Cost-effectiveness of postmastectomy hypofractionated radiation therapy vs conventional fractionated radiation therapy for high-risk breast cancer

BackgroundThe phase 3 NCT00793962 trial demonstrated that postmastectomy hypofractionated radiation therapy (HFRT) was noninferior to conventional fractionated radiation therapy (CFRT) in patients with high-risk breast cancer. This study assessed the cost-effectiveness of postmastectomy HFRT vs CFRT based on the NCT00793962 trial.MethodsA Markov model was adopted to synthesize the medical costs and health benefits of patients with high-risk breast cancer based on data from the NCT00793962 trial. Main outcomes were discounted lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). We employed a time-dependent horizon from Chinese, French and USA payer perspectives. Model robustness was evaluated with one-way and probabilistic sensitivity analyses.ResultsPatients receiving CFRT versus HFRT gained an incremental 0.0163 QALYs, 0.0118 QALYs and 0.0028 QALYs; meanwhile an incremental cost of $2351.92, $4978.34 and $8812.70 from Chinese, French and USA payer perspectives, respectively. Thus CFRT versus HFRT yielded an ICER of $144,281.47, $420,636.10 and $3,187,955.76 per QALY from Chinese, French and USA payer perspectives, respectively. HFRT could maintain a trend of >50% probabilities of cost-effectiveness below a willingness-to-pay (WTP) of $178,882.00 in China, while HFRT was dominant relative to CFRT, regardless of the WTP values in France and the USA. Sensitivity analyses indicated that the ICERs were most sensitive to the parameters of overall survival after radiotherapy.ConclusionsPostmastectomy HFRT could be used as a cost-effective substitute for CFRT in patients with high-risk breast cancer and should be considered in appropriately selected patients.     

SARS-CoV-2 neutralizing antibodies after first vaccination dose in breast cancer patients receiving CDK4/6 inhibitors

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.     

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I²) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I² = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I² = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I² = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I² = 38%) were equivalent for combined BCT and mastectomy.ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.     

Can supplementary contrast-enhanced MRI of the breast avoid needle biopsies in suspicious microcalcifications seen on mammography? A systematic review and meta-analysis

PurposeTo analyze the rate of potentially avoidable needle biopsies in mammographically suspicious calcifications if supplementary Contrast-Enhanced MRI (CE-MRI) is negative.MethodsUsing predefined criteria, a systematic review was performed. Studies investigating the use of supplemental CE-MRI in the setting of mammographically suspicious calcifications undergoing stereotactic biopsy and published between 2000 and 2020 were eligible. Two reviewers extracted study characteristics and true positives (TP), false positives, true negatives and false negatives (FN). Specificity, in this setting equaling the number of avoidable biopsies and FN rates were calculated. The maximum pre-test probability at which post-test probabilities of a negative CE-MRI met with BI-RADS benchmarks was determined by a Fagan nomogram. Random-effects models, I²-statistics, Deek’s funnel plot testing and meta-regression were employed. P-values <0.05 were considered significant.ResultsThirteen studies investigating 1414 lesions with a cancer prevalence of 43.6% (range: 22.7–66.9%) were included. No publication bias was found (P = 0.91). CE-MRI performed better in pure microcalcification studies compared to those also including associate findings (P < 0.001). In the first group, the pooled rate of avoidable biopsies was 80.6% (95%-CI: 64.6–90.5%) while the overall and invasive cancer FN rates were 3.7% (95%-CI: 1.2–6.2%) and 1.6% (95%-CI 0–3.6%), respectively. Up to a pre-test probability of 22%, the post-test probability did not exceed 2%.ConclusionA negative supplementary CE-MRI could potentially avoid 80.6% of unnecessary stereotactic biopsies in BI-RADS 4 microcalcifications at a cost of 3.7% missed breast cancers, 1.6% invasive. BI-RADS benchmarks for downgrading mammographic calcifications would be met up to a pretest probability of 22%.     

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability

The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons’ communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences.     

