Decision-analytic model and cost-effectiveness evaluation of postmastectomy radiation therapy in high-risk premenopausal breast cancer patients.

PURPOSE: To present a decision model that describes the clinical and economic outcomes of node-positive breast cancer with and without postmastectomy radiation therapy (PMRT). METHODS: A Markov process was constructed to project the natural history of breast cancer following mastectomy in premenopausal node-positive women. Biannual hazards of local and distant recurrence without PMRT were derived from a large meta-analysis of adjuvant systemic therapy trials for breast cancer. The addition of PMRT reduced the risk of disease relapse by an odds ratio of 0.69. Costs of PMRT ($11,600) and recurrent breast cancer ($4,250 to 16,200/year) were estimated from available literature. The model projected number of recurrences, relapse-free and overall survival, and costs to 15 years, using a discount rate of 3%. Cost-effectiveness ratios were calculated per incremental year of life and quality-adjusted year of life gained. One- and two-way sensitivity analyses were performed to determine the sensitivity of results to clinical and economic assumptions. RESULTS: The model projected 15-year relapse-free survival of 52% and 43% with and without PMRT, respectively. Overall survival was increased from 48% to 55% with PMRT, resulting in an incremental 0.29 years of life gained per subject. PMRT increased 15-year costs from $40,800 to $48,100. Cost per year of life gained was $24,900, or $22,600 when survival was adjusted for quality of life. Results of the model were relatively sensitive to radiation therapy cost and breast cancer relapse risk. CONCLUSION: This analysis suggests that PMRT offers substantial clinical benefits achieved in a cost-effective manner, with an average cost per year of life gained of $24,900. Results of the model were robust under a wide range of clinical and economic parameters.     

Long-term outcome after postmastectomy radiation therapy for breast cancer patients at high risk for local-regional recurrence

PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.     

Phase I study of concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients

Background

Postmastectomy chest wall irradiation is recommended for high-risk breast cancer patients, such as those with ≥4 positive nodes. Irradiation is performed sequentially rather than concurrently with chemotherapy. However, the 5-year locoregional recurrence-free survival was statistically better in the concurrent method in node-positive patients in a prior study. The benefit of concurrent chemoradiotherapy for postmastectomy breast cancer patients is uncertain. Vinorelbine is often used as concurrent chemoradiotherapy for non-small cell lung cancer in Japan and has antitumor activity in breast cancer as well. Thus, we planned this dose-finding study of concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients.

Methods

High-risk postmastectomy breast cancer patients were recruited. Patients received weekly vinorelbine administered concurrently with radiation therapy. The radiation dose was 50 Gy in 25 fractions over 5 weeks. Vinorelbine was administered weekly without a break, so the maximum number of vinorelbine cycles was five. A 3 + 3 dose-escalation design was used for determining maximal tolerable dose, recommended dose and safety.

Results

A total of 10 patients were enrolled in cohorts of 10 and 15 mg/m². Dose-limiting toxicity was observed in one case in 10 mg/m² and two cases in 15 mg/m². Therefore, the maximal tolerable dose was defined at 15 mg/m² and the recommended dose was determined at 10 mg/m². The main adverse events included radiation dermatitis and neutropenia. Recurrence was observed in one patient with a median follow-up of 40 months.

Conclusions

Concurrent vinorelbine and radiation therapy has a manageable safety profile at 10 mg/m² in high-risk postmastectomy breast cancer patients.

     

Low complication rates are achievable after postmastectomy breast reconstruction and radiation therapy

