Compromised margins following mastectomy for stage I-III invasive breast cancer.

BACKGROUND: We investigated factors associated with positive margins following mastectomy and the impact on outcomes. METHODS: We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). RESULTS: Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. CONCLUSIONS: Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed.

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial.

A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20-29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10-19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.

ACR appropriateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast.

This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.

American College of Radiology appropriateness criteria on conservative surgery and radiation: stages I and II breast carcinoma.

BACKGROUND: During the past 2 decades, breast conservation therapy (BCT) has become firmly established as a standard therapeutic approach for eligible women with early-stage breast cancer. Breast radiation after conservative surgery is an integral component of BCT, resulting in comparable local control and equivalent survival to mastectomy. Successful breast conservation relies on understanding key elements for patient selection, evaluation, treatment contraindications, radiation therapy methods, and integration with systemic therapy. METHODS: The Appropriateness Criteria Committee of the American College of Radiology convened an expert panel to examine BCT for early-stage breast cancer. By using a modified Delphi technique to generate consensus, the expert panel responded to questionnaires on 9 clinical cases that address various key elements of breast conservation. A literature review on BCT led to the generation of an evidence table to support the consensus and overview. RESULTS: Consensus for appropriateness criteria for BCT was produced for various clinical scenarios commonly encountered in practice. These topics include radiation oncology management issues related to young patient age, sentinel node biopsy, elderly patients, other histology, positive margins, extensive intraductal component, node-positive breast cancer, genetic breast cancer, partial breast irradiation, and systemic therapy. Radiation methods for BCT are reviewed. CONCLUSION: The Breast Cancer Panel has generated a consensus of up-to-date guidelines for the appropriate use of radiation for BCT by using a modified Delphi process for the American College of Radiology Appropriateness Criteria.

CT localization of axillary lymph nodes in relation to the humeral head: significance of arm position for radiation therapy planning.

Irradiation of the axillary nodes is often indicated in the clinical radiotherapy of patients with lymphoma and breast cancer. The relative location of the axillary nodes and the humeral head has historically been estimated based on lymphangiographic data. Since CT offers more precise definition, the axillary nodal region in relation to the humeral head was systematically studied in 61 patients undergoing CT simulation for breast conservation therapy. Differences in arm position (degree of abduction) significantly affected the location of the axillary nodal region in relation to the humeral head. With the arm abducted beyond 55 degrees, humeral head blocking would result in blocking of some of the axillary nodes.

Localization of internal mammary lymph nodes by CT simulation: implications for breast radiation therapy planning.

The efficacy of post-operative radiation therapy in breast cancer management has been evident for several decades. In recent years there has been increasing interest in treating the internal mammary lymph nodes. In an attempt to simplify their localization for treatment planning purposes, the position of the internal mammary lymph nodes was systematically studied in 65 breast cancer patients undergoing CT simulation.

Positron emitting 18F-2-deoxy-2-fluoro-D-glucose: potential hot new therapy.

Preclinical studies suggest that 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) kills breast cancer cells without significant marrow toxicity or parenchymal toxicity. Radiation dose calculations estimated from fluorodeoxyglucose positron emission tomography images in women with metastatic disease indicate that 18F-FDG should be a feasible and safe option in humans. Because the available radiotherapeutic agents, strontium 89 and samarium 153 provide palliation to a limited population of women with bony metastases, new radiopharmaceutical agents with broader applicability are needed. The development of 18F-FDG as the first positron-emitting radiotherapeutic has the potential to be an innovative treatment, not only in osteoblastic disease, but also in osteolytic disease and in soft tissue metastases.

The grading of lymphedema in oncology clinical trials.

