Giovanni Trovato

Background: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality. While metastasectomy could improve survival in selected patients, the role of repeated resections in oligorecurrent disease is less defined. Methods: We retrospectively analyzed patients with mCRC treated at Fondazione Policlinico Universitario Agostino Gemelli-IRCCS (Rome, Italy) between 2010 and 2024. Eligible patients underwent ≥2 resections of metastatic lesions. Disease-free survival after second metastasectomy (DFS2) and overall survival (OS) were the coprimary end points. Prognostic factors were tested with Cox regression, and a composite risk score (Fondazione Policlinico Gemelli Risk Score [FPGRiskScore]) was developed. Results: Among 1586 patients with mCRC, 396 (24.9%) received at least one metastatic surgery and 143 (9%) underwent ≥2 metastasectomies. Median DFS2 was 8.2 months (95% confidence interval [CI]: 7.3-13.1), and 5-years OS rate was 73.1% (95% CI: 64.5-83.0); after a median follow-up from the last metastasectomy of 34.3 months, 49/143 patients (34.2%) were relapse-free and median DFS after the second surgery of the metastases from the last surgery was 13.1 months (95% CI: 9.1-17.5). Patients stratified by FPGRiskScore (disease-free interval [DFI] from the first metastasectomy ≤ vs. >12 months, metastatic burden ≤ vs >5 cm, RAS/BRAF status, and Eastern Cooperative Oncology Group Performance Status [ECOG PS] scale 0 vs. ≥1) showed distinct outcomes: low-risk patients achieved a median DFS2 of 18.4 months and 5-years OS of 87.6%, compared with 7.8 months/72.0% in intermediate-risk and 4.9 months/55.3% in high-risk group. Conclusions: Repeated metastasectomy offers substantial survival benefit in selected patients with oligorecurrent mCRC, with long-term disease control achievable in a subset. Prognostic stratification incorporating clinical and molecular features (FPGRiskScore) may refine patient selection and guide multidisciplinary management.

Background: As COVID-19 has become an epidemic, we conducted an open-label study aimed to identify immunogenicity and reactogenicity of boosters of the BNT162b2 vaccine in a real-world cohort of long-survivor metastatic lung cancer patients (LS-mLC pts). Methods and Analysis: According to the timing of the booster dose (BD) and SARS-CoV-2 infection (Cov-I) during anticancer treatment (ACT), between October 2021 and February 2022, we prospectively enrolled 166 cancer patients into five parallel cohorts. The primary endpoints were seroprevalence of IgG Anti-spike-RBD (anti-S IgG) at two pre-defined timepoints (T1: +30–90 days after BD; T2: +6 months +/− 4 weeks after BD). As an exploratory endpoint, we compared the median pre-vaccination value of four cytokines (IL-6, IL-2R, TNF-α, IL-10) with post-BD values in immunotherapy-treated pts (IO-pts). Results: The anti-S IgG seropositivity rate was 100% at T1 and 98.8% at T2. After 6 months, hybrid immunisation was associated with a higher median anti-S IgG titre compared to vaccine-alone-induced seroconversion (p < 0.0001). In uninfected pts, the median anti-S IgG titre was significantly lower in IO-pts compared to non-IO-pts (p = 0.02); no difference was found when comparing myelosuppressive or not ACT. Among the 68 IO-pts, 5 pts (7.3%) showed a significant increase (≥1.5 fold) of at least two cytokines in post-BD samples, without reporting ir-AEs. Conclusions: Boosters of the COVID-19 mRNA vaccine were effective and safe. In IO-pts without recent Cov-I, additional BDs should be considered to prolong serological immunity.

RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.