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PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .
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Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Ftalazinas , Piperazinas , Neoplasias de la Mama Triple Negativas , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Genes BRCA1 , Genes BRCA2 , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Respuesta Patológica Completa , Ftalazinas/administración & dosificación , Ftalazinas/uso terapéutico , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Supervivencia sin Progresión , Estudios Prospectivos , Análisis de Supervivencia , Factores de Tiempo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/cirugía , Adolescente , Adulto JovenRESUMEN
BACKGROUND: Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes. METHODS: This randomised, multicentre, double-blind, placebo-controlled, phase 2 trial recruited postmenopausal adult women aged at least 18 years with ER-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2, who had relapsed or progressed on an aromatase inhibitor, from across 19 hospitals in the UK. Participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a 500 mg loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off, starting on cycle 1 day 15. Treatment continued until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment was allocated by an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival in the intention-to-treat population. Secondary endpoints shown in this Article were overall survival and safety in the intention-to-treat population, and the effect of tumour PI3K/AKT/PTEN pathway status identified by an expanded testing panel that included next-generation sequencing assays. Recruitment is complete. The trial is registered with ClinicalTrials.gov, number NCT01992952. FINDINGS: Between March 16, 2015, and March 6, 2018, 183 participants were screened for eligibility and 140 (77%) were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up at the data cut-off of Nov 25, 2021, was 58·5 months (IQR 45·9-64·1) for participants treated with fulvestrant plus capivasertib and 62·3 months (IQR 62·1-70·3) for fulvestrant plus placebo. Updated median progression-free survival was 10·3 months (95% CI 5·0-13·4) in the group receiving fulvestrant plus capivasertib compared with 4·8 months (3·1-7·9) for fulvestrant plus placebo (adjusted hazard ratio [HR] 0·56 [95% CI 0·38-0·81]; two-sided p=0·0023). Median overall survival in the capivasertib versus placebo groups was 29·3 months (95% CI 23·7-39·0) versus 23·4 months (18·7-32·7; adjusted HR 0·66 [95% CI 0·45-0·97]; two-sided p=0·035). The expanded biomarker panel identified an expanded pathway-altered subgroup that contained 76 participants (54% of the intention-to-treat population). Median progression-free survival in the expanded pathway-altered subgroup for participants receiving capivasertib (n=39) was 12·8 months (95% CI 6·6-18·8) compared with 4·6 months (2·8-7·9) in the placebo group (n=37; adjusted HR 0·44 [95% CI 0·26-0·72]; two-sided p=0·0014). Median overall survival for the expanded pathway-altered subgroup receiving capivasertib was 38·9 months (95% CI 23·3-50·7) compared with 20·0 months (14·8-31·4) for those receiving placebo (adjusted HR 0·46 [95% CI 0·27-0·79]; two-sided p=0·0047). By contrast, there were no statistically significant differences in progression-free or overall survival in the expanded pathway non-altered subgroup treated with capivasertib (n=30) versus placebo (n=34). One additional serious adverse event (pneumonia) in the capivasertib group had occurred subsequent to the primary analysis. One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment. INTERPRETATION: Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. The expanded biomarker testing suggested that capivasertib predominantly benefits patients with PI3K/AKT/PTEN pathway-altered tumours. Phase 3 data are needed to substantiate the results, including in patients with previous CDK4/6 inhibitor exposure who were not included in the FAKTION trial. FUNDING: AstraZeneca and Cancer Research UK.
