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1.
Cancer Sci ; 115(7): 2147-2158, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38715247

RESUMEN

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2-targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2-targeted drugs in HER2-mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , Mutación , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptor ErbB-2/genética , Femenino , Resistencia a Antineoplásicos/genética , Terapia Molecular Dirigida/métodos , Pronóstico , Ensayos Clínicos como Asunto , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
2.
Radiol Med ; 129(1): 160-173, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37731151

RESUMEN

INTRODUCTION: Reirradiation (reRT) of locally recurrent/second primary tumors of the head and neck region is a potentially curative treatment for patients not candidate to salvage surgery. Aim of the present study is to summarize available literature on both prognostic factors and indications to curative reRT in this clinical setting. MATERIALS AND METHODS: A narrative review of the literature was performed on two topics: (1) patients' selection according to prognostic factors and (2) dosimetric feasibility of reRT. Postoperative reRT and palliative intent treatments were out of the scope of this work. RESULTS: Patient-tumor and treatment-related prognostic factors were analyzed, together with dosimetric parameters concerning target volume and organs at risk. Based on available evidence, a stepwise approach has been proposed aiming to provide a useful tool to identify suitable candidates for curative reRT in clinical practice. This was then applied to two clinical cases, proposed at the end of this work. CONCLUSION: A second course of RT in head and neck recurrence/second primary tumors is a personalized approach that can be offered to selected patients only in centers with expertise and dedicated equipment following a multidisciplinary team discussion.


Asunto(s)
Neoplasias de Cabeza y Cuello , Reirradiación , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Terapia Recuperativa , Recurrencia Local de Neoplasia
3.
Acta Oncol ; 62(11): 1440-1450, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37801288

RESUMEN

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.


Asunto(s)
Supervivientes de Cáncer , Enfermedades Gastrointestinales , Nocturia , Neoplasias de la Próstata , Enfermedades del Recto , Trastornos del Inicio y del Mantenimiento del Sueño , Incontinencia Urinaria , Masculino , Humanos , Calidad de Vida , Próstata , Estudios Prospectivos , Nocturia/complicaciones , Neoplasias de la Próstata/radioterapia , Incontinencia Urinaria/complicaciones , Dolor , Fatiga , Encuestas y Cuestionarios
4.
Radiol Med ; 128(8): 1007-1021, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37415056

RESUMEN

INTRODUCTION: Reirradiation (reRT) of local recurrent/second primary tumors of the head and neck represents a potential curative treatment for patients not candidate to a salvage surgery. Aim of the present study is to summarize literature data on modern radiation techniques and fractionations used in this setting of patients. MATERIALS AND METHODS: A narrative review of the literature was conducted on three topics: (1) target volume delineation (2) reRT dose and techniques and (3) ongoing studies. Patients treated with postoperative reRT and palliative intent were not considered for the current analysis. RESULTS: Recommendations on the target volume contouring have been reported. 3D-Conformal Radiotherapy, Intensity Modulated Radiotherapy, Stereotactic body Radiotherapy Intraoperative Radiotherapy, Brachytherapy and Charged Particles have been analyzed in terms of indication and fractionation in the field of reRT. Ongoing studies on the topic have been reported for IMRT and Charged Particles. Moreover, according to literature data a stepwise approach has been proposed aiming to provide a useful tool to select patients candidate to a curative reRT in daily clinical practice. Two clinical cases were also provided for its application. CONCLUSION: Different radiation techniques and fractionations can be used for a second course of radiotherapy in patients with recurrent/second primary tumor of head and neck region. Tumor characteristics as well as radiobiological considerations should be take into account to define the best reRT approach.


Asunto(s)
Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Reirradiación , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Reirradiación/métodos , Fraccionamiento de la Dosis de Radiación , Radioterapia de Intensidad Modulada/métodos , Dosificación Radioterapéutica , Recurrencia Local de Neoplasia/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia
5.
Radiol Med ; 128(3): 362-371, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36877421

RESUMEN

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.


