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1.
J Transl Med ; 21(1): 75, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36737752

RESUMEN

BACKGROUND: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. METHODS: A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. RESULTS: Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). CONCLUSION: Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.


Asunto(s)
Acetato de Abiraterona , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Acetato de Abiraterona/uso terapéutico , Prednisona/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Prospectivos , Resultado del Tratamiento , Nitrilos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
2.
Cancer Immunol Immunother ; 70(12): 3679-3692, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34351436

RESUMEN

Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated (P = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Neoplasias de la Próstata Resistentes a la Castración/inmunología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Telomerasa/inmunología , Anciano , Antineoplásicos/inmunología , Linfocitos T CD8-positivos/inmunología , Supervivencia sin Enfermedad , Docetaxel/inmunología , Humanos , Inmunidad/inmunología , Inmunización/métodos , Masculino , Antígeno Prostático Específico/inmunología , Linfocitos T Reguladores/inmunología
3.
Anticancer Drugs ; 30(8): 854-858, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31356228

RESUMEN

The phase III PROSELICA trial showed that cabazitaxel 20 mg/m (C20) was not inferior and better tolerated compared to cabazitaxel 25 mg/m (C25) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed during or after docetaxel. Here, we report on a real-world retrospective analysis concerning the safety and the activity of C20 schedule in patients with mCRPC treated at our Institution. We identified 35 patients with mCRPC who received C20 as baseline dose treatment because they were frail or experienced serious toxicities to previous treatments. Adverse events assessment was performed at each visit during the treatment. Progression-free survival (PFS) and overall survival (OS) curves were obtained using the Kaplan-Meyer product-limit estimator. Median age was 71 years. All patients received a previous treatment with docetaxel; 19 patients (54%) received one additional line of therapy and 9 (26%) two or more. Patients received a median of 4 cycles (range: 2-10). Only one patient experienced grade 3 neutropenia (3%), two patients grade 3 anemia (6%), and one patient grade 3 fatigue (3%); three patients were treated with prophylactic Granulocyte colony-stimulating factor (9%). The most frequent adverse events of all grades were: anemia (39%), fatigue (33%), and diarrhea (15%). Median PFS was 3.7 months [95% confidence interval (CI): 3.31-4.09]; median OS was 10.3 months (95% CI: 4.63-15.97). Our real-world analysis confirms that C20 is a feasible option for elderly and heavily pretreated patients with mCRPC, showing activity and good tolerability.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Tasa de Supervivencia , Taxoides/administración & dosificación
4.
Breast Cancer Res Treat ; 172(1): 9-21, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30054831

RESUMEN

PURPOSE: Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a meta-analysis of randomized clinical trials (RCTs) to better define the benefit and the risk of CDK4/6 inhibitors plus ET for endocrine-sensitive or endocrine-resistant population in metastatic HR+/HER2- breast cancer. METHOD: A systematic literature search of Pubmed, Embase, and the Cochrane Library was carried out up to 30 June 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS), as well as odds ratios (ORs) for objective response rates, ≥ G3-G4 adverse events (AEs), and G3-G4 neutropenia were calculated for each trial. A meta-analysis was carried out using the random-effects model. RESULTS: Eight RCTs were eligible including 4578 breast cancer patients. Adding CDK4/6 inhibitors to ET in endocrine-sensitive (HR 0.55, 95% CI 0.50-0.62) or endocrine-resistant setting (HR 0.51, 95% CI 0.43-0.61) significantly improved the PFS of metastatic HR+/HER2- breast cancers regardless of menopausal status and site of metastasis. Moreover, CDK4/6 inhibitors plus ET meaningfully improved objective response rate in endocrine-sensitive (ORs 0.62, 95% CI 0.52-0.73) or endocrine-resistant setting (ORs 0.33, 95% CI 0.24-0.47). The use of these drugs was characterized by a significant increase of G3-G4 AEs (OR 10.88, 95% CI 6.53-18.14). CONCLUSION: Emerging data provide a new standard treatment for advanced HR+/HER2- breast cancer, regardless of menopausal status, prior hormonal/chemotherapy treatments delivered, sites of metastasis. However, benefits should be balanced with longer treatment duration, toxicities, and costs.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 6 Dependiente de la Ciclina/genética , Femenino , Humanos , Metástasis de la Neoplasia , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Receptores de Progesterona/genética
5.
Oncologist ; 20(8): 880-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26099741

