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.
•The optimal therapeutic sequence for mCRPC is unclear.•There is no difference in OS/PFS between first-line abiraterone and enzalutamide.•In second line, docetaxel is better than androgen-receptor ...therapy.•Efforts must be made to better select the optimal first- and second-line treatments.
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.
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.
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.
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.
The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer is still debated. We included all consecutive chemo-naive mCRPC patients who have received first-line ART in two hospitals in France. In the first-line setting, there was no significant difference between abiraterone and enzalutamide. In the second-line setting, taxanes was superior to androgen-receptor therapy (HR: 0.63, 95% CI: 0.41-0.96, P = .034).
This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations.
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 (AS), surgical resection (SR), or systemic treatment as front-line therapy.
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 front-line management was AS in 352 (68.2%), SR 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%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 (hazard ratio HR=1.06; 95% confidence interval CI, 0.65-1.73; p=0.81), or in multivariate analysis (HR=0.91; 95% CI, 0.55-1.49; p=0.71).
We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS.
•We assessed baseline-CT texture analysis’s value in predicting downstaging in rectal cancer.•A multivariable prognostic model including Radscore and clinical factors was created.•CT-derived texture ...analysis helps offer personalized treatment for cancer patients.
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.
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.
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).
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.
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.
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.
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.
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..
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.
The role of both hormonal contraception and pregnancy on the outcomes of desmoid-type fibromatosis (DF) is debatable.
In the present study, we selected female patients of childbearing age from the ...prospective ALTITUDES cohort. The primary study endpoint was event-free survival (EFS), with an event defined as relapse or progression. We estimated the risk of events according to the use of hormonal contraception estrogen–progestin (EP) and progestin and pregnancy status using multivariate time-dependent models, controlling for major confounders.
A total of 242 patients (median age, 34.7 years) were included in the present study. The abdominal wall was the most common tumor site (51%). Patients were managed by active surveillance (80%) or surgery (20%). Pregnancy occurred within 24 months before, at the time of, and after DF diagnosis in 33%, 5%, and 10% of the cases, respectively. Exposure to hormonal contraception was documented within 24 months before, at the time of, and after diagnosis in 44%, 34%, and 39% of the cases, respectively. The 2-year EFS was 75%. After adjusting for DF location, tumor size, front-line treatment strategy, and hormonal contraception, we observed an increased risk of events occurring at 24 months after pregnancy hazard ratio (HR) = 2.09, P = 0.018. We observed no statistically significant association between the risk of events and current EP exposure (HR = 1.28, P = 0.65), recent EP exposure (within 1-24 months, HR = 1.38, P = 0.39), current progestin exposure (HR = 0.81, P = 0.66), or recent progestin exposure (HR = 1.05, P = 0.91).
In our study, a recent history of pregnancy was associated with an increased risk of progression/relapse in patients with newly diagnosed DF, whereas hormonal contraception did not demonstrate an association with progression/relapse.
•The role of hormonal contraception or pregnancy on DF outcomes is debatable.•We estimated the risk of progression or relapse according to the use of hormonal contraception and pregnancy status.•We found that recent exposure to hormonal contraception was not associated with DF outcomes.•A recent pregnancy was associated with a statistically significant increase in progression/relapse.•Abdominal wall DF outcomes showed similar findings as other DF outcomes.