PURPOSE: To report our institution's experience of complications and cosmetic results among patients who underwent modified radical mastectomy followed by reconstruction and radiation therapy (RT). METHODS AND MATERIALS: Between 1987 and 2002, 85 patients with breast cancer underwent modified radical mastectomy, breast reconstruction, and postoperative RT. Reconstruction consisted of tissue expander/implant (TE/I) in 50 patients and an autologous transverse rectus abdominis myocutaneous (TRAM) flap in 35 patients. The primary end point of this study was the actuarial incidence of major and minor complications involving the reconstruction. Cosmesis was also assessed at each follow-up visit. RESULTS: The median follow-up from reconstruction was 28 months. The 5-year major complication rate was 0% in the TRAM group vs. 5% in the TE/I group (p = 0.21). The 5-year minor complication rate was 39% for the TRAM group vs. 14% for the TE/I group (p = 0.04). None (0%) of the TRAM complications required any corrective surgery, whereas 2 (33%) of the TE/I complications required implant removal. Of the TRAM patients with complications, 100% had superior cosmetic scores of excellent/good compared to only 17% of the TE/I patients who had complications (p = 0.003). Use of our custom-fashioned bolus resulted in a lower complication rate compared with standard bolus (p = 0.05). CONCLUSIONS: Patients treated with breast reconstruction and RT can experience a very low rate of major complications. We demonstrate no significant difference in the overall rate of major complications between TRAM and TE/I patients. Bolus can be safely used during postmastectomy RT with reconstruction, and we advocate the use of a custom wax bolus in the treatment of these patients. Postmastectomy RT should be considered in all eligible patients, even in the setting of reconstruction.     

Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: Implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation

PURPOSE: To compare rates of locoregional recurrence (LRR) after mastectomy, doxorubicin-based chemotherapy, and radiation with those of patients receiving mastectomy and doxorubicin-based chemotherapy without radiation and to determine predictors of LRR after postmastectomy radiation. METHODS: Kaplan-Meier freedom-from-LRR rates were calculated for 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five single-institution clinical trials. The LRR rates in these patients were compared to previously reported rates in 1031 patients treated without radiation in the same trials. RESULTS: Median follow-up was 14 years. Irradiated patients had significantly less favorable prognostic factors for LRR than did unirradiated patients. Despite this, in all subsets of node-positive patients, postmastectomy radiation led to lower rates of LRR. This included patients with T1 or T2 tumors and one to three positive nodes (10-year LRR rates of 3% vs. 13%, p = 0.003). Multivariate analysis of LRR for patients with this stage of disease revealed that no radiation, close/positive margins, gross extracapsular extension, and dissection of <10 nodes predicted for increased LRR (hazard ratios 6.25, 4.61, 3.27, and 2.66, respectively). Significant predictors of LRR for patients treated with postmastectomy radiation were higher number and >or=20% positive nodes, larger tumor size, lymphovascular space invasion, and estrogen receptor (ER)-negative disease. Recursive partitioning analysis revealed ER-negative status to be the most powerful discriminator of LRR in irradiated patients. CONCLUSIONS: Postmastectomy radiation decreases LRR for patients with breast cancer, including those with Stage II breast cancer and one to three positive lymph nodes.     

Epidemiologic study of compliance to postmastectomy radiation therapy guidelines in breast cancer patients in China between 1999 and 2008

PurposeTo evaluate compliance with postmastectomy radiation therapy (PMRT) guidelines in breast cancer patients in China over a 10-year period.Methods and MaterialsA hospital-based, nationwide, multicenter retrospective epidemiologic study of primary breast cancer in women was conducted. Seven first-class, upper-level hospitals from different geographic regions of China were selected. One month was randomly selected to represent each year from 1999-2008 in every hospital. All inpatient cases within the selected months were reviewed and demographic, clinical, and pathologic characteristics and treatment patterns were collected. Patients enrolled in this study had to meet the following inclusion criteria: (1) treated with mastectomy and axillary dissection; (2) information regarding whether or not they received postmastectomy radiation therapy was available; and (3) information about staging was available. Patients were divided into 3 groups based on National Comprehensive Cancer Network guidelines. Utilization of PMRT in each group was analyzed and compared between different years and different hospitals.ResultsA total of 2310 patients were analyzed. There were 643 (27.8%) patients in the PMRT recommended group, 557 (24.1%) patients in the controversial group, and 1110 (48.1%) patients in the nonrecommended group. PMRT was used in 48.8% of patients in the recommended group, 15.6% in the controversial group, and 5.7% in the nonrecommended group. There was a trend toward increasing use of radiation therapy in the recommended and controversial groups from 1999-2008. The use of PMRT in the nonrecommended group remained relatively stable from 1999-2008. Fewer positive nodes and nonreceipt of chemotherapy or hormone therapy were associated with underuse of PMRT in the recommended group. In the controversial group, a higher ratio of positive nodes was associated with use of PMRT.ConclusionsThere is an apparent underuse of PMRT in the PMRT recommended group. Efforts should be made to improve the compliance to PMRT guidelines.     

