Insurance Approval for Proton Beam Therapy and its Impact on Delays in Treatment.

PURPOSE: Prior authorization (PA) has been widely implemented for proton beam therapy (PBT). We sought to determine the association between PA determination and patient characteristics, practice guidelines, and potential treatment delays. METHODS AND MATERIALS: A single-institution retrospective analysis was performed of all patients considered for PBT between 2015 and 2018 at a National Cancer Institute-designated Comprehensive Cancer Center. Differences in treatment start times and denial rates over time were compared, and multivariable logistic regression was used to identify predictors of initial denial. RESULTS: A total of 444 patients were considered for PBT, including 396 adult and 48 pediatric patients. The American Society for Radiation Oncology model policy supported PBT coverage for 77% of the cohort. Of adult patients requiring PA, 64% were initially denied and 32% remained denied after appeal. In patients considered for reirradiation or randomized phase 3 trial enrollment, initial denial rates were 57% and 64%, respectively. Insurance coverage was not related to diagnosis, reirradiation, trial enrollment, or the American Society for Radiation Oncology model policy guidelines, but it was related to insurance category on multivariable analysis (P < .001). Over a 3-year timespan, initial denial rates increased from 55% to 74% (P = .034). PA delayed treatment start by an average of 3 weeks (and up to 4 months) for those requiring appeal (P < .001) and resulted in 19% of denied patients abandoning radiation treatment altogether. Of pediatric patients, 9% were initially denied, all of whom were approved after appeal, and PA requirement did not delay treatment start (P = .47). CONCLUSIONS: PA requirements in adults represent a significant burden in initiating PBT and cause significant delays in patient care. Insurance approval is arbitrary and has become more restrictive over time, discordant with national clinical practice guidelines. Payors and providers should seek to streamline coverage policies in alignment with established guidelines to ensure appropriate and timely patient care.

Alternatives to Standard Fractionation Radiation Therapy After Lumpectomy: Hypofractionated Whole-Breast Irradiation and Accelerated Partial-Breast Irradiation.

Adjuvant whole-breast irradiation (WBI) after lumpectomy has been an established standard of care for decades. Standard-fractionation WBI delivered over 5 to 7 weeks can achieve durable tumor control with low toxicity but can be inconvenient for patients and cost ineffective. Hypofractionated WBI can be completed in 3 to 4 weeks and, based on long-term randomized data, is the preferred standard of care in select patients. Accelerated partial-breast irradiation can be delivered using even shorter treatment regimens. Although the available data on accelerated partial-breast irradiation is more limited, early results suggest it is an effective alternative to WBI in select patients.

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

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Radiosensitization effect of Huaier on breast cancer cells.

Radiotherapy is a critical treatment strategy for breast cancer. However, its wide application is sometimes restricted by radioresistance and radiotoxicity. Trametes robiniophila Murr. (Huaier), an officinal fungus used as a traditional Chinese medicine (TCM), is reported to have multi-biological functions during cancer treatment. Yet, its radiosensitization effects have not been evaluated to date. In the present study, using HTA 2.0 transcriptome microarray assay, Huaier was found to downregulate genes related to the cell cycle, cell division, cell cycle phases and DNA repair. This investigation utilized a colony formation assay to confirm the ability of Huaier to sensitize breast cancer cells to radiotherapy. Flow cytometry, immunofluorescence staining and western blotting were used to illustrate the sensitization mechanism. Our findings suggest that Huaier causes G0/G1 arrest through downregulation of cell cycle-regulating proteins in MCF-7 and MDA-MB-468 cells, prolongs the persistence of γ-H2Ax foci after radiotherapy and interferes with the homologous recombination (HR) pathway of DNA repair by downregulating RAD51. These results suggest that Huaier has the ability to sensitize breast cancer cells to radiotherapy through regulation of the cell cycle and DNA repair pathway. Thus, Huaier may be a promising radiosensitizer for the treatment of breast cancer.

ACR Appropriateness Criteria stage I breast cancer: initial workup and surveillance for local recurrence and distant metastases in asymptomatic women.

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Cyclooxygenase-2 expression in postmastectomy chest wall relapse.

PURPOSE: Cyclooxygenase-2 (COX-2) expression has been shown to be associated with radiation resistance, which theoretically could be overcome with the use of COX-2 inhibitors. The purpose of this study was to assess the prognostic significance and clinical correlations of COX-2 expression (COX) in a cohort of patients treated with radiation for postmastectomy chest wall relapse. EXPERIMENTAL DESIGN: Between 1975 and 1999, 113 patients were treated for isolated postmastectomy chest wall relapse. All patients were treated with biopsy and/or excision of the chest wall recurrence followed by radiation therapy. Median follow-up was 10 years. All clinical data, including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy, were entered into a computerized database. Paraffin-embedded chest wall recurrence specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0 to 3+. A score of 2 to 3+ was considered positive. RESULTS: Overall survival from original diagnosis for entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after chest wall recurrence was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after chest wall recurrence. COX was considered positive in 13 of 38 cases. COX was inversely correlated with estrogen receptor (P = 0.045) and progesterone receptor (P = 0.028), and positively correlated with HER-2/neu (P = 0.003). COX was also associated with a shorter time to postmastectomy chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2-positive patients (P = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative. This was of high statistical significance with a P value of 0.003. CONCLUSIONS: Outcome following radiation therapy for postmastectomy chest wall relapse is relatively poor. Positive COX correlated with other markers of poor outcome, including a shorter time to local relapse, negative estrogen receptor/progesterone receptor, and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for postmastectomy chest wall relapse.