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Método Doble Ciego , Femenino , Fulvestrant , Humanos , Recurrencia Local de Neoplasia/patología , Fosfatidilinositol 3-Quinasas/genética , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas c-akt , Pirimidinas , Pirroles , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
BACKGROUND: Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms of the serine/threonine kinase AKT. The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, postmenopausal women aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-2 and oestrogen receptor-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer who had relapsed or progressed on an aromatase inhibitor were recruited from 19 hospitals in the UK. Enrolled participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off (starting on cycle 1 day 15) until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment allocation was done using an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival with a one-sided alpha of 0·20. Analyses were done by intention to treat. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, number NCT01992952. FINDINGS: Between March 16, 2015, and March 6, 2018, 183 patients were screened for eligibility, of whom 140 (76%) were eligible and were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up for progression-free survival was 4·9 months (IQR 1·6-11·6). At the time of primary analysis for progression-free survival (Jan 30, 2019), 112 progression-free survival events had occurred, 49 (71%) in 69 patients in the capivasertib group compared with 63 (89%) of 71 in the placebo group. Median progression-free survival was 10·3 months (95% CI 5·0-13·2) in the capivasertib group versus 4·8 months (3·1-7·7) in the placebo group, giving an unadjusted hazard ratio (HR) of 0·58 (95% CI 0·39-0·84) in favour of the capivasertib group (two-sided p=0·0044; one-sided log rank test p=0·0018). The most common grade 3-4 adverse events were hypertension (22 [32%] of 69 patients in the capivasertib group vs 17 [24%] of 71 in the placebo group), diarrhoea (ten [14%] vs three [4%]), rash (14 [20%] vs 0), infection (four [6%] vs two [3%]), and fatigue (one [1%] vs three [4%]). Serious adverse reactions occurred only in the capivasertib group, and were acute kidney injury (two), diarrhoea (three), rash (two), hyperglycaemia (one), loss of consciousness (one), sepsis (one), and vomiting (one). One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment. One further death in the capivasertib group had an unknown cause; all remaining deaths in both groups (19 in the capivasertib group and 31 in the placebo group) were disease related. INTERPRETATION: Progression-free survival was significantly longer in participants who received capivasertib than in those who received placebo. The combination of capivasertib and fulvestrant warrants further investigation in phase 3 trials. FUNDING: AstraZeneca and Cancer Research UK.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Aromatasa/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Fulvestrant/administración & dosificación , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Pronóstico , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Terapia Recuperativa , Tasa de SupervivenciaRESUMEN
PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.
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Seminoma , Neoplasias Testiculares , Quimioterapia Adyuvante , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estadificación de Neoplasias , Orquiectomía , Seminoma/tratamiento farmacológico , Seminoma/terapia , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/cirugíaRESUMEN
PURPOSE: Hypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy. METHODS: HYBRID is a Phase II randomized trial that was conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle-invasive bladder cancer unsuitable for radical therapy received 36 Gy in 6 weekly fractions, randomized (1:1) to standard planning (SP) or adaptive planning (AP) using a minimization algorithm. For AP, a pretreatment cone beam computed tomography (CT) was used to select the POD from 3 plans (small, medium, and large). Follow-up included standard cystoscopic, radiologic, and clinical assessments. The primary endpoint was nongenitourinary Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (≥G3) toxicity within 3 months of radiation therapy. A noncomparative single stage design aimed to exclude ≥30% toxicity rate in each planning group in patients who received ≥1 fraction of radiation therapy. Local control at 3-months (both groups combined) was a key secondary endpoint. RESULTS: Between April 15, 2014, and August 10, 2016, 65 patients were enrolled (SP, n = 32; AP, n = 33). The median follow-up time was 38.8 months (interquartile range [IQR], 36.8-51.3). The median age was 85 years (IQR, 81-89); 68% of participants (44 of 65) were male; and 98% of participants had grade 3 urothelial cancer. In 63 evaluable participants, CTCAE ≥G3 nongenitourinary toxicity rates were 6% (2 of 33; 95% confidence interval [CI], 0.7%-20.2%) for the AP group and 13% (4 of 30; 95% CI, 3.8%-30.7%) for the SP group. Disease was present in 9/48 participants assessed at 3 months, giving a local control rate of 81.3% (95% CI, 67.4%-91.1%). CONCLUSIONS: POD adaptive radiation therapy was successfully implemented across multiple centers. Weekly ultrahypofractionated 36 Gy/6 fraction radiation therapy is safe and provides good local control rates in this older patient population.