Treatment planning technique in patients receiving postmastectomy radiation therapy

Many of the technical subtleties involved in postmastectomy radiation treatment planning will never be addressed in a robust clinical trial setting. However, these issues are faced daily by practicing radiation oncologists with little to guide them in the published literature. The purpose of this study was to survey a small number of breast care providers in both academic and private practice settings on practical aspects of postmastectomy radiation treatment planning. Topics addressed included the use of sophisticated dose-modulation algorithms, hypofractionation, bolus material, and dose-volume histogram (DVH) constraints. Fifty-two people responded to the survey, 50% in academics and 50% in private practice. As expected, wide variation in clinical practice was seen although a few general trends emerged. We include here, with the survey results, a review of the relevant literature for a number of different treatment-related issues. Although the use of postmastectomy radiation therapy is common, literature guiding the reader on technical aspects of delivery is sparse. The data presented here provide a general framework of what is considered acceptable by currently practicing radiation oncologists in many different practice settings.     

Radiation therapy in breast conservation patients and postmastectomy.

Radiation has played a continuous but changing role in the management of breast cancer. At Memorial Hospital, the past 10 years have seen a marked increase in breast conserving therapy, and changing indications for postmastectomy adjuvant radiation.     

Ⅰ期、Ⅱ期乳腺癌术后局部复发的放疗及预后

目的：探讨乳腺癌术后局部区域复发的规律和再放疗的预后。方法：回顾分析45例Ⅰ期、Ⅱ期乳腺癌术后局部区域复发的情况以及复发后放疗的预后。26例采用局部野放疗，19例采用扩大野放疗。结果：T2及腋窝淋巴结转移数≥4枚或≥20％的病例占复发病例的73％。复发的部位依次为锁骨上、多部位、胸壁、腋窝、内乳。复发后2a生存率40％、无瘤生存率24．4％，2次局部区域复发率31％，术后2a以上复发的2a生存率64％，2a以下29％。首次复发累及多部位生存率18．2％，较单一锁骨上(47．4％)及胸壁(30％)低，累及锁骨上局部复发率高于胸壁，远处转移率低于胸壁，2次局部复发胸壁最高达57％，照射野采用广泛野的局部复发率低于采用局部野。结论：对Ⅰ期、Ⅱ期乳腺癌中腋窝淋巴结阳性≥4枚或≥20％的病例应常规行术后放疗，对术后局部区域复发的病例应采用包括胸壁及锁骨上下大范围照射。     

Long-term outcome after postmastectomy radiation therapy for the treatment of ductal carcinoma in situ of the breast.

Postmastectomy radiation therapy may be recommended for patients with a high risk for local recurrence after mastectomy for ductal carcinoma in situ (DCIS). However, long-term outcomes after postmastectomy radiation therapy are not well described. This study was performed to determine long-term outcomes in patients treated with radiation therapy after mastectomy for DCIS. The authors reviewed the records of all patients with breast cancer treated with postmastectomy radiation therapy between 1978 and 1992. Of 287 total patients treated, three (1%) were for DCIS. These three patients had diffuse microcalcifications on screening mammography. The reason for postmastectomy radiation therapy was a potentially increased risk for local recurrence because of a positive resection margin after mastectomy for DCIS. Surgery consisted of a total mastectomy (n = 2) or a modified radical mastectomy (n = 1). Radiation therapy consisted of 4275-5000 cGy to the chest wall in 200-225 cGy fractions. The energy used was 6-MV photons (n = 2) or 15-MV photons (n = 1). No regional nodal irradiation was used. Bolus was applied to the chest wall every other day in one of the three patients. One patient was treated with a scar boost after chest wall irradiation (boost dose, 1000 cGy; total dose, 5275 cGy). The median age for the three patients was 46 years (range, 41-68 years). No patient received adjuvant chemotherapy or hormonal therapy. With a minimum follow-up of 7.1 years (median, 7.4 years; range, 7.1-19.4 years), no local-regional recurrence or evidence of metastatic disease developed in any of the patients. No long-term complication from radiation therapy was noted, and no contralateral breast cancer developed. All patients were alive and free of relapse at the last follow-up. The use of radiation therapy in this group of three patients has shown no evidence of relapse with a minimum of 7.1 years of follow-up. The authors conclude that radiation therapy may be indicated after mastectomy for DCIS to reduce the risk of recurrence for high-risk patients.     