Asunto(s)
Neoplasias Nasofaríngeas , Oncología por Radiación , Humanos , Neoplasias Nasofaríngeas/radioterapia , Carcinoma Nasofaríngeo/radioterapia , Nasofaringe , Oncología por Radiación/educación , Planificación de la Radioterapia Asistida por Computador/métodos
6.
Int J Mol Sci ; 23(23)2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36498861

RESUMEN

New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients' response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Inhibidores de Proteínas Quinasas , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Biopsia Líquida , MicroARNs/genética , MicroARNs/uso terapéutico , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Purinas/farmacología
7.
Lancet Oncol ; 22(5): 727-736, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33862002

RESUMEN

BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.


Asunto(s)
Quimioradioterapia , Neoplasias de Cabeza y Cuello/terapia , Metaanálisis en Red , Fraccionamiento de la Dosis de Radiación , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino
8.
Int J Med Sci ; 18(10): 2245-2250, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33859534

RESUMEN

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias de la Mama Triple Negativas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante/métodos , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología
9.
J Cell Physiol ; 235(11): 7900-7910, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31943171

RESUMEN

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p = .15), while BMI ≥ 30 was associated with worse OS (p = .003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p = .001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p = .03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.


Asunto(s)
Ado-Trastuzumab Emtansina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Obesidad/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Sobrepeso/complicaciones , Supervivencia sin Progresión , Receptor ErbB-2/genética
10.
Int J Cancer ; 146(7): 1917-1929, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31330065

RESUMEN

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo
11.
Cancer ; 126(24): 5263-5273, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33017867

RESUMEN

BACKGROUND: This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. METHODS: This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). RESULTS: Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). CONCLUSIONS: LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.


Asunto(s)
Neoplasias de Cabeza y Cuello/clasificación , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/clasificación , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Adulto , Factores de Edad , Fraccionamiento de la Dosis de Radiación , Quimioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Análisis de Supervivencia , Resultado del Tratamiento
12.
Int J Mol Sci ; 21(10)2020 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-32429381

RESUMEN

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.


Asunto(s)
Neoplasias de la Mama/terapia , Hormonas/uso terapéutico , Terapia Neoadyuvante , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Femenino , Humanos , Menopausia
13.
J Cell Physiol ; 234(6): 7708-7717, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30536609

RESUMEN

Data from 423 human epidermal growth factor receptor 2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6-35.4) and clinical benefit was 52.7% (95% CI, 48-57.5). ORR was negatively affected by prior exposure to everolimus/exemestane ( p = 0.002) and favorably influenced by early line-treatment ( p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8-16) and median overall survival was 24 months (95% CI, 17-30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2-, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Piperazinas/farmacología , Piridinas/farmacología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/efectos de los fármacos , Resultado del Tratamiento
14.
J Cell Physiol ; 233(3): 2313-2323, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28710865

RESUMEN

We aimed to assess the efficacy of neoadjuvant chemotherapy (NACT) in a cohort of 213 triple-negative breast cancer (TNBC) patients treated in real-world practice at eight Italian cancer centers. We computed descriptive statistics for all the variable of interest. Factors testing significant in univariate analysis were included in multivariate models. Survival data were compared by Kaplan-Meier curves and log-rank test. The median follow-up was 45 months. We observed 60 (28.2%) pathological complete response (pCR). The sequential anthracyclines-taxanes-based regimens produced the highest rate of pCR (42.6%), followed by concomitant anthracycline-taxane (24.2%), and other regimens (15.6%) (p = 0.008). When analyzing the role of baseline Ki-67, a 50% cut-off was the optimal threshold value for pCR prediction (p = 0.0005). The 5-year disease-free survival (DFS) was 57.3% and the 5-year overall survival (OS) was 70.8%. In patients not achieving pCR, the optimal Ki-67 variation between biopsy and surgical specimen with prognostic relevance on long-term outcomes was 13% (p = 0.04). Patients with a Ki-67 reduction (rKi-67)<13% had worse outcomes compared to those who experienced pCR or a rKi-67≥13%. The number of NACT cycles also affected long-term outcomes (5-year DFS 65.7% vs 51.6% in patients having received >6 cycles compared with their counterparts, p = 0.02). In multivariate analysis, node status, grading, and bio-pathological treatment response (including pCR and rKi-67) impacted DFS and OS. Our results confirmed the advantage conferred by more than 6 cycles of a sequential antracycline-taxane-based NACT. Higher baseline Ki-67 values shows greater predictive significance on pathogical response, while the rKi-67 plays a prognostic role on long-term outcomes.


