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1.
Int. braz. j. urol ; 47(1): 120-130, Jan.-Feb. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134327

RESUMO

ABSTRACT Aim: To evaluate the radiotherapy (RT) effect in the pelvic floor muscles (PFM) function in men with prostate cancer (PC). Materials and Methods: A cross-sectional study included three groups of patients with PC and RT indication: 1) Pre-RT group: evaluated before the beginning of RT; 2) Acute group: evaluated between six months and one year after RT; 3) Late Group: evaluated between two and a half years and four years post-RT. PFM assessment was divided into: a) functional assessment through the digital anal palpation (Modified Oxford Scale) and surface electromyography (sEMG) with anal probe; b) anatomical assessment by pelvic magnetic resonance imaging (MRI) with thickness measurements of levator ani muscle and pelvic specific parameters at rest and under Valsalva maneuver. We used Student t test, considering as significant p <0.05. Results: Thirty-three men were assessed: Pre-RT (n=12); Acute (n=10) and Late (n=11) groups. PFM functional assessment showed Late group with lower electromyographic activity, especially in the sustained contractions when compared to the Pre-RT (p=0.003) and Acute groups (p=0.006). There was no significant difference between groups in MRI. Conclusion: PFM functional assessment showed a decrease in sEMG activity in the Late group post-RT. Most of the sample (72.7%) did not know how to actively contract the PFM or had a weak voluntary contraction when assessed by digital anal palpation. Also, these patients presented higher prevalence of pelvic complaints. No changes were observed in the morpho-functional parameters evaluated by MRI, except the measurement of the membranous urethra length when comparing Pre-RT Group and Acute and Late Groups.

2.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431443

RESUMO

Pubic osteomyelitis is a rare and often late-onset complication of radiation therapy and surgery for vulvar and vaginal carcinoma. It typically presents with vulvar pain, fever, vaginal discharge and/or gait disorders. Pubic osteomyelitis is often accompanied by fistulas or wound dehiscence in the pelvic area. Its accurate diagnosis and treatment are challenging and require a multidisciplinary team effort. In our patients, multiple combined surgical procedures, long-term antibiotic treatment and days to weeks of hospital admission were necessary to treat pubic osteomyelitis. We emphasise the importance of timely and adequate diagnosis and multidisciplinary approach resulting in a course of treatment that is as effective as possible, limiting the impact on quality of life, which is generally high in this group of patients.

3.
Cell Death Dis ; 12(1): 69, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33431817

RESUMO

Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients' survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT-DNA-PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN-ATM-CHK2 signal and ATR-CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.

4.
Ann Surg Oncol ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400000

RESUMO

BACKGROUND: Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC. METHODS: Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded αDC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-α, and rintatolimod. RESULTS: Forty-six patients underwent CRS/HIPEC followed by αDC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of αDC1. The αDC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively. CONCLUSIONS: Adjuvant autologous tumor antigen-loaded αDC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that αDC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.

5.
BMC Cancer ; 21(1): 23, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402130

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. METHODS: Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety. RESULTS: From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. CONCLUSION: We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases. TRIAL REGISTRATION: Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

6.
J Hematol Oncol ; 14(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33402221

RESUMO

BACKGROUND: Prior chemotherapy and/or underlying morbidity commonly leads to poor mobilisation of hematopoietic stem cells (HSC) for transplantation in cancer patients. Increasing the number of available HSC prior to mobilisation is a potential strategy to overcome this deficiency. Resident bone marrow (BM) macrophages are essential for maintenance of niches that support HSC and enable engraftment in transplant recipients. Here we examined potential of donor treatment with modified recombinant colony-stimulating factor 1 (CSF1) to influence the HSC niche and expand the HSC pool for autologous transplantation. METHODS: We administered an acute treatment regimen of CSF1 Fc fusion protein (CSF1-Fc, daily injection for 4 consecutive days) to naive C57Bl/6 mice. Treatment impacts on macrophage and HSC number, HSC function and overall hematopoiesis were assessed at both the predicted peak drug action and during post-treatment recovery. A serial treatment strategy using CSF1-Fc followed by granulocyte colony-stimulating factor (G-CSF) was used to interrogate HSC mobilisation impacts. Outcomes were assessed by in situ imaging and ex vivo standard and imaging flow cytometry with functional validation by colony formation and competitive transplantation assay. RESULTS: CSF1-Fc treatment caused a transient expansion of monocyte-macrophage cells within BM and spleen at the expense of BM B lymphopoiesis and hematopoietic stem and progenitor cell (HSPC) homeostasis. During the recovery phase after cessation of CSF1-Fc treatment, normalisation of hematopoiesis was accompanied by an increase in the total available HSPC pool. Multiple approaches confirmed that CD48-CD150+ HSC do not express the CSF1 receptor, ruling out direct action of CSF1-Fc on these cells. In the spleen, increased HSC was associated with expression of the BM HSC niche macrophage marker CD169 in red pulp macrophages, suggesting elevated spleen engraftment with CD48-CD150+ HSC was secondary to CSF1-Fc macrophage impacts. Competitive transplant assays demonstrated that pre-treatment of donors with CSF1-Fc increased the number and reconstitution potential of HSPC in blood following a HSC mobilising regimen of G-CSF treatment. CONCLUSION: These results indicate that CSF1-Fc conditioning could represent a therapeutic strategy to overcome poor HSC mobilisation and subsequently improve HSC transplantation outcomes.

