The Presence of Extensive Lymphovascular Invasion is Associated With Higher Risks of Local-Regional Recurrence Compared With Usual Lymphovascular Invasion in Curatively Treated Breast Cancer Patients.

PURPOSE: Several data sets have demonstrated a correlation between lymphovascular invasion (LVI) and locoregional recurrence (LRR). Whether the observation of "extensive LVI" is a further and incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by (1) absence of LVI (neg), (2) LVI focal or suspicious (FS-LVI), (3) usual (nonextensive) LVI (LVI), and (4) extensive LVI (E-LVI). METHODS AND MATERIALS: Between December 2009 and August 2021, 8837 patients with early-stage breast cancer were treated with curative intent and were evaluable. Clinical-pathologic details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. A matched propensity score analysis compared outcomes between patients with LVI versus E-LVI. RESULTS: Of the 8837 patients studied, 5584 were negative, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. Patients with E-LVI had an adverse risk profile compared with the other groups. The 5- and 10-year LRR cumulative incidence estimates in patients with E-LVI were 9.6% (95% CI, 7.1-13) and 13% (95% CI, 10-17), respectively, which were significantly higher than those observed in the usual LVI group (6.8% [5.7-7.9] and 10% [8.8-12], respectively). A statistically significant difference in LRR was demonstrated in univariable (HR, 1.4; 95% CI, 1.03-1.89; P = .029) and multivariable regression analysis (HR, 1.62; 95% CI, 1.15-2.27; P = .005) compared with nonextensive LVI. In an alternative approach, we performed a 2:1 propensity score matching analysis comparing patients with LVI to those with E-LVI. The hazard ratio for LRR (HR, 1.47; CI 1.02-2.14; P = .041) was suggestive of a higher risk associated with E-LVI. CONCLUSIONS: Our work suggests that patients with E-LVI are at a higher risk for LRR than those with usual LVI. For patients who are borderline candidates for regional nodal irradiation or post-mastectomy radiation therapy, the finding of E-LVI might be decisive in favor of intensified treatment.

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial.

PURPOSE: External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE). METHODS: In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone. The primary outcome of the trial was SRE. Secondary outcomes included hospitalizations for SRE and overall survival (OS). RESULTS: A total of 78 patients with 122 high-risk bone metastases were enrolled between May 8, 2018, and August 9, 2021, at three institutions across an affiliated cancer network in the United States. Seventy-three patients were evaluable for the primary end point. The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). At 1 year, SRE occurred in one of 62 bone metastases (1.6%) in the RT arm and 14 of 49 bone metastases (29%) in the SOC arm (P < .001). There were significantly fewer patients hospitalized for SRE in the RT arm compared with the SOC arm (0 v 4, P = .045). At a median follow-up of 2.5 years, OS was significantly longer in the RT arm (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.89; P = .018), which persisted on multivariable Cox regression analysis (HR, 0.46; 95% CI, 0.23 to 0.85; P = .01). CONCLUSION: Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations. We also observed an improvement in OS with prophylactic radiation, although a confirmatory phase III trial is warranted.