Kathleen C. Horst

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

PURPOSE The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. PATIENT AND METHODS We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. RESULTS Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of

ACR appropriateness criteria ® conservative surgery and radiation - Stage i and II breast carcinoma: Expert panel on radiation oncology: Breast

472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of

Breast cancer treatment across health care systems: Linking electronic medical records and state registry data to enable outcomes research

100,000 per QALY gained. CONCLUSION THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

Trajectory modulated prone breast irradiation: A LINAC-based technique combining intensity modulated delivery and motion of the couch

Abstract:  Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early‐stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long‐term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole‐breast irradiation, and accelerated partial‐breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments.

ACR appropriateness criteria(®) ductal carcinoma in situ.

Understanding of cancer outcomes is limited by data fragmentation. In the current study, the authors analyzed the information yielded by integrating breast cancer data from 3 sources: electronic medical records (EMRs) from 2 health care systems and the state registry.

Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma

PURPOSE External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide-angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast. METHODS AND MATERIALS A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeam™ STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom. RESULTS The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V50% and V100% parameters that have been correlated with EBRT toxicity. CONCLUSIONS The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose-volume parameters correlated with toxicity.

MRI Guidance for Accelerated Partial Breast Irradiation in Prone Position: Imaging Protocol Design and Evaluation

Abstract:  Ductal carcinoma in situ (DCIS) describes a wide spectrum of non‐invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole‐breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow‐up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole‐breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer‐reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Evolving trends in the initial locoregional management of male breast cancer

BACKGROUND The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. MATERIALS AND METHODS We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. RESULTS One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). CONCLUSION(S) BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.BACKGROUND The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. MATERIALS AND METHODS We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. RESULTS One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). CONCLUSION(S) BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

Defining an optimal role for breast magnetic resonance imaging when evaluating patients otherwise eligible for accelerated partial breast irradiation.

PURPOSE To design and evaluate a magnetic resonance imaging (MRI) protocol to be incorporated in the simulation process for external beam accelerated partial breast irradiation. METHODS AND MATERIALS An imaging protocol was developed based on an existing breast MRI technique with the patient in the prone position on a dedicated coil. Pulse sequences were customized to exploit T1 and T2 contrast mechanisms characteristic of lumpectomy cavities. A three-dimensional image warping algorithm was included to correct for geometric distortions related to nonlinearity of spatially encoding gradients. Respiratory motion, image distortions, and susceptibility artifacts of 3.5-mm titanium surgical clips were examined. Magnetic resonance images of volunteers were acquired repeatedly to analyze residual setup deviations resulting from breast tissue deformation. RESULTS The customized sequences generated high-resolution magnetic resonance images emphasizing lumpectomy cavity morphology. Respiratory motion was negligible with the subject in the prone position. The gradient-induced nonlinearity was reduced to less than 1 mm in a region 15 cm away from the isocenter of the magnet. Signal-void regions of surgical clips were 4 mm and 8 mm for spin echo and gradient echo images, respectively. Typical residual repositioning errors resulting from breast deformation were estimated to be 3 mm or less. CONCLUSIONS MRI guidance for accelerated partial breast irradiation with the patient in the prone position with adequate contrast, spatial fidelity, and resolution is possible.

ACR Appropriateness Criteria® Locally Advanced Breast Cancer

The locoregional management of breast cancer in men has evolved over time. Multimodality treatment regimens currently in use are based primarily on large randomized trials that exclusively enrolled women with breast cancer. We retrospectively reviewed cases of male breast cancer treated with radiotherapy at Stanford University Medical Center with an emphasis on 22 patients treated with surgery and locoregional radiotherapy. We report trends in the surgical techniques as well as in the use of adjuvant radiotherapy, chemotherapy, and hormonal therapy. There were no isolated locoregional failures in this cohort, and 5-year disease-free survival was 65%. The use of contemporary surgical and radiotherapeutic techniques in men is discussed. We conclude that treatment guidelines designed for women should be applied to the locoregional management of breast cancer in men. However, large international prospective registries and inclusion of men in cooperative group randomized trials will be important to confirm the safety and efficacy of modern treatment modalities for male breast cancer.