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Purpose: There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re.

Methods: We recently presented the first analysis of a multicenter prospective phase II clinical study aimed at assessing the feasibility and effectiveness of a neoadjuvant chemotherapy + short course of CIRT followed by surgery and adjuvant chemotherapy in the management of bRe/Re PDAC. The study was terminated early due to low patient enrollment.Herein, we reported a post-hoc analysis focusing on toxicity, dosimetry and translational assessment.

Results: In our experience, CIRT can be integrated into a multimodal treatment strategy for bRe/Re PDAC, alongside chemotherapy and surgery. A case of fatal liver failure occurring three months post-surgery has been documented, likely related to the combination approach. Although the treatment plans were satisfactory according to the Local Effect Model (LEM) model, recalculations using the modified Microdosimetric Kinetic Model (mMKM) revealed suboptimal target coverage. Additionally, we observed an increased expression of PD-L1 following CIRT.

Conclusions: This multimodal approach was well tolerated; however, clinicians should carefully monitor for vascular disorders during follow-up and further investigate surgical techniques after CIRT. The increased PD-L1 expression supports the immunogenic effects of particle therapy and lays the groundwork for future studies. To enhance the therapeutic ratio of CIRT treatments, integrating LET-d based objectives into the plan optimization process should be considered.

Trial registration number: ClinicalTrials.gov Identifier: NCT03822936.

Background: Literature is lacking when it comes to oncology nursing attitudes in clinical trial involvement.

Objective: To assess how Italian oncology nurses perceived their attitudes in clinical trials involvement.

Methods: An on-line cohort observational study was carried out. Data collected included: sex, years of work experience in oncology field and 10 items assessing participants' self-perceptions of their attitudes in clinical trials. Linear regression was used to assess associations between work experience and self-perceived preparedness.

Results: A total of 338 Italian oncology nurses were enrolled. Most nurses declared not receiving any specific training in oncology clinical trials (23.1%). No significant associations were reported between self- perceived attitudes in clinical trial involvement in the oncology setting and both work experience and clinical trial involvement.

Conclusions: Cancer centers are improving cancer nursing research in supplying clinical care. But very few centers are involved in training oncology nurses. This gap seems to be very deep in taking into consideration the oncology nursing research in clinical trials, too.

Background: MultiGene Panel Testing (MGPT) allows for simultaneous analysis of multiple cancer-related genes, enabling the identification of pathogenic variants in genes beyond those that would be analyzed based on a specific phenotype. However, a relevant fraction of variants so identified has little or no clinical utility, raising the need for guidance in selecting genes to include in panels and for interpretation of the results.

Methods: Taking advantage of seven real paradigmatic cases, we analyze some of the scenarios where MGPT constitutes a meaningful advantage for diagnosis, as well as situations where panel use increases the risk of misinterpretation or complicates result communication and management.

Results: The use of MGPT facilitates prompt diagnosis in carriers of variants in rare genes (such as NTHL1), which would be diagnosed at a later stage if using a step-wise approach, as well as in carriers of bi-allelic variants (for instance in BRCA or MMR genes) leading to atypical phenotypes. Conversely, finding variants in moderate penetrance genes, such as ATM and CHEK2, may complicate interpretation and clinical management. Furthermore, for some of the genes included in MGPT, for instance NBN, the association with cancer risk has been questioned, leading to potentially misleading results.

Conclusion: Taken together, the cases here described provide some examples of the benefits, as well as risks, involved by the use of MGPT, which may increase awareness among users and reinforce the need for establishing clear recommendations on genes to be included and management of the results.

