Background

Changes in prevalence and therapeutic landscapes of mCRC have translated into a progressive increase of refMCRC population. The efficacy of the available therapies in this setting is limited. Prognostic groups have been evaluated to determine better which patients (pts) could benefit from late-line treatments. We aim to explore the numeric representation of these groups in a real population that would support this strategy as a tool in daily care.

Methods

A cohort of mCRC pts treated at our hospital was retrospectively reviewed using medical charts from 2010 to 2020. Clinical, laboratory and molecular data were evaluated. We divided pts into 3 clinical groups according to previously reported prognostic characteristics: Good Prognostic Characteristics (GPC) defined as ≥18 m since metastatic disease debut, <3 metastatic sites and presence of liver metastasis, Best Prognostic Characteristics (BPC) defined as ≥18 m, since metastatic disease debut, < 3 metastatic sites and absence of liver metastases and Poor Prognostic Characteristics (PPC) defined as < 18m since metastatic disease debut and/or ≥3 metastatic sites. Statistical analysis was done using R version 4.

Results

A total of 735 out of 2365 mCRC pts (35%) were identified as refMCRC. Median age at diagnosis was 59 years, 130 pts (18%) were < 50y. Molecular profiles were: KRAS mutant (mt): 339 (46%), BRAF mt: 87 (12%) and MSI-H 29 (4%). In our cohort, 408/735 (55.51%) pts received > 3 lines of therapy (median lines 4, IQR 3-8) and 50.98% of these pts were included in clinical trials. The prognostic subgroup classification was: 266 pts (36%) GPC, 136 (19%) BPC and 333 (45%) PPC. The mOS of the cohort was 12.6m (11.4-13.9) and OS according to Prognostic Characteristics was: GPC 14.1m (11.8-16.4), BPC 16m (14.6-19.4) and PPC 10m (8.3-11.5).

Conclusions

According to data previously reported, prognostic characteristic subgroups are well represented in this cohort with a similar distribution and survival outcomes. We should further explore the potential utility of this tool in routine clinical practice or clinical trials. Of note, 35% of the pts in our series received a third-line therapy and more than a half were included in clinical trials with longer mOS compared to previous data.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Salva: Financial Interests, Personal, Research Grant: Hoffman-La Roche; Sanofi Aventin; Amgen; Merck Serono; Servier; Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Hoffman-La Roche; Sanofi Aventin; Amgen; Merck Serono; Servier; Bristol-Myers Squibb; Financial Interests, Personal, Sponsor/Funding: Hoffman-La Roche; Sanofi Aventin; Amgen; Merck Serono; Servier; Bristol-Myers Squibb; Financial Interests, Institutional, Other: Hoffman La-Roche. J. Ros: Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Institutional, Other, Clinical trial investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Servier; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi. I. Baraibar: Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Sanofi; Financial Interests, Personal, Other, Honoraria: Sanofi. G. Argiles Martinez: Financial Interests, Personal, Advisory Role: Bayer; Bristol-Myers Squibb; Genentech/Roche; Roche; Servier; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier; Roche; Bayer; Amgen. J.L. Cuadra Urteaga: Financial Interests, Personal and Institutional, Sponsor/Funding: Amgen; Lilly. J. Capdevila: Financial Interests, Personal, Advisory Role: Novartis; Ipsen; Exelixis; Bayer; Eisai; AAA; Amgen; Sanofi; Merck; Financial Interests, Institutional, Other, Honoraria: Eisai; Novartis; Ipsen; AstraZeneca; Pfizer; AAA. D. Paez: Financial Interests, Personal, Speaker’s Bureau: Merck Serono; F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Amgen; Sanofi. G. Villacampa Javierre: Financial Interests, Personal, Speaker’s Bureau: Merck; Astra-Zeneca. Financial Interests, Personal, Expert Testimony: Merck; Financial Interests, Personal, Advisory Role: Astra-Zeneca; R. Dienstmann: Financial Interests, Personal, Advisory Role: Roche; Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Roche; Ipsen; Amgen; Sanofi; Libbs; Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck; Pierre Fabre. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Role: Hoffman La - Roche; Bristol Myers Squibb; Servier; Amgen; Merck Serono; Sanofi; Bayer; Array Biopharma; Financial Interests, Personal, Research Grant: Hoffman La - Roche; Bristol Myers Squibb; Servier; Amgen; Merck Serono; Sanofi; Bayer; Array Biopharma; Financial Interests, Personal, Other, Travel grants: Hoffman La - Roche; Bristol Myers Squibb; Servier; Amgen; Merck Serono; Sanofi; Bayer; Financial Interests, Institutional, Other, Investigator contribution in clinical trials: Array Biopharma; MSD; AbbVie; Amgen; GlaxoSmithKline; AstraZeneca; Merck Sharp & Dohme Corp; Bristol Myers Squibb; Novartis; Boehringer Ingelheim; Hoffman La-Roche; Medimmune; Pierre-Fabre; Sanofi Aventis. J. Tabernero: Financial Interests, Personal, Advisory Role: Array Biopharma; AstraZeneca; Avvinity; Bayer; Boehringer Ingelheim; Chugai; Daiichi Sankyo; F. Hoffmann-La Roche Ltd; Genentech Inc; HalioDX SAS; Hutchison MediPharma International; Ikena Oncology; IQVIA; Lilly; Menarini; Merck Serono; Merus; MSD; Mirati; Neophore; Novartis; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Seattle Genetics; Servier; Taiho; Tessa Therapeutics; TheraMyc; Financial Interests, Personal, Other: Imedex; Medscape Education; MJH Life Sciences; PeerView Institute for Medical Education and Physicians Education Resource (PER). All other authors have declared no conflicts of interest.