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Radioterapia Guiada por Imagen , Neoplasias de la Vejiga Urinaria/radioterapia , Anciano de 80 o más Años , Algoritmos , Tomografía Computarizada de Haz Cónico/efectos adversos , Tomografía Computarizada de Haz Cónico/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Medición de Resultados Informados por el Paciente , Hipofraccionamiento de la Dosis de Radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/efectos adversos , Radioterapia Guiada por Imagen/métodos , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or=4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml(-1) year(-1). Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer.
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Antioxidantes/metabolismo , Micronutrientes/sangre , Neoplasias de la Próstata/sangre , Anciano , Carotenoides/sangre , Humanos , Licopeno , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Vitamina E/sangre , beta Caroteno/sangreRESUMEN
Lobular neoplasia is increasingly being detected, probably due to the widespread screening for breast malignancies. The understanding of lobular neoplasia is undergoing a paradigm shift, from being considered a predictor of recurrence to being considered a pre-invasive lesion, based on molecular studies suggesting a clonal link with invasive lobular cancer. The management of patients diagnosed to have lobular neoplasia is in evolution, with the increasing need for risk stratification and hence the necessity to identify this entity separately as either lobular carcinoma in-situ and atypical lobular hyperplasia. The indications for wide local excision for patients diagnosed to have lobular neoplasia on biopsy are being defined. The evidence for preventive strategies like hormonal treatment with Tamoxifen or aromatase inhibitors for high risk patients is increasing, with the results from prospective interventional trials. The role of screening magnetic resonance imaging for surveillance of high risk patients with lobular neoplasia is under evaluation.
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Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Carcinoma Lobular/epidemiología , Carcinoma Lobular/patología , Neoplasias de la Mama/terapia , Carcinoma Lobular/terapia , Femenino , HumanosRESUMEN
The coronavirus disease-2019 (COVID-19) pandemic has had a significant impact on patients with underlying malignancy. In this article, we summarize emerging data related to patients with cancer and COVID-19. Among patients with COVID-19, a higher proportion have an underlying diagnosis of cancer than seen in the general population. Also, patients with malignancy are likely to be more vulnerable than the general population to contracting COVID-19. Mortality is significantly higher in patients with both cancer and COVID-19 compared with the overall COVID-19-positive population. The early months of the pandemic saw a decrease in cancer screening and diagnosis, as well as postponement of standard treatments, which could lead to excess deaths from cancer in the future.
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PURPOSE: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers. METHODS AND MATERIALS: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity. RESULTS: One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group. CONCLUSIONS: PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established.
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Ganglios Linfáticos/efectos de los fármacos , Irradiación Linfática/métodos , Metástasis Linfática , Próstata/efectos de la radiación , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Anciano , Biopsia , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Pelvis/efectos de la radiación , Resultado del TratamientoRESUMEN
PURPOSE: To conduct prospective electroglottographic analyses of voice outcomes after radical chemoradiotherapy for locally advanced laryngopharyngeal cancers and to compare them with patients who have undergone total laryngectomy (TL). PATIENTS AND METHODS: Twenty-one patients (19 male, 2 female, median age [range] 65 [50-85] years) with Stage III/IV laryngopharyngeal cancer received induction chemotherapy followed by radical chemoradiotherapy. Electroglottography, using the sustained vowel /i/ and connected speech, was performed before treatment and 1, 6, and 12 months after treatment. In addition, single voice recordings were taken from 21 patients (16 male, 5 female, aged 65 [50-84] years) who had undergone TL and surgical voice restoration and from 21 normal controls (18 male, 3 female, aged 65 [33-80] years). RESULTS: Before treatment the vocal measures for the chemoradiotherapy patients were significantly different from normal controls in jitter (p = 0.02), maximum phonation time (MPT) (p = 0.001), and words per minute (WPM) (p = 0.01). At 12 months after treatment MPT and WPM had normalized, but jitter and normalized noise energy were significantly worse than in normal controls. Comparison of voice outcomes at 12 months for chemoradiotherapy patients revealed superiority over the TL group in all parameters except MPT (18.2 s vs. 10.4 s, p = 0.06). Analysis of the recovery of voice up to 12 months after treatment revealed progressive improvement in most electroglottographic measures. CONCLUSIONS: This prospective study demonstrates significantly better outcome for patients treated with chemoradiotherapy as compared with TL. Progressive normalization of many voice parameters occurs over the 12 months following chemoradiotherapy.
