American Radium Society Appropriate Use Criteria Postmastectomy Radiation Therapy: Executive Summary of Clinical Topics.

PURPOSE: To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures. RESULTS: Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction. CONCLUSIONS: Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange.

Radiation Oncology Applications in Plastic and Reconstructive Surgery: A Nonsystematic Review of Concepts and Principles.

SUMMARY: Careful consideration of radiotherapy can determine the success of reconstructive therapy. There is a broad spectrum of radiotherapy modalities, both benign and malignant. Delivery mechanisms differ in the physical design, setup, radiation source, administrable dosage, and mode of delivery. This range of options allows radiation oncologists to tailor individualized treatment; however, radiotherapy concepts can be challenging for nonspecialists. The purpose of this article is to review general radiation oncology concepts, including essential equipment and radiobiology, and provide plastic surgeons with a basic conceptual understanding to facilitate effective multidisciplinary collaboration with radiation oncologists.

ACR Appropriateness Criteria® Stage I Breast Cancer: Initial Workup and Surveillance for Local Recurrence and Distant Metastases in Asymptomatic Women.

As the proportion of women diagnosed with early stage breast cancer increases, the role of imaging for staging and surveillance purposes is considered. National and international guidelines discourage the use of staging imaging for asymptomatic patients newly diagnosed with stage 0 to II breast cancer, even if there is nodal involvement, as unnecessary imaging can delay care and affect outcomes. In asymptomatic patients with a history of stage I breast cancer that received treatment for curative intent, there is no role for imaging to screen for distant recurrences. However, routine surveillance with an annual mammogram is the only imaging test that should be performed to detect an in-breast recurrence or a new primary breast cancer in women with a history of stage I breast cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Role of excision repair cross-complementation 1 expression as a prognostic marker for response to radiotherapy in early-stage laryngeal cancer.

BACKGROUND: High expression of excision repair cross-complementation 1 (ERCC1) predicts for resistance to platinum-based chemotherapy or chemoradiotherapy. We evaluated the prognostic value of ERCC1 expression in a cohort of laryngeal cancer treated with radiotherapy alone. METHODS: ERCC1 expression was examined by immunohistochemical analysis of tissue microarrays constructed from 123 patients with stages I-II laryngeal squamous cell carcinoma treated with standard radiotherapy. RESULTS: ERCC1 expression did not correlate with clinicopathologic risk factors, local control, or overall survival. At 5 years, local control was 75% versus 71% (p = .78) and overall survival was 68% versus 54% (p = .65), for nonexpressors and expressors of ERCC1, respectively. On multivariate analysis, T classification predicted for local control, and T classification and age predicted for overall survival. CONCLUSIONS: ERCC1 expression did not predict for radiotherapy resistance or worse survival. Therefore, radiotherapy remains an effective treatment in tumors with high ERCC1 expression.

BCCIP as a prognostic marker for radiotherapy of laryngeal cancer.

BACKGROUND: Recent studies have shown that BCCIP (BRCA2 and CDKN1A interacting protein) is essential for maintaining the transactivation activity of wild type p53. We analyzed the expression of BCCIP and p53 in a cohort of laryngeal cancer treated with radiotherapy and assessed whether BCCIP and p53, alone or in combination, would correlate with local control and overall survival. METHODS: One hundred twenty-three patients treated between 1975 and 2000 for early stage (stages I and II) squamous cell carcinoma of the larynx were included in the study. Treatment consisted of radiation therapy (RT) with standard fields and fractionation to a median dose of 66Gy. Tissue was collected from pre-RT biopsies and constructed in a tissue microarray, and BCCIP expression and p53 expression were determined using immunohistochemistry. RESULTS: Loss of expression of BCCIP in combination with normal p53 (negative p53 staining) was associated with local recurrence (RR 2.04; 95% CI 0.99-4.56, p=0.05) and poor overall survival (RR 2.09; 95% CI 1.21-4.00, p=0.008) compared to patients who did express BCCIP. Expression of BCCIP or p53 alone was not found to be independently associated with benefits in local control or overall survival. CONCLUSIONS: This study provides clinical evidence that BCCIP contributes to outcomes in patients with laryngeal cancer treated with RT. This benefit may be a result of increased radiosensitivity in patients who have functional BCCIP and p53. These data may be used to identify sub-groups of laryngeal cancer patients who are more likely to be cured with radiotherapy.

