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2.
Urol Oncol ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32653412

RESUMO

OBJECTIVES: To assess contemporary gender, race and stage-specific incidence and trends of bladder cancer among young adults in the United States. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged 20 to 39 years-old with histologically confirmed bladder cancer were included. Age-standardized rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC). RESULTS: From 2000 to 2016, 2,772 new cases were recorded (ASR 0.2, AAPC -1.5%, P = 0.01). ASRs were higher in males than in females (0.3 and 0.1, respectively) and decreased significantly in both genders (AAPC -1.3, P = 0.02 and -2.2% P = 0.03, respectively). non-Hispanic White (NHW) accounted for 70.7% of the cohort and had the highest incidence (ASR 0.3) that decreased over time (AAPC -1.4%, P = 0.02). Conversely, ASRs in other ethnic groups were lower and showed stable trends. The most frequent tumor characteristics were Ta/TisN0M0 stage (71.0%, ASR 0.1, AAPC -1.0%, P = 0.1), low grade (61.6%, ASR 0.1, AAPC -4.3%, P = 0.001) and urothelial histology (95.5%, ASR 0.2, AAPC -1.5%, P = 0.01). CONCLUSIONS: Despite the rarity of bladder cancer in those aged 20 to 39 years, a standard work-up is required to avoid advanced stage at diagnosis. The current data validate initial diagnoses at earliest stage in the vast majority of young adults. Moreover, decreasing ASRs in both genders are encouraging.

3.
World J Urol ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591899

RESUMO

PURPOSE: To retrospectively review our 20 year experience of multidisciplinary management of non-metastatic ductal prostate cancer (dPC), a rare but aggressive histological subtype of prostate cancer whose optimal therapeutic approach is still controversial. METHODS: Histologically confirmed dPC patients undergoing primary, curative treatment [radical prostatectomy (RP), external beam radiotherapy (EBRT), and androgen deprivation therapy (ADT)] were included, and percentage of ductal and acinar pattern within prostate samples were derived. Survival outcomes were assessed using the subdistribution hazard ratio (SHR) and Fine-and-Gray model. RESULTS: From January 1997 to December 2016, 81 non-metastatic dPC fitted selection criteria. Compared to surgery alone, SHR for progression-free survival and cancer-specific mortality were 2.8 (95% CI 0.6-13.3) and 1.3 (95% CI 0.1-16.2) for exclusive EBRT, 2.7 (95% CI 0.6-13.0) and 6.5 (95% CI 0.6-69.8) for adjuvant EBRT, 4.9 (95% CI 0.7-35.5) and 5.8 (95% CI 0.5-65.6) for salvage EBRT post-prostatectomy recurrence, and 3.2 (95% CI 0.7-14.0) and 3.9 (95% CI 0.3-44.1) for primary ADT (P = 0.558; P = 0.181), respectively. Comparing multimodal treatment and monotherapy confirmed the above trends. Local recurrence more typically occurred in pure dPC patients, mixed histology more frequently produced metastatic spread (29.6% relapse in total, P = 0.026). CONCLUSION: Albeit some limitations affected the study, our findings support the role of local treatment to achieve better disease control and improve quality of life. Different behavior, with typical local growth in pure dPC, higher distant metastatization in the mixed form, might influence treatment response. Given its poor prognosis, we recommend multidisciplinary management of dPC.

4.
Cancer Treat Rev ; 88: 102057, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32574991

RESUMO

Despite advances in metastatic prostate cancer therapy, expected survival for patients in the castration-resistant phase of disease is poor. Immune-checkpoints inhibitors significantly prolonged life expectancy in some solid tumors and have been evaluated also in advanced stage prostate cancer. The majority of data available derive from preliminary phase I and II trials evaluating CTLA-4 and PD-1 as monotherapy or in combination with each other, vaccines, radiotherapy or targeted/hormonal therapy, achieving only limited benefits in terms of biochemical and radiologic responses. There are many reasons that may explain why prostate cancer responds poorly to modern immunotherapies, such as its characteristic low tumor mutational burden or immune-suppressive tumor microenvironment. The present review summarizes the results obtained treating advanced prostate cancer patients with immune-checkpoints inhibitors and analyzes potential mechanisms of both resistance and sensitivity, in order to hypothesize possible avenues of special interest for future research.


