The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many ...therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, despite several advances has been achieved in last decades. Few prognostic and predictive biomarkers guide ...therapeutic choice in metastatic CRC (mCRC), among which DNA mismatch repair deficiency and/or microsatellite instability (dMMR/MSI) holds a crucial role. Tumors characterized by dMMR/MSI benefit from immune checkpoint inhibitors. However, most of the mCRC patients (around 95%) are microsatellite stable (MSS), thereby intrinsically resistant to immunotherapy. This represents a clear unmet need for more effective treatments in this population of patients. In this review, we aim to analyze immune-resistance mechanisms and therapeutic strategies to overcome them, such as combinations of immunotherapy and chemotherapy, radiotherapy or target therapies specifically in MSS mCRC. We also explored both available and potential biomarkers that may better select MSS mCRC patients for immunotherapy. Lastly, we provide a brief overview on future perspectives in this field, such as the gut microbiome and its potential role as immunomodulator.
Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumors characterized by different molecular alterations that lead to specific clinical presentations and behaviors. In ...the last twenty years, thanks to the discovery of these mutations, several new treatment options have emerged. This review provides an extensive overview of GISTs' molecular pathways and their respective tailored therapeutic strategies. Furthermore, current treatment strategies under investigation and future perspectives are analyzed and discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-BRCA1/2 genes, the clinical utility is unclear. A comprehensive multi-gene assessment in ...unselected Italian PC patients is missing. We evaluated the prevalence and impact of Pathogenic Variants (PV) in 51 PC susceptibility genes in a real-world series of 422 Italian PC patients unselected for Family History (FH), compared the clinical characteristics and conducted survival analyses. 17% of patients had PVs (70/422), mainly in BRCA1/2 (4.5%, all <70 y), CDKN2A (4.5%, all >50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; p = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all p < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; p = 0.090), comprising ATM carriers (HR 0.33; p = 0.054). In the oxaliplatin-treated subset, PV carriers showed better control of the disease, although this was not statistically significant (67% vs. 56%). CDKN2A, BRCA2 and ATM were the most frequently altered genes. ATM PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried CDKN2A,BRCA2 or ATM PVs, had negative FH and would have been missed by traditional referral. Thus, CDKN2A and ATM should be added to BRCA1/2 testing regardless of FH.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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Background: Colorectal cancer (CRC) patients with mismatch repair system deficiency (dMMR/MSI-H) have shown impressive responses to immune checkpoint inhibitors in any lines of treatment. ...However, almost 30% of these patients are primary refractory and another 30% develop secondary resistance. Thus, many treatment combinations are being pursued to overcome resistance. One of the proposed strategies is the addition of radiotherapy to immunotherapy based on the potential abscopal effect and its consequent on-target and off-target activity. Methods: Between November 2019 and April 2021, we conducted a prospective interventional single-institution study to assess the feasibility, disease control and safety of the combination of pembrolizumab with stereotactic ablative radiotherapy (SABR) in a cohort of 14 consecutive dMMR CRC patients. SABR was administered in combination within the second or third cycle of Pembrolizumab 200 mg infused every 21 days. SABR was delivered on one or more targetable metastases with the ablative dose of 15 Gy in the first fraction followed by a second fraction of 5 Gy. Results: Fourteen patients were enrolled and 11 received radiotherapy in combination with Pembrolizumab as per protocol. Three patients who started Pembrolizumab never received radiotherapy due to deterioration of their general conditions, leading to death within two months. Two out of these three patients were BRAF
V600E
mutated. Five patients (35.7%) received Pembrolizumab as first line, 6 (43%) as second line and 3 (21%) as third or later lines. Six out of 14 patients (42.9%) harboured BRAF
V600E
mutation, 2 out of 14 (14.3%) RAS mutation and the others were RAS/BRAF wild type. Objective response was observed in 4 out of 14 patients (29%) and disease control was achieved in 7/14 patients (50%). Among these, six patients (42%) achieved a disease control lasting more than 15 months. This regimen caused substantial toxicity, mainly linked to SABR. Any grade TRAEs occurred in 50% of patients, with one patient with G1 event, three patients with G2 events, and two patients with G3 events (pneumonia, bowel perforation); no treatment-related deaths were observed. Conclusions: These data do not show hint of added efficacy of Pembrolizumab by SART in unresectable dMMR/MSI-H mCRC.
Germline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other ...cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.
Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A.
11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients.
A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.
●Germline genomic pathogenic variants (gPV) can promote Pancreatic Cancer (PC).●The prevalence of cancer predisposition genes (CPG) gPV in PC in Italy is unknown.●14 % of unselected, consecutive PC patients had a gPV in at least 1/19 CPG tested.●CPG gPV rate remained relevant across different subgroups (age, stage, history).●Multigene germline testing, beyond BRCA1-2, should be offered to all PC patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Over the past 2 years, the COVID-19 pandemic has had short-term and long-term effects on the delivery of cancer care. Some European countries faced an unprecedented widespread crisis during the first ...year of the SARS-CoV-2 pandemic, only being able afterwards to gradually recover, thanks to the improvement in preventive measures, changes in public health and reactive processes in cancer care and a better understanding of the ongoing heath emergency.
The development of SARS-CoV-2 vaccines and COVID-19 specific treatments, the growing testing and tracking capability to limit virus diffusion, and research efforts to better define areas of action have all greatly limited the negative impact of the health emergency on routine cancer care.The need to protect those more vulnerable and to ensure continuity of care for oncology patients has been balanced across the pandemic, with the aim to guarantee an optimal standard of care.
This article aims to provide an overview on the evolving scenario of cancer care throughout the COVID-19 pandemic in Europe, focusing on the particular features that characterized the pandemic course as well as the main differences that were observed across it.
Background
The TOPAZ‐1 phase III trial reported a survival benefit with the anti‐programmed death cell ligand 1 (anti‐PD‐L1) durvalumab in combination with gemcitabine and cisplatin in patients with ...advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real‐world setting.
Methods
The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression‐free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.
Results
From February 2022 to November 2022, 145 patients were enrolled. After a median follow‐up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator‐assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune‐mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non‐viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.
Conclusion
The results reported in this first real‐world analysis mostly confirmed the results achieved in the TOPAZ‐1 trial in terms of PFS, ORR and safety.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world ...efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.
We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS).
666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %.
ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine.
This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.
•Real-world evidence is gaining momentum in clinical oncology in recent years.•Durvalumab improved survival in patients with advanced biliary tract cancer.•666 patients were treated: median OS of 15.1 months and median PFS of 8.2 months.•The results confirmed the results achieved in the TOPAZ-1 trial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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