Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Cancers (Basel) ; 15(21)2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37958348

ABSTRACT

BACKGROUND: In addition to pharmacological prevention, chemotherapy-induced nausea and vomiting (CINV) can be mitigated through patient education; written supporting materials can be beneficial. METHODS: This is a randomized, controlled trial which randomly assigned patients undergoing first chemotherapy cycle to receive oral information regarding CINV prevention and management (control arm) or oral information plus an informative booklet (experimental arm). Overall, 384 cancer patients fulfilling the following inclusion criteria were enrolled: age ≥18 years; life expectancy ≥6 months; no cognitive impairment; written informed consent. After the first cycle, CINV occurrence and its impact on daily activities were assessed using the Functional Living Index Emesis (FLIE). RESULTS: Severe nausea was self-reported by 3.0% and 10.8% of patients in the experimental and control group, respectively (difference: 7.8%; 95% confidence interval: 2.3% to 13.1%). Moderate/high impact of nausea on daily activities was lower in patients also receiving the booklet than in the control group (4.2% and 10.1%, respectively; difference: 5.9%; 95% confidence interval: 0.3% to 11.5%). Vomiting was not statistically different between study arms. CONCLUSIONS: This integrated nursing approach was effective in aiding cancer patients in CINV self-management. Although the beneficial effect was moderate, this intervention demands minimal resources in terms of costs and time.

2.
Viruses ; 15(6)2023 05 30.
Article in English | MEDLINE | ID: mdl-37376576

ABSTRACT

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients.


Subject(s)
COVID-19 , Immunity, Humoral , Humans , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , Vaccination , Antibodies , Immunity, Cellular , Antibodies, Viral
3.
Transl Oncol ; 27: 101585, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36403505

ABSTRACT

BACKGROUND: We previously showed that metabolomics predicts relapse in early breast cancer (eBC) patients, unselected by age. This study aims to identify a "metabolic signature" that differentiates eBC from advanced breast cancer (aBC) patients, and to investigate its potential prognostic role in an elderly population. METHODS: Serum samples from elderly breast cancer (BC) patients enrolled in 3 onco-geriatric trials, were retrospectively analyzed via proton nuclear magnetic resonance (1H NMR) spectroscopy. Three nuclear magnetic resonance (NMR) spectra were acquired for each serum sample: NOESY1D, CPMG, Diffusion-edited. Random Forest (RF) models to predict BC relapse were built on NMR spectra, and resulting RF risk scores were evaluated by Kaplan-Meier curves. RESULTS: Serum samples from 140 eBC patients and 27 aBC were retrieved. In the eBC cohort, median age was 76 years; 77% of patients had luminal, 10% HER2-positive and 13% triple negative (TN) BC. Forty-two percent of patients had tumors >2 cm, 43% had positive axillary nodes. Using NOESY1D spectra, the RF classifier discriminated free-from-recurrence eBC from aBC with sensitivity, specificity and accuracy of 81%, 67% and 70% respectively. We tested the NOESY1D spectra of each eBC patient on the RF models already calculated. We found that patients classified as "high risk" had higher risk of disease recurrence (hazard ratio (HR) 3.42, 95% confidence interval (CI) 1.58-7.37) than patients at low-risk. CONCLUSIONS: This analysis suggests that a "metabolic signature", identified employing NMR fingerprinting, is able to predict the risk of disease recurrence in elderly patients with eBC independently from standard clinicopathological features.

4.
Expert Opin Drug Saf ; 21(11): 1341-1355, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36469577

ABSTRACT

INTRODUCTION: Neo/adjuvant therapy for early-stage breast cancer has become increasingly common in the last few decades; as a consequence, the number of breast cancer survivors experiencing often debilitating long-term side effects has increased, and thus the need for a comprehensive approach to the variety of symptoms involved. AREAS COVERED AND METHODS: We performed a literature search on the main public scientific databases (PubMed, Embase, Cochrane, and CrossRef) from 2000 to April 2022 to identify prevention and management strategies for the most common long-term side effects, including fatigue, insomnia, peripheral neuropathy, cognitive impairment, estrogen deprivation, cardiotoxicity, and second cancers. EXPERT OPINION: Long-term toxicities may affect a majority of breast cancer survivors, significantly interfering with their quality of life. Although there are guidelines for the management of isolated side effects, such as peripheral neuropathy, we aim to provide a more inclusive clinical-oriented approach, focusing on both prevention and therapeutic strategies.