Lymphedema is a common late toxicity of cancer therapy. This article describes the rationale and process utilized by the Lymphedema Working Group for the revision and expansion of the Common Toxicity Criteria version 2 (CTC v2.0) lymphedema criteria to produce the CTC v3.0 lymphedema criteria. Established clinician-based rating scales and quantitative instruments are reviewed in this article. None of the extant rating scales have been formally validated, nor has their reliability been assessed. Drawbacks of current scales were considered in formulating CTC v3.0 criteria. Most rely exclusively on volume to diagnose and grade lymphedema. This imposes significant clinical limitations, particularly in the assessment of toxicity in oncology clinical trials. Volume-based rating scales are of little value in rating the severity of bilateral limb and nonlimb edema. Problems with nonvolumetric staging systems (eg, CTC v2.0) include insufficient detail to permit useful discrimination of severity among the majority of lymphedema patients. Technologies for objectively quantifying lymphedema have been developed and validated. Although these are briefly reviewed, it is recognized that cost and access issues limit their widespread clinical utility and, as such, were not considered in developing the CTC v3.0 criteria. The CTC v3.0 lymphedema criteria adopted several innovations. Principle among these was the decision to generate separate criteria for volumetric increase, dermal changes, and subcutaneous fibrosis. We anticipate the use of the new CTC v3.0 lymphedema criteria to begin in mid-2003 for grading the key clinical features of this disorder in oncology clinical trials. The purpose of this article is to familiarize the reader with (1) background on the clinical features of lymphedema, (2) information on established lymphedema rating systems, (3) the consensus process and rationale of the Lymphedema Working Group, (4) the new CTC v3.0, and (5) quantitative techniques for assessment of lymphedema.

Lymphedema management.

Lymphedema, defined as the abnormal accumulation of protein rich fluid dysfunction of the lymphatic system, is a common sequela of cancer therapy. The incidence is highest among patients who have undergone resection and irradiation of a lymph node bed. Recently, increased attention has been focused on the modification of anticancer therapies in an effort to minimize lymphatic compromise. Sentinel lymph node biopsy is an example of a surgical procedure developed to preserve lymphatic function. Concurrent with the development of less invasive treatments, the field of lymphedema management has evolved rapidly over the past decade. Combined manual therapy, often referred to as complex decongestive physiotherapy (CDP), has emerged as the standard of care. CDP combines compression bandaging, manual lymphatic drainage (a specialized massage technique), exercise, and skin care with extensive patient education. Case series collectively describing a mean 65% volume reduction in over 10,000 patients attest its efficacy. Pneumatic compression pumps were historically widely used to control lymphedema. Their use as an isolated treatment modality is now rare. Reliance on pumps diminished with the recognition that they may exacerbate truncal and genital lymphedema, as well as injure peripheral lymphatics when applied at high pressures. Many noncompressive approaches, particularly the use of benzopyrone medications and liposuction, continue to be used abroad.

The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation.

PURPOSE: To investigate the impact of radiographic parameter and radiation technique on the volumetric dose of lung and heart for intact breast radiation. METHODS AND MATERIALS: Forty patients with both two-dimensional (2D) and computed tomographic (CT) simulations were enrolled in the study. Central lung distance (CLD), maximal heart distance (MHD), and maximal heart length (MHL) were measured under virtual simulation. Four plans were compared for each patient. Plan A used a traditional 2D tangential setup. Plan B used clinical target volume (CTV) based three-dimensional (3D) planning. Both plans C and D used a combination of a medial breast field with shallow tangents. Plan D is a further modification of plan C. RESULTS: Under the traditional tangential setup, the mean ipsilateral lung dose and volume at 20, 30, and 40 Gy correlated linearly with CLD (R = 0.85 approximately 0.91). The mean ipsilateral lung dose (Gy) approximated 4 times the CLD value (cm), whereas the percentage volume (%) of ipsilateral lung at 20, 30, and 40 Gy was about 10 times the CLD (cm). The mean heart dose and percentage volume at 20, 30, and 40 Gy correlated with MHD (R = 0.76 approximately 0.80) and MHL (R = 0.65 approximately 0.75). The mean heart dose (Gy) approximated 3 times the MHD value (cm), and the percentage volume (%) of the heart at 10, 20, 30, and 40 Gy was about 6 times MHD (cm). Radiation technique impacted lung and heart dose. The 3D tangential plan (plan B) failed to reduce the volumetric dose of lung and heart from that of the 2D plan (plan A). The medial breast techniques (plans C and D) significantly decreased the volume of lung and heart receiving high doses (30 and 40 Gy). Plan D further decreased the 20 Gy volumes. By use of the medial breast technique, the lung and heart dose were not impacted by original CLD and MHD/MHL. Therefore, the improvement from the tangential technique was more remarkable for patients with CLD >or= 3.0 cm (p < 0.001). CONCLUSIONS: The CLD and MHD impact the volumetric dose of lung and heart. The application of 3D planning for tangential breast irradiation does not decrease heart and lung dose. Adding a medial breast port significantly decreases percentage volume (PV) of lung and heart receiving high doses, especially when the CLD is excessive.