Background

Gastric cancer (GC) is the third leading cause of cancer worldwide. Clinical and molecular heterogeneity of GC is broadly recognized. TCGA divides GC in four subtypes; Epstein-Barr virus (EBV) positive, MSI, genomically stable, and chromosomal instability. We aimed to better characterize the MSI pts in our cohort by comparing them to the MSS pts and explore prognostic factors in GC pts.

Methods

A review of the retrospective Vall d’Hebron University Hospital EURECCA database of all pts who underwent gastric surgery between 2014 and 2018 was conducted. We analysed clinical and tumour characteristics with immunohistochemistry (IHQ) and studied predictors of mortality across all pts affected by GC. Descriptive and univariate analysis were performed to detect differences between MSI and MSS groups. OS was calculated with the Kaplan-Meier method and univariate Cox models were fitted to estimate hazard ratios with CI95%.

Results

Among all pts who underwent surgery, 134 (92%) were primary GC and 12 (8%) were gastroesophageal junction. Twelve pts (13%) were MSI, 80 pts (87%) MSS, 41 pts (29%) Her2 positive, and four pts (4.4%) EBV. Comparing MSI vs MSS groups, median age was 80 (IRQ 71.2 – 86) vs 70 years (IRQ 62.7 – 78) [p=0.013], 50% vs 27% were women [p=0.17], and 83% vs 50.7% were intestinal histological subtype [p=0.035]. Neoadjuvant chemotherapy was administered in two MSI pts (16.7%), one received adjuvant chemotherapy and nine (75%) surgery alone. With a median follow-up of 49.9 months (m) (IQR 25.7 – 52.5), the MSI median OS was not reached and those with MSS status had a median OS of 70.6m. In the entire cohort, pts with BMI>25 had a 3-year OS of 81.8m vs 51.7m in pts with BMI<25, patients with T≤2 had a median OS of 85.9m vs 42.7m in the ≥T3 group [p<0.001], and patients with negative nodes had a median OS of 81.8m vs 49.3m in the node positive group [p=0.030].

Conclusions

In our cohort, MSI status was detected in 13% of pts by IHQ. In this subgroup most were elderly pts, intestinal histology and presented a better OS than MSS status. In the overall population of GC pts, increased BMI played a positive role in OS and factors linked to disease aggressiveness related to worse OS.

Legal entity responsible for the study

VHIO.

Funding

Has not received any funding.

