R.M. Lanning

Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy.

61 Background: HER2 overexpression is associated with an increased risk of LRR after mastectomy in the era prior to the use of adjuvant trastuzumab. The purpose of this study was to examine the effect of adjuvant trastuzumab on rates of LRR and whether this effect varied with the use of PMRT. METHODS From our institutional database, 474 women with Stage I-III HER2+ invasive breast cancer treated with mastectomy +/- adjuvant therapy from 1999-2007 were identified. Those patients lost to follow-up, treated with lapatinib, or diagnosed between 5/2004 to 5/2005 (when trastuzumab prescribing practices varied) were excluded; leaving 395 in the final study population. Two cohorts were compared: 139 women who received trastuzumab (5/2005-12/2007) and 256 women who did not (prior to 5/2005). Competing risks analyses were used to estimate cumulative incidence of LRR. Competing risks regression was used to evaluate the association between treatment factors and LRR. To minimize lead-time bias, patient data was censored at 5 years after mastectomy in both groups. RESULTS There were 18 LRRs in the entire cohort (16 no trastuzumab, 2 trastuzumab). Women in the no trastuzumab group were less likely to be node positive, receive chemotherapy or PMRT (all p<0.001). The hazard ratio for LRR was 0.218in the trastuzumab group (p= 0.04, 95% C.I. 0.05-0.94) with a 5-year risk of LRR of 1.5% in the trastuzumab versus 6.6% in the no trastuzumab group. After adjusting for PMRT and chemotherapy receipt, trastuzumab trended towards significance in decreasing LRR (p= 0.063). On subset analysis of 139 women who received PMRT, trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab, p=0.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab, p=0.28). CONCLUSIONS Adjuvant trastuzumab significantly reduced LRR in women with HER2+ breast cancer who received PMRT. A trend toward decreased LRR was observed in the entire population, but did not reach statistical significance, suggesting that the benefit is greater in HER2+ patients receiving multimodality therapy.

Predictors of Treatment Response and Survival Outcomes in Meningioma Recurrence with Atypical or Anaplastic Histology

BACKGROUND Recurrence rates for atypical and anaplastic meningiomas range between 9% and 50% after gross total resection and between 36% and 83% after subtotal resection. Optimal treatment of recurrent meningiomas exhibiting atypical/anaplastic histology is complicated because they are often refractory to both surgery and radiation. OBJECTIVE To evaluate clinical determinants of recurrence and treatment‐specific outcomes in patients with recurrent meningiomas exhibiting atypical/anaplastic histology at our institution. METHODS A cohort study was conducted using clinical data of all patients treated for meningiomas with atypical/anaplastic histology at first recurrence between January 1985 and July 2014 at a tertiary cancer center. Predictors of second recurrence were analyzed using competing risks regression models. RESULTS Nine hundred eighteen patients with meningioma were screened, of whom 60 (55% female) had recurrent disease with atypical/anaplastic histology at a median age of 58.1 yr at diagnosis. The median follow‐up from the time of first recurrence was 36.7 mo, with 32 (53%) patients alive at last follow‐up. There was no effect of extent of resection at first recurrence on time to a subsequent recurrence. Inclusion of radiation as primary or adjuvant therapy at first recurrence reduced the risk of progression or subsequent recurrence compared to surgery alone (P = .07). CONCLUSION Treatment of recurrent meningiomas with atypical/anaplastic histology remains challenging. Our data, from one of the largest cohorts, suggest better tumor control with the addition of radiation and challenges the importance of extent of resection at first recurrence. A multicenter effort is needed to confirm these findings and propose treatment guidelines.