RESUMEN

BACKGROUND: We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab. MATERIALS AND METHODS: A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models. RESULTS: In the 202 trastuzumab-naïve patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p = .131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p = .370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p = .045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p = .404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with a TFI of ≥6 months (29.5 vs. 48.3 months; p = .331), nonvisceral involvement (48.0 vs. 60.3 months; p = .270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p = .003), respectively. CONCLUSION: Despite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/uso terapéutico , Trastuzumab/uso terapéutico , Adulto , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trastuzumab/administración & dosificación , Resultado del Tratamiento
6.
Int J Mol Sci ; 16(8): 17181-92, 2015 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-26225965

RESUMEN

PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Moléculas de Adhesión Celular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Periodo Preoperatorio
7.
Anticancer Drugs ; 25(10): 1227-30, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25075796

RESUMEN

Trabectedin is an alkylating agent registered in Europe for the treatment of advanced metastatic soft-tissue sarcomas, whose activity has been documented mainly in liposarcomas or leiomyosarcomas. Here, we report the response achieved in a patient with lung metastases from synovial sarcoma. A man with a large synovial sarcoma of the axilla underwent three cycles of neoadjuvant epirubicin+ifosfamide before complete excision, followed by three additional cycles of chemotherapy and radiotherapy. After 14 months, bilateral lung metastases appeared and were first treated with a prolonged 14-day continuous infusion of high-dose ifosfamide without response, and then with second-line trabectedin. A partial radiological response was achieved; dosage was reduced to 1.1 mg/m because of mild asthenia, grade 3 neutropenia, grade 3 nausea and vomiting, and reversible transaminase elevation. After 9 months of treatment, the lung nodules progressed, the patient received sorafenib, but further progressed and died 19 months after the first appearance of lung metastases. Trabectedin was the only drug that led to a radiological response in this patient with synovial sarcoma, despite being administered at 75% of the standard dose because of dose-limiting nausea and vomiting, in line with more recent data demonstrating activity in translocated sarcomas. We believe that trabectedin represents an attractive option for the treatment of metastatic synovial sarcoma and further clinical studies are warranted.


Asunto(s)
Antineoplásicos/uso terapéutico , Axila/patología , Dioxoles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Sarcoma Sinovial/tratamiento farmacológico , Tetrahidroisoquinolinas/uso terapéutico , Adulto , Terapia Combinada , Epirrubicina/uso terapéutico , Resultado Fatal , Humanos , Ifosfamida/uso terapéutico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundario , Masculino , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Sarcoma Sinovial/radioterapia , Sarcoma Sinovial/secundario , Sorafenib , Trabectedina
8.
Artículo en Inglés | MEDLINE | ID: mdl-38347113

RESUMEN

BACKGROUND: Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC. METHODS: A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC. RESULTS: We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71-82)]. Median ADT duration in HSPC was 24 months (IQR = 14-40). Median follow-up was 91 months (IQR = 62-138), median OS and PFS from ARSI start were 20 (IQR 10-32) and 10 months (IQR = 5-19), respectively. In PP developing metastatic disease (n = 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54-2.64; LAD/ST: HR = 1.73; 95% CI 1.34-2.24; p < 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38-2.45; p < 0.001; LAD/ST: HR = 1.59; 95% CI 1.21-2.10; p < 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06-2.26; p = 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n = 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56-1.02, p = 0.064 and HR = 0.74, 95% CI 0.55-0.99, p = 0.042, respectively). CONCLUSIONS: Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.

