The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.
BACKGROUND: Nipple- or skin-sparing mastectomy and immediate implant-based breast reconstruction (IBR) is potentially associated with long-term unfavorable outcomes such as revision surgery and reconstruction failure. This large patient cohort study aimed to provide long-term data on the incidence of these outcomes and identify predictive risk factors. METHODS: Between 2012 and 2019 1,989 mastectomies with IBR were performed in 1,512 women in our institute. A direct-to-implant (DTI) method was used in 93% and a two-staged method with tissue-expander in 7%. Logistic regression analysis was used to identify patient- and treatment-related risk factors associated with revision surgery or reconstructive failure. RESULTS: Mean follow-up was 62.2 months. IBR failed in 6.7% of all breasts, thus a breast was present in 93.3%. Age older than 44 years old yielded a 2.6- and radiotherapy a 1.7-fold increased risk for reconstruction failure. Revision surgery was performed in 60% of all breasts. Mean number of revisions of all IBRs is 1.2 (range, 0-8; SD 1.37). Factors associated with significant higher rates of revision surgeries were age>44 years (OR=1.23), smoking (OR=1.53), specimen weight>492 grams (OR=1.39), implant volume>422 grams (OR=1.95) and radiotherapy (OR=1.51). Nipple preservation was protective for both outcomes (OR=0.71 and OR=0.42, respectively). DTI did not require any surgical revision in 43%. CONCLUSION: Despite the necessity of revision surgery in the majority of IBRs, nearly half of the breasts did not require any revision surgery, and long-term reconstruction failure rates are extremely low. Therefore, IBR should be offered to all eligible women undergoing mastectomy while understanding the risks.
Abstract Background pCR rates in stage II – III HER2-positive breast cancer have greatly improved since the addition of HER2 targeted agents to neoadjuvant chemotherapy and are associated with excellent long-term survival. While longer treatment regimens increase pCR rate, early complete responses are also common. We evaluated an image-guided approach to tailor chemotherapy duration based on the identification of early complete responders. Methods 45 hospitals across the Netherlands participated in the phase 2 TRAIN-3 trial. Patients received neoadjuvant systemic treatment consisting of paclitaxel, trastuzumab, carboplatin and pertuzumab (PTC-Ptz). Response to treatment was monitored every three cycles and patients were referred for surgery in case of a radiologic complete response (rCR) or after a maximum of 9 cycles. RCR was defined as the absence of pathological enhancement on MRI breast plus negative vacuum assisted core biopsies in case of hormone-receptor positive (HR+) tumors. In addition, negative fine needle aspiration or lymph node biopsy was required in patients with nodal involvement at baseline. The primary endpoint was 3-year event-free survival (EFS). Here, we report locally assessed rCR and pCR rates after 3, 6 and 9 cycles, the negative predictive value of rCR assessment and the incidence of adverse events (AEs). Analyses are stratified by HR-status. Results We included 467 patients between April 2019 and May 2021. Median age was 51 years, 69% had stage II disease and 232 had HR+ tumors. 33.6% of HR- patients and 15.5% of HR+ patients achieved pCR after 3 cycles of PTC-Ptz (see table). The NPV was higher in HR- patients and independent of the number of cycles. AE evaluation is currently ongoing. Conclusion Three cycles of PTC-Ptz induce an early pCR in one in three HR- and one in six HR+ tumors in patients with stage II-III HER2+ breast cancer. Dynamic contrast enhanced MRI-based response evaluation identifies these patients with ±87% certainty in HR- disease and ±58% in HR+ disease. Continuation of PTC-Ptz after 6 cycles further improves pCR rates and can be considered to reduce the need for adjuvant T-DM1. Efficacy and safety of this image-guided approach to tailor treatment duration need to be confirmed with follow-up in EFS and OS analyses. Table 1: Cumulative rCR & pCR according to HR-status *Including patients who underwent surgery for other reasons than rCR Citation Format: Anna van der Voort, Mette S. van Ramshorst, Rob Kessels, Ingrid A. Mandjes, Inge Kemper, Mariëtte J. Agterof, Wim A. van der Steeg, Joan B. Heijns, Marlies L. van Bekkum, Ester J. Siemerink, Philomeen M. Kuijer, Astrid Scholten, Jelle Wesseling, Marie-Jeanne T.F.D. Vrancken Peeters, Ritse M. Mann, Gabe S. Sonke. Image-guided optimization of neoadjuvant chemotherapy duration in stage II and III HER2-positive breast cancer: radiologic and pathologic complete response (pCR) rates in the multicenter phase 2 TRAIN-3 study (BOOG 2018-01) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-06.
