New Breast Cancer Radiotherapy Technology Confers Higher Complications and Costs Before Effectiveness Proven: A Medicare Data Analysis.

A new breast cancer treatment, brachytherapy-based accelerated partial breast radiotherapy (RT), was adopted before long-term effectiveness evidence, potentially increasing morbidity and costs compared with whole breast RT. The aim of this study was to estimate complication rates and RT-specific and 1-year costs for a cohort of female Medicare beneficiaries diagnosed with breast cancer (N = 47 969). We analyzed 2005-2007 Medicare claims using multivariable logistic regression for complications and generalized linear models (log link, gamma distribution) for costs. Overall, 11% (n = 5296) underwent brachytherapy-based RT; 9.4% had complications. Odds of any complication were higher (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.49-1.76) for brachytherapy versus whole breast RT, similarly to seroma (OR: 2.85; 95% CI: 1.97-4.13), wound complication/infection (OR: 1.72; 95% CI: 1.52-1.95), cellulitis (OR: 1.48; 95% CI: 1.27-1.73), and necrosis (OR: 2.07; 95% CI: 1.55-2.75). Mean RT-specific and 1-year total costs for whole breast RT were $6375, and $19 917, $4886, and $4803 lower than brachytherapy ( P < .0001). Multivariable analyses indicated brachytherapy yielded 76% higher RT costs (risk ratio: 1.76; 95% CI: 1.74-1.78, P < .0001) compared with whole breast RT. Brachytherapy had higher complications and costs before long-term evidence proved its effectiveness. Policies should require treatment registries with reimbursement incentives to capture surveillance data for new technologies.

Cost effectiveness of new breast cancer radiotherapy technologies in diverse populations.

Accelerated partial breast radiotherapy (RT) strategies (3-D conformal external-beam RT (3-D CRT) and brachytherapy with balloon catheter) reduce time and transportation burdens of whole breast RT for breast cancer. Long-term clinical trial evidence is unavailable for accelerated modalities, but uncertainty might be acceptable for patients likely to receive suboptimal whole breast RT. The objective of this study is to assess the cost effectiveness of accelerated partial breast RT compared to on-time and delayed whole breast RT. The design used in this study is decision analytic Markov model. The data sources are published literature; and national/federal sources. The target population of this study is a hypothetical cohort of 60 years old women previously treated with breast-conserving surgery for node-negative, estrogen receptor-positive breast cancer with tumors <1 cm. The time horizon is 15 years, and the perspective is societal. The interventions are whole breast RT, 3-D CRT, and brachytherapy breast irradiation. The outcome measures are costs (2008 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. The base-case results were: 3-D CRT was the preferred strategy, costing on average $10,800 and yielding 11.21 QALYs. On-time whole breast RT costs $368,000/QALY compared to 3-D CRT, above the $100,000/QALY WTP threshold. 3-D CRT was also preferred over delayed whole breast RT. Brachytherapy was never preferred. Sensitivity analysis indicated that the results were sensitive to the rate of recurrence outside the initial tumor quadrant ("elsewhere failure") in one-way analysis. Probabilistic sensitivity analysis indicated that results were sensitive to parameter uncertainty, and that the elsewhere-failure rate and treatment preferences may drive results. The limitation of this study is that efficacy estimates are derived from studies that may not fully represent the population modeled. As a conclusion, 3-D CRT was preferred to whole breast RT and for women likely to delay RT, indicating that 3-D CRT could be targeted more efficiently before randomized trial evidence.

Seroma is an expected consequence and not a complication of MammoSite brachytherapy.

Seroma has long been listed as a complication of MammoSite brachytherapy. Palpable abnormalities are clinically apparent months after treatment and a vast majority of patients demonstrate seroma formation in radiologic studies. We embarked on this study to evaluate the actual sonographic incidence and eventual sonographic resolution, possible contributing factors, cosmesis, pain, and local control associated with seroma formation after MammoSite partial breast irradiation (PBI). We investigated 160 patients who underwent MammoSite PBI from 2002 to 2006 of whom 100 patients had serial sonographic information. Clinical and tumor variables, infection, pain, and cosmesis were investigated. Dosimetric data including volume of balloon, dose at balloon surface, and at skin were analyzed. After a median follow-up of 36 months, the incidence of sonographically confirmed post-radiation seroma was 78% within the first 1 year following radiation and steadily decreased with time. The average size of a seroma cavity was 2.3 cm (range 0.6-6 cm) with a decline to an average of 1.4 cm after 1 year, with complete resolution in 65% of patients at 2 years. No statistically significant correlation was found between patient characteristics, tumor variables, and volumetric or dosimetric data for seroma formation. Excellent/good cosmetic scores were achieved in 94% of women with and 92% without seroma. Local control was equivalent between patients with and without seroma. Consecutive sonographic imaging reveals a high rate of seroma formation after MammoSite PBI, with resolution in 65% of patients by 2 years without intervention. Seroma formation does not prevent an excellent cosmetic result or alter local control.

Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: a phase II clinical study.

BACKGROUND: This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). METHODS: Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. RESULTS: The mean follow-up period was 9.5 months (range, 1-24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1-40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% > or =7 mm. No serious adverse events were reported. The infection rate was 4.0%. CONCLUSIONS: Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.

Disease-free survival according to the use of postmastectomy radiation therapy after neoadjuvant chemotherapy.

