Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity testing: a phase 2, single-center, open-label, and non-comparative study.

BACKGROUND: Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options. METHODS: In this phase 2, single-center, open-label, non-comparative study (ClinicalTrials.gov, register NCT03251612), we enrolled 90 patients with metastatic colorectal cancer following progression on or after standard therapy. Participants were 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and metastasis available for biopsy. Biopsies from the metastatic site were cultured using organoids model. Sensitivity testing was performed with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the proportion of patients alive without disease progression at two months per local assessment. RESULTS: Biopsies available from 82 to 90 patients were processed for cell culture, of which 44 successfully generated organoids with at least one treatment suggested. The precision cohort of 34 patients started treatment and the primary endpoint, progression-free survival (PFS) at two months was met in 17 patients (50%, 95% CI 32-68), exceeding the pre-defined level (14 of 45; 31%). The median PFS was 67 days (95% CI 51-108), and the median overall survival was 189 days (95% CI 103-277). CONCLUSIONS: Patient-derived organoids and in-vitro sensitivity testing were feasible in a cohort of metastatic colorectal cancer. The primary endpoint was met, as half of the patients were without progression at two months. Cancer patients may benefit from functional testing using tumor-derived organoids. TRIAL REGISTRATION: ClinicalTrials.gov, register NCT03251612.

Interobserver Reliability and the Sigmoid Takeoff-An Interobserver Study.

Background: Colorectal cancer is the second most common cancer worldwide. The sigmoid takeoff is the landmark where the colon sigmoid curves toward the sacrum viewed from sagittal magnetic resonance imaging (MRI). The purpose of this study was to assess interobserver variability in the assessment of the anal verge and anorectal junction in patients diagnosed with rectal cancer on magnetic resonance imaging (MRI). Materials and Methods: The rectal MRI examinations were performed using a 1.5- or 3.0-tesla unit using an anterior coil and a standard scan protocol. Two senior radiologists assessed MRI scans from patients under investigation for rectal cancer. The two observers assessed the anal verge and takeoff in cm independently. Difference in agreement between the observers were evaluated using intraclass correlation (ICC) and graphically by Bland-Altman plots. Results: The study population (n = 122) included 68 (55.7%) female and 54 (44.3%) male subjects. The overall median age was 69.5 years (range 39-95 years). There was perfect agreement between the two observers when defining rectal tumor above or below the takeoff landmark. The reliability of measuring the distance from the anal verge to the sigmoid takeoff was 0.712. Conclusion: Overall, the study found a moderate reliability in assessing the location of the sigmoid takeoff, with a low difference in the distance measuring, as well as a good consensus concerning the determination of tumors in relation to the sigmoid takeoff. Routine implementation of this information within the report seems reasonable.

CT and 3 Tesla MRI in the TN Staging of Colon Cancer: A Prospective, Blind Study.

(1) Background: Computer tomography (CT) scanning is currently the standard method for staging of colon cancer; however, the CT based preoperative local staging is far from optimal. The purpose of this study was to investigate the sensitivity and specificity of magnetic resonance imaging (MRI) compared to CT in the T- and N-staging of colon cancer. (2) Methods: Patients underwent a standard contrast-enhanced CT examination. For the abdominal MRI scan, a 3 Tesla unit was used, including diffusion weighted imaging (DWI). Experienced radiologists reported the CT and MRI scans blinded to each other and the endpoint of the pathological report. (3) Results: From 2018 to 2021, 134 patients received CT and MRI scans. CT identified 118 of the 134 tumors, whereas MRI identified all tumors. For discriminating between stage T3ab and T3cd, the sensitivity of CT was 51.1% and of MRI 80.0% (p = 0.02). CT and MRI showed a sensitivity of 21.4% and 46.4% in detecting pT4 tumors and a specificity of 79.0% and 85.0%, respectively. (4) Conclusion: Compared to CT, the sensitivity of MRI was statistically significantly higher in staging advanced T3cd and T4 tumors. MRI has the potential to be used in the treatment planning of colon cancer.

Diagnostic yield and complications of transthoracic computed tomography-guided biopsies.