Postoperative concurrent chemoradiotherapy with mitomycin in advanced squamous cell carcinoma of the head and neck: results from three prospective randomized trials.

UNLABELLED: Recent prospective randomized trials have shown concurrent chemoradiotherapy improves locoregional control in postoperative patients with squamous cell carcinoma of the head and neck using cisplatin-based regimes. This report presents data pooled from three randomized trials employing mitomycin, selecting those patients treated postoperatively, to evaluate the long-term benefit of mitomycin in the postoperative setting and to compare these results with those of two other recently published randomized trials. METHODS AND MATERIALS: Between 1980 and 1999, a total of 331 patients with squamous cell carcinoma of the head and neck from the three prospective trials were enrolled. Of the 205 postoperative patients in these trials, 103 were randomized to receive mitomycin and radiation, while 102 received radiation alone or radiation with porfiromycin in the third trial. Patients were treated with standard daily radiotherapy to a total median dose of 60 Gy over 47 days. Patients who were randomized to mitomycin C received 15 mg/m2 of the drug on days 5 and 47 (or last day). RESULTS: The 5-year rate of locoregional control was higher in the mitomycin arms. There was no statistically significant difference in the rates of overall survival or distant metastasis. Patients had a lower percentage of high-risk factors in both arms of the study, compared with patients in the large prospective trials, including positive margins, two or more positive lymph nodes, or oropharynx primary tumors. The gains in locoregional control realized with mitomycin were similar to the improvements in the recently published randomized trials using platinum. CONCLUSIONS: These results confirm significant gains in locoregional control using concurrent chemoradiotherapy in the postoperative setting for patients with squamous cell carcinoma of the head and neck. The lack of consensus over a benefit in the rates of overall survival and distant metastasis emphasizes the need for further prospective trials in the postoperative management of squamous cell carcinoma of the head and neck.

Fos-related antigen 2 controls protein kinase A-induced CCAAT/enhancer-binding protein beta expression in osteoblasts.

Transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) plays an important role in hormone-dependent gene expression. In osteoblasts C/EBPbeta can increase insulin-like growth factor I (IGF-I) transcription following treatment with hormones that activate protein kinase A, but little is known as yet about the expression of C/EBPbeta itself in these cells. We initially showed that prostaglandin E2 (PGE2) rapidly enhances C/EBPbeta mRNA and protein expression, and in this study we identified a 3'-proximal region of the C/EBPbeta promoter containing a 541-bp upstream sequence that could account for this effect. PGE2-dependent activation of C/EBPbeta was blocked by expression of a mutated regulatory subunit of protein kinase A or by mutation of two previously identified cAMP-sensitive cis-acting regulatory elements within the promoter between bp -111 and -61. Nuclear protein binding to these elements was induced by PGE2, required new protein synthesis, and was sensitive to antibody to the transcription factor termed Fos-related antigen 2 (Fra-2). Fra-2 cDNA generated from rat osteoblasts by reverse transcriptase PCR was 95% homologous to human Fra-2, and PGE2 rapidly induced Fra-2 mRNA and protein expression. Consistent with these findings, over-expression of Fra-2 significantly increased C/EBPbeta promoter activity in PGE2-induced osteoblasts, whereas expression of Fra-2 lacking its activation domain had a dominant negative inhibitory effect. Together, these results reveal a significant, hormone-dependent role for Fra-2 in osteoblast function, both directly, through its ability to increase new C/EBPbeta gene expression, and indirectly, through downstream C/EBP sensitive genes.