of cancer patients with alkylating agents could alter the serum proteins and modify their binding capacity, and this should be taken into account in the simultaneous treatment of these patients with other basic drugs like penbutolol, e.g., methadone.     

唑来膦酸注射液治疗恶性肿瘤骨转移疼痛的临床疗效观察

目的:评价唑来膦酸注射液治疗恶性肿瘤引起的骨转移疼痛的有效性和安全性。方法:将恶性肿瘤骨转移疼痛患者52例随机分为两组,治疗组给予唑来膦酸注射液4mg静脉滴注15min;对照组给予帕米膦酸二钠注射液90mg静脉滴注6h。结果:治疗组和对照组用药后止痛有效率分别为73.08%和69.23%,无显著性差异(P>0.05);用药后止痛中位起效时间分别为第5天和第7天,无显著性差异(P>0.05);两组用药后第7天ECOG评分,治疗组用药前后及两组间比较差异有统计学意义(P<0.001)。结论:唑来膦酸注射液治疗恶性肿瘤骨转移疼痛有效,用量少,用药时间短,能显著改善患者生活质量。     

Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment

Introduction

Circulating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.

Methods

We retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch^®. Progression-free survival and overall survival were compared with the log-rank test between groups, according to CTC count (< 5 vs. ≥ 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients receiving different treatments.

Results

At a median follow-up of 18 months, the CTC count was confirmed to be a robust prognostic marker in the overall population (median progression-free survival 12.0 and 7.0 months for patients with CTC < 5 and ≥ 5, respectively; P < 0.001). Conversely, in patients with human epidermal growth factor receptor-2-overexpressed/amplified tumors receiving trastuzumab or lapatinib, the baseline CTC count was not prognostic (median progression-free survival 14.5 months for patients with CTC < 5 and 16.1 months for those with CTC ≥ 5; P = 0.947). Furthermore, in patients with human epidermal growth factor receptor-2 normal tumors, a baseline CTC count ≥ 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.

Conclusions

This analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.     

Ibandronate: efficacy in the treatment of metastatic bone disease

Ibandronate is a bisphosphonate treatment for metastatic bone disease. In Phase III trials in breast cancer patients, intravenous and oral formulations of ibandronate lowered the incidence of skeletal-related events, reduced metastatic bone pain scores throughout 2 years of treatment, and had significant positive effects on patient quality of life, demonstrating its efficacy in this condition. Recent pilot studies in other primary cancers suggest that a loading dose of ibandronate may relieve severe or opioid-resistant metastatic bone pain. In safety analyses, ibandronate was well tolerated with a safety profile comparable to placebo. Ibandronate therefore represents a treatment choice with documented efficacy and safety in metastatic bone disease from breast cancer.     

唑来膦酸治疗恶性肿瘤骨转移疼痛的临床观察

目的:评价唑来膦酸治疗恶性肿瘤引起骨疼痛的有效性和安全性.方法:对62例确诊为恶性肿瘤骨转移的患者静脉注射唑来膦酸注射液4mg,静脉滴注15min,4周为1周期.3周期后评价疗效.结果:癌性骨转移疼痛止痛总有效率58.1%(36/62).其中初治组骨痛完全缓解23.5%(8/34),部分缓解47.1%(16/34),总有效率为70.6%(24/34).显著高于复治组42.9%(P<0.05).QOL较治疗前明显改善.主要不良反应为低热,无需特殊处理.结论:唑来膦酸能改善恶性肿瘤骨转移患者疼痛,显著改善生活质量,不良反应可耐受.     

唑来膦酸治疗恶性肿瘤骨转移疼痛的临床观察

目的：评价唑来膦酸治疗恶性肿瘤引起骨疼痛的有效性和安全性。方法：对62例确诊为恶性肿瘤骨转移的患者静脉注射唑来膦酸注射液4mg,静脉滴注15min,4周为1周期。3周期后评价疗效。结果：癌性骨转移疼痛止痛总有效率58．1％（36／62）。其中初治组骨痛完全缓解23．5％（8／34）,部分缓解47．1％（16／34）,总有效率为70．6％（24／34）。显著高于复治组42．9％（P〈0．05）。QOL较治疗前明显改善。主要不良反应为低热,无需特殊处理。结论：唑来膦酸能改善恶性肿瘤骨转移患者疼痛,显著改善生活质量,不良反应可耐受。