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1.
Bioact Mater ; 19: 550-568, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35600969

RESUMEN

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

2.
Anticancer Res ; 42(4): 2095-2104, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35347033

RESUMEN

BACKGROUND/AIM: The standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. We retrospectively analyzed the clinical outcomes of radiotherapy (RT) in elderly and younger patients with T4 esophageal cancer. PATIENTS AND METHODS: Sixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged <70 years were defined as the younger group. The total dose of RT was set at 60 Gy in 30 fractions. Chemotherapy combined with 5-fluorouracil and cisplatin was administered concurrently with RT in general. The overall survival (OS) rate was estimated using the Kaplan-Meier method. Adverse events were assessed using CTCAE v4.0. RESULTS: The median survival time (MST) of the elderly group (n=35) was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group (n=34) was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. No significant difference in OS was observed between the two groups (p=0.767). Toxicities were not significantly different between the two groups except for thrombocytopenia and esophageal fistula (p=0.012 and p=0.022, respectively). CONCLUSION: The clinical outcomes of RT for T4 esophageal cancer in elderly patients were generally similar to those in the younger group.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Anciano , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Cisplatino/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Humanos , Estudios Retrospectivos
3.
BJUI Compass ; 3(3): 243-250, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35492227

RESUMEN

Objective: To analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy. Subjects and methods: We identified 12 784 patients with intermediate- or high-risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60-69, and ≥70 years old). Outcomes included immediate PSA response (3-month post-RT PSA and 2-year PSA nadir, grouped into <0.10 ng/ml, 0.10-0.49 ng/ml, and ≥0.50 ng/ml), biochemical recurrence, and PCa-specific mortality. Multivariable regression models included ordinal logistic regression for short-term PSA outcomes, Cox regression for biochemical recurrence, and Fine-Gray competing risks regression for PCa-specific mortality. Results: A total of 2136 patients (17%) were ≤59 years old at diagnosis, 6107 (48%) were 60-69 years old, and 4541 (36%) were ≥70 years old. Median follow-up was 6.3 years. Younger age was associated with greater odds of higher 3-month PSA group (≤59 vs. ≥70: adjusted odds ratio [aOR] 1.90, 95% CI 1.64-2.20; p < 0.001) and higher 2-year PSA nadir group (≤59 vs. ≥70: aOR 1.89, 95% CI 1.62-2.19, p < 0.001). Younger age was associated with greater risk of biochemical recurrence (≤59 vs. ≥70: adjusted hazard ratio 1.45, 95% CI 1.26-1.67, p < 0.001) but not PCa-specific mortality (p = 0.16). Conclusion: In a large nationwide sample of US veterans treated with ADT and RT for localized PCa, younger age was associated with inferior short-term PSA response and higher risk of biochemical recurrence.

4.
J Contemp Brachytherapy ; 14(2): 115-122, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35494181

RESUMEN

Purpose: This study aimed to investigate status of displacement of gold-198 (198Au) grains in patients with oral cancers as well as factors and countermeasures for the displacement of 198Au grains. Material and methods: The present study included 34 patients with oral cancers, who were exclusively treated with 198Au grain brachytherapy between 2013 and 2019. Timing and duration of the 198Au grain displacement from the oral cavity and reduction in radiation dose were estimated. Location of the displaced grain was classified as either inside or outside of gross tumor volume. Number and location of the displacement of 198Au grains, primary lesion, and growth type were evaluated. Results: Of the 34 patients included in this study, 198Au grains were displaced in 4 patients (11.8%) during hospitalization. A total of 5 grains (1.4%) were displaced out of an overall count of 367 grains implanted in these 34 patients. Of the four patients who experienced displacement of 198Au grains, three had tongue cancer, and one had lip cancer. All four patients whose grains were displaced had superficial lesions. Conclusions: When performing brachytherapy with 198Au grains for superficial lesions on the tongue or lips, care should be taken to avoid grain displacement.

