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1.
J Neurooncol ; 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39466561

RESUMO

PURPOSE: Pituitary neuroendocrine tumors (pitNETs) are benign tumors that may recur after surgical resection or persist following medical management. The objective of this study was to evaluate outcomes and toxicities of patients with pitNETs treated with stereotactic radiosurgery (SRS) at a single institution. METHODS: We completed a retrospective, single-institution study of patients with pitNETs treated with frame-based, single-fraction, cobalt-60 SRS between September 2005 and June 2023. The primary endpoint was local tumor control. Secondary endpoints included endocrine control (for functional tumors), overall survival, and toxicities. RESULTS: A total of 88 lesions in 83 patients were treated with SRS. Most lesions (70%) were non-functional tumors. Of the 26 functioning tumors, 6 patients achieved endocrine remission with SRS alone (23%), and the remainder achieved remission with combined medical management. With a median patient follow-up of 4.7 years, no local tumor recurrences were observed with an estimated local control probability of 100%. Two- and five-year overall survival estimates were 97% (95% confidence interval [CI] 89-99) and 95% (95% CI 84-98), respectively. Causes of death were unrelated to PitNET or SRS. Twelve patients (14%) developed hypopituitarism after SRS. Despite the 34 lesions that were ≤ 3 mm from optic structures, no patients developed any optic neuropathy or visual decline post SRS. CONCLUSIONS: SRS is a highly effective modality for recurrent or residual pitNETs. This study observed a local control of 100% with no cases of optic toxicities after a median follow-up of 4.7 years. These observed findings suggest that dose de-escalation may be possible for future treatment of pitNETs.

2.
Pediatr Blood Cancer ; : e31414, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39502008

RESUMO

BACKGROUND: Spinal cord compression (SCC) is a severe complication in pediatric patients with relapsed, progressing, or refractory solid malignancies. This study aims to report the presentation, treatment, and role of proactive radiation therapy in these patients. METHODS: This retrospective study reviewed 28 patients with relapsed, progressing, or refractory solid tumors who were referred for radiation therapy consultation due to potential (impending) or actual spinal cord compression (pSCC and aSCC, respectively) over a 12-year period. Collected data included disease characteristics, details of SCC events, management approaches, and patient outcomes. RESULTS: Among the 28 patients, 34 SCC events were identified (18 pSCC, 16 aSCC), with neuroblastoma being the most frequent diagnosis (46.4%). No significant differences were noted between pSCC and aSCC groups in pre-event imaging follow-up, age distribution, or malignancy status at SCC presentation. However, aSCC patients exhibited significantly more symptoms at diagnosis. Both groups received SCC-targeted therapy, with no significant differences in functional outcomes, event-free survival (EFS), or overall survival (OS). Pain assessments post treatment showed comparable improvements in both groups. CONCLUSIONS: Proactive radiotherapy for pSCC did not yield superior outcomes compared to reactive treatment for aSCC. Given the limited benefits observed, proactive RT should be considered on an individual basis, balancing potential QoL improvements against treatment burdens. Further research in larger cohorts is necessary to refine therapeutic strategies for SCC in pediatric oncology.

3.
Support Care Cancer ; 29(3): 1643-1652, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32761517

RESUMO

BACKGROUND: To investigate the relationship between attendance to a pre-treatment psychoeducational intervention (prehab) with treatment outcomes and toxicities in patients receiving radiotherapy for head and neck cancers (HNCs). METHODS: Patients were included from prehab inception in 2013 to 2017, comparing overall survival (OS), locoregional recurrence-free survival (LRFS), and locoregional recurrence (LRR) between prehab attendees (PA) and non-attendees (PNA). Multivariable analysis was performed for OS and LRFS. RESULTS: Among 864 PA and 1128 PNA, 2-year OS was 88% vs 80% (p < 0.001), and LRFS was 84% vs 75% (p < 0.001). On multivariable analysis (MVA), OS and LRFS were independently and unfavourably associated with PNA. The PA cohort had a lower frequency of a "rocky treatment course" compared with the PNA cohort (52/150, 35% vs 71/150, 47%; p = 0.034). CONCLUSIONS: Prehab at our institution is associated with improved long-term oncologic outcomes. Prospective data is needed to better understand this association.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia Cognitivo-Comportamental/métodos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
4.
Biomed Phys Eng Express ; 10(2)2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241733

RESUMO

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5-91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient's preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.