Hereditary breast and/or ovarian cancer syndromes are inherited disorders in which there is an increased risk of developing breast and/or ovarian cancer in the lifetime, usually at a younger age compared to the general population. Cancer prevention in these syndromes includes prophylactic surgeries, personalized surveillance programs and chemopreventive strategies. Chemoprevention exploits the use of certain drugs or other substances to help lower the risk of developing cancer. In this context, tamoxifen was the first agent considered for breast cancer prevention, followed by raloxifene and the third-generation aromatase inhibitors. On the other hand, the first and most widespread type of chemoprevention for ovarian cancer was combined hormonal contraceptive use. Although several strategies have been studied and showed promising results, only a few of these are currently applied in daily clinical practice. Side effects along with several psychological variables such as cancer perceived risk, worries and related distress, strongly influence women's decision on chemoprevention. The present review explores and summarizes the available evidence on breast and ovarian cancer chemoprevention approaches.

Background: The management of individuals with familial adenomatous polyposis (FAP) includes invasive prophylactic surgery and intensive endoscopic surveillance to reduce their risk of colorectal cancer. FAP patients frequently ask for dietary recommendations to alleviate bowel disturbances after prophylactic colectomy, and to prevent the formation and growth of new adenomas. We have enriched the multidisciplinary outpatient clinic for FAP with nutritional support. This paper presents the results of the first six months of this nutritional activity.

Methods: Sixty-eight individuals with FAP, >18 years of age, who underwent a prophylactic total colectomy, entered in this observational study. At the baseline visit, participants underwent anthropometric measurements, answered the Mediterranean Diet Adherence Screener (MEDAS), the Faecal Incontinence Quality of Life (FIQL) questionnaire, and reported the number of their diarrhoeal discharges per day. They received dietary recommendations including specific information about the inflammatory food to reduce (red/processed meat, sugar, sweets), and the Mediterranean food to increase (vegetables, fruits, whole grain cereal in cream and legumes' hummus).

Results: After six months, participants repeated the same baseline measurements. Fifty-three individuals with FAP completed the six-month follow-up. The before-after analysis showed significant improvements in patients' body composition measurements and MEDAS score. Participants significantly reduced the number of diarrhoeal discharges per day. FIQL results showed improvements in lifestyle, behaviour, and depression scores.

Conclusions: These results suggest that targeted low-inflammatory Mediterranean dietary recommendations are effective in improving anthropometric parameters, diet quality, and various aspects of quality of life related to bowel function in individuals with FAP.

Progress in the discovery and understanding of cancer susceptibility genes and ever-cheaper genomic technologies are generating precious opportunities to optimize the identification of individuals with a hereditary cancer predisposition.Any such effort will have a more significant impact if it prioritizes those most at risk of developing cancer. This premise is central to cascade genetic testing, in which healthcare professionals encourage cancer patients carrying a predisposing gene variant to discuss the implications of their test results with their at-risk relatives so that, ideally, all the at-risk individuals in that family have the option to seek genetic counseling and testing in turn. Among the relatives found to have the gene variant, those who have developed cancer can then access targeted treatment and follow-up, those who are asymptomatic can benefit from enhanced preventive measures, while those who test negative can avoid unnecessary, costly, and time-consuming screening.Despite its life-saving potential, cascade genetic testing in hereditary cancer syndromes is often reported to have disappointing uptake rates, particularly among historically disadvantaged and underrepresented communities, for reasons that include barriers in intrafamilial genetic risk communication and low health and genetic literacy.This paper will discuss the challenges of cascade genetic testing in hereditary cancer syndromes, addressing some of the ethical questions arising from its current model, from strategies aimed at improving its uptake, as well as from alternative approaches to identifying asymptomatic individuals who may carry a cancer- associated pathogenic variant.

Introduction: Individuals with Familial Adenomatous Polyposis (FAP) or APC-associated polyposis, an autosomal dominant inherited condition, develop multiple adenomatous polyps and have an increased colorectal cancer (CRC) risk. A change in diet can help reduce cancer risk, and several dietary components have an antitumor effect. We aimed to evaluate the potential of the anti-inflammatory and anticancer substances quercetin (QER), epigallocatechin gallate (EGG) and fisetin (FIS) in decreasing the risk of CRC by reducing the growth of polyps in an organoid model.

