Urban and non-urban disparities in the use of post-mastectomy radiation for breast cancer

Post-mastectomy radiation therapy (PMRT) is indicated for local-regionally advanced breast cancer (LABC). We hypothesized that candidates for PMRT from non-urban areas would receive lower rates of RT than urban patients and would have poorer overall survival (OS) and disease-specific survival (DSS). We used the Surveillance, Epidemiology, and End Results database to identify patients diagnosed with LABC and treated with mastectomy in Sacramento and its surrounding 13 counties between 2000 and 2006. All patients were eligible to receive RT according to established guidelines, with tumors >5 cm size, ≥ 4 metastatic lymph nodes, or both. According to a United States Department of Agriculture scale, we designated counties as urban or non-urban and used multivariate logistic regression and Cox proportional hazards models to predict the use of RT, overall survival (OS), and disease-specific survival (DSS). Density of radiation oncologists in non-urban and urban counties was determined using the American Medical Association database in relation to census-derived populations of the respective counties. Entry criteria were met by 1,507 patients. Most (56.5%) were from urban counties; only 61% received RT. There was no radiation oncologist listed for 8/10 non-urban counties and 2/4 urban counties. Each radiation oncologist served 88,804 people in non-urban counties and 68,624 residents in urban counties. On multivariate analysis, non-urban patients (OR 0.56, CI 0.44-0.72) and increasing age were the only factors predicting a decreased likelihood of receiving RT (OR 0.97, CI 0.96-0.98). Patients not receiving PMRT experienced poorer OS (HR 1.77, CI 1.39-2.25; P < 0.001) and DSS (HR 1.62, CI 1.23-2.15; P = 0.001); however, non-urban status did not predict OS or DSS. Non-urban residents with LABC are less likely to receive indicated PMRT. This discrepancy may be due to limited RT access in non-urban areas. The lack of poorer OS and DSS due to this disparity requires further study.     

Facts and controversies in the use of trastuzumab in the adjuvant setting

The human epidermal growth factor receptor-2 (HER2) is overexpressed and/or amplified in up to 25% of breast cancer patients, and this feature is associated with an aggressive phenotype, high recurrence rate and reduced survival. Until recently, combination chemotherapy (with or without endocrine therapy) was the only effective adjuvant treatment for HER2-positive patients. Trastuzumab is a monoclonal antibody directed against the HER2 extracellular domain, and five recent adjuvant breast cancer trials have demonstrated an astonishing and highly reproducible benefit in halving the recurrence rate and reducing mortality in patients with this phenotype. Many questions related to trastuzumab use in the adjuvant setting still remain; these include the optimum timing and duration of treatment, trastuzumab use with taxanes and radiotherapy, its role in small node-negative tumors, the optimum chemotherapy regimens and cost-effectiveness. This Review outlines the five adjuvant trastuzumab studies and discusses the controversies and challenges that have emerged for both the clinician and healthcare authorities worldwide as a consequence of the results from these trials.     

Late skin changes following twice-weekly electron beam radiation to post-mastectomy chest walls

We analyzed patients treated after mastectomy with 7-MeV electron beam. The fractions were delivered twice-weekly over a five-week period for a time-dose fractionation (TDF) of 82. We observed an unacceptable incidence of late skin changes in follow-up. The degree of late skin changes did not correlate with the acute toxicity. The reasons for the observed late changes are unclear. Several mechanisms may be responsible. It is possible the fractionation schedule contributed to the observed changes. We encourage institutions using large, infrequent fractions to analyze their material for late tissue damage.     

Variability in radiation oncologists' opinion on the indication of a bolus in post-mastectomy radiotherapy: an international survey

AimsPost-mastectomy radiotherapy (PMRT) decreases locoregional recurrence and increases survival for women with large tumours and/or node-positive disease. The American Society of Clinical Oncology has published treatment guidelines, but has also indicated that the optimal technique for PMRT remains unknown. The objective of this study was to evaluate the variability in which a bolus is currently used in PMRT and to identify the clinical situations in which a bolus is used.Materials and methodsIn 2004, an e-mail survey was sent to all active physician members of the American Society for Therapeutic Radiology and Oncology, the Canadian Association of Radiation Oncologists and the European Society for Therapeutic Radiology and Oncology. The survey focused on the technical details regarding the use of a bolus in PMRT.ResultsIn total, 1035 responses were obtained: 642 from the Americas (568 from the USA), 327 from Europe and 66 from Australasia. Respondents from the Americas were significantly more likely to always use a bolus (82%) than the Europeans (31%), as were the Australasians (65%) (P < 0.0001). Europeans were significantly more likely to use a bolus for specific indications (P < 0.0001). The results also showed wide variation in the schedule of application (every day [33%] and alternate days [46%]) and thickness used (<1 cm [35%] and ≥1 cm [48%]).ConclusionsThere is a wide variation in the use of a bolus in PMRT with significant regional differences. This probably translates into a variation in the dose delivered to the skin and may have an effect on local recurrence and/or toxicity. A randomised clinical trial is needed to evaluate the benefit and toxicity associated with the use of a bolus in PMRT.     

