Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy.

BACKGROUND: The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. PATIENTS AND METHODS: This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. RESULTS: Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. CONCLUSION: In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence.

Lack of Prognostic Value of CTNNB1 Mutation Profile in Desmoid-Type Fibromatosis.

PURPOSE: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations. EXPERIMENTAL DESIGN: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS; progression, relapse, or death). We enrolled 628 patients managed by active surveillance, surgical resection, or systemic treatment as first-line therapy. RESULTS: Overall, 516 (82.2%) patients [368 females (71.3%), median age 40.3 years (range, 1-89)] were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The first-line management was active surveillance in 352 (68.2%), surgical resection in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% [95% confidence interval (CI), 60.5%-71.2%]. DF harboring p.S45F was significantly associated with male sex (P = 0.03), non-abdominal wall sites (P = 0.05), pain (P = 0.007), and large tumor size (P = 0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (HR, 1.06; 95% CI, 0.65-1.73; P = 0.81) or in multivariate analysis (HR, 0.91; 95% CI, 0.55-1.49; P = 0.71). CONCLUSIONS: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS. See related commentary by Greene and Van Tine, p. 3911.

Studies of Intra-Fraction Prostate Motion During Stereotactic Irradiation in First Irradiation and Re-Irradiation.

BACKGROUND: Understanding intra-fractional prostate motions is crucial for stereotactic body radiation therapy (SBRT). No studies have focused on the intra-fractional prostate motions during re-irradiation with SBRT. The objective was to evaluate these translational and rotational motions in primary treated patients and in the context of re-irradiation. METHODS: From January 2011 to March 2020, 162 patients with histologically proven prostate cancer underwent prostate SBRT, including 58 as part of a re-irradiation treatment. We used the continuous coordinates of the fiducial markers collected by an orthogonal X-ray dual-image monitoring system. The translations and rotations of the prostate were calculated. Prostate deviations representing overall movement was defined as the length of the 3D-vectors. RESULTS: A total of 858 data files were analyzed. The deviations over time in the group of primary treated patients were significantly larger than that of the group of re-irradiation, leading to a mean deviation of 2.73 mm (SD =1.00) versus 1.90 mm (SD =0.79), P<0.001. In the re-irradiation group, we identified displacements of -0.05 mm (SD =1.53), 0.20 mm (SD =1.46); and 0.42 mm (SD =1.24) in the left-right, superior-inferior and anterior-posterior planes. Overall, we observed increasing deviations over the first 30 min followed by a stabilization related to movements in the three translational axes. CONCLUSION: This is the first study to focus on intrafraction prostate motions in the context of re-irradiation. We observed that intra-fraction prostate motions persisted in the setting of re-irradiation, although they showed a significant reduction when compared with the first irradiation. These results will help to better estimate random errors during SBRT treatment of intra-prostatic recurrence after irradiation.

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma.

BACKGROUND: Most patients with advanced pancreatic adenocarcinoma (PA) treated with FOLFIRINOX experience adverse events requiring dose reduction. We aimed to assess the association between relative dose intensity (RDI) and disease control in a European setting. METHODS: We retrospectively included patients with advanced PA treated with three or more cycles of FOLFIRINOX between 2011 and 2018 in six French centers. We computed the cumulative single-agent RDI (csRDI) before the first reassessment for each FOLFIRINOX agent (oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion) and the cumulative multi-drug RDI (cmRDI) of their combination. The association between RDI and disease control or objective response at first reassessment was evaluated using multivariable logistic regression models controlling for performance status, liver metastases, and center. RESULTS: We included 243 patients. Median csRDIs were 81%, 79%, 75%, and 85% for oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion, respectively. Median cmRDI was 80%. None of the RDIs was significantly associated with disease control or objective response. Including RDI in a clinical model did not improve its ability to predict disease control; the area under the curve was 0.79 (95% CI: 0.73-0.85) with RDI versus 0.78 (95% CI: 0.72-0.85) without. Similar results were observed for the objective response. CONCLUSION: Pragmatic dose adjustments of FOLFIRINOX should be made by oncologists without considering a loss of effect.

Home hospitalization for palliative cancer care: factors associated with unplanned hospital admissions and death in hospital.