Disclosure

O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Grupo Pacifico; Other, Other, Travel Expenses: Kyowa kirin; Other, Other, Travel Expenses and Conference Fee: Sanofi. J. Tabernero: Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Avvinity; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: F.Hoffman-La Roche; Financial Interests, Personal, Advisory Board: Genetech Inc; Financial Interests, Personal, Advisory Board: HalioDX SAS; Financial Interests, Personal, Advisory Board: Hutchinson MedPharma International; Financial Interests, Personal, Advisory Board: Ikena Oncology; Financial Interests, Personal, Advisory Board: IQVIA; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Neophore. M. Diez: Financial Interests, Personal, Speaker’s Bureau: Lilly. T. Macarulla Mercade: Financial Interests, Personal, Advisory Role: Ability Pharma; Financial Interests, Personal, Advisory Role: Advance Medical HCMS; Financial Interests, Personal, Advisory Role: Batxer; Financial Interests, Personal, Advisory Role: BioLineRX; Financial Interests, Personal, Advisory Role: Celgene SLU; Financial Interests, Personal, Advisory Role: EISAI; Financial Interests, Personal, Advisory Role: Genzyme; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Ipsen Pharma Lab; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Sharp and Dhome; Financial Interests, Personal, Advisory Role: QED Therapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Role: Sanofi-Aventis; Financial Interests, Institutional, Funding: Agios; Financial Interests, Institutional, Funding: Aslan; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Genetech; Financial Interests, Institutional, Funding: Hallozyme; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Merimarck; Financial Interests, Institutional, Funding: Millenim; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche. All other authors have declared no conflicts of interest.

Background

Vitamin D (Vit.D) deficiency is a poor prognostic factor in mCRC patients (pts). To evaluate if this is attributable to an impaired immunity boosting effect, we analysed peripheral inflammatory/immune components in Vit. D deficient mCRC pts.

Methods

Pts eligible for 1st line chemotherapy were tested for serum Vit.D levels and association of Vit.D with OS was analyzed (Kaplan Meier and Cox regression methods). Differences in 24 peripheral inflammatory/immune variables [i.e.: white blood cells(WBC), neutrophils (N), lymphocytes (L), NL ratio (NLR), platelet/L ratio, monocytes, sum of mononuclear cells, systemic inflammatory index, CRP, LDH, albumin, albumin-to-globulin ratio, D-Dimer, different subsets of lymphocytes] between Vit.D deficient (<10 ng/dL) vs non-deficient (>10 ng/dL) pts were analyzed (Mann-Whitney-Wilcoxon test).

Results

135 pts were included [74 males, median(m) age 64 yrs, range 30-84]. mVit.D was 14.8 ng/ml (range 3-160); mOS for Vit D <10 ng/mL (63 pts) vs >10 ng/mL (70 pts) was 12.3 vs 24.5 months, respectively [HR 2.03, p 0.002]. Vit.D deficient pts had a significant increase in mN (69% vs 65%, p 0.04), mNLR (3.5 vs 2,9, p 0.05) and CD4+/L (48% vs 40%, p 0.04) and a significant decrease in CD19+/L (4% vs 7%, p 0.03) as compared to non-deficient pts. In Vit.D deficient pts, N count could further stratify prognosis: mOS for < vs > 6000/μl was 19.1 vs 8.1 [HR 2.76, p 0.006]. No significant difference in survival between Vit.D deficient pts with low N and non-deficient pts was observed (p 0.07).

Conclusions

Vit.D deficiency is confirmed to be a poor prognostic factor in mCRC pts and correlates with meaningful inflammatory/immune changes. The observed increase in T helper cells (CD4+) might be restricted to Th1 activation with a possible surge in proinflammatory cytokine production reflected, peripherally, by higher N and NLR values. Further evaluation of the Th1/Th2/Th17/Treg balance and effector cytokines is underway. The observed B cell (CD19+) depletion might be due to the lack of Vit.D-induced differentiation.

Editorial acknowledgement

This research work has been conducted under the Programme on Experimental System and Medicine (XXXV cycle) at the University of Rome Tor Vergata.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Combination therapy with anti-PD1 and low-dose ipilimumab has shown reduced rate of immune-related adverse effects compared with standard dose used in the Checkmates studies 067 and 204. However, the discussion whether low-dose ipilimumab may hamper the response rate in advanced melanoma is still open.

Methods

We conducted a retrospective analysis of response evaluation based on 18F-FDG PET/CT for patients with advanced melanoma treated with combination of nivolumab 3mg/kg plus ipilimumab 1mg/kg for 4 cycles (N3+I1) followed by anti-PD1 maintenance therapy and compared the results to RECIST 1.1 response criteria in the same population.