5.
Anticancer Res ; 42(5): 2657-2663, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35489760

RESUMEN

BACKGROUND/AIM: Many head-and-neck cancer patients receive radiotherapy, which may be associated with significant toxicities. Xerostomia is considered one of the most debilitating late adverse events. This study was performed to identify risk factors for xerostomia. PATIENTS AND METHODS: Several characteristics were investigated for associations with late xerostomia in 159 patients irradiated for head-and-neck cancer including age, sex, tumor site and size, underlying pathology, histologic grading, upfront resection, systemic treatment, and type and dose of radiotherapy. RESULTS: Ninety (57%) and 35 (22%) patients experienced grade ≥2 and ≥3 xerostomia, respectively. Grade ≥2 xerostomia was significantly associated with tumor site (nasopharynx/oropharynx/oral cavity/floor of mouth, p=0.049). Grade ≥3 xerostomia was significantly associated with age ≥61 years (p=0.035); trends were found for tumor site (p=0.088), bilateral nodal involvement (p=0.093), definitive treatment (p=0.082), and systemic treatment (p=0.055). CONCLUSION: Risk factors for xerostomia following radiotherapy of head-and-neck cancers were identified including older age, unfavorable tumor site, bilateral involvement of lymph nodes, definitive treatment, and addition of systemic therapies. For patients with risk factors, sparing of the salivary glands is particularly important.


Asunto(s)
Neoplasias de Cabeza y Cuello , Xerostomía , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Persona de Mediana Edad , Factores de Riesgo , Glándulas Salivales , Xerostomía/epidemiología , Xerostomía/etiología
6.
Prostate ; 82 Suppl 1: S73-S85, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35657158

RESUMEN

Our ability to prognosticate the clinical course of patients with cancer has historically been limited to clinical, histopathological, and radiographic features. It has long been clear however, that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. The advent of efficient genomic sequencing has led to a revolution in cancer care as we try to understand and personalize treatment specific to patient clinico-genomic phenotypes. Within prostate cancer, emerging evidence suggests that tumor genomics (e.g., DNA, RNA, and epigenetics) can be utilized to inform clinical decision making. In addition to providing discriminatory information about prognosis, it is likely tumor genomics also hold a key in predicting response to oncologic therapies which could be used to further tailor treatment recommendations. Herein we review select literature surrounding the use of tumor genomics within the management of prostate cancer, specifically leaning toward analytically validated and clinically tested genomic biomarkers utilized in radiotherapy and/or adjunctive therapies given with radiotherapy.


Asunto(s)
Neoplasias de la Próstata , Biomarcadores de Tumor/genética , Toma de Decisiones Clínicas , Genómica , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia
7.
World Neurosurg ; 2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35660671

RESUMEN

BACKGROUND: Data on the outcomes of CyberKnife-based hypofractionated stereotactic radiosurgery (hSRS) for intracranial and extracranial nonvestibular schwannomas (nVSs) are not sufficient. METHODS: Patients who underwent hSRS for nVSs between 2010 and 2019 were retrospectively reviewed. RESULTS: A total of 39 patients with 39 nVSs were identified. The mean age was 53 (±18) years, and 20 patients (51%) were women. Twenty-five patients (64%) had previous surgeries. Seventeen patients (44%) had nVSs extending outside the cranium. The mean prescribed dose covering 95% of the planning target volume was 22 Gy (±3.7 Gy), the mean fractionation was 4 (±2), and the mean target volume was 13 cm3 (±16 cm3). The radiological tumor control rate was 100% during the mean follow-up period of 67 months (±37 months). Thirty-seven patients (95%) were clinically stable during the mean follow-up period of 72 months (±35 months). Nine patients (23%) suffered from transient adverse radiation effects (AREs), including transient tumor expansion, and 2 (5%) suffered from permanent AREs. CONCLUSIONS: We summarized the treatment outcomes of hSRS for nVSs. Although all patients achieved radiological tumor control, the risk of either transient or permanent ARE was high. Therefore, it is necessary to monitor patients for clinical deterioration due to AREs.