Asunto(s)
Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Taxoides/administración & dosificación , Neoplasias de la Mama Triple Negativas/terapia , Adulto , Anciano , Antraciclinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante/efectos adversos , Clasificación del Tumor , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taxoides/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología
15.
J Transl Med ; 16(1): 129, 2018 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-29769125

RESUMEN

BACKGROUND: Cancer and coagulation activation are tightly related. The extent to which factors related to both these pathologic conditions concur to patient prognosis intensely animates the inherent research areas. The study herein presented aimed to the development of a tool for the assessment and stratification of risk of death and disease recurrence in early breast cancer. METHODS: Between 2008 and 2010, two hundreds thirty-five (N: 235) patients diagnosed with stage I-IIA breast cancer were included. Data on patient demographics and clinic-pathologic features were collected in course of face-to-face interviews or actively retrieved from clinical charts. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), fragment 1 + 2 (F1 + 2), thrombin antithrombin complex (TAT), factor VIII (FVIII), and D-dimer (DD) were measured at breast cancer diagnosis and prior to any therapeutic procedure, including breast surgery. The risk of death was computed in terms of overall survival (OS), which was the primary outcome. For a subset of patients (N = 62), disease free survival (DFS) was also assessed as a measure of risk of disease recurrence. RESULTS: Median follow up was 95 months (range 6-112 months). Mean age at diagnosis was 60.3 ± 13.4 years. Cancer cases were more commonly intraductal carcinomas (N: 204; 86.8%), pT1 (131; 55.7%), pN0 (141; 60%) and G2 (126; 53.6%). Elevated levels of PAI-1 (113; 48.1%) represented the most frequent coagulation abnormality, followed by higher levels of F1 + 2 (97; 41.3%), DD (63; 27.0%), TAT (34; 40%), and FVIII (29; 12.3%). In univariate models of OS, age, pT, DD, FVIII were prognostically relevant. In multivariate models of OS, age (p = 0.043), pT (p = 0.001), levels of DD (p = 0.029) and FVIII (p = 0.087) were confirmed. In the smaller subgroup of 62 patients, lymph node involvement, percent expression of estrogen receptors and levels of FVIII impacted DFS significantly. CONCLUSIONS: We developed a risk assessment tool for OS including patient- and cancer-related features along with biomarkers of coagulation activation in a cohort of early BC patients. Further studies are warranted to validate our prognostic model in the early setting and eventually extend its application to risk evaluation in the advanced setting for breast and other cancers.


Asunto(s)
Coagulación Sanguínea , Neoplasias de la Mama/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Factores de Riesgo , Análisis de Supervivencia
16.
Prof Inferm ; 70(3): 214-221, 2017.
Artículo en Italiano | MEDLINE | ID: mdl-29460558

RESUMEN

BACKGROUND: Cancer patients often report symptoms related to therapeutic treatment, whose management is based on traditional medicine. In recent years, however, there has been growing interest towards adopting some form of complementary medicine, among these, Reiki. The aim of this study is to evaluate how this type of discipline can contribute to managing radiotherapy-related symptoms in patients with head and neck cancer. METHOD: The study was performed in the Radiotherapy Department at the Regina Elena National Cancer Institute in Rome. To assess QoL, the FACT-H N questionnaire was used, while the CTCAE Scale was adopted to evaluate mucositis, cutaneous toxicity and salivation. RESULTS: 10.5% of patients were reported to experience strong pain in the fifth week, compared to 21.1% of patients in the previous week; a degree of mucositis equal to G3 was also found in 15.5% of cases according to the clinical evaluation, as well as in 10.5% of patients according to the functional one. Only one case (5.3%) of grade 3 cutaneous toxicity was registered. CONCLUSION: The study shows how the Reiki treatment benefits patients in most cases, with both psychological support to help deal with the therapeutic process together with integrated support towards pain therapy.


Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Tacto Terapéutico , Humanos , Proyectos Piloto , Radioterapia/efectos adversos
17.
J Cell Physiol ; 231(11): 2541-7, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27187274

RESUMEN

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Terapia Neoadyuvante , Taxoides/uso terapéutico , Trastuzumab/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Índice de Masa Corporal , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Docetaxel , Relación Dosis-Respuesta a Droga , Epirrubicina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Taxoides/efectos adversos , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversos
18.
Strahlenther Onkol ; 190(11): 1001-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24756139

RESUMEN

PURPOSE: To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. MATERIALS AND METHODS: Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. RESULTS: A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). CONCLUSIONS: Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.


Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Glándula Parótida/diagnóstico por imagen , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/etiología , Radioterapia Conformacional/efectos adversos , Xerostomía/diagnóstico por imagen , Xerostomía/etiología , Absorciometría de Fotón , Enfermedad Aguda , Diagnóstico Precoz , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Italia , Masculino , Tamaño de los Órganos/efectos de la radiación , Glándula Parótida/efectos de la radiación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Estados Unidos
19.
Acta Oncol ; 53(5): 662-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24274389

RESUMEN

BACKGROUND: To assess the risk of subclinical neck nodal involvement of levels IB, IV and V for early T-stage, node positive, human papilloma virus (HPV)-related oropharyngeal carcinoma. MATERIAL AND METHODS: We retrospectively identified the patients with clinically positive and un-violated neck that underwent upfront ipsilateral neck dissection for HPV-related oropharyngeal cancer between 1998 and 2010. From the pathology report we extracted the prevalence rate of involvement of each selected level and then estimated the risk that a level that does not contain any node larger than 10 mm at computed tomography (CT) harbors subclinical disease. Predictors of involvement were investigated as well. RESULTS: Ninety-one patients were analyzed. The risk of subclinical disease in both levels IB and V is < 5%, while it is 6.5% (95% CI 3.1-9.9%) for level IV. Level IB subclinical involvement slightly exceeds 5% when 2 + ipsilateral levels besides IB are involved. The risk of occult disease in level IV tends to be < 5% when level III is not involved. CONCLUSION: These data support the exclusion from the elective nodal volume of level V and level IB but when 2 + other levels are involved. Level IV might also be spared when level III is negative. Clinical implementation within a prospective study is justified.


Asunto(s)
Metástasis de la Neoplasia/patología , Neoplasias Orofaríngeas/patología , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Disección del Cuello , Estadificación de Neoplasias , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo
20.
Curr Oncol ; 31(9): 5224-5232, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39330014

RESUMEN

BACKGROUND: In high-risk breast cancer patients with skin infiltration, the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential inadequate dose distribution of a standard bolus due to air gaps between the bolus and the skin. In this pilot study, we introduced into clinical practice the use of a personalized 3D-printed bolus filled with ultrasound transmission gel. METHODS: Seven patients undergoing radiotherapy after mastectomy were selected. A 3D-printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and, subsequently, on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control were assessed. RESULTS: Overall, for the clinical cases, the percentage median difference between the measured and calculated doses was -2.7% (-7.0-4.9%). The median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. CONCLUSIONS: A personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus' consistency and provide accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study, and further investigations are needed.


Asunto(s)
Neoplasias de la Mama , Impresión Tridimensional , Humanos , Femenino , Proyectos Piloto , Neoplasias de la Mama/radioterapia , Persona de Mediana Edad , Anciano , Piel/efectos de la radiación , Dosificación Radioterapéutica , Adulto
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