Utilization and impact of a postmastectomy radiation boost for invasive breast cancer

PurposeAdditional radiation following postmastectomy radiation (PMRT) has an undefined benefit. We investigate those likely to be selected for a chest wall boost (CWB) and its effect on breast cancer survival (BCS) and overall survival (OS).Methods and materialsA total of 4747 women diagnosed from 2005 to 2009 were treated with PMRT identified from the California Cancer Registry (CCR); 2686 (57%) received a CWB. Univariate and multivariate analyses compared those receiving and not receiving a CWB for BCS and OS.ResultsWith a median follow-up of 43.6 months, patients likely to receive a CWB were stage III (P ≤ .001), grade 3/4 (P = .03), positive nodes (P = .04), HER 2 + (P = .02). CWB was not related to BCS in the univariate (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.82-1.21), multivariate (HR, 1.04; 95% CI, 0.86 -1.26) analyses, and was not related OS for the univariate (HR, 0.92; 95% CI, 0.78-1.10), multivariate (HR, 0.95; 95% CI, 0.80-1.13) analyses. However, in multivariate analysis, patients not receiving chemotherapy who had a CWB had better BCS (HR, 1.77; 95% CI, 1.11-2.83).ConclusionsThe majority of patients were treated with a CWB. We found no difference in BCS or OS with the addition of a CWB.     

Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation

BACKGROUND:

The objective of this study was to identify predictors of locoregional recurrence (LRR) after neoadjuvant therapy (NAT) and postmastectomy radiation (PMRT) in a cohort of patients with stage II through III breast cancer and to determine whether omission of the supraclavicular field had an impact on the risk of LRR.

METHODS:

The authors reviewed records from 464 patients who received NAT and PMRT from January 1999 to December 2009.

RESULTS:

The median patient age was 50 years (range, 25‐81 years). Clinical disease stage was stage II in 29% of patients, stage III in 71%, and inflammatory in 14%. Receptor status was estrogen receptor (ER)‐positive in 54% of patients, progesterone receptor (PR)‐positive in 39%, human epidermal growth factor receptor 2 (HER2)‐positive in 24%, and negative for all 3 receptors (triple negative) in 32%. All patients received NAT and underwent mastectomy, and 19.6% had a complete pathologic response in the breast and axilla, 17.5% received radiation to the chest wall only, and 82.5% received radiation to the chest wall and the supraclavicular field; omission of the supraclavicular field was more common in patients with lower clinical and pathologic lymph node status. The median follow‐up was 50.5 months, and the 5‐year cumulative incidence of LRR was 6% (95% confidence interval, 3.9%‐8.6%). Predictors of LRR were clinical stage III (P = .038), higher clinical lymph node status (P = .025), higher pathologic lymph node status (P = .003), the combination of clinically and pathologically positive lymph nodes (P < .001), inflammatory presentation (P = .037), negative ER status (P = .006), negative PR status (P = .015), triple‐negative status (P < .001), and pathologic tumor size >2 cm (P = .045). On univariate analysis, omission of the supraclavicular field was not associated significantly with LRR (hazard ratio, 0.89; P = .833); however, on multivariate analyses, omission of the supraclavicular field was associated significantly with LRR (hazard ratio, 3.39; P = .024).

