BackgroundDual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy.... Show moreBackgroundDual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.MethodsNeoadjuvant lapatinib and/or trastuzumab treatment optimisation (NCT00553358) is an international, randomised, open-label, phase III study investigating the addition of lapatinib to chemotherapy plus trastuzumab in HER2-positive early BC. Ten-year event-free survival (EFS), overall survival (OS) and safety were assessed on intention-to-treat population. The association between pCR and EFS or OS was investigated in landmark population.ResultsA total of 455 patients were randomised to receive lapatinib (154), trastuzumab (149) or the combination (152). Ten-year EFS estimates were 63% (95% confidence interval [CI], 54%–71%) in the lapatinib group, 64% (95% CI, 55%–72%) in the trastuzumab group and 67% (95% CI, 58%–74%) in the combination group. Ten-year OS rates were 76% (95% CI, 67%–83%), 75% (95% CI, 66%–82%) and 80% (95% CI, 73%–86%) in the lapatinib, trastuzumab and combination groups, respectively. Women who achieved a pCR had improved EFS (hazard ratio 0.48, 95% CI, 0.31–0.73) and OS (hazard ratio 0.37, 95% CI, 0.20–0.63) compared with those who did not. The numerical difference in survival according to pCR status was greater in women treated with the combination and those with hormone-receptor-negative tumours. There were no new or long-term safety concerns.ConclusionsPatients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2, irrespective of treatment arm. Patients who achieve pCR have significantly better outcomes than patients without pCR. Show less
Objective: This study evaluated the correlation between intratumoural stmma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with... Show moreObjective: This study evaluated the correlation between intratumoural stmma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer.Methods: This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation (r(s)).Results: The ADC values between stroma-low and stroma-high tumours were not significantly different. Intraclass correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84-0.86 for single slice and 0.86-0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADC(mean), r(s) = -0.162 (p= 0.38) and ADC(m)(in), r(s) = 0.041 (p= 0.82) for the single-slice and r(s) = -0.108 (p= 0.55) and r(s) = 0.019 (p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADC(mean )r(s) = -0.022 (p= 0.86) and ADC(min), r(s) = 0.049 (p= 0.69) for the single-slice and r(s) = -0.064 (p= 0.59) and r(s) = -0.063 (p= 0.61) for the whole-volume measurements.Conclusions: Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer. Show less