Results

Between December 2017 and August 2020, 45 patients with advanced melanoma treated with N3+I1 in first-line setting were identified.

Unresectable stage III/stage IV were 2/43 patients, respectively. Among stage IV patients, 60.5% were M1c, 23.3% had elevated LDH and 28% had brain metastasis (3 or more brain lesions: 58%). At a median follow-up of 16.7 months, 11 patients (24.4%) had G3/G4 toxicity. During induction phase, three patients (6.6%) discontinued all drugs and 2 other patients (4.4%) interrupted only ipilimumab. Review of response evaluation by RECIST was possible in 36 patients and showed an objective response of 50%. Complete response (CR): 11% and partial response (PR): 39%. Eight percent presented progressive disease (PD). In 37 patients, review of response evaluation using 18F-FDG PET/CT was possible. Twenty-four patients (65%) achieved metabolic CR, 5 (13.5%) PD and 8 (21.5%) were classified as non-CR non-PD. Median progression-free survival (PFS) and overall survival (OS) were not reached. 12-month PFS and OS were: 72.5 and 89%, respectively. During the study follow-up, only 1 patient with metabolic complete response relapsed and 3 out of 8 with non-CR non-PD progressed.

Conclusions

Using low-dose ipilimumab combination does not hamper the response rates and, possibly due to fewer protocol interruptions, these patients may achieve more complete responses as showed by 18F-FDG PET/CT evaluation.

Legal entity responsible for the study

A.C. Camargo Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Death at home is an increasingly more common measure for improving the quality of palliative care services. The study analyzes the factors that may influence the place of death of oncology patients in palliative care (hospital/home), focusing on clinical characteristics.

Methods

Study design: longitudinal, prospective single-cohort, analytical. 427 people were studied in 2018 in the Bahia de Cadiz-La Janda District (Andalusia, Spain). Data were collected during initial evaluation, follow-up, Last Days and Hours of Life (LDHL) and after death. Among the data gathered: place of death, Palliative Performance Scale (PPS), Palliative Care Complexity Index (IDC-Pal), Charlson Comorbidity Index (CCI), hospital admissions, advanced treatments and symptoms during follow-up and LDHL.

Results

52.2% of patients died at home and 47.8% died in the hospital. Among the individuals who died at home, the results reveal: - A less complex situation (IDC-Pal) throughout the entire process (60.9%, 84.1% and 88.4%; p<0.02 in all these cases). - Less prognosis of survival at initial evaluation (PPS) (57.2 vs 52.4; p=0.003). - Absence of hospital admissions (26.8% vs 78.6%; p<0.001) or a lower number of admissions (0.32 vs 1.12; p<0.001). - Absence of toxicity to opioids (p=0.05), as well as lower pain intensity during LDHL (3.45 vs 4.31; p=0.01), dyspnea (2.94 vs 3.89; p=0.009), nausea/vomiting (1.31 vs 1.72; p=0.031) and anxiety (4.31 vs 5.10; p=0.030). No significant differences were found in place of death (home/hospital) according to age, sex, advanced complementary treatment and other symptoms/complications studied.

Conclusions

The main clinical characteristics that have been found to influence the place of death are: case complexity, survival prognosis, hospital admissions and number of admissions during the process, toxicity to opioids, and intensity of certain symptoms in LDHL, such as: pain, dyspnea, nausea/vomiting and anxiety. It is essential to conduct a thorough evaluation of this type of patient and process, but it may prove especially important to prioritize the aspects herein identified.

Legal entity responsible for the study

The authors.

Funding

Biomedical Research and Innovation Institute of Cádiz (INiBICA). Project subsidized within the framework of the Integrated Territorial Initiative (ITI) 2014-2020 for Cádiz by the Andalusian Consejería de Salud and by the European Regional Development Fund (FEDER).

Disclosure

All authors have declared no conflicts of interest.

Background

Approximately 15–20% of breast cancers (BC) overexpress the HER2 receptor (HER2+). The introduction of anti-HER2 therapies to the treatment of BC HER2+ has brought about a revolution in terms of survival and quality of life. However, some of these treatments have also led to an increase of cardiotoxicity at expense of decrease the left ventricular function (LVEF). Meanwhile, pertuzumab (PER) has not been shown to increase the risk of cardiac events. The aim of this study is to evaluate the existence of an increase in cardiotoxicity associated with PER treatments in BC HER2+ via a systematic review.

