Spontaneous regression of crizotinib-associated complex renal cysts during continuous crizotinib treatment.
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ABSTRACT:
SUBMITTER: Klempner SJ
PROVIDER: S-EPMC4153456 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
Publications
Spontaneous regression of crizotinib-associated complex renal cysts during continuous crizotinib treatment.
Klempner Samuel J SJ Aubin Golnaz G Dash Atreya A Ou Sai-Hong Ignatius SH
The oncologist 20140805 9
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Project description:An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Serious adverse event (SAE) reports of renal cysts from a safety database of 1375 patients from four clinical trials were reviewed. A blinded, retrospective, independent radiologic review (IRR) was performed using scans from patients on study for ? 6 months in three clinical trials; risk factors for renal cyst development were assessed. Among 17 patients with renal cysts reported as SAEs, evidence of invasion into adjacent structures was noted in seven patients, with no evidence of malignancy found. These patients generally did not require dose reductions, none required permanent crizotinib discontinuation due to this AE, and most continued treatment with clinical benefit. In the blinded IRR, among 255 crizotinib-treated patients, 22%, 3%, and 2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6-month tumor assessment, 9% of all patients had acquired new cysts, and 2% of patients with preexisting cysts had developed new cysts and enlargements (>50%) of preexisting simple cysts. Asians appeared to have an increased risk of developing new cysts on treatment; Koreans in particular had 5.18 times higher odds of developing cysts than non-Asians (95% confidence interval, 1.51-17.78; P = 0.05). Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK-positive NSCLC. While close monitoring is recommended, dosing modification was not generally necessary, allowing patients to remain on crizotinib treatment.
| S-EPMC4472211 | biostudies-literature
Project description:Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa. While the initial dosing recommendation for renally competent patients and patients undergoing continuous renal replacement therapy (cRRT) was 500 mg every 8 h (q8h), the dose for renally competent patients was updated to 1 g q8h in June 2012. There are no updated data for the dosing of patients on continuous renal replacement therapy. The original dosing regimen for cRRT patients was based on nonseptic patients, while newer publications chose comparatively low target concentrations for a carbapenem. Thus, there is an urgent need for updated recommendations for dosing during cRRT. In the trial presented here, we included 13 oliguric septic patients undergoing cRRT in an intensive care setting. Five patients each were treated with hemodiafiltration or hemodialysis, while three patients received hemofiltration treatment. All patients received 1 g doripenem every 8 h. Doripenem concentrations in the plasma and ultrafiltrate were measured over 48 h. The mean hemofilter clearance was 36.53 ml/min, and the mean volume of distribution was 59.26 liters. The steady-state trough levels were found at 8.5 mg/liter, with no considerable accumulation. Based on pharmacokinetic and pharmacodynamic considerations, we propose a regimen of 1 g q8h, which may be combined with a loading dose of 1.5 to 2 g for critically ill patients. (This study has been registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).
| S-EPMC4775919 | biostudies-literature
Project description:Crizotinib is highly effective against anaplastic lymphoma kinase-positive and c-ros oncogen1-positive non-small cell lung cancer. Renal dysfunction is associated with crizotinib therapy but the mechanism is unknown. Here, we report a case of anaplastic lymphoma kinase positive non-small cell lung cancer showing multiple cysts and dysfunction of the kidneys during crizotinib administration. We also present results demonstrating that long-term crizotinib treatment induces fibrosis and dysfunction of the kidneys by activating the tumor necrosis factor-α/nuclear factor-κB signaling pathway. In conclusion, this study shows the renal detrimental effects of crizotinib, suggesting the need of careful monitoring of renal function during crizotinib therapy.