7.
Radiat Oncol ; 16(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407611

RESUMO

BACKGROUND: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients. METHODS: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. RESULTS: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related. CONCLUSIONS: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation. TRIAL REGISTRATION: retrospectively registered.

8.
Radiat Oncol ; 16(1): 5, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407637

RESUMO

BACKGROUND: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone. METHODS: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group). RESULTS: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05-0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37-5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01-0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09-0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06-0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03-0.57; P = 0.007) had improved OS with AbiRT. CONCLUSIONS: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.

9.
Radiat Oncol ; 16(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407647

RESUMO

BACKGROUND: To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection. METHODS: In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection. RESULTS: Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49-0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19-24 LNs removed (aHR 0.78; 95% CI 0.73-1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with < 18 LNs. The protective effect was not seen in those with 18-24 LNs (aHR 1.07; 95% CI 0.59-1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed. CONCLUSION: Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.

10.
Radiat Oncol ; 16(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407648

RESUMO

BACKGROUND: Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study. METHODS: Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement. RESULTS: Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy. CONCLUSIONS: Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.

11.
Theranostics ; 11(4): 1721-1731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408777

RESUMO

Development of a powerful sensitization system to alleviate radioresistance for enhanced tumor radiotherapy (RT) remains to be explored. Herein, we present a unique dual-mode endogenous and exogenous nanosensitizer based on dendrimer-entrapped gold nanoparticles (Au DENPs) to realize enhanced tumor RT. Methods: Generation 5 poly(amidoamine) dendrimers partially modified with 1,3-propanesultone were used for templated synthesis of Au NPs, and the created zwitterionic Au DENPs were adopted for serum-enhanced delivery of siRNA to lead to the knockdown of hypoxia-inducible factor-1α (HIF-1α) protein and downstream genes to relieve tumor invasion. The Au DENPs/siRNA polyplexes were also used for dual-mode endogenous and exogenous sensitization of tumor RT in vivo. Results: Due to the dual-mode endogenous sensitization through HIF-1α gene silencing and the exogenous sensitization through the existing Au component, enhanced RT of cancer cells in vitro and a tumor model in vivo can be realized, which was confirmed by enhanced cytotoxic reactive oxygen species (ROS) generation in vitro and double-strand DNA damage verified from the γ-H2AX protein expression in tumor cells in vivo. By integrating the advantages of HIF-1α gene silencing-induced downregulation of downstream genes and the dual-mode sensitization-enhanced RT, simultaneous inhibition of primary tumors and metastasis can be readily realized. Conclusions: The developed zwitterionic Au DENPs may be used as a promising platform for dual-mode endogenously and exogenously sensitized RT of other tumor types.

12.
World J Surg ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481081

RESUMO

BACKGROUND: Metastatic adrenocortical carcinoma (ACC) is an aggressive cancer with poor prognosis, with limited treatment options. The survival benefit of adrenal surgery in patients with synchronous metastatic disease has not been well explored. METHODS: Patients with ACC with synchronous metastases were identified from the Surveillance, Epidemiology, and End Results database (2010-2016). The effect of adrenal surgery on different patterns of distant metastases was assessed. The overall survival was estimated by the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival outcome. RESULTS: A total of 202 patients with synchronous metastatic ACC were identified from the SEER database, 76 (37.6%) patients underwent adrenal surgery. Compared to nonsurgical patients, patients who underwent adrenal surgery had a better survival (median overall survival: 4 vs. 13 months, P < 0.001). In sub-analyses, except for patients with liver metastases (P = 0.670), adrenalectomy could consistently confer a significant survival benefit in patients with lung metastases (P = 0.003), bone metastases (P = 0.020), and multiple metastases (P = 0.002). Cox regression analysis revealed that in addition to adrenalectomy [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.45-0.92; P = 0.017], metastasectomy (HR = 0.48, 95% CI 0.26-0.86; P = 0.013), and chemotherapy (HR = 0.59, 95% CI 0.42-0.82; P = 0.002) were also associated with improved survival. CONCLUSIONS: Our findings support the view that adrenal surgery may be associated with improved survival in patients with synchronous metastatic ACC (except for patients with liver metastases), and the metastatic sites have significant prognostic implications on survival outcomes with adrenal surgery.

