Tumori最新文献

{"title":"The challenges of cascade genetic testing in hereditary cancer syndromes: A few ethical considerations.","authors":"Linda Battistuzzi","doi":"10.1177/03008916241297782","DOIUrl":"https://doi.org/10.1177/03008916241297782","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"3008916241297782"},"PeriodicalIF":2.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS inhibitors in drug resistance and potential for combination therapy.","authors":"Lala S Rathod, Nikhil S Sakle, Santosh N Mokale","doi":"10.1177/03008916241289206","DOIUrl":"10.1177/03008916241289206","url":null,"abstract":"<p><p>Kirsten Rat Sarcoma (KRAS) is a potent target for cancer therapy because it acts as a signaling hub, engaging in various signaling pathways and regulating a number of cellular functions like cell differentiation, proliferation, and survival. Recently, an emergency approval from the US-FDA has been issued for KRAS^G12C inhibitors (sotorasib and adagrasib) for metastatic lung cancer treatment. However, clinical studies on covalent KRAS^G12C inhibitors have rapidly confronted resistance in patients. Many methods are being assessed to overcome this resistance, along with various combinatorial clinical studies that are in process. Moreover, because KRAS^G12D and KRAS^G12V are more common than KRAS^G12C, focus must be placed on the therapeutic strategies for this type of patient, along with sustained efforts in research on these targets. In the present review, we try to focus on various strategies to overcome rapid resistance through the use of combinational treatments to improve the activity of KRAS^G12C inhibitors.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"3008916241289206"},"PeriodicalIF":2.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of anti-inflammatory molecules from food on organoids derived from adenomatous polyps of FAP subjects.","authors":"Oscar Illescas, Antonino Belfiore, Luca Varinelli, Davide Battistessa, Susanna Zanutto, Clorinda Brignola, Francesco Segrado, Irene Cafferati, Maria Teresa Ricci, Giovanna Sabella, Massimo Milione, Vito Ladisa, Stefano Signoroni, Marco Vitellaro, Patrizia Pasanisi, Manuela Gariboldi","doi":"10.1177/03008916241291301","DOIUrl":"https://doi.org/10.1177/03008916241291301","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals with Familial Adenomatous Polyposis (FAP) or <i>APC</i>-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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Three PDO lines with different inactivating pathogenic variants in the <i>APC</i> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"3008916241291301"},"PeriodicalIF":2.0,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PALB2</i> analysis in the diagnostic process of breast cancer: An Italian monocentric experience.","authors":"Maria Grazia Tibiletti, Ileana Carnevali, Sofia Facchi, Laura Libera, Corrado Chiappa, Fausto Sessa, Stefano La Rosa, Francesca Rovera","doi":"10.1177/03008916241290738","DOIUrl":"https://doi.org/10.1177/03008916241290738","url":null,"abstract":"<p><strong>Background: </strong>The clinical utility of germline <i>BRCA1</i> and <i>BRCA2</i> testing is well established in patients with family history suggestive for hereditary breast and ovarian cancer syndrome. Recently, germline <i>PALB2</i> 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 <i>BRCA1</i>, <i>BRCA2</i> and <i>PALB2</i>.</p><p><strong>Objectives and methods: </strong>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 <i>BRCA1</i>, <i>BRCA2</i> and <i>PALB2</i> germline genetic test.</p><p><strong>Results: </strong>The frequency of <i>PALB2</i> pathogenic variants was 1.2% compared to 3.5% and 3.2% for <i>BRCA1</i> and <i>BRCA2</i>, respectively, whereas class 3 variants were detected in 0.3% and 0.5% of the <i>BRCA1</i> and <i>BRCA2</i> investigated patients, respectively. <i>PALB2</i> pathogenic variants were identified in patients with a strong family history for breast cancer. Moreover, <i>PALB2</i> variants were significantly associated with a younger age of breast cancer onset (mean age, 40.25 years) compared to <i>wild-type</i> patients (mean age 51.2 years, p-value = 0.0331). Similar to <i>BRCA</i>-associated breast cancer, the majority of <i>PALB2</i> breast cancers were identified at an advanced clinical stage. Pedigree analysis revealed a family history of breast and ovarian cancer syndrome in all <i>PALB2</i> pathogenic variants carriers (early breast cancer onset, bilateral breast cancer and ovarian cancer).</p><p><strong>Conclusion: </strong>In conclusion, the germline analysis of <i>BRCA1, BRCA2</i> and <i>PALB2</i> should be included in breast cancer clinical practice as a not negligible number of <i>PALB2</i> carriers could be identified and referred to specific surveillance protocols.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"3008916241290738"},"PeriodicalIF":2.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized treatment using predictive biomarkers in solid organ malignancies: A review.","authors":"Haoming Tang, Yi Xin Li, Jun Jie Lian, Hsin-Yueh Ng, Samuel Sherng Young Wang","doi":"10.1177/03008916241261484","DOIUrl":"10.1177/03008916241261484","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"386-404"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of chemotherapy/chemoradiation vs. R2 surgical debulking vs. palliative care in nonresectable locally recurrent rectal cancer.","authors":"Luca Sorrentino, Andrea Scardino, Luigi Battaglia, Raffaella Vigorito, Giovanna Sabella, Filippo Patti, Michele Prisciandaro, Elena Daveri, Alessandro Gronchi, Filiberto Belli, Marcello Guaglio","doi":"10.1177/03008916241253130","DOIUrl":"10.1177/03008916241253130","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"360-365"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secular trends in incidence and mortality of non-Hodgkin's lymphoma in China, 1990-2019, and predictions to 2030: Outlook for the future burden of disease.","authors":"Hongbo Su, Shuping Xie, Jun Lyu, Yan Liu, Yanbo Zhang","doi":"10.1177/03008916241261166","DOIUrl":"10.1177/03008916241261166","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to analyze the trend of non-Hodgkin's lymphoma incidence and mortality in China from 1990 to 2019, along with assessing the effects of age, period, and cohort, as well as to predict future trends.