Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

Lymph node yield in the pathological staging of resected nonmetastatic colon cancer: The more the better?

INTRODUCTION: Guidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival. MATERIALS AND METHODS: Patients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage. RESULTS: We included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC. CONCLUSION: LNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.

SARS-CoV-2 Antibody Seroprevalence in Patients With Cancer on Systemic Antineoplastic Treatment in the First Wave of the COVID-19 Pandemic in Portugal.

At the time of the first wave of the COVID-19 pandemic, patients with cancer were considered to be at high risk of serious illness and had a higher exposure risk since they needed frequent and nondeferrable hospital visits. Serological tests were not routinely used, and seroprevalence in this population was unknown. A single-center, cross-sectional study was developed to determine the seroprevalence of anti-SARS-CoV-2 antibodies (Abs) in patients with cancer undergoing systemic antineoplastic treatment. One hundred patients were consecutively recruited in a two-week period (6th-20th May 2020), and serum samples were tested for the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) Abs directed against both spike (S) and nucleocapsid (N) SARS-CoV-2 proteins in two distinct time points (at recruitment and 4-8 weeks later). IgG-positive results were subject to confirmation, in the same serum sample, using two distinct assays. At the time of the first study visit, no patient had a previously confirmed diagnosis of COVID-19, one reported previous contact with a COVID-19 patient, and all had a baseline SARS-CoV-2-negative RT-PCR. Two patients tested positive for SARS-CoV-2 IgG in the first study visit, which was not confirmed in either of the two confirmatory assays. Seventy-two patients were tested at the second study visit, all with negative IgG tests. IgM was persistently positive at both study visits in one patient and was positive in another patient at the second study visit, both with negative RT-PCR and serum IgG. No patient tested positive for RT-PCR within the study timeframe. No evidence of prior or acute SARS-CoV-2 infection was documented in this cohort of patients with cancer undergoing systemic treatment, and no additional exposure risk was documented compared to general population seroprevalence studies. The study was inconclusive regarding the role of SARS-CoV-2 serology in patients with cancer in the early phase of the pandemic. This study did show that, with adherence to recommended preventive measures, it was safe to maintain systemic cancer therapy.

Loss of HER2 and disease prognosis after neoadjuvant treatment of HER2+ breast cancer.

INTRODUCTION: HER2 overexpression/amplification occurs in 15-20% breast cancers (BC) and is associated with worse prognosis. The addition of anti-HER2 treatment to neoadjuvant chemotherapy significantly improves the pathological complete response (pCR) rate. Changes in HER2 status after neoadjuvant treatment (NAT) have been reported and may affect prognosis. The aim of this study was to assess the efficacy of NAT in patients with HER2+ BC and its influence on HER2 status and associated prognostic impact. METHODS: Retrospective chart review and pathologic evaluation of all consecutive patients with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between 2010-2015 in three Portuguese Hospitals. RESULTS: One hundred eight female patients were included; 40 with stage II, 68 with stage III. Hormone receptors were positive in 70. pCR (ypT0/isN0) was achieved in 48 patients (44%). With a median follow-up of 52 months, there were 5 disease free survival (DFS) events among pCR patients and 19 among non-pCR (P = 0.02). Of the 60 patients with residual disease at surgery, 52 remained HER2+ and 8 (13%) lost HER2 overexpression/amplification. 5y-DFS and 5y-OS was 70% and 84%, respectively, for patients whose residual tumors remained HER2+, and 21% and 50% for patients whose residual tumors became HER2 negative (P = 0.02 and < 0.001). DISCUSSION: We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS and OS. Despite the retrospective design and small sample size, these results suggest that it is important to retest HER2 after NAT, to better refine patient outcome.

Treatment adoption and relative effectiveness of aromatase inhibitors compared to tamoxifen in early breast cancer: A multi-institutional observational study.

BACKGROUND: Since 2005, aromatase inhibitors (AIs) have been the adjuvant treatment of choice for postmenopausal women with early breast cancer (BC). In this study we characterize the adoption of AIs in Portugal, variables associated with treatment administration, and compare its effectiveness (either in monotherapy or sequential therapy) to tamoxifen monotherapy (TAM). PATIENTS AND METHODS: This was a retrospective cohort study that included postmenopausal women with stage I-III hormone receptor (HR) positive BC diagnosed from 2006 to 2008 and treated with adjuvant endocrine therapy in four participating institutions. RESULTS: Of the 1283 eligible patients, 527 (41%) received an AI (16% as monotherapy, 25% as sequential therapy) and 756 (59%) TAM. Patients treated with AI had less differentiated tumors, with higher TNM stage, and were more frequently HER2-positive. Use of AI also differed by center (use range from 33% to 75%, p < 0.001). With a median follow-up of 6.3 years and controlling for clinicopathological and treatment characteristics, treatment with AI had a better overall survival (OS) when compared with TAM (adjusted-HR 0.55, 95% CI 0.37-0.81). CONCLUSION: AIs were successfully introduced as adjuvant treatment for HR-positive BC in Portuguese hospitals. Its use was influenced by tumor and patient characteristics, but also center of care. In this large cohort, AI use was associated with an OS benefit.

Mixed testicular germ cell tumour in a patient with previous pineal germinoma.

Germ cell tumours (GCT) are a relatively common malignancy in men aged 15-35 years. They occur most frequently in the gonads, but 3-5% have extragonadal origin, mainly in the pineal gland, neurohypophysis, mediastinum and retroperitoneum. Although intracranial germinomas may present with synchronous midline lesions, development of metachronous testicular germ cell primaries seems to be extremely rare, and confirmed dissemination of intracranial GCT to the testes has never been reported. We report the case of a 32-year-old man, with previously treated pineal germinoma at age 16 years, who later developed mixed GCT of the left testis.