Methods

A systematic review was carried out according to PRISMA criteria based on clinical trials in BC HER2+ in all stages that included first-line PER treatment in either arm. The clinical trials included studies conducted between 1 January 2005 and 31 December 2020. The flow diagram included 459 articles, of which only 25 were ultimately selected. The statistical analysis was expressed in terms of the number of cardiac events, LVEF and deaths of cardiac origin. Statistical analysis was performed with SPSSv25.

Results

Of the 25 clinical trials evaluated, 10 addressed metastatic stages of BC, 14 focussed on localised BC and one BC in all stages. The total number of patients (pts) evaluated was 11,678, of which 7,768 (66,52%) belonged to PER-receiving groups and 3,910 (33,48%) were members of control groups. The numbers of cardiac events were 176 (2,31%) in the PER groups and 48 (1,23%) in groups without PER. LVEF was observed more frequently in groups with PER (179 events, 2,3%), compared to groups without PER (55 events, 1,41%), with the differences observed in pts with PER in localised, versus metastatic, stages of BC. The number of cardiac deaths was 12 (0,15%) among those given PER and 2 (0,05%) among without PER.

Conclusions

Despite the limitation of having no data on clinical trials directed toward the study of cardiotoxicity with PER, our study showed a higher tendency for BC HER2+ treatments with PER to present greater cardiotoxicity. Clinical trials in this field evaluating the true effect of these treatments on cardiac toxicity will be necessary to demonstrate our conclusions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The literature reviewed show discord between the preferences of place of death expressed by people in Palliative Care and the actual place of death. It is necessary to analyze this situation, highlighting the importance of the wishes and preferences of patients and their caregivers.

Methods

Study design: longitudinal, prospective single-cohort, analytical. 427 people were studied in 2018 in the Bahia de Cadiz-La Janda District (Andalusia, Spain). Among other variables, this investigation studied the preferences of place of death expressed by the patient and their caregiver (home, hospital or undefined) during the initial evaluation (IE) and Last Days and Hours of Life (LDHL), as well as the actual place of death (home or hospital).

Results

52.2% of patients died at home and 47.8% died in the hospital. The place preferred by patients and caregivers is home, which is the case both at the time of the IE (Patient: 36.5% home, 11.8% hospital and 51.8% undefined; Caregiver: 40.3%, 21.3% and 38.4%) and LDHL (Patient: 41.9%, 15.9% and 42.2%; Caregiver: 51.2%, 32.0% and 16.8%). (See Table) A significant association is found (p<0.05) between the preference stated during IE and during LDHL and the actual place of death, both for the patient (59.5% and 81.3% congruence, respectively) and the caregiver (68.9% and 87.7%). This relationship is more intense in the case of the wishes expressed during LDHL, both by the patient (59.9% vs 81.3%) and the caregiver (68.9% vs 87.7%), and more intense in the case of the caregiver’s preference (87.7%) than that of the patient (81.3%). Table: CN10

Congruence between actual and preferred place of death by patient and caregiver at time of initial evaluation (IE) and last days and hours of life (LDHL)

Conclusions

There is a significant relationship/congruence between the actual and preferred place of death by patients and caregivers. This relationship is stronger in the case of preferences during LDHL and for caregivers, which must be taken into consideration when planning care prior to death.

Legal entity responsible for the study

The authors.

Funding

Biomedical Research Management Foundation of Cádiz (INiBICA). Project subsidized within the framework of the Integrated Territorial Initiative (ITI) 2014-2020 for Cádiz by the Andalusian Consejería de Salud and by the European Regional Development Fund (FEDER)

Disclosure

All authors have declared no conflicts of interest.

Background

Cardiotoxicity (CTx) associated with cancer treatments may mitigate its benefit and limit therapeutic options. Increasing evidence suggests a significant role for high-sensitivity troponin (hs-cTn) and type-B natriuretic peptide (BNP) in the detection of CTx and in the therapeutic orientation of cancer patients. The objective of this work is to evaluate the predictive role of these biomarkers in the detection of CTx and, more specifically, the predictive role of hs-cTn in cardioprotective Tx orientation.