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Project description:ObjectiveThe prenatal diagnosis of fetal intra-abdominal cysts is challenging. This study aimed to evaluate the diagnostic ability of prenatal ultrasound for fetal intra-abdominal cysts and to develop a predictive method for pre- and postnatal outcomes.MethodsWe retrospectively reviewed fetuses with ultrasound-detected intra-abdominal cysts between January 2013 and January 2020. The maternal-fetal clinical characteristics and ultrasound parameters were integrated into a model of pre- or postnatal outcomes.ResultsThe study enrolled 190 eligible fetuses, including 94 cases of spontaneous regression, 33 cases of conservative management and 63 cases of surgical intervention. For the 63 cases of surgical intervention, prenatal ultrasound was found to identify fetal intra-abdominal cysts with 80.00% sensitivity (95% CI: 67.03%-89.57%), 37.50% specificity (95% CI: 8.52%-75.51%), 89.80% positive predictive value (95% CI: 83.51%-93.86%), 21.43% negative predictive value (95% CI: 8.80%-43.53%) and 74.60% accuracy (95% CI: 62.06%-84.73%). The predictive model of prenatal spontaneous regression was as follows: y = -3.291 + 0.083 × gestational age + 1.252 × initial diameter, with an area under the curve (AUC) of 0.819 (95% CI: 0.739-0.899) and an optimal cut-off value of 0.74. The large cyst diameter before delivery was an independent predictor of postnatal surgical intervention (p < 0.001), with an AUC of 0.710 (95% CI: 0.625-0.794) and an optimal cut-off value of 3.35 cm.ConclusionAlthough ultrasound has a limited ability in the accurate diagnosis of fetal abdominal cysts, a simple method of measuring the diameter can predict fetal outcomes and identify the cases that may require surgical intervention or spontaneous regression.
| S-EPMC9891233 | biostudies-literature
Project description:ObjectiveThe objective was to assess the interobserver agreement rate, progression rates and malignancy rates in the assessment of complex renal cysts (≥ Bosniak IIF) using a population-based database.MethodsA regional database identified 452 complex renal cysts in 415 patients between 2009 and 2019. Each patient was tracked and followed up using a unique identifier and deterministic linkage methodology. The interobserver agreement rate between radiologists was calculated using a weighted kappa statistic. Progression and malignancy rates of cysts (Bosniak ≥IIF) over the 11-year period were calculated.ResultsThe linear-weighted kappa value was 0.69 for all complex cysts. The rate of progression and regression of Bosniak IIF cysts was 4.6% (7/151) and 3.3% (5/151), respectively. All malignant IIF cysts progressed within 16 months of diagnosis. The malignancy rate of surgically resected Bosniak III and IV cysts was 79.3% (23/29) and 84.5% (39/46), respectively. Of all malignant tumours, 73.8% and 93.7% were of low ISUP grade and low stage, respectively.ConclusionsThis study further confirms that there is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. The progression rate of Bosniak IIF cysts is low, but the malignancy rates of surgically resected Bosniak IIF, III and IV cysts are high. Benign cysts are frequently resected, and a very high proportion of histopathologically confirmed cancers in complex renal cysts are of low grade and stage.Key points• There is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. • The rate of progression of Bosniak IIF cysts is low, and malignant cysts progress early during surveillance. Although the malignancy rates of resected Bosniak IIF, III and IV cysts are high, the rate of benign cyst resection is significant.
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Project description:BACKGROUND:Bosniak III and IV cysts have a high risk of malignancy and have traditionally been managed surgically. However, growing evidence suggests that many can be managed by active surveillance. The main objective of this study was to characterize the use of surveillance in the management of complex renal cysts. METHODS:A web-based survey was sent to all registered, active members of the Canadian Urological Association (N?=?583) in October 2018. RESULTS:The survey response rate was 24.7%. Management of Bosniak III cysts varied considerably. A large proportion of respondents (33.1%) offered active surveillance in >?50% of cases. Only 13.7% of respondents reported never or rarely (<?5% of cases) offering surveillance. In contrast, for Bosniak IV cysts, 60.1% of urologists never or rarely offered surveillance, while only 10.1% offer it in >?50% of cases. A significantly greater proportion of academic urologists, compared to non-academic urologists, viewed surveillance as a management option for patients with a Bosniak III or IV cyst. The most commonly reported barriers to a greater adoption of surveillance were concerns regarding its oncologic safety, the lack of data to support surveillance in this population, and the lack of triggers for discontinuation of active surveillance and intervention. CONCLUSIONS:Despite active surveillance being included as a management option in guidelines, many Canadian urologists are reluctant to offer surveillance to patients with Bosniak III or IV cysts. Practice patterns are heterogeneous among those offering surveillance. High-quality studies are required to better define the benefits and risks of cystic renal mass surveillance.
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