INTRODUCTION: The purpose of the study was to determine predictors of recurrence for patients treated with neoadjuvant chemotherapy (NAC) and mastectomy according to the use of postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS: An analysis of 161 clinically staged T1 to T3/N0 to N3 patients treated with NAC and mastectomy with and without PMRT at our institution from 2003 to 2010 was conducted. The Kaplan-Meier product limit method was used to estimate survival and time to recurrence rates and the log-rank test was used to compare groups. A Cox proportional hazard regression analysis was carried out for time to recurrence, radiation therapy, and their interaction in the model. RESULTS: The median follow-up period was 48 months and 18 patients developed a recurrence. The 5-year recurrence rate and overall survival was 16.1% (95% confidence interval [CI], 9.6%-26.3%) and 93.6% (95% CI, 88.2%-97.0%), respectively. Patients who underwent PMRT had a decreased risk of recurrence compared with patients who did not (hazard ratio [HR], 0.25; 95% CI, 0.097-0.661; P < .005). The 5-year disease-free survival (DFS) rate for those who received PMRT was 91.3% (95% CI, 82.8%-95.7%) and 64.8% (95% CI, 37.8%-82.4%) for those who did not (P = .0126). Among all clinicopathologic factors examined, pathologic T stage (ypT) and pathological N stage (ypN) significantly correlated with the risk of recurrence (P < .05). Patients with any pathological nodal disease had an increased risk of recurrence compared with patients who were pathologically node-negative (HR, 7.196; 95% CI, 2.05-25.264; P < .002). CONCLUSION: Patients treated with NAC and mastectomy, but without PMRT had a higher risk recurrence with increasing ypT and ypN stages. PMRT might increase DFS.

Decision to adopt medical technology: case study of breast cancer radiotherapy techniques.

OBJECTIVE: To understand decision making concerning adoption and nonadoption of accelerated partial breast radiotherapy (RT) prior to long-term randomized trial evidence. METHODS: A total of 36 radiation oncologists and surgeons were recruited through purposive and snowball sampling strategies from September 2010 through January 2013. Semistructured phone interviews were conducted and audio-recorded and lasted 20-45 minutes. Qualitative analysis was conducted using a framework approach, iteratively exploring key concepts and emerging issues raised by subjects. Interviews were transcribed and imported into Atlas.ti v6. Transcripts were independently coded by 3 researchers shortly after each interview, followed by consensus development on each coded transcript. Barriers and facilitators of adoption, practice patterns, and informational/educational sources concerning accelerated partial breast RT were all assessed to determine major themes. RESULTS: Nearly half of physicians were surgeons (47%), and half were radiation oncologists (53%), with 61% overall in urban settings. Twenty-nine of the 36 physicians interviewed used brachytherapy-based partial breast RT. Five major factors were involved in physicians' decisions to adopt accelerated partial breast RT: facilitators encouraging adoption (e.g., enthusiastic colleagues and patient convenience), financial and prestige incentives, pressures to adopt (e.g., potential declines in referrals), judgment concerning acceptable level of scientific evidence, and barriers (e.g., not having appropriate machinery or referral mechanism in place). If technology was adopted, clinical guideline adherence varied. CONCLUSIONS: Technology adoption is based on financial and social pressures, along with often-limited scientific evidence and what seems "best" for patients. For technology adoption and diffusion to be rational and evidence-based, we must encourage appropriate financial payment models to curb use outside of research studies and promote development of additional treatment registries until sufficient evidence is gathered.

Is there a tradeoff in using modified high tangent field radiation for treating an undissected node-positive axilla?

INTRODUCTION: Recent data are changing axillary management in patients with 1 to 2 positive sentinel nodes. The proposed omission of completion axillary node dissection calls into question the need for axillary nodal irradiation. This study evaluates the difference in dose to the lung and heart and risk of radiation pneumonitis (RP) for patients treated with standard tangent fields (STF) compared with modified high tangent fields (MHTF). MATERIALS AND METHODS: Plans of 30 patients treated with STF were evaluated. A second plan (MHTF) was developed to include axillary levels I (Ax1) and II (Ax2). Ax1 and Ax2 volumes were contoured based on the RTOG (Radiation Therapy Oncology Group) Atlas guidelines. Dose-volume histograms of the 2 plans were used to compare doses received by Ax1, Ax2, lung, and heart volumes. The risk of RP was calculated using normal tissue complication probability (NTCP) modeling. RESULTS: The D95 (dose to 95% of volume) received by Ax1 and Ax2 volumes increased from 16.38 Gy and 5.71 Gy for STF to 49.38 Gy and 48.08 Gy for MHTF, respectively. Mean lung dose increased from 5.40 Gy for STF to 9.47 Gy for MHTF. Mean ipsilateral lung V5, V10, and V20 values increased from 19%, 14%, and 10%, respectively, for STF, to 32%, 24%, and 18%, respectively, for MHTF. Mean heart dose increased from 1.98 Gy for STF to 3.93 Gy for MHTF. Mean heart V25 and V30 values increased from 2% and 1%, respectively, for STF, to 4% and 3%, respectively, for MHTF. NTCP for RP increased from near 0% for STF to 1% for MHTF. CONCLUSION: Modified high tangent fields are necessary for definitive coverage of Ax1 and Ax2. This technique increases mean ipsilateral lung and heart doses as well as the V5, V10, and V20 of ipsilateral lung and the V25 and V30 of the heart. Risk of RP remains low by use of MHTF.