Methods: Patient-derived organoid (PDO) lines were generated from polyps obtained from patients with FAP undergoing prophylactic colectomy. PDOs were treated with QER, EGG, or FIS to determine their effect on cell growth. Changes in caspase 3/7 activity and expression of inflammation and apoptosis mediators were assessed by luminescent and colorimetric assays.

Results: Three PDO lines with different inactivating pathogenic variants in the APC gene were developed using a combinatorial approach. FIS was the most active of the three substances tested, presenting the lowest IC50 in all PDO lines (range: 42.6-9.2 uM). The IC50 was defined as the concentration required to halve the number of cells after 72 hours. All molecules tested induced apoptosis through activation of caspases 3/7.

Conclusions: QER, EGG, and FIS can be easily taken from foods or dietary supplements, show toxicity on PDOs derived from adenomatous polyps, while they are known to be harmless on normal cells. Diets enriched with these substances could be potential supplemental treatments to reduce the risk of CRC in individuals with FAP.

Background: The clinical utility of germline BRCA1 and BRCA2 testing is well established in patients with family history suggestive for hereditary breast and ovarian cancer syndrome. Recently, germline PALB2 pathogenic variants were also associated with an increased risk of breast and other cancers and, in the Italian population, it has been described in few studies without a systematic germline analysis of BRCA1, BRCA2 and PALB2.

Objectives and methods: In this study, we described ASST Sette Laghi cancer genetic counselling services' experience in the analysis of 402 patients with suspected breast and ovarian cancer syndrome, by using BRCA1, BRCA2 and PALB2 germline genetic test.

Results: The frequency of PALB2 pathogenic variants was 1.2% compared to 3.5% and 3.2% for BRCA1 and BRCA2, respectively, whereas class 3 variants were detected in 0.3% and 0.5% of the BRCA1 and BRCA2 investigated patients, respectively. PALB2 pathogenic variants were identified in patients with a strong family history for breast cancer. Moreover, PALB2 variants were significantly associated with a younger age of breast cancer onset (mean age, 40.25 years) compared to wild-type patients (mean age 51.2 years, p-value = 0.0331). Similar to BRCA-associated breast cancer, the majority of PALB2 breast cancers were identified at an advanced clinical stage. Pedigree analysis revealed a family history of breast and ovarian cancer syndrome in all PALB2 pathogenic variants carriers (early breast cancer onset, bilateral breast cancer and ovarian cancer).

Conclusion: In conclusion, the germline analysis of BRCA1, BRCA2 and PALB2 should be included in breast cancer clinical practice as a not negligible number of PALB2 carriers could be identified and referred to specific surveillance protocols.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

Locally recurrent rectal cancer is resected with clear margins in only 50% of cases, and these patients achieve a three-year survival rate of 50%. Outcomes and therapeutic strategies for nonresectable locally recurrent rectal cancer have been much less explored. The aim of the study was to assess the three-year progression-free survival and the three-year overall survival in locally recurrent rectal cancer patients treated by chemotherapy/chemoradiation only vs. chemotherapy/chemoradiation and R2 surgical debulking vs. palliative care. A total of 86 patients affected by nonresectable locally recurrent rectal cancer were included: three-year progression-free survival was 15.8% with chemotherapy/chemoradiation vs. 20.3% with R2 surgical debulking (Log-rank p=0.567), but both rates were higher than best palliative care (0.0%, Log-rank p=0.0004). Three-year overall survival rates were respectively 62.0%, 70.8% and 0.0% (Log-rank p<0.0001). Chemotherapy/chemoradiation (HR 0.33, p=0.028) and R2 surgical debulking with or without chemotherapy/chemoradiation (HR 0.23, p=0.005) were independent predictors of improved progression-free survival on multivariate analysis. In conclusion, both chemotherapy/chemoradiation alone and R2 surgery with or without chemotherapy/chemoradiation provide a survival benefit over palliative care in nonresectable locally recurrent rectal cancer. However, considering that pelvic debulking is burdened by a high rate of complications, and considering its negligible impact on progression-free survival and overall survival when associated to medical therapy, surgery should be avoided in this setting.