The treatment delivery time of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) is generally longer than that of conventional radiotherapy. In theory, removing the flattening filter from the treatment head may reduce the beam-on time by enhancing the output dose rate, and then reduce the treatment delivery time. And in practice, there is a possibility of delivering the required fluence distribution by modulating the unflattened non-uniform fluence distribution. However, the reduction of beam-on time may be discounted by the increase of leaf-travel time and (or) verification-and-recording (V&R) time. Here we investigate the overall effect of flattening filter on the treatment delivery time of IMRT with MLCs implemented in the step and shoot method, as well as with compensators on six hybrid machines. We compared the treatment delivery time with/without flattening filter for ten nasopharynx cases and ten prostate cases by observing the variations of the ratio of the beam-on time, segment number, leaf-travel time and the treatment delivery time with dose rate, leaf speed and V&R time. The results show that, without the flattening filter, the beam-on time reduces for both static MLC and compensator-based techniques: the number of segments and the leaf-travel time increase slightly for the static MLC technique; the relative IMRT treatment delivery time decreases more with lower dose rate, higher leaf speed and shorter V&R overhead time. The absolute treatment delivery time reduction depends on the fraction dose. It is not clinically significant at a fraction dose of 2 Gy for the technique of removing the flattening filter, but becomes significant when the fraction dose is as high as that for radiosurgery.
The purpose of this work is to develop an online plan modification technique to compensate for the interfractional anatomic changes for prostate cancer intensity-modulated radiation therapy (IMRT) treatment based on daily cone beam CT (CBCT) images. In this proposed technique, pre-treatment CBCT images are acquired after the patient is set up on the treatment couch using an in-room laser with the guidance of the setup skin marks. Instead of moving the couch to rigidly align the target or re-planning using the CBCT images, we modify the original IMRT plan to account for the interfractional target motion and deformation based on the daily CBCT image feedback. The multileaf collimator (MLC) leaf positions for each subfield are automatically adjusted in the proposed algorithm based on the position and shape changes of target projection in the beam's eye view (BEV). Three typical prostate cases were adopted to evaluate the proposed technique, and the results were compared with those obtained with bony-structure-based rigid translation correction, prostate-based correction and CBCT-based re-planning strategies. The study revealed that the proposed modification technique is superior to the bony-structure-based and prostate-based correction techniques, especially when interfractional target deformation exists. Its dosimetric performance is closer to that of the re-planned strategy, but with much higher efficiency, indicating that the introduced online CBCT-guided plan modification technique may be an efficient and practical method to compensate for the interfractional target position and shape changes for prostate IMRT.
IMPORTANCE Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma.OBJECTIVE To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTSThis cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020.EXPOSURES Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. MAIN OUTCOMES AND MEASURESThe main outcomes were DFS and patterns of recurrence. RESULTS A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In (continued) Key Points Question Are there any differences in prognoses or recurrence patterns associated with gastric neuroendocrine carcinoma, mixed adenoneuroendocrine carcinoma, or adenocarcinoma? Findings This cohort study included 3689 patients with resectable gastric adenocarcinoma, gastric neuroendocrine carcinoma, or gastric mixed adeno...
Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy. Several targeted therapeutic agents have been developed and clinically used for the treatment of solid tumors such as breast cancer, non-small cell lung cancer, and renal cancer. Some of these reagents modulate growth factors and/or their receptors, which are abundant in cancer cells. Other reagents target the downstream signal transduction, survival pathways, and angiogenesis pathways that are abnormally activated in transformed cells or metastatic tumors. We will review current developments in this field, focusing specifically on treatments that can be applied to prostate cancers. Finally we will describe aspects of the future direction of the field with respect to discovering biomarkers to aid in identifying responsive prostate cancer patients.
To produce proinflammatory master cytokine IL-1β in macrophages, two stimulation pathways are needed including TLRs-NF-κB axis and NLRPs/ASC-caspase-1 axis. Different signals including exogenous and endogenous trigger inflammatory response distinctly. Among them, the role of endogenous stimulators of inflammation is poorly understood. As a component of hemoglobin, free heme is released when hemolysis or extensive cell damage occur which results in inflammatory response. Here, we find that heme induces IL-1β secretion through activating NLRP3 inflammasome in macrophages. Heme activates NLRP3 through P2X receptors, especially the P2X7R and P2X4R. Most importantly, significantly enhancement of heme level and activation of NLRPs/ASC-caspase-1 axis were observed in mice kidney after unilateral ureteral obstruction which could be inhibited by enforced expression of heme oxygenase-1 (HO-1). Our study proves that heme is a potential danger activator of NLRP3 inflammasome that plays an essential role in IL-1β secretion during kidney inflammation and provides new insight into the mechanism of innate immune initiation. Further investigation will be beneficial to develop new molecular target and molecular diagnosis indicator in therapy of kidney inflammation.
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