Imaging for local recurrence of breast cancer.

PURPOSE: Isolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI. Since early detection is crucial for morbidity and mortality, the evaluation and constant improvement of imaging methods of the breast is necessary. METHODS: We retrospectively analyzed the data of 1499 former BC patients that received imaging of the breast at a tertiary-care university hospital between 2015 and 2020. The analysis comprised various patient characteristics, such as breast density, age, tumor size and subtype, and their influence on BC detection rates by the different imaging methods. RESULTS: Within the patient sample, 176 individuals (11.7% of former BC patients) were diagnosed with either ILRR or CBC. CBC was observed in 32.4% of patients, while both ILRR and secondary breast cancer occurred in 20.5% and 23.9% of all patients. Sensitivity of MRI, mammography, and ultrasound for recurrent malignancy was 97.9%, 66.3%, and 67.8%, respectively. ILRR and CBC detection rates were similar for patients with and without HBOC history. Lower breast density and larger tumor size increased the detection rates of all imaging modalities. CONCLUSION: In breast cancer survivors, MRI might improve the early detection of ILRR and CBC in both HBOC and nHBOC patients.

Potential of employing a quantum iterative reconstruction algorithm for ultra-high-resolution photon-counting detector CT of the hip.

INTRODUCTION: This study investigated the image quality of a new quantum iterative reconstruction algorithm (QIR) for high resolution photon-counting CT of the hip. METHODS: Using a first-generation photon-counting CT scanner, five cadaveric specimens were examined with ultra-high-resolution protocols matched for radiation dose. Images were post-processed with a sharp convolution kernel and five different strength levels of iterative reconstruction (QIR 0 - QIR 4). Subjective image quality was rated independently by three radiologists on a five-point scale. Intraclass correlation coefficients (ICC) were computed for assessing interrater agreement. Objective image quality was evaluated by means of contrast-to-noise-ratios (CNR) in bone and muscle tissue. RESULTS: For osseous tissue, subjective image quality was rated best for QIR 2 reformatting (median 5 [interquartile range 5-5]). Contrarily, for soft tissue, QIR 4 received the highest ratings among compared strength levels (3 [3-4]). Both ICCbone (0.805; 95% confidence interval 0.711-0.877; p < 0.001) and ICCmuscle (0.885; 0.824-0.929; p < 0.001) suggested good interrater agreement. CNR in bone and muscle tissue increased with ascending strength levels of iterative reconstruction with the highest results recorded for QIR 4 (CNRbone 29.43 ± 2.61; CNRmuscle 8.09 ± 0.77) and lowest results without QIR (CNRbone 3.90 ± 0.29; CNRmuscle 1.07 ± 0.07) (all p < 0.001). CONCLUSION: Reconstructing photon-counting CT data with an intermediate QIR strength level appears optimal for assessment of osseous tissue, whereas soft tissue analysis benefitted from applying the highest strength level available. IMPLICATIONS FOR PRACTICE: Quantum iterative reconstruction technique can enhance image quality by significantly reducing noise and improving CNR in ultra-high resolution CT imaging of the hip.

Evaluation of the nutritional status of older hospitalised geriatric patients: a comparative analysis of a Mini Nutritional Assessment (MNA) version and the Nutritional Risk Screening (NRS 2002).