Assuntos
Neoplasias da Próstata , Radioterapia Guiada por Imagem , Masculino , Humanos , Estudos de Viabilidade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia
5.
J Clin Oncol ; 39(34): 3813-3821, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570616

RESUMO

PURPOSE: Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS: We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS: Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION: Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Perda Auditiva/induzido quimicamente , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
6.
Neuro Oncol ; 23(3): 487-497, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33151327

RESUMO

BACKGROUND: The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors. METHODS: We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (P*) were adjusted for multiple comparisons. RESULTS: Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (P* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (P* = 0.006) and WMI (P* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (P* = 0.009 for each). Presence of a ventriculoperitoneal shunt decreased FSIQ by 10 points. CONCLUSIONS: We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.


Assuntos
Neoplasias Encefálicas , Inteligência , Neoplasias Encefálicas/radioterapia , Criança , Humanos , Testes de Inteligência , Memória de Curto Prazo , Testes Neuropsicológicos
7.
Int J Radiat Oncol Biol Phys ; 108(3): 676-685, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407932

RESUMO

PURPOSE: Neoadjuvant chemotherapy (NAC) is standard of care for locally advanced breast cancer. There is wide variation in radiation therapy (RT) practice and limited data describing locoregional relapse (LRR) after NAC. We hypothesized a low LRR risk with modern NAC, surgery, and RT and aimed to elucidate patterns of LRR and predictors of disease-free survival (DFS) and overall survival (OS) in these patients. METHODS AND MATERIALS: Data from 416 patients with stage II/III breast cancer treated between 2008 and 2015 with NAC, surgery, and adjuvant RT were reviewed retrospectively. DFS and OS rates were calculated using the Kaplan-Meier method. The LRR rate was estimated using the cumulative incidence function, treating death as a competing risk. Multivariable survival analysis was performed using Cox regression. RESULTS: Median follow-up was 4.7 years. Most patients had cT2/3 (74%) cN1 (61%) disease and underwent mastectomy (75%) and axillary dissection (84%). Pathologic complete response (pCR) was achieved in 22% of patients. There were 27 LRRs (including 4 isolated LRRs) and 89 distant failures. Two patients developed LRR 2 months after surgery, before adjuvant RT. LRR could be mapped in 23 patients: most (20) recurred within the RT field; 1 in- and out-of-field; and 2 out-of-field. Five-year LRR, DFS, and OS were 6.4%, 77%, and 90%, respectively. On multivariable analysis, triple-negative subtype (hazard ratio [HR] 2.82; 95% confidence interval [CI], 1.78-4.47; P < .001), stage III disease (HR 1.72; 95% CI, 1.11-2.69; P = .016), and non-pCR (HR 4.76; 95% CI 2.13-10.0; P < .001) were associated with poor DFS and OS (HR 4.13 [95% CI, 2.21-7.72; P < .001]; HR 1.94 [95% CI, 1.001-3.75; P = .049]; and HR 2.38 [95% CI, 0.98-5.88; P = .055], respectively). CONCLUSIONS: Patients with breast cancer treated with modern NAC, surgery, and RT have a low 5-year LRR risk, with the majority occurring in-field. Triple-negative subtype, stage III disease, and non-pCR were associated with inferior DFS and OS.


Assuntos
Neoplasias da Mama/terapia , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante/métodos , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
8.
Methods Mol Biol ; 1568: 33-44, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28421487

RESUMO

Current freezing technology, especially the vitrification method, has markedly improved oocyte survival rate after warming, and the pregnancy rate is comparable to that achieved with fresh oocytes. However, most groups report using oocytes matured in vivo for vitrification. Although immature oocytes can be vitrified successfully, clinical outcomes do not reach that of vitrification of matured oocytes. The current literature suggests that oocytes should be vitrified at mature metaphase II (M-II) stage following IVM rather than at the immature germinal vesicle (GV) stage, because the potential for oocyte maturation is reduced when vitrification is performed on immature oocytes at the GV stage.


