Partial breast irradiation versus whole breast radiotherapy for early-stage breast cancer: a decision analysis

PURPOSE: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. METHODS AND MATERIALS: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. RESULTS: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adjusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. CONCLUSIONS: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.     

早期乳腺癌保乳术后调强放疗

现行早期乳腺癌保乳术后的常规切线野放射治疗技术存在靶区内剂量不均匀的缺陷.国内外多位研究者将调强放疗(IMRT)应用于保乳术后患者,以期在提高靶区剂量均匀性、降低危及器官受量及改善美容效果方面体现出一定优势.     

早期乳腺癌保乳术后调强适形放疗的应用

传统的保乳术后放疗方法是做全乳腺照射5～6周,引起的不良反应多见.随着放射治疗技术的发展,以最小的侵袭或损伤达到最佳疗效,已成为肿瘤学者追求的目标.调强适形放疗(IMRT)的发展有很大的空间,日益受到广大学者的重视,将可能会成为早期乳腺癌保乳术后的标准治疗方式.     

Dosimetric evaluation of whole breast radiotherapy using field-in-field technique in early-stage breast cancer

Background  

The purpose of this study is to evaluate the dosimetric benefits of whole breast radiotherapy (WBRT) using the field-in-field technique compared with conventional tangential field radiotherapy with physical wedges for WBRT.     

Hypofractionated whole breast radiotherapy in breast conservation for early-stage breast cancer: a systematic review and meta-analysis of randomized trials

Purpose

Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer.

Methods

377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios.

Results

While HLA-ABC and HLA-A expressions showed a positive correlation with CD8+ and FOXP3+ TIL infiltration, IDO expression showed a negative correlation with FOXP3+/CD4+ and FOXP3+/CD8+ T cell ratios. Expressions of HLA-ABC, HLA-A, and IDO shared an association with negative estrogen receptor status. Infiltration of CD4+, CD8+, and FOXP3+ TILs was significantly higher in tumors with high histologic grade, negative hormone receptor status, HER2 amplification, high Ki-67 index, and p53 overexpression. In survival analyses, increased CD4+ TIL infiltration was associated with better prognosis of the patients while other TIL subset infiltration and expression of immunomodulatory proteins had no prognostic significance. In subgroup analyses, high CD4+ TIL infiltration was revealed as an independent good prognostic factor in hormone receptor-negative subgroup while high FOXP3+/CD8+ T cell ratio was found to be an independent adverse prognostic factor in hormone receptor-positive subgroup, especially in luminal A subtype.

Conclusion

CD4+ TIL subset and FOXP3+/CD8+ T cell ratio have different prognostic significance in breast cancer according to hormone receptor status.

     

Skin-sparing radiation using intensity-modulated radiotherapy after conservative surgery in early-stage breast cancer: a planning study

PURPOSE: To evaluate the feasibility of skin-sparing by configuring it as an organ-at-risk (OAR) while delivering whole-breast intensity-modulated radiotherapy (IMRT) in early breast cancer. METHODS AND MATERIALS: Archival computed tomography scan images of 14 left-sided early-breast tumor patients who had undergone lumpectomy were selected for this study. Skin was contoured as a 4- to 5-mm strip extending from the patient outline to anterior margin of the breast planning target volume (PTV). Two IMRT plans were generated by the helical tomotherapy approach to deliver 50 Gy in 25 fractions to the breast alone: one with skin dose constraints (skin-sparing plan) and the other without (non-skin-sparing plan). Comparison of the plans was done using a two-sided paired Student t test. RESULTS: The mean skin dose and volume of skin receiving 50 Gy were significantly less with the skin-sparing plan compared with non-skin-sparing plan (42.3 Gy vs. 47.7 Gy and 12.2% vs. 57.8% respectively; p < 0.001). The reduction in skin dose was confirmed by TLD measurements in anthropomorphic phantom using the same plans. Dose-volume analyses for other OARs were similar in both plans. CONCLUSIONS: By configuring the skin as an OAR, it is possible to achieve skin dose reduction while delivering whole-breast IMRT without compromising dose profiles to PTV and OARs.     

早期乳腺癌乳房保留治疗的疗效分析

目的 评价早期乳腺癌保乳术后伞乳放疗的生存率和局部.区域控制率,探讨影响局部控制的因素.方法 近10年收治的早期乳腺癌接受保乳术者335例,其中术后单纯放疗、序贯化放疗、同期放化疗、化放化疗分别为25、194、80、36例.312例接受腋窝淋巴结清扫,2例前哨淋巴结活榆.310例接受辅助化疗.256放疗范围为单纯乳房,79例包括区域淋巴结照射.全乳和区域淋巴结照射剂量为50 Gy分25次,中位瘤床剂量为60 Gy分30次.放疗和手术间隔时问<4、4～8、>8～20、>20周的比例分别为16.4%、23.6%、37.3%、22.7%.结果 中位随访期48.0个月(25.3～146.7个月).5年局部一区域控制率和同侧乳房控制率分别为94.5%和95.6%;5年无病生存率、无转移牛存牢和总生俘率分别为88.6%、93.2%和98.8%.单因素分析发现脉管受侵、神经受侵犯和Ⅱ期切除的5年局部控制率下降,手术与放疗间隔时间、化疗与放疗结合方式的局部榨制率均相似.多因素分析发现脉管侵犯和Ⅱ期切除是独立的预后因素.序贯化放疗+单纯放疗、同期放化疗、化放化疗≥3级皮肤反应(湿性脱皮)发生率分别为4.5%、80.0%、77.0%(χ2=226.00,P=0.000).结论 早期乳腺癌保乳术加术后伞乳放疗等可获得良好的局部控制率和牛存率.脉管受侵与否和Ⅱ期切除是影响局部控制率的独立预后因素.未发现手术与放疗间隔时间、放疗与化疗结合方式对局部控制率有影响,但同期放化疗或化放化疗者发生皮肤湿性脱皮的概率明显增高.     