13.
Ann Surg Oncol ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481124

RESUMO

BACKGROUND: Malnutrition after gastrectomy is associated with a poor prognosis; however, no accurate model for predicting post-gastrectomy malnutrition exists. Hence, we conducted a retrospective study to develop a prediction model identifying gastric cancer patients at high risk of malnutrition after gastrectomy. METHOD: Gastric cancer patients who underwent curative gastrectomy with more than one weight measurement during a 3-year follow-up period were included. Malnutrition was defined as body mass index (BMI) < 18.5 kg/m2 according to the European Society of Clinical Nutrition and Metabolism diagnostic criteria. BMI-loss pattern was analyzed using a group-based trajectory model. A prediction model for malnutrition 6 months after gastrectomy was developed based on significant risk factors, and then validated. RESULTS: Overall, 1421 patients were examined. The BMI-loss trajectory model showed significant BMI loss at 6 months after gastrectomy. Severe BMI loss (mean 21.5%; n = 109) was significantly associated with the elderly, female sex, higher preoperative BMI, advanced cancer stage, open surgery, total gastrectomy, Roux-en-Y reconstruction, chemotherapy, and postoperative complications (all p < 0.05). Malnutrition 6 months after gastrectomy was observed in 152 (11.9%) of 1281 patients. Preoperative BMI, sex, and type of operation were included in the final prediction model as predictive factors (p < 0.05). The C-index of the developmental set and bootstrap validation of the prediction model was 0.91 (95% confidence interval 0.89-0.94) and 0.91, respectively. CONCLUSION: The prediction model for the risk of malnutrition 6 months after gastrectomy was accurately developed, with three independent risk factors: low preoperative BMI, female sex, and total or proximal gastrectomy.

14.
J Neurooncol ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481148

RESUMO

INTRODUCTION: Stereotactic radiosurgery (SRS) has been increasingly employed to treat patients with intracranial metastasis, both as a salvage treatment after failed whole brain radiation therapy (WBRT) and as an initial treatment. "Several studies have shown that SRS may be as effective as WBRT with the added benefit of preserving neuro-cognition". However, some patients may have local failure following SRS for intracranial metastasis, defined as increase in total lesion volume by 25% after at least 3 months of follow up. METHODS: The SRS registry, established by the Neuro point alliance (NPA) under the auspices of the American Association of Neurological Surgeons (AANS), was queried for patients with intracranial metastasis receiving SRS at the participating sites. Demographic, clinical symptoms, tumor, and treatment characteristics as well as follow up status were summarized for the cohort. A multivariable explanatory cox- regression was performed to evaluate the impact of each of the factors on time to local failure.at last follow-up. RESULTS: A total of 441 patients with 1255 intracranial metastatic lesions undergoing SRS were identified. The most common primary cancer histology was non-small cell lung cancer (43.8%, n = 193). More than half of the cohort had more than 1 metastatic lesion (2-3 lesions: 29.5%, n = 130; more than 3 lesions: 25.2% (n = 111). The average duration of follow-up for the cohort was found to be 8.4 months (SD = 7.61). The mean clinical treatment volume (CTV), after adding together the volume of each lesion for each patient was 5.39 cc (SD = 7.6) at baseline. A total of 20.2% (n = 89) had local failure (increase in volume by > 25%) with a mean time to progression of 7.719 months (SD = 6.09). The progression free survival (PFS) for the cohort at 3, 6 and 12 months were found to be 94.9%, 84.3%, and 69.4%, respectively. On multivariable cox regression analysis, factors associated with increased hazard of local failure included male gender (HR 1.65, 95% CI 1.03-2.66, p = 0.037), chemotherapy at or before SRS (HR = 2.39, 95% CI 1.41-4.05, p = 0.001), WBRT at or before SRS (HR = 2.21, 95% CI 1.16- 4.22, p = 0.017), while surgical resection (HR 0.45, 95% CI 0.21-0. 97, p = 0.04) and immunotherapy (0.34, 95% CI 0.16-0.50, p = 0.014) were associated with lower hazard of local failure. CONCLUSION: Factors found to be predictive of local failure included higher RPA score and those receiving chemotherapy, while patients undergoing surgical resection and those with occipital lobe lesions were less likely to experience local failure. Our analyses not only corroborate those previously reported but also demonstrate the utility of a multi-institutional registry to advance real-world SRS research for patients with intracranial metastatic lesions.