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Background: The main treatments for mCRPC are 2 new ART (ABI, ENZA) and 2 taxanes doctaxel (DOC) and Cabazitaxel. The optimal sequence is currently not defined. An increasing number ...of pts are first treated with one of ART. In this population, data about efficacy of 2nd line (L2) are spare. We designed a retrospective study to evaluate activity of DOC vs ART in mCRPC pts treated with ART as L1 therapy. Methods: In this observational cohort study, we included all consecutive pts with ENZA or ABI as L1 for chemo-naïve mCRPC. We measured PFS and OS during both L1 & L2. To compare the efficacy of DOC versus ART as L2, we measured Growth Modulation Index (GMI=Time To progression with L2/TTP with L1) and we used Cox model to compare PFS/OS in both arm, in both univariate & multivariate analysis using propensity score. Results: We included 175 pts, including 75 treated ENZA and 100 with ABI as L1. 69 (39%) pts received DOC and 30 (17%) pts received ART as L2; 76 (43%) did not receive L2. Median follow-up was 36 months (CI95%: 30.4 - 40). From the starting of L1, PFS was 13.0 months (CI95% 11.0 – 15.0), OS was 34.5 months (CI95%: 28.7 – 38.6). There was no difference between ENZA and ABI in PFS and OS (p=0.684). From the start of L2, the median PFS was 6.0 months (CI95%: 5.0 – 6.6) and the median OS was 18.0 months (CI95%: 13.9 – 21.4). We found a significant benefit in PFS for DOC vs ART in L2 (6.7 months vs 4.0 months, HR 0.60 CI95%: 0.31 – 0.96, p=0.03). This benefit did not reach the level of significance in OS (19.5 months vs 12.0 months, HR 0.60 CI95%: 0.35 – 1.03, p=0.1). ECOG-PS and time of castration resistance were associated with OS in multivariable analysis and then used in propensity score. After adjustment to both parameters, we found no difference in PFS (p=0.2) and OS (p=0.1) in pts receiving DOC vs ART as L2. Only 56% of pts received L2. Probability for GMI being >1.33 was not significantly different between DOC (19%) and ART (13%), p=0.099. Conclusions: ABI and ENZA are similarly active in L1 mCRPC. In univariate analysis, L2 with DOC seemed more active than ART. However this benefit was not retained after adjustment to propensity score.
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11510
Background: DF rare locally aggressive fibroblastic non-metastasizing tumor, with an unpredictable course. Its management remains challenging, there is a current shift in standard ...of care from large surgical resection (SR) to active surveillance (AS). Most of DF display somatic mutation of CTNNB1, with three major hotpots: S45F, T41A and S45P. The poor prognosis of S45F is a matter of debate (Timbergen et al. Ann Surg 2019). Methods: ALTITUDES (NCT02867033) is a nationwide prospective registry of DF, diagnosed from January 2016 to December 2020 and confirmed by central pathological review. CTNNB1 mutations were identified by NGS. Primary endpoint was event-free survival (including disease progression or relapse). We have selected pts managed by AS, SR or systemic treatments as front-line. Pt undergoing R2 resection and then managed by follow-up were part of AS group. Prognostic factors were assessed using univariate and multivariate Cox Model. Results: From the 630-pts enrolled in ALTITUDES, 500 (79.3%) were eligible for the present analysis. Exclusion criteria were diagnosis before 2016 in 13 pts, multiple DF in 33 pts, 39 pts without CTNNB1 mutation analysis, and 45 pts receiving other treatments. The study population included 349 females (69.8%), the median age was 40 years (range 1-89). Abdominal wall was the predominant primary site: 161 pts (32.2%). In 430 (86.0%) cases, there was a CTNNB1 mutation, including, S45F in 56 cases (11.2%). In 70 cases (14.0%), we did not identify CTNNB1 mutation. The front-line managements were AS in 361 pts (72.2%), SR with R0/R1 margins in 57 cases (11.4%) and systemic treatments in 82 pts (16.5%). The median follow-up was 23 months (Range, 0.4-55). Overall, progression or relapse occurred in 128 pts (25.6%). We observed a significant EFS-difference between treatment groups, both in univariate and multivariate analysis with, compared to AS, a better outcome in patients with SR and worse outcome in patients who had received a systemic treatment (p = 0.01 in multivariate analysis). The risk of event was significantly associated with the tumor size, with a HR = 1.46 in tumors larger than 50 mm compared to smaller tumors (95%CI, 1.01-2.10, p = 0.04). We did not observe any significant association between the CTNNB1 mutational status and the outcome: compared to patients with another mutation, the hazard ratio associated with a S45F mutation was HR = 0.84 (95%CI, 0.48-1.46, p = 0.53) in multivariate analysis. Age, gender, location (abdominal wall versus other) were not associated with EFS. Conclusions: In this large prospective study, S45F was not an independent poor prognostic factor in DF. Size and front-line treatment drive both the outcome. The understanding and prediction of natural course of DF require further studies.
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