Breast cancer: chest wall recurrences.

Irradiation is indicated for patients undergoing mastectomy as surgical management for breast cancer treatment when clinical or pathologic tumor and nodal features predict risk of local/regional recurrence. Such features include: tumor size >/= 5 cm, inadequate surgical margins; skin, facial, or skeletal muscle invasion; dermal lymphatic invasion; poorly differentiated tumor histology; four or more lymph nodes positive; gross extracapsular tumor nodal extension into soft tissues; and matted lymph nodes or enlarged lymph nodes > 2 cm. Patients who were treated with irradiation after mastectomy can develop local/regional recurrences despite such adjuvant therapy. General management for chest wall and nodal recurrences is structured on the extent and volume of local/regional disease, the absence of distant metastases, the general health of the patient, and the extent of prior local/regional therapies, especially irradiation. Management of local/regional recurrence in the setting of no prior irradiation includes tumor debulking by systemic or surgical treatment followed by comprehensive chest wall and regional lymphatic irradiation. Doses are selected by tissue tolerances and volume of remaining disease. The management strategy for the patient with a history of irradiation parallels the nonirradiated patient with respect to systemic and surgical therapies to debulk the tumor to maximal response or no gross clinical disease. Radiation field design is determined by prior therapies. Doses to these fields are adjusted to normal tissue tolerance. Irradiation is given with a sensitizer such as hyperthermia or 5-fluorouracil chemotherapy. Use of radiation sensitizers can allow for a more meaningful biologic tumor effect when normal tissue tolerances prohibit delivery of standard tumor doses. Hyperthermia has been used effectively to promote complete tumor responses with use of irradiation in re-treatment cases.

Feasibility of assessing the carcinogenicity of neutrons among neutron therapy patients.

Nuclear workers, oil well loggers, astronauts, air flight crews, and frequent fliers can be exposed to low doses of neutrons, but the long-term human health consequences of neutron exposure are unknown. While few of these exposed populations are suitable for studying the effects of neutron exposure, patients treated with neutron-beam therapy might be a source of information. To assess the feasibility of conducting a multi-center international study of the late effects of neutron therapy, we surveyed 23 cancer centers that had used neutron beam therapy. For the 17 responding institutions, only 25% of the patients treated with neutrons (2,855 of 11,191) were alive more than 2 years after treatment. In a two-center U.S. pilot study of 484 neutron-treated cancer patients, we assessed the feasibility of obtaining radiotherapy records, cancer incidence and other follow-up data, and of estimating patient organ doses. Patients were treated with 42 MeV neutrons between 1972 and 1989. Applying a clinical equivalence factor of 3.2 for neutrons, total average organ doses outside the treatment beam ranged from 0.14 to 0.29 Gy for thyroid, 0.40 to 2.50 Gy for breast, 0.63 to 2.35 Gy for kidney, and 1.12 to 1.76 Gy for active bone marrow depending upon the primary cancer treatment site. We successfully traced 97% of the patients, but we found that patient survival was poor and that chemotherapy was not confirmable in a quarter of the patients. Based on our findings from the international survey and the feasibility study, we conclude that a large investigation could detect a fivefold or higher leukemia risk, but would be inadequate to evaluate the risk of solid cancers with long latent periods and therefore would likely not be informative with respect to neutron-related cancer risk in humans.