The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with ...oligometastatic renal cell carcinoma.
This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA). Patients (aged ≥18 years) with five or fewer metastatic lesions, an Eastern Cooperative Oncology Group status of 0–2, and no more than one previous systemic therapy (if this therapy was stopped at least 1 month before enrolment) without limitations on renal cell carcinoma histology were eligible for inclusion. Patients were treated with stereotactic body radiotherapy (defined as ≤5 fractions with ≥7 Gy per fraction) to all lesions and maintained off systemic therapy. When lesion location precluded safe stereotactic body radiotherapy, patients were treated with hypofractionated intensity-modulated radiotherapy regimes consisting of 60–70 Gy in ten fractions or 52·5–67·5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of progression. Co-primary endpoints were feasibility (defined as all planned radiotherapy completed with <7 days unplanned breaks) and progression-free survival. All efficacy analyses were intention-to-treat. Safety was analysed in the as-treated population. A second cohort, with the aim of assessing the feasibility of sequential stereotactic body radiotherapy alone in patients with low-volume metastatic disease, was initiated and will be reported separately. This study is registered with ClinicalTrials.gov, NCT03575611.
30 patients (six 20% women) were enrolled from July 13, 2018, to Sept 18, 2020. All patients had clear cell histology and had a nephrectomy before enrolment. All patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks. At a median follow-up of 17·5 months (IQR 13·2–24·6), median progression-free survival was 22·7 months (95% CI 10·4–not reached; 1-year progression-free survival 64% 95% CI 48–85). Three (10%) patients had severe adverse events: two grade 3 (back pain and muscle weakness) and one grade 4 (hyperglycaemia) adverse events were observed. There were no treatment-related deaths.
Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma.
Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Institute.
Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid ...lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them.
The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG) lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses.
The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4%) in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples.
These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Metastatic head and neck cancers (HNCs) predominantly affect the lungs and have a two‐year overall survival (OS) of 15% to 50%, if amenable for pulmonary metastasectomy.
Methods
...Retrospective review of the two‐year local control (LC), local‐regional control (LRC) within the same lobe, OS, and toxicity rates in consecutive patients with metastatic pulmonary HNC who underwent stereotactic ablative radiotherapy (SABR) January 2007 to May 2018.
Results
Evaluated 82 patients with 107 lung lesions, most commonly squamous cell carcinoma (SCC; 64%). Median follow‐up was 20 months (range: 9.0‐97.6). Systemic therapy administered in 34%. LC, LRC, and OS rates were 94%, 90%, and 62%. Patients with oligometastatic disease had a higher OS than polymetastatic disease, 72% vs 44% (HR = 0.30, 95% CI: 0.14‐0.64; P = .008). OS in oligometastatic non‐SCC and SCC were 100% and 66% (P = .03). There were no grade ≥3 toxicities.
Conclusions
Metastatic pulmonary HNCs after SABR have a two‐year OS rate comparable to pulmonary metastasectomy.
Background
The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) ...clinic compared with nationwide trends.
Methods
In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics.
Results
Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low‐risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high‐risk disease, with a substantial portion of high‐risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate‐risk and high‐risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true.
Conclusions
Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low‐risk disease to nondefinitive strategies of patients with high‐risk disease to definitive treatment, and it may obviate the influence of race.
Presentation at a multidisciplinary clinic facilitates the appropriate disposition of low‐risk patients into nondefinitive strategies and of high‐risk patients into definitive treatment, and it may obviate the confounding influence of race. By comparison, nationwide, the disposition of patients may be confounded by pretreatment demographic factors.
Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment ...(16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM.
Objective
To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without ...compromising disease control or survival.
Patients and Methods
We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow‐up imaging. Time‐to‐event end‐points were calculated from the start of RT.
Results
A total of 72 patients were identified (median follow‐up 22 months, 95% confidence interval CI 19–32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non‐spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87–99%); progression‐free survival (PFS), 52% (95% CI 40–63%); and overall survival, 91% (95% CI 82–96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2–27.2) months, 10.1 (6.9–13.2) months, and 9.8 (2.4–28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation.