Assuntos
Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/terapia , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Vacinas Anticâncer/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Masculino , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Cancer Epidemiol ; 67: 101762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32585430

RESUMO

BACKGROUND: The burden of renal cell carcinoma (RCC) in young adults received marginal attention. We assessed contemporary gender, race and stage-specific incidence and trends of RCC among young adults (20-39 years-old) in the United States. METHODS: Within Surveillance, Epidemiology, and End Results database (2000-2016), patients aged 20-39 years with histologically confirmed RCC were included. Age-standardized incidence rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC). RESULTS: From 2000-2016, 7767 new RCC cases were recorded (ASR 0.6, AAPC + 5.0 %, p < 0.001). ASRs were higher in males than in females (0.7 and 0.5, respectively) and increased significantly in both genders (AAPC + 5.0 % and +4.7 % both p < 0.001, respectively). Non-Hispanic American Indian/Alaska Native had the highest incidence (ASR 1.0) vs. non-Hispanic Asian or Pacific Islander the lowest (ASR 0.3). ASRs significantly increased in all ethnic groups. T1aN0M0 and T1bN0M0 stages showed the highest incidence and increase (ASR 0.3, AAPC + 5.9 %, p < 0.001 and ASR 0.1, AAPC + 5.7 %, p < 0.001, respectively). Also regional and distant stages increased (AAPC + 3.7 %, p = 0.001 and AAPC + 1.5 %, p = 0.06). The most frequent tumor characteristics were G2 (44.4 %, ASR 0.3, AAPC + 6.3 %, p < 0.001) and G1 (13.1 %, ASR 0.1, AAPC + 1.1 %, p = 0.2), as well as clear cell histology (54.8 %, ASR 0.3, AAPC + 7.6 %, p < 0.001). CONCLUSIONS: RCC in young adults is rare, but increasing. This is mainly due to T1aN0M0 tumors. Nonetheless, also regional diseases are significantly increasing. Differences between ethnic groups exist and may warrant further research.

6.
Endocrine ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488839

RESUMO

Insulinoma is a rare pancreatic neuroendocrine tumor (pNET) potentially associated with severe hypoglycaemic crisis. The great majority of these tumors are benign. In patients with metastatic malignant insulinoma, systemic therapies aim to control both the syndrome and tumor growth. Everolimus is a drug approved for the management of advanced pNETs that can achieve both these goals. According to international guidelines and regulatory authorities, everolimus in patients with pNET should be continued until the demonstration of disease progression with standard radiologic imaging techniques. The drug is neither recommended nor authorized beyond progression. This could not be the case of advanced insulinoma patients since the antineoplastic and the glycaemic effects of everolimus seem to follow independent mechanisms. The authors present here their point of view in favor of continuing everolimus beyond progression in symptomatic insulinoma patients on the basis of a robust rationale and describing a case.

7.
J Clin Endocrinol Metab ; 105(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449514

RESUMO

CONTEXT: Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. OBJECTIVE: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. PATIENTS: A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. SETTING: Retrospective study at 12 ACC referral centers. MAIN OUTCOME MEASURE: Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). RESULTS: Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. CONCLUSIONS: SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.

