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result(s) for
"Dognini, Giuseppina"
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Immune Checkpoint Inhibitors Beyond Progression in Various Solid Tumors: A Systematic Review and Pooled Analysis
by
Dottorini, Lorenzo
,
Ghilardi, Mara
,
Dognini, Giuseppina
in
Colorectal cancer
,
Comparative analysis
,
Cytotoxicity
2025
Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced cancers; however, the value of continuing treatment after radiologic progression remains uncertain. We systematically assessed the efficacy and safety of ICI continuation beyond progression, focusing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Methods: PubMed/MEDLINE, Embase, and the Cochrane Library were searched from inception to 31 March 2025. Eligible reports included retrospective cohorts, prospective trials, post hoc analyses, and pooled regulatory reviews that compared outcomes after ICI continuation versus discontinuation or historical controls. Quality was appraised with the Newcastle–Ottawa Scale (observational designs) and the Cochrane Risk-of-Bias tool (randomized trials). Results: Fifty studies involving 8989 patients met the inclusion criteria: 41 retrospective cohorts; 6 post hoc analyses; 2 randomized trials (1 phase III, 1 phase II); and 1 pooled FDA review. Continuing ICIs beyond progression produced ORRs of 9.3–39% in non-small cell lung cancer (n = 5102), 14–100% in melanoma (n = 669), and 8–33% in renal cell carcinoma (n = 458). Median OS ranged from 8.9 to 18.2 months in lung cancer, 12 to 29.9 months in melanoma, and up to 34.8 months in RCC. Modest but clinically meaningful benefits were reported in colorectal, head-and-neck, gastric, liver, and urothelial tumors. Conclusions: Select patients—particularly those with melanoma, lung cancer, RCC, or gastric cancer—may derive sustained benefit from ICI therapy after radiologic progression. Decisions should incorporate tumor biology, performance status, and emerging biomarkers. Prospective, biomarker-driven trials are needed to define optimal patient selection and the duration of post-progression immunotherapy.
Journal Article
Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses
2023
Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. Methods: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55–2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55–2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. Conclusions: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.
Journal Article
Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
2020
Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
Journal Article
COVID-19 and Lung Cancer Survival: An Updated Systematic Review and Meta-Analysis
by
Dottorini, Lorenzo
,
Ghilardi, Mara
,
Dognini, Giuseppina
in
Comorbidity
,
Complications and side effects
,
Coronaviruses
2022
Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.
Journal Article
Lower limb myalgias in a man who used to “climb the stairs”: an atypical abdominal aortic aneurysm
by
Cadeo, Gianluca
,
Gilardoni, Lodovico
,
Forloni, Franco
in
Aortic Aneurysm, Abdominal - complications
,
Aortic Aneurysm, Abdominal - diagnosis
,
Aortic Rupture - complications
2012
Atypical presentation of emergency abdominal aortic aneurysm comprises a wide spectrum of symptoms. Lower limbs' involvement is infrequent, usually monolateral and with clear vascular features. We report the case of a 58-year-old patient who complained exclusively about symmetric lower limb myalgias without vascular features, after having repeatedly climbed the stairs of the school he worked in. The surprising final diagnosis was of rupturing abdominal aortic aneurysm; the patient was sent to emergency surgery and survived.
Journal Article
Lower limb myalgias in a man who used to \climb the stairsaeuro: an atypical abdominal aortic aneurysm
2012
[...]he had blood hypertension, was an ex-smoker, and had undergone coronarography plus stenting 10 years before because of ischemic coronary disease. No relevant neurologic findings were noticed. Because of the comorbidities and nonspecific but worsening symptoms, the patient underwent laboratory examinations (Table 1) and, according to arterial blood gas analysis (Table 2) and d-dimer level, was thereafter submitted to contrasted thorax computed tomographic (CT) scan (documenting thoracic descending aorta enlargement of approximately 36 mm, with no signs of pulmonary embolism) and cardiological evaluation comprising heart ultrasonography (no pathologic findings reported).
Journal Article
Efficacy of Treatment with Irinotecan and Oxaliplatin Combination in FU-Resistant Metastatic Colorectal Cancer Patients
by
Toffolatti, Luisa
,
Dognini, Giuseppina
,
Cortinovis, Diego
in
Adult
,
Aged
,
Antineoplastic Combined Chemotherapy Protocols - adverse effects
2004
Objectives: As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer. Methods: FU resistance was defined as disease progression during or within 6 months of discontinuing first-line or adjuvant FU/leucovorin chemotherapy. The study treatment consisted of irinotecan 150 mg/m 2 on days 1 and 8 followed by oxaliplatin 85 mg/m 2 on day 1 every 3 weeks. In order to improve the safety profile, we changed the schedule during the study to irinotecan 300 mg/m 2 on day 1 and oxaliplatin 85 mg/m 2 on day 2 every 3 weeks. Results: Of 54 patients treated, the 45 patients with measurable disease were assessed in the efficacy analysis, whereas all patients receiving at least one cycle were evaluated in the safety analysis. Of the patients assessed for efficacy analysis, 19 cases received the first schedule and 26 patients received the second schedule. Twenty-two patients (49%) responded, 10 of the first schedule and 12 of the second schedule group. Stable disease was observed in 35% of all patients. The median response duration was 6.5 months (range 3–10), the median time to progression was 8 months (range 6–10), and the overall survival was 15 months (10–26+). The NCI-CTC grade 3 side effects documented in all of the treated patients were: nausea/vomiting (11%), diarrhea (18%), and neutropenia (7%); grade 4 diarrhea was observed in 2% of patients. Conclusion: The combination of irinotecan followed by oxaliplatin combination is well tolerated and highly active in FU-resistant metastatic colorectal cancer patients.
Journal Article