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Impedancia Eléctrica , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/radioterapia , Laringectomía/métodos , Calidad de la Voz/fisiología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Glotis/fisiopatología , Humanos , Neoplasias Hipofaríngeas/cirugía , Neoplasias Laríngeas/cirugía , Laringectomía/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inteligibilidad del Habla/efectos de los fármacos , Inteligibilidad del Habla/efectos de la radiación , Estadísticas no Paramétricas , Factores de Tiempo , Trastornos de la Voz/prevención & controlRESUMEN
BACKGROUND AND PURPOSE: To measure voice outcomes following accelerated hypofractionated radiotherapy for larynx cancer. MATERIALS AND METHODS: Twenty-five patients with T1/T2 glottic cancer underwent serial electroglottographic and acoustic analysis (sustained vowel/i/ and connected speech) before radiotherapy and 1, 6 and 12 months post-treatment. Twenty-five normal subjects served as a reference control population. RESULTS: Pre-treatment measures were significantly worse for larynx cancer patients. Median jitter (0.23% vs 0.97%, p=0.001) and shimmer (0.62dB vs 0.98dB, p=0.05) and differences in data ranges reflected greater frequency and amplitude perturbation in the larynx cancer patients. Pre-treatment Mean Phonation Time (MPT) was significantly reduced (21s vs 14.8s, p=0.002) in larynx cancer patients. There was a trend towards improvement of jitter, shimmer and normalized noise energy at 12 months post-treatment. MPT improved but remained significantly worse than for normal subjects (21s vs 16.4s, p=0.013). Average fundamental frequency resembled normal subjects, including improvement of the measured range (91.4-244.6Hz in controls vs 100-201Hz in post-treatment larynx cancer patients). CONCLUSIONS: This non-invasive technique effectively measures post-treatment vocal function in larynx cancer patients. This study demonstrated improvement of many key parameters that influence voice function over 12 months after radiotherapy.
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Impedancia Eléctrica , Neoplasias Laríngeas/radioterapia , Calidad de la Voz/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Laríngeas/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Dosificación Radioterapéutica , Recuperación de la Función , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS: In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS: In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1-28) months. In responders, the median duration of the PSA response was 11.6 (1-24) months. CONCLUSION: Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored.
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Antineoplásicos Hormonales/uso terapéutico , Dexametasona/uso terapéutico , Orquiectomía , Antígeno Prostático Específico/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Progresión de la Enfermedad , Evaluación de Medicamentos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate-specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment. PATIENTS AND METHODS: A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of < 15 ng/mL, a Gleason score of < or = 7 with primary grade < or = 3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics. RESULTS: In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity (P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34-1.77) ng/mL per year and 0.35 (-0.06, 0.80) ng/mL per year, respectively. CONCLUSIONS: PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment.
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Antígeno Prostático Específico/sangre , Próstata/patología , Neoplasias de la Próstata/patología , Adulto , Anciano , Biopsia con Aguja , Conducta de Elección , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias/métodos , Estudios Prospectivos , Prostatectomía/métodos , Neoplasias de la Próstata/terapia , Factores de RiesgoRESUMEN
BACKGROUND: A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. METHODS: The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. RESULTS: Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. CONCLUSIONS: Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.
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Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Humanos , Modelos Lineales , Masculino , Estudios Prospectivos , Antígeno Prostático Específico/análisis , Reproducibilidad de los ResultadosRESUMEN
Primary adenoid cystic carcinoma occurring in the orbital apex is rare. We present the clinical features of a patient who initially presented with the clinical and radiologic features of an orbital pseudotumor. He developed features of orbital apex syndrome and repeat imaging showed a tumor of the orbital apex with intracranial invasion. He underwent radical skull base surgery and pathologic examination revealed adenoid cystic carcinoma in the orbital apex with a normal lacrimal apparatus. He received post operative radiation and the outcome in the light of a review of available literature is being discussed.