8.
Eur Urol Focus ; 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32456993

RESUMO

BACKGROUND: Recent data showed that North America has the highest incidence of renal cell carcinoma (RCC) worldwide. OBJECTIVE: To assess contemporary gender-, race-, and stage-specific incidence; survival rates; and trends of RCC patients in the USA. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged ≥18 yr with histologically confirmed renal parenchymal tumors were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age-adjusted incidence rates and 5-yr cancer-specific survival (CSS) rates were estimated. Temporal trends were calculated through Joinpoint regression analyses to describe the average annual percent change (AAPC). RESULTS AND LIMITATIONS: The age-adjusted incidence rate of RCC was 11.3/100 000 person years (AAPC+2.0%, p<0.001). Five-year CSS rates increased from 78.4% to 84.5% (AAPC +0.8%, p<0.001). Male incidence was double that of females (15.5 and 7.7, respectively). CSS marginally favored females (84.5% vs 82.0%), but improved equally in both genders (both AAPC +0.8%). The highest incidence (14.1/100 000 person years, AAPC +2.8%) and lowest survival (80.1%) were recorded in non-Hispanic American Indian/Alaska Native populations. T1aN0M0 had the highest incidence rates (4.6/100 000 person years), the highest increase over time (AAPC +3.6%), and the highest CSS (97.6%) of all stages. Limitations include retrospective nature and lack of information on risk factors. CONCLUSIONS: The incidence of RCC increased significantly from 2001 to 2016, and 5-yr CSS after RCC improved. This was mainly due to T1aN0M0 tumors that showed the highest increase in the incidence and highest CSS. Unfavorable outcomes in specific ethnic groups warrant further research. PATIENT SUMMARY: We examined contemporary incidence and cancer-specific survival rates of kidney cancer. Males had double the incidence rates of females, but lower survival. Natives showed the highest incidence rates and the lowest survival rates. Small renal masses showed the highest incidence and survival rates.

9.
Neuroendocrinology ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32365350

RESUMO

BACKGROUND: Little information is available concerning prognostic factors of bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical and molecular approach could be used for their prognostic evaluation. METHODS: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p-40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, MDM2) and genomic (TP53, RB1, ATM, JAK2, KRAS, STK11) findings were analyzed from BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). Ki-67 was expressed as a percentage of positive cells in hot spot as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNEC, Ki-67 was evaluated only in the LCNEC component. RESULTS: 111 LCNECs were distinguished in: 70 pure LCNECs, 35 co-LCNECs [27 with adenocarcinoma (ADC); 8 with squamous cell carcinoma (SqCC) and 6 LCNECs with only napsin A immunoreactivity]. Ki-67 cut off at 55% evaluated in the NE component was the most powerful OS predictor (Log-rank P=0.0001) in all LCNECs: 34 LCNECs-A Ki-67 <55% and 77 LCNECs-B Ki-67 ≥55%; statistical differences in OS (Log-rank P=0.0001) were also observed between pure and co-LCNECs. A significant difference in OS was found between pure LCNEC-A and co-LCNEC-A (P<0.05) but not between pure LCNEC-B and Co-LCNEC-B. Co-LCNEC-ADC and LCNEC Napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (Log-rank P=0.0001). At multivariable analysis, tumor location, pure vs combined features and napsin A, but no single gene mutation, were significantly associated with OS, after adjustment for Ki-67 and study center (P<0.05). CONCLUSIONS: The Ki-67 proliferation index and the morphologic characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.

10.
J Geriatr Oncol ; 11(6): 976-981, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32299685

RESUMO

PURPOSE: Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. METHODS: We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. RESULTS: The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). CONCLUSIONS: This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.

11.
ESMO Open ; 5(2)2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32220946

RESUMO

Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice.To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was to raise awareness on the importance of bone preservation in this complex setting, while providing an instrument to support physicians and facilitate the management of bone health.Current evidence regarding the effects on bone health of ADT, of novel hormone therapies (which improve progression delay, pain control and QoL while consistently carrying the risk of non-pathological fractures in both non-metastatic and metastatic PCa) and of bone turnover inhibitors (whose use is frequently suboptimal) is reviewed. Finally, the expert opinion to optimise bone health preservation is given.