8.
Clin Nutr ; 41(7): 1566-1577, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35667273

RESUMEN

BACKGROUND & AIM: Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity. METHODS: The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out. RESULTS: First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-ß, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS. CONCLUSION: As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity.

9.
Cir Esp (Engl Ed) ; 2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-35671974

RESUMEN

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

10.
Artículo en Inglés | MEDLINE | ID: mdl-35682472

RESUMEN

The aim of the study was to use thermal imaging to evaluate long-term chest temperature changes in patients who had previously been treated with radiotherapy. The examination with a thermal imaging camera involved 144 women-48 of them were patients after RT, 48 were females before breast cancer radiotherapy and the last group of participants were 48 healthy women. All patients (before and after radiotherapy) were divided into women after mastectomy and those after conservative surgery. In addition, the first group of women, those who had received radiotherapy, were divided into three other groups: up to 1 year after RT, over 1 year and up to 5 years after RT and over 5 years after RT. Due to this, it was possible to compare the results and analyse the differences between the temperature in the healthy and treated breasts. The comparison of obtained temperature results showed that the area treated by ionizing radiation is characterized by a higher temperature even a few years after the finished treatment. It is worth mentioning that despite the fact that the difference was visible on the thermograms, the patients had no observable skin lesion or change in color at the treatment site. For the results of the study provided for the group of healthy patients, there were no significant differences observed between the average temperatures in the breasts. The use of thermal imaging in the evaluation of skin temperature changes after radiotherapy showed that the average temperature in the treated breast area can change even a long time after treatment.


Asunto(s)
Neoplasias de la Mama , Temperatura Cutánea , Mama , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Masculino , Mastectomía , Radioterapia Ayuvante , Termografía
11.
PLoS One ; 17(6): e0270528, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35749525

RESUMEN

BACKGROUND: The effect of postmastectomy radiotherapy (PMRT) on T1-2N1M0 triple-negative breast cancers (TNBC) remains unclear. The population-based study aimed to investigate the survival outcomes of T1-2N1M0 TNBC patients who underwent PMRT or not. METHODS: We selected 1743 patients with T1-2N1M0 TNBC who underwent mastectomy between 2010 and 2015 through the Surveillance, Epidemiology and End Results (SEER) database. After propensity score matching (PSM), the PMRT and no-PMRT groups consisted of 586 matched patients, respectively. The Kaplan-Meier method was applied to calculate breast cancer-specific survival (BCSS) and cox proportional hazard model was used to determine the prognostic factors of T1-2N1M0 TNBC. RESULTS: The 5-year BCSS for the PMRT and no-PMRT groups was 79.1% and 74.7%, respectively. Analysis showed that in patients with three nodes positive, radiotherapy could significantly improve BCSS (HR = 0.396, 95% CI = 0.175-0.900, P = 0.027), but it brought no significant advantage in BCSS in patients with one or two nodes positive (HR = 1.061, 95% CI = 0.725-1.552, P = 0.761; HR = 0.657, 95% CI = 0.405-1.065, P = 0.088). In addition, PMRT improves the BCSS in TNBC patients with T2 tumor concomitant with three positive lymph nodes (HR = 0.343, 95% CI = 0.132-0.890, P = 0.028). CONCLUSION: TNBC patients with T2 tumor concomitant with three positive lymph nodes can benefit from PMRT.