The controversies and pitfalls in modeling normal tissue radiation injury/damage

Highly conformal fields have become achievable in routine clinical practice. The optimal shape of the resultant dose distributions depends on information that is not currently available. This missing information is the dose-volume response of the normal tissues at risk. These functions are now the subject of aggressive research. The research involves collecting the dose-response data, modeling the dose-response function, and fitting the models to the data. The controversies addressed here influence the selection of the biomathematical model that one might use to describe such a function. The form that the dose-volume response function takes depends on the nature of the volume effect. The nature of the volume effect for a given radiation response is the subject of considerable debate. Related to this debate, this report addresses the existence of the volume effect, the existence of a threshold volume, and the existence of functional subunits. The pitfalls relate to the problems in accurate determination and application of the dose-response functions.     

保乳术后放疗对乳腺癌局部淋巴结转移患者预后的影响

  目的  探讨术后放疗(post-mastectomy radiation therapy, PMRT)对局部淋巴结阳性行保乳手术的乳腺癌患者预后的影响, 针对不同的pN分期以及淋巴结转移率(lymph node ratio, LNR)提出更具针对性的术后放疗方案。  方法  回顾性分析天津医科大学肿瘤医院1998年2月至2007年3月152例行保乳手术并有局部淋巴结转移的原发浸润性乳腺癌患者的临床病理资料, 比较LNR和pN分期对患者预后的指导意义, 并在LNR基础上, 根据PMRT与否比较无病生存期(disease-free survival, DFS)和总生存期(overall survival, OS)。  结果  152例患者被分为pN1(114例)、pN2(23例)、pN3(15例), 其中LNR < 0.21为114例, 位于0.21~0.65为26例, >0.65为12例。单因素分析显示淋巴结切检总数、pN、LNR、雌激素受体(estrogen receptor, ER)状态、孕激素受体(progesterone receptor, PR)状态、放疗与否均与DFS、OS具有相关性(P < 0.05), 诊断年龄和化疗方案仅与OS具有相关性(P < 0.05)。多因素分析显示, LNR、PMRT依然是DFS、OS的独立预测指标(P < 0.05), 而pN差异无统计学意义(P>0.05);分组分析时仅在LNR < 0.21术后放疗对预后的影响差异有统计学意义。  结论  LNR作为一个独立预测指标, 可用于评价行保留乳房手术治疗发生淋巴结转移的乳腺癌患者的预后。针对不同的LNR分级, 需要进一步细化PMRT的适应症。      

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation

We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II–III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray’s test and by Fine and Gray’s modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2–8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.     

The roles and controversies of radiation therapy in breast conserving therapy for breast cancer

Breast conserving therapy (BCT) is defined as a combination of conservative surgery for resection of the primary tumor, followed by radiation therapy (RT) for the eradication of residual microscopic disease in the breast. At NIH Consensus Development Conference in 1990, BCT was recognized as the preferred treatment for the majority of women with Stage I and II breast cancer. RT is a potent locoregional treament and its role in BCT in reducing local recurrence is already established. On the other hand, the influence of RT on survival outcome has not yet been closely demonstrated so far. RT appears to be useful as neoadjuvant therapy, and also as exclusive local treatment for patients achieving complete regression (CR) after neoadjuvant chemotherapy. The other possible role of RT is to use it as an alternative to axillary dissection in patients with clinically uninvolved nodes. The question of the appropriateness of using RT in all BCT cases is raised. Since the subgroup of patients who would not deserve any benefit by RT has not yet identified, RT should be delivered as standard treatment following breast conserving surgery for early stage breast cancer.     

Lymphoscintigraphy in the diagnosis and prognosis of post-mastectomy edema of the extremities

Dynamic lymphoscintigraphy provides adequate means for in vivo contrast-enhanced examination of functional lymph collectors in the extremeties which in turn offers best advantage in diagnosing post-mastectomy edema of the arms. A comparative study was concerned with lymph flow in healthy subjects, breast cancer patients and those with post-mastectomy edema and without it after complete course of treatment. A group of risk for edema was formed.     