BACKGROUND: The present study aimed to evaluate a short-form (MNA-SF) version of the Mini Nutritional Assessment (MNA), in which some of the items were operationalised, based on scores from tools used for a comprehensive geriatric assessment, as a method for analysing the nutritional status of hospitalised geriatric patients. We compared this MNA-SF version with the corresponding MNA long-form (MNA-LF) and Nutritional Risk Screening 2002 (NRS 2002) in terms of completion rate, prevalence and agreement regarding malnutrition and/or the risk of this. METHODS: In total, 201 patients aged ≥65 years who were hospitalised in geriatric wards were included in this analysis. RESULTS: The MNA-SF, MNA-LF and NRS 2002 were completed in 98.0%, 95.5% and 99.5% of patients (P = 0.06), respectively. The MNA-SF, MNA-LF and NRS 2002 categorised 93.4%, 91.1% and 66.0% of patients as being malnourished or at risk of being malnourished (P < 0.001). Agreement between the MNA-SF and MNA-LF was substantial (κ = 0.70, P < 0.001). No agreement between the MNA-SF and NRS 2002 was found (κ = -0.12, P < 0.001). Interestingly, NRS 2002 part 1 (prescreening) revealed a false negative rate of 21.0% (only in patients aged ≥70 years who showed moderate disease severity) in relation to the NRS 2002 part 2. CONCLUSIONS: The MNA-SF version emerged as a useful tool for evaluating the nutritional status of hospitalised geriatric patients. The NRS 2002 part 1 showed limited value as a prescreening aid in relation to the NRS 2002 part 2 in the same group of patients.

A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer.

BACKGROUND: This phase 1 clinical trial was conducted to determine the safety, maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC). METHODS: Patients with refractory stage IV CRC were treated with bevacizumab 5 mg kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour, endothelial, and immune cell subsets were measured. RESULTS: Thirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks. Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased insignificantly after adding cyclophosphamide. Seven patients (20%) experienced stable disease for >6 months. Circulating tumour, endothelial, or immune cells were not associated with progression-free survival. CONCLUSION: The combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level.

Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis.

BACKGROUND: Temozolomide (TMZ) is widely used for chemotherapy of metastatic melanoma. We hypothesized that epigenetic modulators will reverse chemotherapy resistance, and in this article, we report studies that sought to determine the recommended phase 2 dose (RP2D), safety, and efficacy of decitabine (DAC) combined with TMZ. PATIENTS AND METHODS: In phase I, DAC was given at two dose levels: 0.075 and 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m(2) qd for weeks 2-5 of a 6-week cycle. The phase II portion used a two-stage Simon design with a primary end point of objective response rate (ORR). RESULTS: The RP2D is DAC 0.15 mg/kg and TMZ 75 mg/m(2). The phase II portion enrolled 35 patients, 88% had M1c disease; 42% had history of brain metastases. The best responses were 2 complete response (CR), 4 partial response (PR), 14 stable disease (SD), and 13 progressive disease (PD); 18% ORR and 61% clinical benefit rate (CR + PR + SD). The median overall survival (OS) was 12.4 months; the 1-year OS rate was 56%. Grade 3/4 neutropenia was common but lasted >7 days in six patients. CONCLUSIONS: The combination of DAC and TMZ is safe, leads to 18% ORR and 12.4-month median OS, suggesting possible superiority over the historical 1-year OS rate, and warrants further evaluation in a randomized setting.

Phase I study investigating the safety and feasibility of combining imatinib mesylate (Gleevec) with sorafenib in patients with refractory castration-resistant prostate cancer.

BACKGROUND: Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients. METHODS: Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay. RESULTS: Seventeen patients were enrolled; 10 evaluable (6 at 400 mg S qd with 300 mg IM qd (DL0) and 4 at 400 mg S bid with 300 mg IM qd (DL1)); inevaluable patients received <1 cycle. The median age was 73 (57-89); median prostatic serum antigen was 284 ng ml(-1) (11.7-9027). Median number of prior non-hormonal therapies was 3 (1-12). Dose-limiting toxicities were diarrhoea and hand-foot syndrome. Maximum tolerated dose was 400 mg S and 300 mg IM both daily. No biochemical responses were observed. Two patients had stable disease by RECIST. Median time to progression was 2 months (1-5). Median OS was 6 months (1-30+) with 3/17 patients (17%) alive at 21 months median follow-up. Ten patients had PK data suggesting that S reduced IM clearance by 55%, resulting in 77% increased exposure (P=0.005; compared with historical data). CONCLUSION: This is the first report showing that S+IM can be administered in CRPC at a dose of 400 mg S and 300 mg IM, daily.