12.
JCO Clin Cancer Inform ; 6: e2100176, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35749675

RESUMEN

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

13.
J Colloid Interface Sci ; 625: 532-543, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35749848

RESUMEN

The rising risk of lung cancer has become a primary global concern with high mortality and mobility. Presently, clinically used anticancer drugs show limited efficacy and significant side effects. A new generation of anticancer weapons is in great demand for lung cancer therapy. Herein, we have developed a novel style of biomimetic zeolitic imidazolate framework-8 (ZIF-8) based on the merits of cell membranes derived from human bone marrow mesenchymal stem cells (hBMSCs), which can navigate biological bombs herpes simplex virus type I thymidine kinase-encoded plasmids (pHSVtk) and ganciclovir (GCV) to treat lung cancer. The biological bomb-loaded structure can kill transfected lung cancer cells and neighboring lung cancer cells through the "bystander effect," which induces efficient suppression of lung cancer both in vitro and in vivo. The biomimetic nanoparticles show an enhanced circulation lifetime and drug accumulation in the tumor tissues and significantly inhibit the tumors. We have developed a straightforward approach to deliver biological bombs with biomimetic metal-organic frameworks for efficient lung cancer therapy. To the best of our knowledge, this is the first report of such a strategy for lung cancer therapy.

14.
Radiother Oncol ; 2022 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-35750106

RESUMEN

BACKGROUND AND PURPOSE: To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS: This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n=201) and internal validation set (n=101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n=95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS: The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index:0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation set (C-index:0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p<0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p<0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p<0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index:0.82), internal (Cindex: 0.78), and external validation set (C-index:0.76). Calibration curves showed good agreement. CONCLUSIONS: The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.

15.
Clin Lung Cancer ; 2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35750570

RESUMEN

INTRODUCTION/BACKGROUND: For early stage medically inoperable lung cancer treated with fractionated stereotactic body radiotherapy (SBRT), higher local failure is associated with squamous carcinoma (SqC) compared to adenocarcinoma (AC). This study explored whether histology influences single-fraction SBRT local control. MATERIALS AND METHODS: We surveyed our prospective data registry from 12/2009 to 12/2019 for SF-SBRT cases with biopsy-proven AC or SqC only. Outcomes of interest included local (LF), nodal (NF), distant (DF) failure rates and overall survival (OS), as well as treatment-related toxicity. RESULTS: For the 10-year interval surveyed, 113 patients met study criteria. There was no association between histology and dose received (34 Gy or 30 Gy). Median follow up was 22.9 months. Patient characteristics were balanced between histologic cohorts. Median tumor size was 1.9 cm. Comparing total AC vs. SqC cohorts, 2-year LF rates (%) were 7.3 vs. 9.6, respectively (P = .9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.8 vs. 6.4; 10.5 vs. 16.2; 15.8 vs. 13.0; 77.9 vs.71.2 (all P = non-significant). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.8 vs. 8.1; 5.9 vs. 18.0; 23.5 vs. 9.7; 70.6 vs. 77.1 (all P = non-significant). When considering toxicities, there were no grade 4/5 toxicities and no significant differences in any other toxicity rate by histology or dose. CONCLUSION: SF-SBRT local control was not associated with histology, unlike fractionated schedules. This novel finding adds to the evolving understanding of this treatment schedule.

16.
Brachytherapy ; 2022 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-35750619

RESUMEN

PURPOSE: Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. METHODS AND MATERIALS: We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. RESULTS: The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). CONCLUSIONS: Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

17.
Brachytherapy ; 2022 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-35750620

RESUMEN

PURPSOE: Colorectal cancer liver metastasis (CCLM) in anatomically challenging locations is difficult to treat. This retrospective study aimed to evaluate the effectiveness and safety of permanent 125I seeds implantation (ISI) for treatment of CCLM in anatomically challenging locations after failure of systemic chemotherapy. METHODS AND MATERIALS: A total of 31 liver metastases (in 25 patients) were treated by ISI under computerized tomography guidance from January 2011 to December 2017. Post-treatment follow-up was for 40 months. Adverse events were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events. Tumor response was evaluated by the mRECIST criteria. Objective response rate, overall survival rate, and complications were retrospectively analyzed. RESULTS: All ISI procedures were performed successfully. Most patients only complained of fatigue and mild pain after ISI. Only one patient had liver rupture during the procedure. Serum alanine aminotransferase and aspartate aminotransferase levels at 1 month after ISI were not significantly different from pre-procedure levels (p > 0.05). Computed tomography at 6 months after ISI treatment showed completed response in 11 (11/31, 35.5%) lesions, partial response in 14 (14/31, 45.2%) lesions, stable disease in 4 (4/31, 12.9%) lesions, and disease progression in 2 (2/31, 6.5%) lesions; thus, the objective response rate was 80.6%. Median survival was for 12 months. The 1 and 2 year overall survival rates were 52.0% and 20.0%, respectively. CONCLUSIONS: 125I seeds implantation for CCLM in anatomically challenging locations is safe and effective. Survival benefit is limited in the salvage setting where patients have high intrahepatic tumor load after failed systemic chemotherapy.