RESUMEN
Retrospective analysis in 150 patients with metastatic prostate cancer was conducted to determine whether early detection with MRI spine and treatment of clinically occult spinal cord compromise (SCC) facilitate preservation of neurologic function. Our results suggest that prophylactic radiotherapy for patients with back pain or radiological SCC without neurologic deficit may facilitate preservation of neurologic function. Thus MRI surveillance for SCC may be important for prostate cancer patients with bone metastases.
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Compresión de la Médula Espinal/diagnóstico , Compresión de la Médula Espinal/radioterapia , Anciano , Anciano de 80 o más Años , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias de la Próstata/complicaciones , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Primary Non Hodgkin's Lymphoma (NHL) of the lacrimal sac is rare. METHODS: The clinical features of a 78 year old female who presented with epiphora and swelling of the left lacrimal sac are described. RESULTS: Computerised tomography showed a mass involving the left lacrimal sac. Histopathological examination revealed a diffuse large B cell NHL. Immunohistological examination demonstrated B cell origin. Chemotherapy could not be administered due to co morbid conditions. The patient was treated with radiotherapy to a dose of 45 Gy in 25 fractions. Patient is disease free and on follow up after 36 months. CONCLUSION: Primary radiotherapy is a treatment option with curative potential for localized NHL of the lacrimal sac and may be considered in patients who cannot tolerate appropriate chemotherapy.
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BACKGROUND: Extraskeletal Ewings sarcoma are rare tumors for which there is no consensus on optimal management. METHODS: A retrospective review of the clinical features, treatment and outcome of patients with extraskeletal Ewings sarcoma who reported to a single institution between January 1992-December 2003 is reported. RESULTS: A total of 19 patients with extraskeletal Ewings sarcoma were identified. Of these, 4 patients had metastatic disease at presentation and 15 patients with non-metastatic disease received combined modality treatment with primary combination chemotherapy followed by local treatment with radiotherapy or surgery. Disease free survival and overall survival for patients with non metastatic disease after combined modality treatment were 60% and 30% respectively. The significant predictors for prolonged disease free survival and overall survival were high haemoglobin (p = 0.002), low lactate dehydrogenase (p = 0.028), chemotherapy with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide and Etoposide regime (p = 0.008) and complete response to chemotherapy (p = 0.001). CONCLUSION: Aggressive combination chemotherapy followed by complete surgery or radiotherapy to a dose of more than 50 Gy is essential to confer optimal outcome for patients with extraskeletal Ewings sarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Causas de Muerte , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/mortalidad , Adolescente , Adulto , Anciano , Biopsia con Aguja , Niño , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/mortalidad , Neoplasias Pélvicas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/patología , Estudios Retrospectivos , Medición de Riesgo , Sarcoma de Ewing/patología , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/patología , Análisis de Supervivencia , Neoplasias Torácicas/tratamiento farmacológico , Neoplasias Torácicas/mortalidad , Neoplasias Torácicas/patología , Adulto JovenRESUMEN
Nasopharyngeal cancer is rare in childhood and results with radiotherapy are far from encouraging. A total of 52 patients with stage I to IVB nasopharygeal cancer and age <18, received radiotherapy to 60-66 Gy in 2-Gy fractions to the nasopharynx and cervical nodes, while 22 of these patients also received chemotherapy with cisplatin and 5 FU. Three-year disease-free survival with concurrent chemotherapy was 82% compared to 40% for patients who had radiotherapy alone (p = .001; HR 0.33; 95% CI 0.25-0.74). The 3-year overall survival in the patients who received radiotherapy was 72% and that in the patients who received concurrent chemotherapy was 77% (p = .38). A statistically significant improvement in disease-free survival was observed with concurrent chemoradiation in nonmetastatic nasopharyngeal cancer in young patients.