</p><p><strong>Material and methods: </strong>Using data from the Global Burden of Disease Study 2019 we calculated the estimated annual percentage changes in the incidence and mortality of non-Hodgkin's lymphoma. Age-period-cohort analysis was used to assess the independent effects of these elements. Incidence and mortality until 2030 were predicted using a Bayesian age-period-cohort approach.</p><p><strong>Results: </strong>During 1990-2019, there was a significant increase in the age-standardized incidence and mortality rate in non-Hodgkin's lymphoma. Strong effects of birth cohort and period on non-Hodgkin's lymphoma incidence and mortality were observed. In terms of prediction, future non-Hodgkin's lymphoma incidence and mortality in China will continue to increase, while the mortality rate will decrease; for women, both the rates are projected to rise, but they will remain lower than men.</p><p><strong>Conclusions: </strong>Currently, the non-Hodgkin's lymphoma burden is high in China, and it is expected to continue increasing in the future. Policymakers need to prioritize addressing the factors contributing to sex differences in disease burden, including variations in environmental exposures and lifestyles among men and women.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"348-354"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity of radiotherapy on bone metastases from prostate adenocarcinoma: What is the future for the combination with radiotherapy/immunotherapy?","authors":"Pierre Cornillon, Wafa Bouleftour, Thomas Reynaud, Gregoire Pigne, Denis Maillet, Salima Hamizi, Marie Beguinot","doi":"10.1177/03008916241249366","DOIUrl":"10.1177/03008916241249366","url":null,"abstract":"<p><p>Bone metastatic prostate cancers (PCa) are resistant to usual immunotherapies such as checkpoint inhibitors. The main hypothesis related to this immunoresistance is the lack of antigens to stimulate anti-tumor immunity. External radiation is a potential inducer antigens presentation and thus to immunotherapy proprieties. The aim of this review is to describe the tumor microenvironment specificities, especially in bone metastasis and the immune modifications after radiation therapy on a metastatic castration-resistant PCa population. PCa microenvironment is immunosuppressive because of many tumor factors. The complex interplay between PCa cells and bone microenvironment leads to a 'vicious circle' promoting bone metastasis. Furthermore, the immune and bone systems, are connected through an osteoclastogenic cytokine: the Receptor Activator Nuclear Factor Kappa B ligand. Adapted doses of ionizing radiation play a dual role on the tumor. Indeed, radiotherapy leads to immunogenicity by inducing damage associated with molecular patterns. However, it also induces an immunosuppressive effect by increasing the number of immunosuppressive cells. Interestingly, the abscopal effect could be used to optimize immunotherapy potential, especially on bone metastasis. Radiotherapy and immunotherapy combination is a promising strategy, however further studies are necessary to determine the more efficient types of radiation and to control the abscopal effect.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"319-326"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Italian translation, cultural adaptation and pilot testing of Psychosocial Assessment Tool (PAT 3.1) in pediatric cancer.","authors":"Chiara Battaglini, Mario Giordano, Paola Quarello, Nicoletta Bertorello, Giulia Zucchetti, Franca Fagioli","doi":"10.1177/03008916241259933","DOIUrl":"10.1177/03008916241259933","url":null,"abstract":"<p><strong>Introduction: </strong>Experiences related to pediatric oncology diagnosis cause great imbalances within the family structure. Assessing the frailties and needs of families and children with cancer from a psychosocial perspective is an important step in providing appropriate pediatric psychology care.</p><p><strong>Methods: </strong>The aim of this study was to develop an Italian translation of the last version of the Psychosocial Assessment Tool questionnaire (PAT 3.1) and to pilot-test it among pediatric oncological families. The guidelines for cross-cultural adaptation of health-related quality of life measures were followed. Specifically, two independent forward translations were produced, followed by a reconciliation step by a multidisciplinary expert committee and back-translation. Revision of the original text and all translations were performed by the expert committee leading to a final version, which was pilot-tested by cognitive debriefing on five families. Subsequently, the final Italian PAT 3.1 version was approved.</p><p><strong>Results: </strong>The Italian version of the PAT 3.1 generated in the present study is a useful instrument to examine the psychosocial risk of the families with a child with cancer.</p><p><strong>Conclusions: </strong>This instrument will be a valuable tool for future clinical trials and it will help clinicians to target specific pediatric psychology support intervention. The questionnaire will be further validated through a multicenter Italian study on psychosocial screening of pediatric oncology and pediatric general diseases.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"355-359"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.","authors":"João Barbosa-Martins, Ana Rolo, Bárbara Lima, José Carlos Pereira, Cláudia Araújo, Jorge Guimarães, José Dinis, Cláudia Vieira","doi":"10.1177/03008916241257099","DOIUrl":"10.1177/03008916241257099","url":null,"abstract":"<p><strong>Background: </strong>Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting.</p><p><strong>Methods: </strong>We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival.</p><p><strong>Results: </strong>A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%).</p><p><strong>Conclusion: </strong>Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.</p>","PeriodicalId":23349,"journal":{"name":"Tumori","volume":" ","pages":"340-347"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}