9.
Clin Genitourin Cancer ; 22(5): 102185, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217072

RESUMEN

BACKGROUND: Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged ≥ 75 is challenging due to limited data. Regardless of age, in real-world clinical practice, most mCRPC still derive from failure of androgen deprivation therapy (ADT) with or without docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC). As abiraterone acetate plus prednisone (AA) and enzalutamide (Enza) are common first-line treatments for mCRPC. The impact of prior use of D for mCSPC on the efficacy and safety of AA or Enza in this older population remains unclear. METHODS: A cohort of patients aged ≥ 75 years starting AA or Enza as first-line therapy for mCRPC from January 2015 to April 2019 was identified from the registries of 10 institutions. Patients were categorized into 2 groups based on previous use of D for mCSPC. Primary endpoints were cancer-specific survival (CSS) from AA or Enza start, CSS from ADT onset, and safety. We used Kaplan-Meier method to estimate the endpoints distribution, including median values with 95% confidence intervals (95% CI). RESULTS: Of the 337 patients identified, 24 (7.1%) received ADT+D and 313 (92.9%) received ADT alone for mCSPC. Median follow-up from AA/Enza start was 18.8 months. Median CSS from ADT or AA/Enza was not significantly different between ADT+D and ADT alone cohorts (71.9 vs. 52.7 months, P = .97; 25.4 vs. 27.2 months, P = .89, respectively). No statistically significant difference in adverse events (AEs) of any grade rate (58.3% vs. 52.1%, respectively; P = .67) or grade ≥ 3 (12.5% vs. 15.7%, respectively; P = 1.0) was found between ADT+D and ADT alone cohorts. CONCLUSIONS: Despite the innate limitations of a retrospective design and relatively small size of the ADT+D cohort, this analysis suggests that elderly men receiving AA or Enza as first-line therapy for mCRPC have similar survival outcomes and tolerability, regardless of previous D for mCSPC.


Asunto(s)
Acetato de Abiraterona , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Sistema de Registros , Humanos , Masculino , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Anciano , Acetato de Abiraterona/uso terapéutico , Acetato de Abiraterona/administración & dosificación , Nitrilos/administración & dosificación , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Anciano de 80 o más Años , Sistema de Registros/estadística & datos numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Prednisona/administración & dosificación , Prednisona/uso terapéutico
10.
J Immunol ; 186(10): 6044-55, 2011 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-21498665

RESUMEN

Influenza vaccination is generally recommended for non-Hodgkin's lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27(+) memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission.


Asunto(s)
Anticuerpos Antivirales/sangre , Linfocitos B/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Orthomyxoviridae/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/inmunología , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Femenino , Humanos , Inmunoglobulina M/sangre , Memoria Inmunológica , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Rituximab , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
11.
Diagnostics (Basel) ; 13(17)2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37685271

RESUMEN

Prostate cancer still represents one of the most frequent cancers and causes of death worldwide, despite the huge therapeutic advances in the last decades. The introduction into clinical practice of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has significantly improved diagnostic capacity, allowing for the identification of lesions previously undetectable. The case we are presenting is about a 90-year-old man affected by metastatic prostate cancer and treated with hormonal therapies. At the second progression, the restaging with PSMA PET/CT pointed out a millimetric cardiac intra-atrial metastasis, on which little/scarce literature data are still available. On one hand, this finding confirms the high sensitivity of this technique, which should be preferred over traditional imaging. On the other hand, it suggests that introducing next-generation imaging into clinical practice may provide novel insights about prostate cancer metastatic spread.

12.
Acta Biomed ; 94(S1): e2023232, 2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37606060

RESUMEN

Basal cell carcinoma (BCC) of the prostate is a very rare histologic variant of prostate cancer, of difficult diagnosis and uncertain prognosis. In fact, despite the frequency of prostate cancer, only 100 cases have been described in the literature, and most of the data derived from case reports. Because of the rarity of this disease, therapeutic options for these patients are scarce and no randomized trials are available. Here, we report the case of a 63-year-old man treated for a prostatic BCC (pBCC) that was challenging in terms of both diagnosis and treatment. We also performed a review of the literature to provide an overview of the therapeutic options for this rare tumor type and to better understand the role of molecular characterization in rare prostate cancer histologies. Given the rarity of pBCC worldwide, further collection of real-world data is needed to better understand the optimal diagnostic and therapeutic strategies for this rare disease.