Subject(s)
Breast Neoplasms , Cancer Survivors , Peripheral Nervous System Diseases , Female , Humans , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Peripheral Nervous System Diseases/drug therapy , Quality of Life
5.
Cancers (Basel) ; 15(1)2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36612170

ABSTRACT

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data.

6.
Cancers (Basel) ; 13(14)2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34298718

ABSTRACT

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22-2.32; p = 0.002 and HR,4.89; 95% CI, 3.33-7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer.

7.
Clin Nutr ; 40(1): 286-294, 2021 01.
Article in English | MEDLINE | ID: mdl-32546390

ABSTRACT

BACKGROUND: Body composition, has been established as a risk factor for colorectal cancer diagnosis and disease progression. Aim of this study was to investigate the prognostic role of adiposity, especially visceral fat (VAT), in patients (pts) with metastatic colorectal cancer (MCRC). MATERIAL AND METHODS: A retrospective cohort of 71 MCRC pts treated between 2013 and 2017 was evaluated. VAT was measured as cross-sectional (cm2) area at the L3 level divided by the square of the height (m2). A ROC analysis was performed to define a prognostic threshold according to VAT. RESULTS: Before first-line therapy start, 40 pts (56%) had a body mass index (BMI) > 25 kg/m2. The obtained cut-off value for VAT was 44. Median OS was 30.97 months. At univariate analysis, primary tumor resection (HR 0.40, p = 0.029), VAT>44 (HR 2.85, p = 0.011) and metastasectomy (HR 0.22, p = 0.005) were significantly associated with OS. By multivariate analysis, VAT>44 (HR 2.6; p = 0.020) and metastasectomy were still significantly associated with OS. CONCLUSION: This exploratory study suggests a prognostic role for VAT in MCRC pts, with higher VAT values predicting worse outcome.


Subject(s)
Body Composition , Colorectal Neoplasms/mortality , Colorectal Neoplasms/physiopathology , Intra-Abdominal Fat/physiopathology , Risk Assessment/statistics & numerical data , Aged , Body Mass Index , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Neoplasm Metastasis/physiopathology , Pilot Projects , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment/methods , Risk Factors , Survival Analysis
8.
Drugs Aging ; 37(9): 677-689, 2020 09.
Article in English | MEDLINE | ID: mdl-32681401

ABSTRACT

BACKGROUND: The role of platinum-based chemotherapy (PBC) for the treatment of older patients with non-small cell lung cancer (NSCLC) is still a matter of debate, despite the advent of immunotherapy. OBJECTIVE: The aim of the study was to identify factors associated with first-line PBC prescription and, secondly, to evaluate the impact of first-line PBC on survival, treatment intensity, risk of hospitalization, and subsequent treatments. PATIENTS AND METHODS: We reviewed a consecutive series of 474 older patients (age ≥ 70 years) diagnosed with stage IIIB-IV NSCLC at the Department of Oncology, University Hospital of Udine, Italy from January 2009 to March 2017. RESULTS: Overall, 198 patients were deemed eligible, and 65.2% received a PBC. At multivariate analysis, older age was the only factor associated with PBC prescription. In the whole cohort, 46 patients (23.2%) were hospitalized for chemotherapy-related toxicity. Both PBC prescription (odds ratio [OR] 2.23, 95% confidence interval [CI] 1.02-4.87, p = 0.04) and tumor burden (OR 2.39, 95% CI 1.07-5.32, p = 0.03) emerged as independent risk factors for hospitalization. Moving to significant predictors of patterns of care, Eastern Cooperative Oncology Group (ECOG) performance status > 0 was associated with greater risk of first-line failure (OR 2.20, 95% CI 1.15-4.20, p = 0.02), while bone metastases (OR 0.29, 95% CI 0.12-0.69, p = 0.005) and a Charlson Comorbidity Index score ≥ 3 (OR 0.40, 95% CI 0.19-0.84, p = 0.016) independently predicted lower probability of receiving second-line therapy. Remarkably, PBC did not significantly impact overall survival (hazard ratio [HR] 0.83, 95% CI 0.61-1.14, p = 0.24) and progression-free survival (HR 0.95, 95% CI 0.70-1.28, p = 0.73) compared to single-agent chemotherapy (SAC). However, according to an exploratory landmark analysis, patients who received four cycles of treatment or maintenance therapy experienced prolonged overall survival, regardless of PBC use. CONCLUSIONS: This study evaluated the real-world use of PBC in older patients with NSCLC, offering an insight into the determinants of its prescription and the pattern of care of these patients. Of note, PBC use was associated with a higher likelihood of hospitalization for chemotherapy-related toxicity, with no benefit on survival compared to SAC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Female , Humans , Italy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Progression-Free Survival , Retrospective Studies
9.
J Geriatr Oncol ; 11(8): 1268-1273, 2020 11.
Article in English | MEDLINE | ID: mdl-32576519