18.
Trends Cancer ; 2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35750630

RESUMEN

Radiation is frequently administered for cancer treatment, but resistance or remission remains common. Cancer cells alter their metabolism after radiotherapy to reduce its cytotoxic effects. The influence of altered cancer metabolism extends to the tumor microenvironment (TME), where components of the TME exchange metabolites to support tumor growth. Combining radiotherapy with metabolic targets in the TME can improve therapy response. We review the metabolic rewiring of cancer cells following radiotherapy and put these observations in the context of the TME to describe the metabolic hallmarks of radiotherapy in the TME.

19.
Blood Cancer J ; 12(6): 95, 2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35750691

RESUMEN

Functional precision medicine in AML often relies on short-term in vitro drug sensitivity screening (DSS) of primary patient cells in standard culture conditions. We designed a niche-like DSS assay combining physiologic hypoxia (O2 3%) and mesenchymal stromal cell (MSC) co-culture with multiparameter flow cytometry to enumerate lymphocytes and differentiating (CD11/CD14/CD15+) or leukemic stem cell (LSC)-enriched (GPR56+) cells within the leukemic bulk. After functional validation of GPR56 expression as a surrogate for LSC enrichment, the assay identified three patterns of response, including cytotoxicity on blasts sparing LSCs, induction of differentiation, and selective impairment of LSCs. We refined our niche-like culture by including plasma-like amino-acid and cytokine concentrations identified by targeted metabolomics and proteomics of primary AML bone marrow plasma samples. Systematic interrogation revealed distinct contributions of each niche-like component to leukemic outgrowth and drug response. Short-term niche-like culture preserved clonal architecture and transcriptional states of primary leukemic cells. In a cohort of 45 AML samples enriched for NPM1c AML, the niche-like multiparametric assay could predict morphologically (p = 0.02) and molecular (NPM1c MRD, p = 0.04) response to anthracycline-cytarabine induction chemotherapy. In this cohort, a 23-drug screen nominated ruxolitinib as a sensitizer to anthracycline-cytarabine. This finding was validated in an NPM1c PDX model.

20.
Sci Rep ; 12(1): 10729, 2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35750892

RESUMEN

The optimal sequence of chemotherapy (CT) and radiotherapy (RT) after surgery in breast cancer patients is unclear. There is a lack of literature on RT given between anthracycline and taxane administration. We evaluated the effect of RT sequence on long-term outcome in breast cancer. Two hundred patients who underwent surgery between January 2009 and December 2012 for node-positive breast cancers were evaluated retrospectively. All patients were treated with doxorubicin and cyclophosphamide (AC) followed by taxane. Sandwich RT group that received RT between AC and taxane was compared to the group that received RT after CT. The mean follow-up period was 105.4 months. The locoregional recurrence (LRR) rate was lower in sandwich RT group (P = 0.012) and there was no significant difference in distant metastasis between the two groups. The RT sequence was an important predictor for LRR in multivariable analysis (P = 0.017). For luminal A subtype, disease-free survival (DFS) was better in sandwich RT group than in CT followed by RT group (P = 0.001). The overall survival did not correlated with RT sequence regardless of subtype. Sandwich RT can offer DFS benefit in luminal A subtype breast cancer. A tailored approach of sequencing chemotherapy and radiotherapy would be needed considering the factors that can influence outcome.

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