Asunto(s)
Carcinoma Basocelular , Neoplasias de la Próstata , Neoplasias Cutáneas , Masculino , Humanos , Persona de Mediana Edad , Próstata , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/cirugía , Enfermedades Raras , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia
13.
Sci Rep ; 13(1): 17791, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853018

RESUMEN

Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51-8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Ceramidas , Lipidómica , Pronóstico , Antagonistas de Receptores Androgénicos/uso terapéutico
14.
Diagnostics (Basel) ; 13(3)2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36766492

RESUMEN

BACKGROUND: treated prostate cancer (PCa) patients develop biochemical recurrence (BCR) in 27-53% of cases; the role of MRI in this setting is still controversial. In 2021 a panel of experts proposed a "Prostate Imaging-Recurrence Reporting" (PI-RR) score, aiming to standardize the reporting. The aim of our study is to evaluate the reproducibility of the PI-RR scoring system among readers with different expertise. METHODS: in this monocentric, retrospective observational study, the images of patients who underwent MRI with BCR from January 2017 to January 2022 were analyzed by two radiologists and a radiology resident. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were obtained. Interobserver agreement was calculated. The percentage of the PI-RR score of 3 was estimated to find out the proportion of uncertain exams reported among the readers. RESULTS: a total of seventy-six patients were included in our study: eight previously treated with RT and sixty-eight who underwent surgery. The accuracy range was 75-80%, the sensitivity 68.4-71.1%, the specificity 81.6-89.5%, PPV 78.8-87.1%, and NPV 72.1-75.6%. The inter-reader agreement using a binary evaluation (PI-RR ≥ 3 as positive mpMRI) demonstrated a correlation coefficient (k) of 0.74 (95% CI: 0.62-0.87). The percentage for the PI-RR score of 3 was 6.6% for reader one, 14.5% for reader two, and 2.6% for reader three. CONCLUSION: this study confirmed the good accuracy of mpMRI in the detection of local recurrence of PCa and the good reproducibility of PI-RR score among all readers, confirming it to be a promising tool for the standardization of the assessment of patients with BCR.

15.
Ther Adv Med Oncol ; 15: 17588359231156147, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36895852

RESUMEN

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC. Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1-62.2 months] versus AA (51.6 months; 95% CI, 42.6-60.6 months; p = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0-55.7 months) than those having AA (22.0 months; 95% CI, 18.1-26.0 months; p = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza (p = 0.51 and p = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA. Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.

16.
Cancers (Basel) ; 15(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36612319

RESUMEN

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13−38.00 vs. 40.93 months, 95% CI: 40.93−40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the "tip of the iceberg", by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

17.
Front Oncol ; 12: 1048526, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36530979

RESUMEN

The first-line therapy in advanced kidney cancer has changed in recent years due to the introduction of combinations of tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptors (VEGFR) and immune checkpoint inhibitors (ICIs). Although immune-related adverse events are well-known, in the case of combination treatments, the determination of which drug is related to an adverse event may be challenging. We reported two cases of patients who developed muscle enzyme elevation in association with hypothyroidism during therapy with pembrolizumab plus axitinib for metastatic kidney cancer. The myopathy rapidly resolved after hormone replacement therapy with levothyroxine. Hypothyroid myopathy is a scarcely known and underreported adverse event. This adverse event may be relevant in the differential diagnosis with immune-related myositis, which has an autoimmune pathogenesis and a potentially fatal course.

18.
Diagnostics (Basel) ; 12(3)2022 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-35328134

RESUMEN

The role of 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in the management of prostate cancer (PCa) patients is increasingly recognised. However, its clinical role is still controversial. Many published studies showed that FDG PET/CT might have a prognostic value in the metastatic castration-resistant phase of the disease, but its role in other settings of PCa and, more importantly, its impact on final clinical management remains to be further investigated. We describe a series of six representative clinical cases of PCa in different clinical settings, but all characterised by a measurable clinical impact of FDG PET/CT on the patients' management. Starting from their clinical history, we report a concise narrative literature review on the advantages and limitations of FDG PET/CT beyond its prognostic value in PCa. What emerges is that in selected cases, this imaging technique may represent a useful tool in managing PCa patients. However, in the absence of dedicated studies to define the optimal clinical setting of its application, no standard recommendations on its use in PCa patients can be made.

19.
Cancers (Basel) ; 14(5)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35267553

RESUMEN

In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.

20.
Ann Nucl Med ; 36(4): 373-383, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35044592

RESUMEN

OBJECTIVE: Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. PATIENTS AND METHODS: Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. RESULTS: SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. CONCLUSION: The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Antagonistas de Andrógenos/uso terapéutico , Benchmarking , Fluorodesoxiglucosa F18 , Humanos , Masculino , Músculo Esquelético/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/uso terapéutico , Estudios Retrospectivos
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