ABSTRACT

BACKGROUND: Aging induces meaningful changes in the immune system and inflammation response with increase in monocyte-lymphocyte ratio (MLR) and serum lactate dehydrogenase (LDH) levels. Aim of this study was to explore the prognostic role of MLR and LDH levels in older patients (pts) with metastatic colorectal cancer (mCRC). METHODS: We conducted a retrospective analysis of a consecutive cohort of 168 older (>70 years) patients with mCRC. The prognostic impact of MLR and LDH levels on overall survival (OS) was investigated through uni-and multivariate Cox regression analyses. Moreover, we categorized patients into three groups according to MLR and LDH levels (group 1: MLR-low and LDH-low; group 2: MLR-high or LDH-high; group 3: MLR-high and LDH-high). RESULTS: By univariate analysis, high LDH level (HR 1.74, 95% CI 1.05-2.90) and high MLR level (HR 2.19, 95% CI 1.48-3.44) were significantly associated with a worse OS. Conversely, primary tumor resection and left-sidedness were significantly associated with a longer OS. By multivariate analysis, high LDH level (HR 2.00, 95% CI 1.13-3.55) and high MLR level (HR 2.99, 95% CI 1.68-5.33) were independent prognostic factors of worse prognosis. Compared to group 1, a shorter survival was reported for patients included in group 2 (HR 1.97, 95% CI 1.21-3.23 in univariate; HR 2.54, 95% CI 1.43-4.51 in multivariate) or in group 3 (HR 2.42, 95% CI 24-4.74, p = .010 in univariate; HR 5.59, 95% CI 2.15-14.54 in multivariate) CONCLUSIONS: High baseline levels of LDH, MLR or both are independent unfavorable prognostic factors in older patients treated with first-line chemotherapy for mCRC.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Aged , Biomarkers , Biomarkers, Tumor , Humans , Lymphocytes , Prognosis , Retrospective Studies
10.
Future Oncol ; 16(27): 2059-2073, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32598185

ABSTRACT

Aim: A monitoring strategy for metastatic breast cancer patients (M-MBC) has been little studied. Materials & methods: This retrospective study analyzed a consecutive cohort of 382 MBC patients to analyze different M-MBC strategies to identify factors influencing intensive M-MBC. Results: Elevated baseline serum tumor markers (STM) was the strongest factor associated with increased use of STM tests. Having more frequent oncology office visits was associated with more intensive chemotherapy/magnetic resonance imaging (MRI) using. Increased use of imaging tests was associated with participation to clinical trial. Single and elderly patients were less likely to have frequent testing. Having clinically measurable disease was less likely to have more intensive M-MBC. Conclusion: STM testing and scans were frequently ordered in M-MBC. In the present study, strategies are little influenced by clinico-pathological characteristics.


Subject(s)
Breast Neoplasms/diagnosis , Diagnostic Imaging , Radiography , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Clinical Decision-Making , Comorbidity , Diagnostic Imaging/methods , Disease Management , Female , Humans , Middle Aged , Multimodal Imaging/methods , Neoplasm Staging , Odds Ratio , Radiography/methods , Retrospective Studies , Watchful Waiting
11.
Sci Rep ; 10(1): 7010, 2020 04 24.
Article in English | MEDLINE | ID: mdl-32332763

ABSTRACT

High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche.


Subject(s)
Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Exosomes/metabolism , Lymphocytes/metabolism , Aged , Breast Neoplasms/mortality , Disease Progression , Dynamic Light Scattering , Female , Humans , Kaplan-Meier Estimate , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , T-Lymphocytes/metabolism
12.
Oncologist ; 25(8): 661-668, 2020 08.
Article in English | MEDLINE | ID: mdl-32202020

ABSTRACT

BACKGROUND: Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). MATERIAL AND METHODS: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. RESULTS: At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I., 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. CONCLUSION: MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. IMPLICATIONS FOR PRACTICE: High monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR-LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR-LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Colorectal Neoplasms/diagnosis , Humans , Lactate Dehydrogenases , Lymphocytes , Monocytes , Neutrophils , Prognosis , Retrospective Studies
13.
Recent Pat Anticancer Drug Discov ; 14(3): 203-225, 2019.
Article in English | MEDLINE | ID: mdl-31362664