BACKGROUND: Home hospitalization at the end of life can sometimes be perturbed by unplanned hospital admissions (UHAs, defined as any admission that is not part of a preplanned care procedure), which increase the likelihood of death in hospital. The objectives were to describe the occurrence and causes of UHAs in cancer patients receiving end-of-life care at home, and to identify factors associated with UHAs and death in hospital. METHODS: A retrospective, single-center study (performed at a regional cancer center in the city of Lille, northern France) of advanced cancer patients discharged to home hospitalization between January 2014 and December 2017. We estimated the incidence of UHA over time using Kaplan-Meier method and Kalbfleish and Prentice method. We investigated factors associated with the risk UHA in cause-specific Cox models. We evaluated factors associated with death in hospital in logistic regressions. RESULTS: One hundred and forty-two patients were included in the study. Eighty-two patients (57.7 %) experienced one or more UHAs, a high proportion of which occurred within 1 month after discharge to home. Most UHAs were related to physical symptoms and were initiated by the patient's family physician. A post-discharge palliative care consultation was associated with a significantly lower incidence of UHAs. Sixty-five patients (47.8 % of the deaths) died in hospital. In a multivariate analysis, living alone and the presence of one or more children at home were associated with death in hospital. CONCLUSIONS: More than 40 % of cancer patients receiving end of life home hospitalization were not readmitted to hospital, reflecting the effectiveness of this type of palliative care setting. However, over half of the UHAs were due to an acute intercurrent event. Our results suggest that more efforts should be focused on anticipating these events at home - primarily via better upstream coordination between hospital physicians and family physicians.

Validation of Smartphone-Based Retinal Photography for Diabetic Retinopathy Screening.

BACKROUND AND OBJECTIVE: Screening for diabetic retinopathy (DR) is cost-effective when compared with disability loss for those who go blind in the absence of a screening program. We aimed to evaluate the sensitivity and specificity of a smartphone-based device for the screening and detection of DR. PATIENTS AND METHODS: A cross-sectional study of 220 patients with diabetes (440 eyes, all patients age 25 years or older) was completed. Tropicamide 0.5% was used for iris dilation followed by an indirect ophthalmoscopy using a 20-D lens. Retinal images were later obtained using a smartphone attached to an adaptable camera device. Retinal images permitted the visualization of the macular and papillary regions and were sent without compression via the internet to a retinal specialist for interpretation. Sensitivity and specificity were calculated for all cases and stages of DR. RESULTS: Using our standard examination method, the prevalence of DR and macular edema were 13.6% and 6.4%, respectively. With the smartphone-based retinal camera, the prevalence of DR and macular edema were 18.2% and 8.2%, respectively. Sensitivity and specificity for the detection of all stages of DR was 73.3% and 90.5%, respectively. For the detection of macular edema, sensitivity was 77.8%, and specificity was 95%. For severe nonproliferative DR (NPDR), sensitivity and specificity were 80% and 99%, respectively; for proliferative DR (PDR), they were both 100%. In the early stages of DR, specificity was 89.8% for mild NPDR and 97.1% for moderate NPDR. Sensitivity was 57.1% and 42.9%, respectively. CONCLUSION: Screening for DR using a smartphone-based retinal camera has a satisfactory specificity at all DR stages. Its sensitivity seems to be high only in the stages of DR necessitating a specific therapeutic decision (eg, macular edema, severe NPDR, and PDR). A smartphone-based retinal camera may be a useful device to screen for DR in resource-limited settings. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:S18-S22.].

Prognostic value of the texture analysis parameters of the initial computed tomographic scan for response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Baseline contrast-enhanced computed tomography (CT)-derived texture analysis in locally advanced rectal cancer could help offer the best personalized treatment. The purpose of this study was to determine the value of baseline-CT texture analysis in the prediction of downstaging in patients with locally advanced rectal cancer. PATIENTS AND METHODS: We retrospectively included all consecutive patients treated with neoadjuvant chemoradiation therapy (CRT) followed by surgery for locally advanced rectal cancer. Tumor texture analysis was performed on the baseline pre-CRT contrast-enhanced CT examination. Based on the selected model of downstaging with a penalized logistic regression in a training set, a radiomics score (Radscore) was calculated as a linear combination of selected features. A multivariable prognostic model that included Radscore and clinical factors was created. RESULTS: Of the 121 patients included in the study, 109 patients (90%) had T3-T4 cancer and 99 (82%) had N+ cancer. A downstaging response was observed in 96 patients (79%). In the training set (79 patients), the best model (ELASTIC-NET method) reduced the 36 texture features to a combination of 6 features. The multivariate analysis retained the Radscore (odds ratio [OR] = 13.25; 95% confidence interval [95% CI], 4.06-71.64; p < 0.001) and age (OR = 1.10/1 year; 1.03-1.20; p = 0.008) as independent factors. In the test set, the area under the curve was estimated to be 0.70 (95% CI, 0.48-0.92). CONCLUSION: This study presents a prognostic score for downstaging, from initial computed tomography-derived texture analysis in locally advanced rectal cancer, which may lead to a more personalized treatment for each patient.