Breast-conserving surgery and radiotherapy in early-stage breast cancer: the importance of local control

Breast-conserving therapy is a successful, well-studied, and scientifically validated treatment of early-stage breast carcinoma. This approach has enormously improved the quality of life and cosmetic outcome for appropriately selected and treated patients while achieving the same long-term survival rates as mastectomy. This article reviews the evidence showing the importance of achieving initial local control to maximize breast cancer-specific survival rates, the impact of systemic therapy on the local control rates achieved with breast-conserving therapy, the integration of chemotherapy with radiation therapy, and the role of breast magnetic resonance imaging in breast-conserving therapy.     

早期乳腺癌保乳术后全乳放疗替代模式

全乳房照射已被用于降低早期乳腺癌保乳术后同侧乳腺肿瘤复发的风险,并且多项随机临床试验和荟萃分析已经证明这一放疗模式安全有效,但随着放疗技术的进步以及患者生存期的延长,这种标准治疗模式目前也面临着一些挑战,其替代模式受到了越来越多的关注.其中部分乳腺照射、全乳大分割放疗、省略放疗针对不同的乳腺癌患者,疗效与全乳腺常规照射相当,且降低了不良反应,同时缩短了治疗时程,减轻了患者负担,值得在临床推广应用.     

早期乳腺癌保乳术后的放疗时机

早期乳腺癌保留乳房手术加放疗的疗效与根治术相同。对术后放疗时机的问题有一些回顾性和随机性研究,但无明确结论,近期的一些随机研究尚需要长期随访。总的来说,对于无需术后化疗的病人应尽早放疗,建议手术放疗间隔最好不超过8周。术后放疗、化疗顺序对疗效无显著影响,先放疗或先化疗均可以。对于腋窝淋巴结转移数较多的远地转移高危病人,术后可先做辅助化疗,但放疗不应延迟到术后7个月以后。如果手术切缘阳性,放疗应尽早开始。同步放化疗可以在不延迟放化疗的基础上提高局部疗效,但疗效提高有限,同时会增加急性和晚期毒副作用,不宜作为常规治疗。特殊病人需要使用时,应选择有效低毒的化疗方案,以降低治疗带来的急性毒副作用和晚期并发症。缩短放疗总时间对需要化疗的病人可以缩短手术到化疗的时间间隔,目前可行的方式有大分割放疗和乳腺瘤床同步补量技术。缩短放疗总时间是否能对疗效改善有影响,有待于临床资料证实。     

早期乳腺癌保乳术中低能X线放疗安全及可行性初步研究

目的 探讨早期乳腺癌保乳手术中放疗的短期并发症及美容效果。方法 回顾分析2013—2015年间30例早期乳腺癌患者资料。全部患者均行乳腺癌保乳手术及低能X线术中放疗,术中予以适配器表面20 Gy处方剂量,术后观察手术区域并发症、放射性损伤、乳房美容效果。结果无严重3、4级不良反应;短期并发症为4例(13%)出现血清肿,其中2例需要外科抽吸处理;3例(10%)出现1—2级乳腺皮肤红斑;美容效果优秀率为50%。患者均未出现LR及远处转移。结论 低能X线术中放疗在乳腺癌保乳手术中安全可行,在部分早期低危乳腺癌患者中可作为瘤床补量的一种选择参考。     

Her-2 prognostic value in very early-stage breast cancer: a single-institution retrospective analysis