ABSTRACT

BACKGROUND: Malignant melanoma is a skin cancer responsible for 90% of cutaneous cancer- related deaths. In recent years, breakthroughs in treatment strategy have revolutionized the prognosis in both early and advanced melanoma patients. In particular, treatment with monoclonal antibodies targeting co-inhibitory checkpoints or specific molecular pathways leads to a new era of promising options, by prolonging the survival time of these patients. Moreover, unlike the chemotherapy that was used until some time ago, these new drugs have a good and more manageable toxicity profile. However, because of the recent introduction in clinical practice of the new agents, there is a learning curve among physicians regarding early recognition and management of the associated side effects. OBJECTIVES: The analysis of the toxicity profiles of the different agents currently studied for the treatment of early and advanced melanoma, and the description of several relevant recent patents in this field, are the aims of this review. METHODS: This is a systematically conducted review based on current clinical guidelines and on international Pharmacovigilance databases (AERS-Eudravigilance - WHO Vigibase). RESULTS: Our systematic analysis outlines a comprehensive overview of the pharmacology, clinical application and the safety of recent anticancer drugs to treat melanoma, which can be an essential instrument for health professionals and researchers. CONCLUSION: The new oncological therapies against melanoma are based on increasingly specific biological and immunological targets. For this reason, the potential toxicities that are expected from patients would be less relevant than the systemic "classical" chemotherapy. However, the new therapies are not free from the risk of causing adverse reactions, some of which must be managed promptly and appropriately; moreover, the multiplicity of the metabolic pathways exposes the new target therapies to relevant potential interactions. This review can help to understand how important it is not to underestimate potential adverse drug reactions related to new targeted therapies.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Clinical Trials as Topic , Drug Approval/methods , Humans , Melanoma/pathology , Molecular Targeted Therapy , Neoplasm Metastasis , Patents as Topic , Pharmacovigilance , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Skin Neoplasms/pathology , Melanoma, Cutaneous Malignant
14.
Cancers (Basel) ; 11(9)2019 Aug 24.
Article in English | MEDLINE | ID: mdl-31450641

ABSTRACT

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40-5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16-5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00-7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

15.
Cancers (Basel) ; 11(6)2019 Jun 20.
Article in English | MEDLINE | ID: mdl-31226812

ABSTRACT

Mucositis is one of the most common debilitating side effects related to chemotherapy (CT), radiation therapy (RT), targeted agents and immunotherapy. It is a complex process potentially involving any portion of the gastrointestinal tract and injuring the mucosa, leading to inflammatory or ulcerative lesions. Mechanisms and clinical presentation can differ according both to the anatomic site involved (oral or gastrointestinal) and the treatment received. Understanding the pathophysiology and management of mucosal injury as a secondary effect of anti-cancer treatment is an important area of clinical research. Prophylaxis, early diagnosis, and adequate management of complications are essential to increase therapeutic success and, thus, improve the survival outcomes of cancer patients. This review focuses on the pathobiology and management guidelines for mucositis, a secondary effect of old and new anti-cancer treatments, highlighting recent advances in prevention and discussing future research options.

16.
Ann Transl Med ; 7(1): 14, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30788361

ABSTRACT

We reported the case of a male patient suffering from a metastatic squamous cell carcinoma, harboring a complex inframe deletion in exon 19 of epidermal growth factor receptor (EGFR), treated with erlotinib and osimertinib and subsequently with immunotherapy. A 54-year-old male, with a light smoking history, presented in October 2015 with metastatic squamous cell lung cancer (SqCLC). Deletion p.E746_S752>V in EGFR exon 19 was found and after progression to erlotinib treatment, the liquid biopsy-based re-assessment highlighted a p.T790M EGFR mutation. Osimertinib was then started. After 5 cycles disease progression was detected and nivolumab was started. A subsequent clinical and radiological progression occurred after 3 nivolumab administrations. Next-generation sequencing (NGS) analysis, performed on metastatic tissue, confirmed the original EGFR deletion and showed also the presence of EGFR p.G724S and TP53 p.P152L mutations. Patient died in December 2017. The reported case highlighted tumor's molecular features prominent role over histology, offering further insights about druggable mutations in SqCLC. Furthermore, we confirm the emerging role of EGFR p.G724S mutation as a Osimertinib resistence mechanism.