15.
Thorac Cancer ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481353

RESUMO

BACKGROUND: Currently, there is no consensus on the role of postoperative adjuvant radiotherapy (PORT) for resected stage IIIA/N2 non-small cell lung cancer (NSCLC). Our study sought to determine which patients may be able to benefit from PORT, based on a patient prognostic score. METHODS: A retrospective cohort study was conducted to identify patients diagnosed with IIIA/N2 NSCLC between 1988 and 2016 in the SEER database. Eligible patients were divided into the following two groups: PORT group and non-PORT group. We classified patient prognostic scores as an ordinal factor and stratified patients based on prognostic scores. A Cox proportional hazards model with propensity score weighting was performed to evaluate cancer-specific mortality (CSM) between the two groups. RESULTS: We identified 7060 eligible patients with IIIA/N2 NSCLC, 2833 (40.1%) in the PORT group and 4227 (59.9%) in the non-PORT group. Overall, the 10-year CSM rate in the weighted cohorts was 70.4% in the PORT group, 72.0% in the non-PORT group, and patients who received PORT had a lower CSM rate (p = 0.001). Compared with the non-PORT group, significant survival improvements in the PORT group were observed in patients with higher age, grade, T stage and lymph node ratio (LNR), and without chemotherapy. The improved survival of patients receiving PORT was significantly correlated with patient prognostic scores (p < 0.001). CONCLUSIONS: In our population-based study, the prognostic score was associated with the survival improvement offered by PORT in IIIA/N2 NSCLC, suggesting that prognostic scores and clinicopathological characteristics may be helpful in proper candidate selection for PORT.

16.
Am J Dermatopathol ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33481376

RESUMO

ABSTRACT: Basal cell carcinoma (BCC) has been linked mostly to ultraviolet radiation exposure, but ionizing radiation has also been implicated in the genesis of a subset of BCCs occurring after radiotherapy. We present a 93-year-old woman with 4 BCCs of the scalp after radiotherapy for tinea capitis, diagnosed after a latency period of over 80 years. The largest lesion was located on the right temporal region and corresponded to a BCC of mixed type, with nodular, infiltrative, and micronodular components. We performed genomic study with array comparative genomic hybridization in samples from each BCC, which revealed more imbalances in the largest lesion than in the remaining ones, correlating with its higher histological complexity. Furthermore, this was the only lesion presenting loss at 2p22.3, where is mapped the BIRC6 gene associated with regulation of apoptosis, and loss at 16q24.3, where is mapped FANCA gene, responsible for DNA repair and maintenance of chromosome stability. Despite these differences, there were aberrations shared by all tumor samples, suggesting a common genetic signature. Our report describes, to the best of our knowledge, the longest latency period between exposure to radiotherapy and the diagnosis of BCC. The genomic study showed imbalances common to all tumor samples but also differences that could explain their heterogeneity in terms of histological subtype and biological potential. In addition, these differences could also be a consequence of different times in the evolution of the lesions at the moment of presentation, thus having a diverse combination of accumulated genomic imbalances.

17.
Childs Nerv Syst ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404720

RESUMO

BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare childhood hematopoietic disorder typically presenting with hepatosplenomegaly, lymphadenopathy, pallor, fever, and cutaneous findings. The authors report the first case, to our knowledge, of JMML presenting in a pediatric patient with a subdural hematoma. CASE DESCRIPTION: A 7-month old male with recurrent respiratory infections and a low-grade fever presented with a full fontanelle and an increasing head circumference and was found to have chronic bilateral subdural collections. Abusive head trauma, infectious, and coagulopathy workups were unremarkable, and the patient underwent bilateral burr holes for evacuation of the subdural collections. The postoperative course was complicated by the development of thrombocytopenia, anemia, and an acute subdural hemorrhage which required evacuation. Cytologic analysis of the subdural fluid demonstrated atypical cells, which prompted flow cytometric analysis, a bone marrow biopsy, and ultimately a diagnosis of JMML. Following chemotherapy, the patient's counts improved, and he subsequently underwent a hematopoietic stem cell transplant. CONCLUSION: Subdural collections may rarely represent the first presenting sign of hematologic malignancies. In patients with a history of recurrent infections and a negative workup for abusive head trauma, clinicians should include neoplastic etiologies in the differential for chronic subdural collections and have a low threshold for fluid analysis.