CONCLUSIONS:

Presenting stage, receptor status, pathologic response to neoadjuvant therapy, and omission the supraclavicular field were identified as risk factors for LRR after neoadjuvant therapy and PMRT. Cancer 2013. © 2012 American Cancer Society.     

乳腺癌改良根治术后放疗患者上肢淋巴水肿与腋淋巴结手术结果的相关性分析

背景与目的：上肢淋巴水肿是乳腺癌常见的治疗相关不良反应,显著影响乳腺癌患者的生存质量。本研究旨在观察乳腺癌改良根治术后放疗患者的上肢淋巴水肿发生情况,分析淋巴水肿发生与患者腋淋巴结手术结果(阳性淋巴结个数、切除淋巴结总数及两者的比值,即淋巴结阳性率)的相关性,以及年龄、体质量指数和其他治疗相关因素对上肢淋巴水肿发生的影响。方法：前瞻性收集2015年1月1日—12月31日在上海市黄浦区中心医院行乳腺癌改良根治术后放疗的患者共202例,采用上肢周径测量法,观察这些患者从放疗开始至放疗结束后12个月期间的上肢淋巴水肿发生情况。结果：共有197例患者完成随访观察,其中38例诊断为上肢淋巴水肿(19.3%)。单因素分析结果显示,发生与未发生上肢淋巴水肿的患者在切除淋巴结总数(P ＜0.001)、阳性淋巴结个数(P＜0.001)与淋巴结阳性率(P=0.002)方面差异均有统计学意义,而在年龄、体质量指数和其他治疗相关因素方面差异无统计学意义。多因素分析结果显示,切除淋巴结总数的增多是乳腺癌改良根治术后放疗患者上肢淋巴水肿发生的独立危险因素(P＜0.001)。结论：乳腺癌改良根治术后放疗患者的上肢淋巴水肿发生情况与腋淋巴结手术结果具有相关性,其中切除淋巴结总数的增多是淋巴水肿发生的独立危险因素。因此,对于切除淋巴结总数较多的患者,在制定术后相关治疗方案时要充分重视其较高的乳腺癌相关淋巴水肿发生风险。     

Long-term outcomes in breast cancer patients undergoing immediate 2-stage expander/implant reconstruction and postmastectomy radiation

BACKGROUND:

Breast reconstruction with tissue expander (TE)/permanent implant (PI) followed by postmastectomy radiation (PMRT) is an increasingly popular treatment for breast cancer patients. The long‐term rates of permanent implant removal or replacement (PIRR) and clinical outcomes in patients treated with a uniform reconstructive surgery and radiation regimen were evaluated.

METHODS:

Between 1996 and 2006, 1639 patients with stage II‐III breast cancer received modified radical mastectomy (MRM) at Memorial Sloan‐Kettering Cancer Center. A total of 751 received TE placement at the time of mastectomy. Of these, 151 patients went on to receive chemotherapy and exchange of the TE for a permanent implant, followed by PMRT. Clinical outcomes and PIRR‐free rates were estimated by Kaplan‐Meier methods. Cox regression model was used to examine patient, disease, and treatment characteristics associated with PIRR.

RESULTS:

Median follow‐up was 86 months (range, 11‐161 months). The 7‐year PIRR‐free rate was 71% (38 PIRRs in 35 patients). The 7‐year rate of PI replacement was 17.1% (21), and removal was 13.3% (17). Reasons for PIRR included infection (15); implant extrusion, shift, leak, or rupture (4); patient request (1), or multifactorial (17). On univariate analysis, no factor was significantly associated with PIRR. Two patients experienced local recurrence in the chest wall, both after 7 years. The 7‐year distant metastasis–free survival rate was 81% and overall survival 93%.

CONCLUSIONS:

Favorable 7‐year PIRR rates and clinical outcomes were achieved in a sizable cohort of patients treated with homogeneous sequencing, radiation, and reconstructive surgery and lengthy follow‐up. Factors predictive for high risk of PIRR were not identifiable in this population. Cancer 2012. © 2011 American Cancer Society.