INTRODUCTION: The widespread use of computed tomography (CT) improves detection of pulmonary lesions, which are not only detected at an increased rate but also at a smaller size. CT-guided lung biopsies are now more frequently used than fluoroscopy-guided lung biopsies. The main aim of the present paper was to investigate the outcome and complications of the biopsies. METHODS: We retrospectively collected the results and information from 520 CT-guided thorax biopsies. All biopsies were performed with CT-guided "beam-through" technique, using a 64-slice CT scanner. RESULTS: In 86% of the biopsies, the tissue material was found to be sufficient. In 32% of the biopsies, a complication arose, mostly pneumothorax (30%), but chest drainage was needed in only 15% of the 520 cases. Patients with more than ten cigarette pack-years had a complication risk that was twice as high at that of patients with fewer pack-years. We found that the risk of pneumothorax increased the further the lesion was from the skin surface, the smaller the lesions were and when the patient was biopsied in a lateral position. We also found a higher risk of complications in females than in males. CONCLUSIONS: CT-guided biopsy is an excellent tool for analysing pulmonary lesions. The present study clearly shows that the risk of developing a pneumothorax is significantly increased among smokers and former smokers with more than ten pack-years. FUNDING: none. TRIAL REGISTRATION: not relevant.

Inter- and intraobserver agreement in detection of testicular microlithiasis with ultrasonography.

BACKGROUND: Ultrasonography of the testis is a well-established diagnostic tool in detection of testicular microlithiasis (TML). Operator-dependent diagnostic variation related to skill, knowledge, and operator consistency are factors that influence detection of TML. PURPOSE: To determine inter- and intraobserver agreement for detection of TML using ultrasonography for a group of physicians with no or limited experience compared to a group of experience senior radiologists. MATERIAL AND METHODS: Between May and September 2014 a total of six observers evaluated 34 patients scrotal ultrasonography recorded from September to December 2013. The observers were blinded to patient history and previous ultrasonography. Three of the observers had no or limited experience with detection of TML, and three of the observers had more than 15 years of experience. Each observer reviewed all the scrotal ultrasonography recordings twice with a time interval of 3 months. RESULTS: The inter-observer agreement showed substantial agreement and up to almost perfect agreement (κ = 0.86). Both the experienced and less experienced observers had a higher agreement in detecting and grading TML in their second reading. CONCLUSION: The ultrasonography grading system of TML in this study showed to be reproducible, with an inter- and intraobserver agreement ranging between substantial agreement and up to almost perfect agreement with many years of experience not necessarily being essential.

Elastography and diffusion-weighted MRI in patients with rectal cancer.

OBJECTIVE: The current literature has described the usefulness of elastography and diffusion-weighted MRI in patients with cancer, but to the best of our knowledge so far none of them has compared the two new methods. The tumour cell density is related to the MRI-measured apparent diffusion-weighted coefficient (ADC). The purpose of the present study was to compare quantitative elastography based on ultrasound shear wave measurements with MRI ADC. METHODS: We prospectively examined 52 patients with histopathologically proven rectal cancer. The mean age was 67 years (range 42-90 years). Males: 39, females: 13. Tumour elasticity was measured transgluteally using the acoustic radiation force impulse (ARFI) to generate information on the mechanical properties of the tissue. The objective quantitative elastography shear wave velocity was blindly compared with the ADC measurements using a 1.5-T MRI system. RESULTS: The mean tumour elasticity was 3.05 m s(-1) [standard deviation (SD): 0.79], and the mean ADC was 0.69 × 10(-3) mm(2) s(-1) (SD: 0.27). Elasticity was inversely strongly correlated with ADC, r = -0.65 (Salkin scale). ARFI = 4.392 - 1.949 × ADC, R(2) = 0.43, p < 0.0001. Intercept = 4.392 (95% CI: 3.92 to 4.86), slope = -1.949 (95% CI: -1.31 to -2.59), p < 0.0001. CONCLUSION: Elasticity correlates with the estimated diffusion restriction by MRI ADC measurements in rectal tumours. The relationship between ARFI and ADC measurement was linear in our study population. ADVANCES IN KNOWLEDGE: This work describes a correlation between tissue elasticity and diffusion in rectal cancer.

Transrectal ultrasound and magnetic resonance imaging measurement of extramural tumor spread in rectal cancer.

