Neoadjuvant Chemotherapy Cohort Research Articles

Impact of Chemotherapy on Postoperative Complications After Mastectomy and Immediate Breast Reconstruction

To determine the impact of chemotherapy and the timing of chemotherapy on postoperative outcomes after mastectomy and immediate breast reconstruction. Retrospective review. University tertiary care institution. One hundred sixty-three consecutive patients undergoing mastectomy and immediate breast reconstruction. Systemic chemotherapy for breast cancer. Postoperative complications following mastectomy and immediate breast reconstruction. One hundred sixty-three patients underwent mastectomy and immediate breast reconstruction during the study period, with a mean postoperative follow-up of 19.2 months. Sixty-six percent of the patients had expander/implant reconstruction, while 33% underwent autologous reconstruction. Fifty-seven patients received neoadjuvant chemotherapy and 41 received postoperative chemotherapy. Eighteen patients (44%) in the adjuvant chemotherapy cohort developed postoperative infections, compared with 13 patients (23%) in the neoadjuvant chemotherapy group and 16 patients (25%) who did not receive any chemotherapy (P=.05). Overall, 31% of patients had a complication requiring an unplanned return to the operating room; this rate did not differ between groups (P=.79). Of patients who underwent expander/implant reconstruction, 8 women (26%) in the neoadjuvant chemotherapy cohort, 7 women (22%) in the adjuvant chemotherapy cohort, and 8 women (18%) without chemotherapy required expander or implant removal (P=.70). Although the highest rate of surgical site infections was in the adjuvant chemotherapy group, there were no differences between groups with respect to unplanned return to the operating room, expander loss, and donor-site complications. Neither the inclusion of chemotherapy nor the timing of its administration significantly affected the complication rates after mastectomy and immediate breast reconstruction in this population.

Greater Anti-Angiogenic Effects with Docetaxel Compared with Anthracyclines in the Neoadjuvant Treatment of Breast Cancer.

Abstract Background: Dynamic contrast-enhanced MRI (DCE-MRI) allows for the functional assessment of tumour permeability and perfusion and has been previously shown to predict for clinical and pathologic response in women with breast cancer undergoing neoadjuvant anthracycline based chemotherapy1. Changes in DCE-MRI kinetic parameters after 2 cycles of neoadjuvant chemotherapy (NAC) predicts clinical and pathological benefit, with transfer constant Ktrans being the best predictive biomarker. This study examines (1) whether DCE-MRI can predict for final clinical response in women undergoing neoadjuvant docetaxel and (2) whether taxanes demonstrate greater anti-angiogenic activity over anthracyclines in the NAC setting.Methods: 30 patients with histologically proven primary breast cancer (T2-4, N0-1, M0) due to receive neoadjuvant docetaxel chemotherapy underwent DCE-MRI before and after 2 cycles of NAC as part of a prospective study. Whole tumour regions of interest were outlined and values for inflow transfer constant (Ktrans), outflow rate constant (kep), leakage space (ve), initial area under gadolinium-time curve (IAUGC60), relative blood volume (rBV), Mean Transit Time (MTT) and relative blood flow (rBF) calculated. Both baseline and changes in DCE-MRI kinetic parameters were correlated with final clinical response using the Mann-Whitney U test. DCE-MRI results of the docetaxel NAC cohort were compared with a previously analysed cohort of 28 patients who received neoadjuvant FEC chemotherapy1. MRI data acquisition and pharmacokinetic modelling analysis for both cohorts were identical.Results: 25 docetaxel patients were assessable (median age 42, range 26-62; docetaxel 100mg/m2; median number of cycles 4, range 2-6). 1 patient received 1 cycle of docetaxel only and 4 were not able to complete their imaging. There were 21 clinical responders (CR)(9 complete and 12 partial responders) and 4 non-responders (NR)(3 with SD, 1 with PD). There was no significant difference in pretreatment parameters between CR and NR. The median reduction in Ktrans in CR was -58.1% vs -8.9% in NR (95% CI -81.1 to -19.8, p=0.011) and in IAUGC60, -57.6% vs -3.7% (95% CI -79.9 to -14.7, p=0.011). ROC analysis revealed that both Ktrans and IAUGC60 changes were good predictors of clinical response (Ktrans: sensitivity 81%, specificity 100%, area under ROC curve 0.89; IAUGC60: sensitivity 76%, specificity 100%, area under ROC curve 0.89). Comparison of docetaxel versus FEC cohorts showed greater reductions in kinetic parameters in clinical responders in the docetaxel group (Ktrans: -58.1% vs -29.5%, p=0.022; IAUGC60 values: -57.5% vs -20.4%, p=0.006).Discussion: Early changes in DCE-MRI biomarkers depicting tumour vascularity can predict clinical benefit from docetaxel NAC in breast cancer, similar to a finding previously shown for anthracyclines. Significantly larger changes in DCE-MRI biomarkers related to tumour perfusion and permeability in responding patients suggest a greater anti-angiogenic effect with docetaxel.

Commentary on Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder: A contemporary series: Weight CJ, Garcia JA, Hansel DE, Fergany AF, Campbell SC, Gong MC, Jones JS, Klein EA, Dreicer R, Stephenson AJ, Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, OH

The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting. From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle-invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database. Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3-4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle-invasive bladder cancer to RC was 208 days (interquartile range, 149–327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0–17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43–81 patients) had non-organ confined residual cancer, and the overall median progression-free survival was 10.5 months (95% CI, 7–14 months). Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non-MVAC based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC.

Lack of pathologic down‐staging with neoadjuvant chemotherapy for muscle‐invasive urothelial carcinoma of the bladder

The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting. From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle-invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database. Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3-4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle-invasive bladder cancer to RC was 208 days (interquartile range, 149 days -327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0 patients-17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43 patients-81 patients) had nonorgan-confined residual cancer, and the overall median progression-free survival was 10.5 months (95% CI, 7 months -14 months). Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non-MVAC-based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC.

In reply to Dr. Monsour

In reply to Dr. Monsour