Purpose
Unresectable intrahepatic cholangiocarcinoma (ICC) signifies a poor prognosis with limited treatment options beyond systemic chemotherapy. This study’s purpose was to evaluate the safety, ...efficacy, and potential for downstaging to resection of yttrium-90 (Y90) radioembolization for treatment of unresectable ICC.
Materials and Methods
From 2004 to 2020, 136 patients with unresectable ICC were treated with radioembolization at a single institution. Retrospective review was performed of a prospectively collected database. Outcomes were (1) biochemical and clinical toxicities, (2) local tumor response, (3) time to progression, and (4) overall survival (OS) after Y90. Univariate/multivariate survival analyses were performed. A subgroup analysis was performed to calculate post-resection recurrence and OS in patients downstaged to resection after Y90.
Results
Grade 3+ clinical and biochemical toxicities were 7.6% (
n
= 10) and 4.9% (
n
= 6), respectively. Best index lesion response was complete response in 2 (1.5%), partial response in 42 (32.1%), stable disease in 82 (62.6%), and progressive disease in 5 (3.8%) patients. Median OS was 14.2 months. Solitary tumor (
P
< 0.001), absence of vascular involvement (
P
= 0.009), and higher serum albumin (
P
< 0.001) were independently associated with improved OS. Eleven patients (8.1%) were downstaged to resection and 2 patients (1.5%) were bridged to transplant. R0-resection was achieved in 8/11 (72.7%). Post-resection median recurrence and OS were 26.3 months and 39.9 months, respectively.
Conclusion
Y90 has an acceptable safety profile and high local disease control rates for the treatment of unresectable ICC. Downstaging to resection with > 3 years survival supports the therapeutic role of Y90 for unresectable ICC.
Level of Evidence
: Level 3, single-arm single-center cohort study.
Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.
To compare RCB distributions between randomized control and investigational ...treatments within subtypes of breast cancer and explore the relationship with survival.
The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate.
Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery.
Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS).
A total of 938 women (mean SD age, 49 11 years; 66 7% Asian, 103 11% Black, and 750 80% White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio HZR, 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 27%), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 52%), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 21%). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis.
In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy.
ClinicalTrials.gov Identifier: NCT01042379.
This clinical trial combined fulvestrant with the anti-androgen enzalutamide in women with metastatic ER+/HER2- breast cancer (BC). Eligible patients were women with ECOG 0-2, ER+/HER2- measurable or ...evaluable metastatic BC. Prior fulvestrant was allowed. Fulvestrant was administered at 500 mg IM on days 1, 15, 29, and every 4 weeks thereafter. Enzalutamide was given at 160 mg po daily. Fresh tumor biopsies were required at study entry and after 4 weeks of treatment. The primary efficacy endpoint of the trial was the clinical benefit rate at 24 weeks (CBR24). The median age was 61 years (46-87); PS 1 (0-1); median of 4 prior non-hormonal and 3 prior hormonal therapies for metastatic disease. Twelve had prior fulvestrant, and 91% had visceral disease. CBR24 was 25% (7/28 evaluable). Median progression-free survival (PFS) was 8 weeks (95% CI: 2-52). Adverse events were as expected for hormonal therapy. Significant (p < 0.1) univariate relationships existed between PFS and ER%, AR%, and PIK3CA and/or PTEN mutations. Baseline levels of phospho-proteins in the mTOR pathway were more highly expressed in biopsies of patients with shorter PFS. Fulvestrant plus enzalutamide had manageable side effects. The primary endpoint of CBR24 was 25% in heavily pretreated metastatic ER+/HER2- BC. Short PFS was associated with activation of the mTOR pathway, and PIK3CA and/or PTEN mutations were associated with an increased hazard of progression. Thus, a combination of fulvestrant or other SERD plus AKT/PI3K/mTOR inhibitor with or without AR inhibition warrants investigation in second-line endocrine therapy of metastatic ER+ BC.
About 50% of sarcomas have specific pathology-defining molecular alterations including mutations, fusion genes, and gene amplifications. Some of these alterations appear to be oncogenic drivers, and ...a subset can be utilized as targets for standard or experimental molecularly targeted agents in the clinic. In addition, immunotherapies may have a growing role in the treatment of sarcomas in the future.
Purpose: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with
metastatic breast cancer (MBC).
Patients and Methods: Twenty-seven ...MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free
survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical
outcomes.
Results: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The
most common grade 4 toxicities per patient were as follows: 2 (7%)—pulmonary embolus, 1 (4%)—febrile neutropenia, and 1 (4%)—infection;
grade 3 toxicities were 4 (15%)—neutropenia, 4 (15%)—fatigue, 2 (7%)—neuropathy, 2 (7%)—athralgias, 2 (7%)—stomatitis, 1 (7%)—pleural
effusion, and 1 (4%)—hypertension. The overall response rate was 52% 95% confidence interval (95% CI), 32-71%, median response
duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3
months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly
associated with response to the combination.
Conclusion: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating
E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.
Prenatal hydronephrosis is one of the most common anomalies detected on prenatal ultrasonography. Patients with prenatal hydronephrosis and ureteral dilation are at increased risk of urinary tract ...infection (UTI) and continuous antibiotic prophylaxis (CAP) is recommended. However, current guidelines do not define the minimum ureteral diameter that would be considered a dilated ureter in these patients.
We evaluate the definition of clinically relevant hydroureter, its association with UTI, and the impact of CAP.
Patients with prenatal hydronephrosis from seven centers were enrolled into the Society for Fetal Urology Prenatal Hydronephrosis Registry from 2008 to 2020. Patients with ureteral measurement on ultrasound were included. Patients with ureterocele, ectopic ureter, neurogenic bladder, posterior urethral valves, horseshoe or solitary kidney, known ureteropelvic junction obstruction, or follow-up less than one month were excluded. Primary outcome was UTI. Analyses were performed using Cox regression.
Of the 1406 patients enrolled in the registry, 237 were included. Seventy-six percent were male, ureteral diameter ranged from 1 to 34 mm, and median follow-up was 2.2 years. Patients with ureters 7 mm or greater had nearly three times the risk of UTI adjusting for sex, circumcision status, antibiotic prophylaxis and hydronephrosis grade (HR = 2.7, 95% CI: 1.1–6.5, p = 0.03; Figure). In patients who underwent voiding cystourethrogram (VCUG; 200/237), ureteral dilation of 7 mm or more identified patients at increased UTI risk controlling for sex, circumcision status, vesicoureteral reflux and hydronephrosis grade (HR = 2.3, 95% CI: 0.97–5.6, p = 0.06). CAP was significantly protective against UTI (HR = 0.50 (95% CI: 0.28–0.87), p = 0.01). Among patients who underwent VCUG and did not have vesicoureteral reflux, ureteral dilation 7 mm or greater corresponded with higher UTI risk compared to ureteral diameter less than 7 mm on multivariable analysis (HR = 4.6, 95% CI: 1.1–19.5, p = 0.04).
This is the first prospectively collected, multicenter study to demonstrate that hydroureter 7 mm or greater identifies a high-risk group for UTI who benefit from antibiotic prophylaxis. In contrast, patients with prenatal hydronephrosis and non-refluxing hydroureter less than 7 mm may be managed more conservatively. Display omitted
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