Conclusion
Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed.
Purpose To compare the toxicities and cost of proton radiation and stereotactic body radiotherapy (SBRT) with intensity-modulated radiotherapy (IMRT) for prostate cancer among men younger than 65 ...years of age with private insurance. Methods Using the MarketScan Commercial Claims and Encounters database, we identified men who received radiation for prostate cancer between 2008 and 2015. Patients undergoing proton therapy and SBRT were propensity score-matched to IMRT patients on the basis of clinical and sociodemographic factors. Proportional hazards models compared the cumulative incidence of urinary, bowel, and erectile dysfunction toxicities by treatment. Cost from a payer's perspective was calculated from claims and adjusted to 2015 dollars. Results A total of 693 proton therapy patients were matched to 3,465 IMRT patients. Proton therapy patients had a lower risk of composite urinary toxicity (33% v 42% at 2 years; P < .001) and erectile dysfunction (21% v 28% at 2 years; P < .001), but a higher risk of bowel toxicity (20% v 15% at 2 years; P = .02). Mean radiation cost was $115,501 for proton therapy patients and $59,012 for IMRT patients ( P < .001). A total of 310 SBRT patients were matched to 3,100 IMRT patients. There were no significant differences in composite urinary, bowel, or erectile dysfunction toxicities between SBRT and IMRT patients ( P > .05), although a higher risk of urinary fistula was noted with SBRT (1% v 0.1% at 2 years; P = .009). Mean radiation cost for SBRT was $49,504 and $57,244 for IMRT ( P < .001). Conclusion Among younger men with prostate cancer, proton radiation was associated with significant reductions in urinary toxicity but increased bowel toxicity at nearly twice the cost of IMRT. SBRT and IMRT were associated with similar toxicity profiles; SBRT was modestly less expensive than IMRT.
The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage ...interactions, preferential binding of reactive conformations of substrate/H3O+ pairs, and increased substrate basicity. However, the increase in basicity dominates. Experimental structure–activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.
Background
Effective management strategies are crucial in minimizing the adverse consequences associated with the leafhopper,
Amrasca devastans
(Dist.) (Hemiptera: Cicadellidae). Economic limitations ...to entomopathogenic fungi production present a substantial challenge, particularly in developing countries. This study aimed to investigate a cost-effective solid-state fermentation (SSF) for large-scale production of
Purpureocillium lilacinum
PL1 conidia to manage
A. devastans
infestations in okra cultivation.
Results
Rice and maize were demonstrated as highly suitable substrates for producing conidia densities of over 2 × 10
10
conidia g
−1
. Furthermore, the influence of agricultural phytosanitary agents on the growth rates of
P. lilacinum
PL1 was evaluated. Certain pesticides were ineffective on the expansion of
P. lilacinum
PL1 colonies, while fungicides exhibited complete inhibition. The laboratory investigation revealed that 1 × 10
7
conidia ml
−1
of
P. lilacinum
PL1 exhibited a success rate of 88.66% in decreasing the population of
A. devastans
nymphs in vitro. Furthermore, field investigations carried out in okra plantations demonstrated that the utilization of
P. lilacinum
PL1 at the concentration of 1 × 10
7
conidia ml
−1
of resulted in a significant reduction of the pest nymph population by 72.87% subsequent to the 2 applications.
Conclusion
In conclusion, the cost-effective mass production of
P. lilacinum
PL1 conidia through SSF presents a promising solution for managing
A. devastans
infestations in okra farming, particularly in economically challenged regions.
Objectives
To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and ...obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes.
Methods
Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996–2020. Systemic therapy with or without local treatment (surgery, radiotherapy RT, or both). Uni‐ and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression.
Results
The median follow‐up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9–10 (77%), and median baseline prostate‐specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0–1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio HR 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high‐risk pathology (HR 2.05, P = 0.03) was associated with worse survival.
Conclusion
Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases.
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