17.
J Cachexia Sarcopenia Muscle ; 10(2): 368-377, 2019 04.
Article in English | MEDLINE | ID: mdl-30719874

ABSTRACT

BACKGROUND: Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. METHODS: This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross-sectional areas (cm2 ) using CT scan data through the Picture archiving and communication system (PACS) image system. RESULTS: In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2 /m2 . Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2 . Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow-up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression-free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23-3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30-4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil-lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06-1.61, P = 0.010). CONCLUSIONS: Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data.


Subject(s)
Muscle, Skeletal/pathology , Muscular Atrophy/epidemiology , Muscular Atrophy/etiology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/epidemiology , Aged , Aged, 80 and over , Biomarkers , Body Mass Index , Combined Modality Therapy , Comorbidity , Female , Hospitalization , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Prognosis , Quality of Life , Tomography, X-Ray Computed
18.
Expert Opin Biol Ther ; 18(5): 595-603, 2018 05.
Article in English | MEDLINE | ID: mdl-29690797

ABSTRACT

INTRODUCTION: Breast cancer (BC) is the most common cancer diagnosed among women. The development of new personalized therapeutic strategies has reshaped the landscape in this field. However, BC is still the first cause of death among women. Interestingly, several preclinical studies and some clinical evidences are focused their attention on the role of immune system and immunotherapy on cancer control, also in BC. Areas covered: Usually, BC has been considered a not immunogenic tumor for its low mutational load. However, recent studies have evidenced that some subtypes, triple negative and HER-2 positive BC, are 'hot' tumors, thus more immunogenic. Moreover, the presence of immune infiltrate is positively associated with favorable prognosis. Therefore, the use of immune-checkpoint inhibitors seems to be an encouraging treatment option also in BC. Among these drugs, atezolizumab is an anti-PD-L1 monoclonal antibody with a particular structure that reduce antibody-dependent cellular cytotoxicity against T cells, increasing quantitatively and qualitatively the effective response. Expert opinion: The use of immunotherapy is a promising option for BC. However, at the same time it still raises many doubts. Surely, the research and the validation of immune biomarkers can permit to identify patients who more benefit from these drugs.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Breast Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized , B7-H1 Antigen/metabolism , Drug Screening Assays, Antitumor/statistics & numerical data , Female , Humans , Immunotherapy/methods , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
19.
Breast ; 40: 45-52, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29679936

ABSTRACT

BACKGROUND: The optimal strategy for monitoring metastatic breast cancer (M-MBC) is unclear. Nevertheless, M-MBC influences patient's quality of life and it affects the use of resources in terms of both drugs and diagnostic exam prescription. We aim to disclose oncologists' approach on M-MBC, identifying controversial areas. METHODS: An anonymous online survey was conducted among GIM members who, based on their on-field experience, shared their own method for M-MBC planning. Chi-square tests and Fisher exact tests were used as appropriate. RESULTS: The survey was completed by 256 recipients (51%). The majority of them were medical oncologists. Approximately 50% of respondents reported that M-MBC was primarily based on the monitoring strategies used in clinical trials, and for 70% of them M-MBC should be evidence-based. Areas of controversies included the primary goal of M-MBC, the use of tumour markers, the optimal timing for baseline assessment and frequency of repeating testing. Respondents agreed on planning M-MBC before treatment's start and on discussing with the patient about the M-MBC strategy and on choosing CT-scan as the preferred reassessment imaging method. The most relevant factors influencing the M-MBC strategy were performance status, triple negative histology, exam's contraindication, the presence of clinically measurable disease, and treatment safety profile; on the contrary, patients' socio-economic status, exam's cost, and hospital's logistic limits were less relevant. Experienced oncologists seemed less prone to intensive follow-up. CONCLUSION: M-MBC strategy still has controversial issues and its potential clinical effects for breast cancer patients need ad hoc studies.


Subject(s)
Breast Neoplasms/pathology , Medical Oncology/statistics & numerical data , Population Surveillance , Practice Patterns, Physicians'/statistics & numerical data , Adult , Breast Neoplasms/therapy , Chi-Square Distribution , Disease Progression , Female , Humans , Italy , Male , Medical Oncology/methods , Middle Aged , Neoplasm Metastasis , Surveys and Questionnaires
20.
Oncotarget ; 6(7): 4569-84, 2015 Mar 10.
Article in English | MEDLINE | ID: mdl-25625193

ABSTRACT

Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated.


Subject(s)
Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/drug effects , Mitochondria/drug effects , Neoplasms/drug therapy , Neoplastic Stem Cells/drug effects , Humans , Mitochondria/pathology , Neoplasms/pathology , Neoplastic Stem Cells/pathology , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL
...