198 research outputs found
High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA
Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n = 16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P < .01). Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions
Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy
BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia.
METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared.
RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p \u3c 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068).
CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia
Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy
Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018).
Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma.
Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests.
Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding.
Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process
Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy
Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018).
Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma.
Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests.
Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding.
Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process
Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine
Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P<0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P<0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe
A population of luminous accreting black holes with hidden mergers
Major galaxy mergers are thought to play an important part in fuelling the
growth of supermassive black holes. However, observational support for this
hypothesis is mixed, with some studies showing a correlation between merging
galaxies and luminous quasars and others showing no such association. Recent
observations have shown that a black hole is likely to become heavily obscured
behind merger-driven gas and dust, even in the early stages of the merger, when
the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations
further suggest that such obscuration and black-hole accretion peaks in the
final merger stage, when the two galactic nuclei are closely separated (less
than 3 kiloparsecs). Resolving this final stage requires a combination of
high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray
observations to detect highly obscured sources. However, large numbers of
obscured luminous accreting supermassive black holes have been recently
detected nearby (distances below 250 megaparsecs) in X-ray observations. Here
we report high-resolution infrared observations of hard-X-ray-selected black
holes and the discovery of obscured nuclear mergers, the parent populations of
supermassive-black-hole mergers. We find that obscured luminous black holes
(bolometric luminosity higher than 2x10^44 ergs per second) show a significant
(P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a
sample of inactive galaxies with matching stellar masses and star formation
rates (1.1 per cent), in agreement with theoretical predictions. Using
hydrodynamic simulations, we confirm that the excess of nuclear mergers is
indeed strongest for gas-rich major-merger hosts of obscured luminous black
holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the
authors' version of the wor
Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience
Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized
Report of the Topical Group on Dark Energy and Cosmic Acceleration: Complementarity of Probes and New Facilities for Snowmass 2021
The mechanism(s) driving the early- and late-time accelerated expansion of
the Universe represent one of the most compelling mysteries in fundamental
physics today. The path to understanding the causes of early- and late-time
acceleration depends on fully leveraging ongoing surveys, developing and
demonstrating new technologies, and constructing and operating new instruments.
This report presents a multi-faceted vision for the cosmic survey program in
the 2030s and beyond that derives from these considerations. Cosmic surveys
address a wide range of fundamental physics questions, and are thus a unique
and powerful component of the HEP experimental portfolio.Comment: Submitted to the Proceedings of the US Community Study on the Future
of Particle Physics (Snowmass 2021); Topical Group Report for CF06 (Cosmic
Frontier Topical Group on Dark Energy and Cosmic Acceleration:
Complementarity of Probes and New Facilitie
Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein
Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4+CD8+CD69– lymphoma. The CD4+CD8+CD69– cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-κB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRβ-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4+CD8+CD69– thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4+CD8+ CD69– thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas
Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen
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