12.
Eur J Surg Oncol ; 46(7): 1347-1352, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32220544

RESUMO

INTRODUCTION: We tested whether frail patients may benefit from robot-assisted (RARC) relative to open radical cystectomy (ORC). MATERIALS AND METHODS: Frail patients treated with RC were identified within the National Inpatient Sample database (2008-2015). The effect of RARC vs. ORC was tested in five separate multivariable models predicting: complications, failure to rescue (FTR), in-hospital mortality, length of stay (LOS) and total hospital charges (THCs). As internal validity measure, analyses were repeated among non-frail patients. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS: Of 11,578 RC patients, 3477 (30.0%) were frail. RARC was performed in 488 (14.0%) frail patients and 1386 (17.1%) non-frail patients. Among frail, RARC was only independently associated with shorter LOS (median 8 vs. 9 days, relative ratio [RR] 0.79, p < 0.001). Conversely, among non-frail, RARC was independently associated with lower complications (57.3 vs. 59.1%, odds ratio [OR] 0.82, p = 0.004) and shorter LOS (median 6 vs. 7 days, RR 0.88, p < 0.001), but also predicted higher THCs (+2850.3 US dollars, p = 0.001). CONCLUSIONS: In frail patients, the use of RARC did not result in better short-term outcomes except for one-day advantage in LOS. Conversely, in non-frail patients, the use of RARC resulted in lower complication rates and shorter LOS at the cost of higher THCs. In consequence, the benefit of RARC appears relatively marginal in frail patients and our data do not suggest a clear and clinically-meaningful benefit of RARC over ORC in frail radical cystectomy population.

13.
Expert Opin Biol Ther ; 20(3): 319-326, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32011207

RESUMO

Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab.Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC.Results: Of the more than 50 variables analyzed, five showed a significant correlation with DSS: ECOG PS, size of the biggest brain metastasis, number of metastatic sites, toxicity, and malignant pleural effusion. Three variables significantly correlated with TTF: malignant pleural effusion, number of metastatic sites, number of liver metastases. Malignant pleural effusion was the only variable showing a significant correlation with OR, as well as the only one correlating with all the endpoints of the study.Conclusions: This study identified clinical characteristics associated with survival and response during treatment with Nivolumab in NSCLC patients. The unfavorable association between malignant pleural effusion and objective response is a novel finding with important translational implications.

15.
Adv Ther ; 37(3): 1145-1155, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32002809

RESUMO

INTRODUCTION: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. METHODS: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging. RESULTS: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes. CONCLUSIONS: Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.

16.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633759

RESUMO

CONTEXT: We investigated the role of Gallium 68 dodecanetetraacetic acid Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/computed tomography (PET/CT) in detecting somatostatin receptors (SSTRs) in 19 patients with metastatic adrenocortical carcinoma (ACC) and explored the activity of yttrium-90/lutetium-177 (90Y/177Lu-DOTATOC) peptide receptor radionuclide therapy (PRRT). CASE DESCRIPTION AND METHODS: 68Ga uptake in metastatic sites was scored in terms of intensity and anatomical uptake distribution of standard uptake value (SUV). Tissue expression of SSTR2A and SSTR5 was also evaluated by immunohistochemistry (IHC) on primary tumors. Eight (42%) patients displayed radiometabolic uptake of any-grade intensity with focal and limited distribution. Two (11%) patients displayed strong uptake in multiple lesions and were treated with PRRT. Both obtained an overall disease control lasting 4 and 12 months, respectively. CONCLUSIONS: ACC can express SSTRs as detected by IHC and 68Ga-DOTATOC PET. SSTRs-based PRRT may represent a potential treatment opportunity for a minority of patients with advanced ACC. This treatment modality deserves further investigation.