18.
Haematologica ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33440921

RESUMO

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure disorder with pure red blood cell aplasia associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with DBA have mutations in a gene encoding ribosomal protein S19 (RPS19). Our previous proof-of-concept studies demonstrated that DBA phenotype could be successfully treated using lentiviral vectors in Rps19-deficient DBA mice. In our present study, we developed a clinically applicable single gene self-inactivating lentiviral vector, containing the human RPS19 cDNA driven by the human elongation factor 1α short promoter, that can be used for clinical gene therapy development for RPS19-deficient DBA. We examined the efficacy and safety of the vector in a Rps19-deficient DBA mouse model and in human primary RPS19-deficient CD34+ cord blood cells. We observed that transduced Rps19-deficient bone marrow cells could reconstitute mice longterm and rescue the bone marrow failure and severe anemia observed in Rps19-deficient mice, with a low risk of mutagenesis and a highly polyclonal insertion site pattern. More importantly, the vector can also rescue impaired erythroid differentiation in human primary RPS19-deficient CD34+ cord blood hematopoietic stem cells. Collectively, our results demonstrate the efficacy and safety of using a clinically applicable lentiviral vector for the successful treatment of Rps19-deficient DBA in a mouse model and in human primary CD34+ cord blood cells. These findings show that this vector can be used to develop clinical gene therapy for RPS19-deficient DBA patients.

19.
Vet Comp Oncol ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443307

RESUMO

The role of systemic inflammation in cancer's progression has been widely investigated, especially in melanoma in humans. Pre-treatment leukocytes count and ratios play a recognized prognostic role in several types of malignancies, but no information is available regarding canine oral malignant melanoma (COMM). The purpose of this explorative retrospective study was to investigate the prognostic impact of pre-treatment neutrophil to lymphocyte (NLR) and lymphocyte to monocyte (LMR) ratios in dogs with oral malignant melanoma that underwent surgical resection and immunotherapy with adjuvant CSPG4-antigen electrovaccination. Thirty-nine dogs with histologically confirmed oral melanoma and with available pre-treatment haematological analyses, performed at maximum 60 days before the first treatment, were retrospectively enrolled. Statistical analysis was performed to explore possible correlations among NLR and LMR with age, clinical stage, tumour pigmentation, tumour size, nuclear atypia, mitotic index, Ki67, CSPG4 status, ulceration, bone invasion and excision margins status. The impact of NLR and LMR on overall survival time (OST) was explored among various ratio cut off and across different time points with Kaplan Meier method. No significant relationship was identified between leukocytes ratios and histological parameters, CSPG4 expression, excision margin status, age, tumour size and clinical stage. NLR and LMR did not display a prognostic impact on the survival time of the entire population. Pre-treatment leukocytes ratios may not represent a useful prognostic factor in dogs with oral melanoma, especially in absence of distant metastatic disease. This article is protected by copyright. All rights reserved.

20.
BMC Surg ; 21(1): 36, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441131

RESUMO

BACKGROUND: Horner syndrome (HS), mainly characterized by symptoms including ptosis, miosis, and anhidrosis on the affected face, is a condition that is well documented but rarely reported as a postoperative complication of thyroidectomy, particularly in endoscopic thyroid surgery (ETS). We hereby report a case of HS due to ETS with a brief literature review on this topic. CASE PRESENTATION: A 31-year-old female was admitted to our hospital with an unexpected physical examination finding of two thyroid nodules that were hypoechoic, had an irregular shape, and exhibited calcification. Subsequently, the results of a fine-needle aspiration (FNA) biopsy from the thyroid nodules and BRAFV600E mutation further confirmed the malignancy of these nodules. Thus, total thyroidectomy combined with central lymph node dissection (CLND) by ETS via the bilateral axillo-breast approach was performed on this patient. Histology confirmed the diagnosis of papillary thyroid microcarcinoma (PTMC) concurrent with Hashimoto's thyroiditis (HT). However, this patient developed HS with ptosis in her left eye on postoperative day 3. All symptoms gradually resolved before the 3-month follow-up. CONCLUSION: HS subsequent to ETS is a rare complication. Thus, standardized and appropriate operative procedures, as well as subtle manipulation, are essential in preventing and reducing the occurrence of HS. In addition, the early diagnosis and management of this rare complication are also important for a favorable outcome.


Assuntos
Carcinoma Papilar/cirurgia , Doença de Hashimoto/cirurgia , Síndrome de Horner/etiologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireoidectomia/efeitos adversos , Adulto , Carcinoma Papilar/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Doença de Hashimoto/patologia , Síndrome de Horner/diagnóstico , Humanos , Complicações Pós-Operatórias/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Resultado do Tratamento
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