Intra-arterial Mitomycin C infusion in a large cohort of advanced liver metastatic breast cancer patients: safety, efficacy and factors influencing survival.

PURPOSE: The aim of this study was to determine the safety and efficacy of Mitomycin C (MMC) infusion in a large cohort of advanced liver metastatic breast cancer patients (LMBC) and to determine factors influencing overall survival (OS). METHODS: We retrospectively analysed LMBC patients, treated with MMC infusion between 2000 and 2017. Hepatic response was measured with baseline CT scans and first available CT scan after MMC infusion by RECIST 1.1 criteria. Adverse events were registered by the CTCAE version 5.0. OS and hepatic progression free survival (hPFS) were evaluated using Kaplan-Meier estimates. After univariable analysis, a stepwise forward multivariable (MV) prediction analysis was developed to select independent pre-treatment factors associated with OS. RESULTS: We included 176 patients with a total of 599 MMC infusions, mostly heavily pre-treated patients with a median time from diagnosis of MBC to MMC infusion of 36.9 months. RECIST evaluation of liver lesions (n = 132) showed a partial response rate of 15%, stable disease of 43% and progressive disease in 17%. Adverse events grade 3 and 4 were reported in 17.5%. Median PFS was 5.5 months and median OS was 7.8 months. Significant independent baseline predictors of worse OS included number of prior systemic chemotherapy lines, prior liver ablation, higher liver tumour burden and elevated levels of bilirubin and ALT. CONCLUSION: MMC infusion is safe and effective in advanced LMBC patients. An increased number of prior therapies, a higher liver tumour burden and elevated levels of bilirubin and ALT were associated with a worse OS.

Intra-Arterial Therapies for Liver Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Performing a systematic review and meta-analysis to assess the evidence of intra-arterial therapies in liver metastatic breast cancer (LMBC) patients. METHODS: A systemic literature search was performed in PubMed, EMBASE, SCOPUS for studies regarding intra-arterial therapies in LMBC patients. Full text studies of LMBC patients (n ≥ 10) published between January 2010 and December 2020 were included when at least one outcome among response rate, adverse events or survival was available. Response rates were pooled using generalized linear mixed models. A weighted estimate of the population median overall survival (OS) was obtained under the assumption of exponentially distributed survival times. RESULTS: A total of 26 studies (1266 patients) were included. Eleven articles reported on transarterial radioembolization (TARE), ten on transarterial chemoembolization (TACE) and four on chemo-infusion. One retrospective study compared TARE and TACE. Pooled response rates were 49% for TARE (95%CI 32-67%), 34% for TACE (95%CI 22-50%) and 19% for chemo-infusion (95%CI 14-25%). Pooled median survival was 9.2 months (range 6.1-35.4 months) for TARE, 17.8 months (range 4.6-47.0) for TACE and 7.9 months (range 7.0-14.2) for chemo-infusion. No comparison for OS was possible due to missing survival rates at specific time points (1 and 2 year OS) and the large heterogeneity. CONCLUSION: Although results have to be interpreted with caution due to the large heterogeneity, the superior response rate of TARE and TACE compared to chemo-infusion suggests first choice of TARE or TACE in chemorefractory LMBC patients. Chemo-infusion could be considered in LMBC patients not suitable for TARE or TACE. LEVEL OF EVIDENCE: 3a.

Preoperative radiochemotherapy is successful also in patients with locally advanced rectal cancer who have intrinsically high apoptotic tumours.

BACKGROUND: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC. PATIENTS AND METHODS: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed. RESULTS: Apoptotic levels, quantified as the number of apoptotic cells/mm(2) tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only. CONCLUSION: Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.

Local recurrence in rectal cancer can be predicted by histopathological factors.

AIM: The main cause of local recurrence (LR) in rectal cancer is involvement of the circumferential resection margin (CRM). However, patients with a negative CRM can also develop LR, suggesting that additional factors are important for LR. The aim of this study was to identify histopathological factors predictive for the development of LR after primary rectal cancer treatment. METHODS: T x N x M0 patients treated for locally recurrent rectal cancer at the Catharina hospital from 1994 to 2006 (n=92) were matched with a control group of patients who did not develop LR after primary rectal cancer treatment for at least 2 years (n=185) based on the type of neoadjuvant treatment in a 1:2 ratio. The pathology of all primary rectal cancers was reviewed. Patient, treatment and histopathological characteristics were studied in relation to the development of LR with logistic regression. RESULTS: Logistic regression indicated the presence of lymphovascular invasion (LVI, OR 4.66, P<0.001), extramural venous invasion (EMVI, OR 4.54, P<0.001), positive CRM (OR 2.56, P=0.032), serosal involvement (OR 6.74, P=0.035) and poor differentiation (OR 2.59, P=0.012) as factors with an increased risk to develop LR. Older age was a protective factor (OR 0.95, CI 0.93-0.98, P=0.001). CONCLUSION: Apart from a positive CRM and serosal involvement, LVI, EMVI and poor differentiation are important independent predictive factors for the development of LR. Adjuvant therapy may be considered in the presence of these features in order to decrease the risk of a local recurrence.

Linitis plastica of the rectum secondary to bladder carcinoma: a report of two cases and its MR features.

Rectal linitis plastica (RLP) is a circumferentially infiltrating intramural anaplastic carcinoma that results in a rigid constricted rectum with thickened walls. A long delay between the onset of symptoms and the diagnosis often occurs because RLP can mimic a lot of diseases and endoscopy and biopsies are often negative, owing to the fact that the mucosa is frequently unaffected in RLP. RLP secondary to bladder cancer is rarely described in the English literature. We present the first report of the MR features of secondary rectal linitis plastica from a bladder carcinoma. Two patients presented with changed bowel habits. All diagnostic tests were inconclusive. In both patients, pelvic T(2) weighted MR images revealed a double-layered thickening of the rectal wall with an inner isointense circumferential thickening of the submucosa and outer hypointense circumferential thickening of the muscular rectal wall. Based on MRI, further investigations were performed and secondary RLP was diagnosed. It is important to establish the diagnosis of RLP early because of its bad prognosis. The value of MRI in supporting the diagnosis of RLP should not be underestimated. As endoscopy plus biopsy can often be negative, we suggest that, if pelvic MRI shows a concentric double layered thickening of the rectal wall over a long segment, then the diagnosis of RLP should be considered. This should prompt further investigations either to confirm or rule out the diagnosis of RLP by performing endoscopy with deep rectal wall biopsies.