心脏正对射野(弧)对乳腺癌根治术后放疗剂量学风险和收益分析

目的 研究乳腺癌根治术后不同放疗技术靶区、正常组织剂量学差异。方法 对2012—2013年间31例乳腺癌(左侧9例、右侧22例)根治术后患者采用改良野中野IMRT计划(P₁)、4个野IMRT计划(P₂)、含心脏正对野5个野IMRT计划(P₃)、含心脏正对弧VMAT计划(P₄)分别计算靶区CI、HI,心脏、冠状动脉左前降支、右冠状动脉、患侧肺剂量学参数,分别用NTCP_RSM、NTCP_Lyman、LQ-TCP-Poisson模型计算左右侧乳腺癌患者放射性心脏病概率、RP概率、TCP,结果用方差分析或χ²检验。结果 P₁—P₄间左侧和右侧乳腺癌患者靶区CI、HI值均不同(P=0.009、P=0.000和P=0.000、0.000),放射性心脏病概率平均值相近[左侧2.7%、1.1%、1.3%、0.86%(P=0.397);右侧0.19%、4.76×10^－3%、0、0(P=0.568)],RP概率平均值也相近[左侧9.73%、7.52%、8.86%、10.73%(P=0.953),右侧11.73%、8.65%、7.02%、11.25%(P=0.437)],但TCP均不同(左侧P=0.000,右侧P=0.000)。结论 乳腺癌根治术后增加心脏正对射野(弧)不同放疗计划对放射性心、肺并发症概率均无显著影响,但可显著改善计划靶区的CI、HI,增加TCP;5个野IMRT和VMAT技术可选为乳癌根治术后放疗手段。     

Precautions in the use of intensity-modulated radiation therapy

Intensity-modulated radiation therapy (IMRT) represents a significant technological advancement in the ability to deliver highly conformal radiation therapy. Thanks to increased availability, general clinical implementation has become progressively more common. However, there are several precautions worthy of comment regarding the clinical applications of IMRT. In theory, the increased irradiated volume and leakage radiation that occasionally accompanies IMRT could contribute to unanticipated complications and safety concerns. The protracted delivery time of IMRT with the associated increased linac monitor units can result in photoactivation of elements within the linac collimator, thereby inadvertently increasing radiation exposure to patients and staff when high-energy photons are used. The increased volumes of normal tissue exposed to lower doses of radiation through IMRT theoretically could promote carcinogenesis and complications due to the bystander effect, low-dose hyper-radiosensitivity, and diminished repair of double strand DNA breaks at very low doses. Tumor control may be adversely affected by the lower radiation dose-rates of delivery sometimes associated with IMRT as well the occasionally seen low dose "cold shoulder" on the dose-volume histograms. Unusual clinical reactions can appear as a result of the complex, unfamiliar dose-distributions occasionally generated by IMRT treatment planning. Here we discuss some of the precautions worthy of consideration when using IMRT and how these might be addressed in routine practice.     

Role of radiation therapy in the management of stage III non-small cell lung cancers:current status and controversies

The treatment of stage III non-smal cel lung cancer (NSCLC) consisting of the heterogeneous stage subsets remains a chal enge. Overal , it has been gradual y recognized that radiation therapy (RT) play...     

Low locoregional recurrence rates in patients treated after 2000 with doxorubicin based chemotherapy, modified radical mastectomy, and post-mastectomy radiation

Purpose

To determine the rate of locoregional recurrence (LRR) associated with modern tri-modality therapy.

Methods

We retrospectively reviewed data from 291 consecutive PMRT patients treated from 1999 to 2001. These patients were compared to an historical group of 313 patients treated from 1979 to 1988 who had fluoroscopic simulation and contour-generated 2D planning. 1999-2001 spans the adoption of CT simulators for breast radiation therapy and a comparison was made between patients simulated before and after the implementation of CT simulation. Five-year actuarial rates for LRR, distal metastasis (DM), and overall survival (OS) between the pre and post CT simulation cohorts were compared as well.

Results

Compared to a 2D planned historic control, the combined contemporary patients had improved outcomes at 5 years for all endpoints studied; LRR 3.0% vs. 11.5%, DM 29.2% vs. 39.2%, and OS 79.2% vs. 70.6% (p = 0.0004, 0.0052, 0.0012, respectively). Significant factors in a multivariate analysis for LRR were: advanced T-stage (RR = 2.14, CI = 1.11-4.11, p = 0.023), and percent positive nodes (RR = 1.01, CI = 1.00-1.02, p = 0.012). The comparison of the pre and post CT-simulated PMRT patients (1999-2001) found no significant difference in any endpoint.

Conclusions

The rate of locoregional control for PMRT patients treated with modern radiotherapy is outstanding and has improved significantly compared to historical controls.