《伤寒论》六经辨证在IgA肾病诊治中的指导价值

《伤寒论》六经辨证是在《黄帝内经》六经理论及脏象、经络两学说的基础上发展、完善而得来的,是中医的鼻祖。本文的主要目的是探讨《伤寒论》六经辨证在IgA肾病诊治中应用价值。IgA肾病又称为原发性肾小球疾病,在我国常见,其整个发病过程可视为从三阳经(太阳、阳明、少阳)转变为三阴经(太阴、少阴及厥阴)。IgA肾病在各经为病,脉症特点并不相同,因此IgA肾病采用六经辨证为指导,判断病情,能够有效防治IgA肾病,对临床具有重要的意义及价值。     

动态增强磁共振成像在评估女性乳房乳头乳晕血供的应用

目的探究动态增强磁共振成像(DCE-MRI)用于评估女性乳房乳头乳晕血供特点的可行性,为乳房整形手术提供乳头乳晕的血供参考。方法从2012年3月至2019年10月华中科技大学同济医学院附属同济医院影像数据库中收集女性乳腺DCE-MRI图像资料,选择未发现肿物的正常乳房的DCE-MRI图像进行研究。在西门子工作站将患者乳腺DCE-MRI图像通过图像减影获取乳房血管图像,分别对轴位、冠状位和矢状位的最大密度投影(MIP)图像进行评估,结合三维MIP图像识别所有供应乳头乳晕的血管。乳头乳晕的血供被划分为内上、内侧、内下、外上、外侧、外下、中央、上方和下方9个象限,对各个象限血管进行统计和分析,并测量血管至乳房皮肤表面投影的最大距离。采用SPSS 19.0软件进行统计分析,通过卡方检验分别比较左侧与右侧乳房的乳头乳晕复合体(NAC)血供象限分布构成比。计算血管到皮肤距离的平均值、标准差及95%置信区间,通过方差分析比较各象限血管至皮肤距离的差异。P<0.05为差异具有统计学意义。结果共收集到245例患者490只女性乳房DCE-MRI图像,其中97例患者97只乳房发现有乳腺肿物,其余393只为正常乳房(97例单侧乳房、148例双侧乳房),将其作为研究对象。患者年龄23~72岁,平均43.7岁。393只乳房(左侧200只、右侧193只)共发现有637条(左侧311条、右侧326条)乳头乳晕供应血管。在637条血管中,内上象限269条(42.2%),外上180条 (28.3%),内侧57条(8.9%),下方37条(5.8%),中央30条(4.7%),内下25条(3.9%),外下25条(3.9%),上方11条(1.7%),外侧3条(0.5%)。卡方检验表明左侧乳房和右侧乳房在NAC血供象限分布构成比差异无统计学意义(χ2 =6.4,P=0.602)。除中央象限血管以外,所有血管到皮肤表面投影最大距离的平均值为0.91 cm, 95%置信区间为0.86~0.96 cm。方差分析表明各象限供血血管到皮肤投影的最大距离,差异有统计学意义(F=11.4,P<0.001)。结论 DCE-MRI可以清晰地显示乳头乳晕的血供来源。乳头乳晕血供主要来源于内上象限和外上象限的血管,血管在皮下约1 cm深度走行。     

Retrospective study of functional outcomes and disability after non-ischaemic vascular causes of spinal cord dysfunction

Objective: Describe demographic characteristics, functional outcomes and disability following rehabilitation for non-ischemic vascular spinal cord dysfunction (SCDys).Design: Retrospective, open cohort, case series.Setting: Tertiary rehabilitation unit, Victoria, Australia.Participants: Patients with non-ischemic vascular SCDys admitted over a 21-year-period (01/01/1995–31/12/2015) were identified using International Classification of Diseases codes.Outcome Measures: Demographic characteristics, etiology, neurologic classification, length of stay (LOS), and complications. On admission and discharge, the following were collected: functional independence measure (FIM) motor subscale, details on bowel, bladder, mobility, living arrangement, and support services.Results: 36 patients (female 58%; mean age 69 ± 16 years) were identified. The main causes of non-ischemic vascular SCDys were epidural hematoma (39%), dural arteriovenous fistula (17%), and arteriovenous malformation (11%). 22 cases (61%) were iatrogenic. Most (86%) had incomplete paraplegia. Urinary tract infection was the most common complication (64%). Median LOS in rehabilitation was 68 days. Significant improvement in FIM motor scores was observed from admission (median 25, interquartile range [IQR] 20–38) to discharge (median 69, IQR 38–77) (P < 0.001). On discharge, 4 patients (11%) walked >100 m unaided, 6 (17%) walked >100 m with assistive device, 10 (28%) walked >10 m with assistive device, 15 (41%) were wheelchair dependent and 1 (3%) patient remained non-mobile. 20 patients (56%) were discharged home, 8 (22%) to nursing home, and 8 (22%) transferred to another hospital.Conclusion: Most patients returned home with significantly improved functional outcomes compared to rehabilitation admission, but with the majority having ongoing major disabilities based on FIM motor scores.