17.
Surg Oncol ; 32: 8-13, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31683158

RESUMO

BACKGROUND: Relatively few studies investigated the importance of frailty in radical cystectomy (RC) patients. We tested the ability of frailty, using the Johns Hopkins Adjusted Clinical Groups indicator, to predict early perioperative outcomes after RC. METHODS: RC patients were identified within the National Inpatient Sample database (2000-2015). The effect of frailty, age and Charlson Comorbidity Index were tested in five separate multivariable models predicting: (1) complications, (2) failure to rescue (FTR), (3) in-hospital mortality, (4) length of stay (LOS) and (5) total hospital charges (THCs). All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS: Of 23,967 RC patients, 5833 (24.3%) were frail, 7721 (32.2%) were aged ≥75 years and 2832 (11.8%) had CCI ≥2. Frailty, age ≥75 years and CCI ≥2 were non-overlapping in 86.3% of the cohort. Any two or three of these features were recorded in 12.4 and 1.3%, respectively. Frailty was an independent predictor of all five examined endpoints and the magnitude of its association was stronger or at least equal than that of age ≥75 years and CCI ≥2. CONCLUSION: Frailty, advanced age and comorbidities represent non-overlapping patients' characteristics. Of those, frailty represents the most consistent and strongest predictor of early adverse outcomes after RC. Ideally, all three indicators should be considered in retrospective, as well as prospective analyses. Pre-surgical recognition of frail patients should be ideally incorporate in clinical practice in order to address these patients to multimodal pre-habilitation programs that may potentially improve the perioperative prognosis.

18.
J Geriatr Oncol ; 11(4): 718-723, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31257163

RESUMO

OBJECTIVES: Historical data showed worse perioperative outcomes after cytoreductive nephrectomy (CN) in older patients. Additionally, the CARMENA trial questioned the survival benefit of cytoreductive CN. We reassessed complication, failure to rescue (FTR) and mortality rates after CN in a contemporary cohort of older patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: From National Inpatient Sample (NIS) database (2008-2015), mRCC patients treated with CN were abstracted. Univariable and multivariable logistic regression models tested for the relationship between age (≤55 vs. 56-70 vs ≥71 years), Charlson Comorbidity Index (CCI) and modified Frailty Index (mFI) categories and complications, FTR and in-hospital mortality. All models were clustered, weighted and adjusted for all available patient and hospital characteristics. RESULTS: Of 3644 mRCC patients treated with CN, 924 (25.4%) were ≥ 71 years old, 435 (11.9%) had CCI ≥ 2 and 749 (20.6%) were frail. In multivariable logistic regression models, age ≥ 71 (odds ratio [OR] 1.4, p < .001), CCI ≥ 2 (OR 1.88, p < .001) and frail status (OR 1.91, p < .001) were independent predictors of overall complications. Age ≥ 71 was also an independent predictor of FTR (OR 2.27, p = .04), but not of in-hospital mortality. Both CCI and mFI were not significantly associated with either FTR or in-hospital mortality. CONCLUSION: Older patients with mRCC are more likely to experience higher rates of overall complications, FTR and in-hospital mortality following CN. These results highlight the importance of rigorous selection criteria for older surgical candidates. Moreover, timely recognition and rapid response to complications are particularly critical in this population.

19.
J Immunother ; 43(1): 1-7, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574022

RESUMO

Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of irAEs versus no irAEs according to fixed or random-effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. A total of 30 studies that included a total of 4324 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death [HR=0.49, 95% confidence interval (CI): 0.38-0.62; P<0.001]. Similarly, the occurrence of irAEs was associated with a reduced risk of progression (HR=0.51, 95% CI: 0.42-0.64; P<0.001). The odds of response was 4.56 (95% CI: 3.72-5.59; P<0.001). In patients treated with ICIs, irAEs predict survival and response. Although this correlation cannot be fully explained, it may be related to the strongest T-cell activation.

20.
PLoS One ; 14(11): e0224151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31675380

RESUMO

BACKGROUND: There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. METHODS: The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. RESULTS: At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. CONCLUSIONS: An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.


Assuntos
Procedimentos Clínicos , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
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