Assuntos
Criopreservação/métodos , Oócitos/citologia , Animais , Diferenciação Celular , Humanos , Oogênese , Vitrificação
11.
Cancer Res ; 75(20): 4351-63, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26297734

RESUMO

The treatment of breast cancer has benefitted tremendously from the generation of estrogen receptor-α (ERα)-targeted therapies, but disease relapse continues to pose a challenge due to intrinsic or acquired drug resistance. In an effort to delineate potential predictive biomarkers of therapy responsiveness, multiple groups have identified several uncharacterized cofactors and interacting partners of ERα, including Split Ends (SPEN), a transcriptional corepressor. Here, we demonstrate a role for SPEN in ERα-expressing breast cancers. SPEN nonsense mutations were detectable in the ERα-expressing breast cancer cell line T47D and corresponded to undetectable protein levels. Further analysis of 101 primary breast tumors revealed that 23% displayed loss of heterozygosity at the SPEN locus and that 3% to 4% harbored somatically acquired mutations. A combination of in vitro and in vivo functional assays with microarray-based pathway analyses showed that SPEN functions as a tumor suppressor to regulate cell proliferation, tumor growth, and survival. We also found that SPEN binds ERα in a ligand-independent manner and negatively regulates the transcription of ERα targets. Moreover, we demonstrate that SPEN overexpression sensitizes hormone receptor-positive breast cancer cells to the apoptotic effects of tamoxifen, but has no effect on responsiveness to fulvestrant. Consistent with these findings, two independent datasets revealed that high SPEN protein and RNA expression in ERα-positive breast tumors predicted favorable outcome in patients treated with tamoxifen alone. Together, our data suggest that SPEN is a novel tumor-suppressor gene that may be clinically useful as a predictive biomarker of tamoxifen response in ERα-positive breast cancers.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Morte Celular , Linhagem Celular Tumoral , Estudos de Coortes , Hibridização Genômica Comparativa , Proteínas de Ligação a DNA , Receptor alfa de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Humanos , Mutação , Proteínas Nucleares/genética , Prognóstico , Proteínas de Ligação a RNA , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Transcrição Gênica , Proteínas Supressoras de Tumor/genética
13.
PLoS One ; 8(12): e81740, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367492

RESUMO

Most women with estrogen receptor expressing breast cancers receiving anti-estrogens such as tamoxifen may not need or benefit from them. Besides the estrogen receptor, there are no predictive biomarkers to help select breast cancer patients for tamoxifen treatment. CCND1 (cyclin D1) gene amplification is a putative candidate tamoxifen predictive biomarker. The RSF1 (remodeling and spacing factor 1) gene is frequently co-amplified with CCND1 on chromosome 11q. We validated the predictive value of these biomarkers in the MA.12 randomized study of adjuvant tamoxifen vs. placebo in high-risk premenopausal early breast cancer. Premenopausal women with node-positive/high-risk node-negative early breast cancer received standard adjuvant chemotherapy and then were randomized to tamoxifen (20 mg/day) or placebo for 5 yrs. Overall survival (OS) and relapse-free survival (RFS) were evaluated. Fluorescent in-situ hybridization was performed on a tissue microarray of 495 breast tumors (74% of patients) to measure CCND1 and RSF1 copy number. A multivariate Cox model to obtain hazard ratios (HR) adjusting for clinico-pathologic factors was used to assess the effect of these biomarkers on Os and RFS. 672 women were followed for a median of 8.4 years. We were able to measure the DNA copy number of CCND1 in 442 patients and RSF1 in 413 patients. CCND1 gene amplification was observed in 8.7% and RSF1 in 6.8% of these patients, preferentially in estrogen receptor-positive breast cancers. No statistically significant interaction with treatment was observed for either CCND1 or RSF1 amplification, although patients with high RSF1 copy number did not show benefit from adjuvant tamoxifen (HR = 1.11, interaction p = 0.09). Unlike CCND1 amplification, RSF1 amplification may predict for outcome in high-risk premenopausal breast cancer patients treated with adjuvant tamoxifen.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ciclina D1/genética , Proteínas Nucleares/genética , Tamoxifeno/uso terapêutico , Transativadores/genética , Humanos , Hibridização in Situ Fluorescente , Pré-Menopausa , Resultado do Tratamento
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