To evaluate overall survival, distant metastases-free survival and local relapse-free survival rates in a subgroup of patients affected by breast cancer expressing Her-2/neu. Data of 195 women affected by very early-stage breast cancer (pT1a-b pN0) who underwent whole breast radiotherapy after conservative surgery with or without chemotherapy and/or hormone therapy between January 2000 and December 2006 were evaluated. Chi-square test was used to compare the distribution of variables (age, tumour histology, oestrogens and progesterone receptors, tumour grading and adjuvant chemotherapy) between Her-2-positive and Her-2-negative patients. Survival rates were analysed with Kaplan–Meier curves; impact of variables on poor outcome was evaluated with Cox regression method. Median follow-up time was 63.5 months (range 13.8–113.6). Her-2/neu-positive patients (32/16.4%), compared to Her-2/neu-negative patients (163/83.6%), were younger (P = 0.0001), were affected by ductal infiltrating carcinoma (P = 0.039), had negative oestrogens receptors (P = 0.0001) and were not treated with chemotherapy (P = 0.001). Her-2-positive patients had lower overall survival (P = 0.00001) and lower distant metastases-free survival (P = 0.00001) compared to Her-2-negative patients, but no difference in local relapse-free survival was found between the two groups (P = 0.28). After multivariate analysis, Her-2-positive status was a prognostic factor for overall survival (P = 0.00001) and for distant metastases-free survival (P = 0.0001), but not for local relapse-free survival (P = 0.97). Her-2-positive patients have lower overall survival and distant metastases-free survival when compared to Her-2 negative patients but similar local relapse-free survival rates. These patients could be treated with conservative surgery, if feasible, but should receive more aggressive and tailored systemic adjuvant therapies.     

Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer.

PURPOSE: Tamoxifen (TAM) is thought to exert a cytostatic effect on hormone-sensitive breast cancer cells. Some preclinical studies show reduced radiosensitivity in irradiated malignant mammary epithelial cells when pretreated with TAM; other studies refute these results. Recent randomized clinical trials suggest an antagonistic effect of TAM on cytotoxic therapy, with improved disease-free survival (DFS) with sequential versus concurrent TAM. An exploratory analysis was undertaken to evaluate the optimal sequencing of TAM and radiotherapy (RT) after breast-conserving surgery. PATIENTS AND METHODS: Southwest Oncology Group trial 8897 (Intergroup 0102) randomly assigned node-negative women with T1-3 breast cancers to cyclophosphamide, doxorubicin, fluorouracil (CAF); CAF --> TAM; cyclophosphamide, methotrexate, fluorouracil (CMF); and CMF --> TAM. For this analysis, data are reported only in the TAM groups. RT was allowed either before adjuvant therapy (sequential [SEQ] RT; 107 patients) or after chemotherapy but concurrent with TAM (concurrent [CONC] RT; 202 patients). Survival data were adjusted for receptor status, age, and tumor size. RESULTS: With a median follow-up of 10.3 years, 10-year DFS values were 83% and 83% for CONC versus SEQ RT groups (log-rank P = .73; P = .76 adjusted for patient characteristics), and 10-year overall survivals were 88% and 90%, respectively (log-rank P = .59; adjusted P = .65). Patterns of failure showed no increase in in-breast recurrence rates between CONC RT and SEQ RT groups, with 10-year local recurrence rates of 7% for CONC RT and 5% for SEQ RT (hazard ratio, 0.73; 95% CI, 0.26 to 2.04; P = .54). CONCLUSION: The current analysis does not suggest an adverse effect on local or systemic control with CONC versus SEQ TAM and RT in node-negative breast cancer. A randomized trial is encouraged to validate these results.     

Preoperative breast MRI in early-stage breast cancer

Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34?days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1?% (versus the range of 3.6-33?% reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes.     

早期乳腺癌保乳术后未行放疗原因调查与分析

目的 调查和分析乳腺癌保乳手术患者未进行术后放疗的原因。方法 对2012-2016年在本院保乳手术而未行术后辅助放疗的55例患者未接受放疗的临床病理特征和社会经济原因分析。结果 55例未放疗患者中25例因低的局部复发风险,12例因经济或家庭原因,12例恐惧放疗不良反应,5例基层医师未建议放疗。另外有多发远处转移3例,并发甲状腺癌3例未行放疗。结论 低的局部复发风险是未作术后放疗的主要原因,其次是患者担心放疗不良反应和经济原因。通过患者教育和医保可能提高术后放疗的依从性。     

Impact of locoregional treatment on the early-stage breast cancer patients: a retrospective analysis

Although adequate locoregional treatment improves local and regional control in early-stage breast cancer, uncertainty still exists about the role of locoregional therapy with respect to survival. To study the impact of surgery and radiotherapy on locoregional control and survival, we combined the data of three European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer Group trials including early-stage breast cancer patients with long-term follow-up. Risk ratios (RR) were estimated for locoregional recurrence and overall survival using Cox regression models. All analyses were adjusted for tumour size, nodal status, age, adjuvant radiotherapy, adjuvant chemotherapy and trial. The combined data-set consisted of 3648 patients. The median follow-up period was 11 years. 5.9% of the patients who underwent mastectomy and 10.8% of the patients who underwent breast-conserving therapy had a locoregional recurrence (P<0.0001). The risk of death after breast-conserving therapy was similar compared with mastectomy (RR 1.07, P=0.37). Adjuvant radiotherapy after mastectomy was associated with a lower risk for locoregional recurrence (RR 0.43, P<0.001) and death (RR 0.73, P=0.001). Patients with 1-3 positive nodes benefited the most from radiotherapy after mastectomy. Breast-conserving therapy was associated with an impaired locoregional control. However, breast-conserving therapy was not associated with a worse overall survival. Adjuvant radiotherapy in mastectomised patients was associated with both a significantly superior locoregional control and overall survival. The effect of adjuvant radiotherapy was most profound in patients who had 1-3 positive nodes.