Methods

Unicentric retrospective study of 185 breast cancer patients treated with neoadjuvant and adjuvant chemotherapy (ChT) and anti-HER2 therapy, from January 2017 to September 2019. All patients were evaluated by ECG, TTE and analytical study including the values of hs-cTn and BNP before the start of treatment and up to 12 months after. CTx was defined by a decline in ejection fraction (EF) >10% from baseline or EF <50%.

Results

The median age was 50 years of age (26-76). The majority of patients (89.2%) belonged to the high-risk group according to the Cardiotoxicity Risk Score. ChT scheme containing anthracyclines (AC) was used in 82% of the patients, with 42% undergoing anti-HER2 Tx. It was found that 38 (21.3%) and 9 (5.1%) patients had a significant increase in hs-cTn (≥34 ng / L) and BNP (≥100 pg/ mL), respectively. CTx occurred in 13 (7.1%) patients, 11 (84.6%) of whom were undergoing antiHER2 Tx and 2 (15.4%) AC. Anti-HER2 Tx was significantly associated with the development of CTx (p = 0.001). The same was not true for the increase in hs-cTn (p = 0.56) and BNP (p = 0.60). On the other hand, the variation in the mean values of hs-cTn and EF was significant at the 3rd (p = 0.001) and 12th month (p = 0.009), respectively, while that of the BNP was greater from the 3rd to the 6th month (p = 0.423). In the subgroup of patients with elevated hs-cTn, the institution of cardioprotective Tx appeared to be associated with a decrease in the occurrence of CTx (p = 0.03).

Conclusions

Periodic monitoring of hs-cTn and BNP values combined with the assessment of EF in patients with breast cancer undergoing ChT treatment with AC and / or anti-HER2 Tx will identify patients at risk of CTx in a timely manner and allow early implementation of cardioprotective strategies.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Pseudocirrhosis (PC) is defined by radiological abnormalities suggesting cirrhosis in patients (pts) with liver metastasis (mets), especially metastatic breast cancer (mBC). The cause of PC can be due to liver disease progression (DP), treatment toxicity or response to systemic treatment. PC is associated with high mortality.

Methods

A retrospective study was conducted at a Cancer Center with mBC pts and PC in the period 2010-2020. Age, histologic type, mets sites, radiological alterations, ascites, hepatic burden disease, prior treatments, bilirubin, AST and ALT levels, cause of PC and OS were analyzed. Kaplan-Meier method was used for survival analysis, log-rank test to compare survival curves, Cox regression to multivariable analysis and Chi-square test to compare proportions groups.

Results

44 pts were included, the median age of 55.5 years, 83.3% of luminal subtype, 54,6% with either mets outside liver. Liver lobular contour was the most frequent radiological finding (31%) and 57.7% of pts had ≥ 5 liver nodules. Median time from liver mets until PC was 33.3m and median OS from PC was 3.18m. PC was due to DP in 63.4% of cases and OS was lower compared to those without DP (2.16m vs 15.4m; hazard ratio [HR] 2.37; p < 0.03; 95% CI 1.06 to 5.27). In 31,7% of pts, PC was due to clinical response to treatment, and OS reached 15.7m vs. 2.16m for those not responding to treatment (HR 2.60; p 0.02; 95% IC 1.10 to 6.17). Only 4.9% of pts had PC due to treatment toxicity, with an OS of 1.8m. OS varied according to lines of mBC treatment, being 15.8m for those with ≤ 1 prior endocrine therapy vs 8.1m for those who used ≥ 2 lines (HR 2.39; p 0.03; 95% IC 1.08 to 5.25) and 22.12m in patients ≥ 1 line of chemotherapy (CT) vs. 6.46m for ≥ 2 CT lines (HR 3.34; p < 0.01; 95% IC 1.36 to 8.17). AST levels ≥ 2 times the upper limit correlated with a worse outcome (OS of 2.16m vs. 15.24m. HR 2.90; p 0.01; 95% IC 1.19 to 7.05), also observed with ALT levels - OS 1.87m vs. 3.97m (HR 2.38; p 0.03; 95% IC 1.04 to 5.46) and abnormal values of bilirubin (1.77m vs. 15.24m; HR 4.18; p < 0.01; 95% IC 1.80 to 9.69).

Conclusions

This is one of the largest series of PC in mBC. PC overall survival is low, varies according to its cause and some markers would indicate a worse outcome. These parameters should be strongly valued in PC pts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.