AIM: To evaluate the agreement between transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) in classification of ≥ T3 rectal tumors. METHODS: From January 2010 to January 2012, 86 consecutive patients with ≥ T3 tumors were included in this study. The mean age of the patients was 66.4 years (range: 26-91 years). The tumors were all ≥ T3 on TRUS. The sub-classification was defined by the penetration of the rectal wall: a: 0 to 1 mm; b: 1-5 mm; c: 6-15; d: > 15 mm. Early tumors as ab (≤ 5 mm) and advanced tumors as cd (> 5 mm). All patients underwent TRUS using a 6.5 MHz transrectal transducer. The MRI was performed with a 1.5 T Philips unit. The TRUS findings were blinded to the radiologist performing the interpretation of the MRI images and measuring the depth of extramural tumor spread. RESULTS: TRUS found 51 patients to have an early ≥ T3 tumors and 35 to have an advanced tumor, whereas MRI categorized 48 as early ≥ T3 tumors and 38 as advanced tumors. No patients with tumors classified as advanced by TRUS were found to be early on MRI. The kappa value in classifying early versus advanced T3 rectal tumors was 0.93 (95% CI: 0.85-1.00). We found a kappa value of 0.74 (95% CI: 0.63-0.86) for the total sub-classification between the two methods. The mean maximal tumor outgrowth measured by TRUS, 5.5 mm ± 5.63 mm and on MRI, 6.3 mm ± 6.18 mm, P = 0.004. In 19 of the 86 patients the following CT scan or surgery revealed distant metastases; of the 51 patients in the ultrasound ab group three (5.9%) had metastases, whereas 16 (45.7%) of 35 in the cd group harbored distant metastases, P = 0.00002. The odds ratio of having distant metastases in the ultrasound cd group compared to the ab group was 13.5 (95% CI: 3.5-51.6), P = 0.00002. The mean maximal ultrasound measured outgrowth was 4.3 mm (95% CI: 3.2-5.5 mm) in patients without distant metastases, while the mean maximal outgrowth was 9.5 mm (95% CI: 6.2-12.8 mm) in the patients with metastases, P = 0.00004. Using the MRI classification three (6.3%) of 48 in the MRI ab group had distant metastases, while 16 (42.1%) of the 38 in the MRI cd group, P = 0.00004. The MRI odds ratio was 10.9 (95% CI: 2.9-41.4), P = 0.00008. The mean maximal MRI measured outgrowth was 4.9 mm (95% CI: 3.7-6.1 mm) in patients without distant metastases, while the mean maximal outgrowth was 11.5 mm (95% CI: 7.8-15.2 mm) in the patients with metastases, P = 0.000006. CONCLUSION: There is good agreement between TRUS and MRI in the pretreatment sub-classification of ≥ T3 tumors. Distant metastases are more frequent in the advanced group.

Interobserver and intermodality agreement for detection of small bowel Crohn's disease with MR enterography and CT enterography.

BACKGROUND: Magnetic resonance enterography (MRE) and computed tomography enterography (CTE) visualizes small bowel Crohn's disease (CD) and its complications with high accuracy. The aim of this study was to determine the interobserver and intermodality agreement for detection of small bowel CD. METHODS: Fifty patients with suspected or known CD were included in the study and all patients underwent MRE and CTE on the same day. Four radiologists with experience in MRE and CTE techniques participated. Observers were blind to patient histories, results of ileocolonoscopies, and other small bowel examinations. Readers assessed the image quality, the presence of small bowel CD, and seven findings consistent with CD. RESULTS: The image quality was better with CTE than MRE (P < 0.001) but the diagnostic yields were comparable (P = 0.4). For detection of small bowel CD, the interobserver agreement was substantial in CTE (κ = 0.64) and moderate in MRE (κ = 0.48). The intermodality agreement was fair to substantial (κ = 0.40-0.64) for different observers. Two abscesses were detected and confirmed at subsequent surgery. One abscess was not detected with MRE and only recorded by two observers in CTE. A total of 10 fistulas were detected: three were confirmed at subsequent surgery and four were false-positive findings. CONCLUSIONS: MRE and CTE have comparable diagnostic yields in patients with suspected or known CD. However, CTE provides better image quality and interobserver agreement. In a substantial number of patients the diagnosis of small bowel CD is observer- and modality-dependent.