The Added Diagnostic Value of Transcatheter CT Hepatic Arteriography for Intraprocedural Detection of Previously Unknown Colorectal Liver Metastases During Percutaneous Ablation and Impact on the Definitive Treatment Plan.

PURPOSE: This study assessed the diagnostic value of CT hepatic arteriography (CTHA) for the intraprocedural detection of previously unknown colorectal liver metastases (CRLM) and the impact on the definitive treatment plan. MATERIALS AND METHODS: All patients treated with CTHA-guided percutaneous ablation for CRLM between January 2012 and March 2022 were identified from the Amsterdam Colorectal Liver Met Registry (AmCORE). Radiology reports of the ablative procedure and follow-up imaging were reviewed to see if (a) previously unknown CRLM were detected intra-procedurally and if (b) new CRLM, potentially missed on CTHA, appeared within 6 months following the procedure; three abdominal radiologists re-reviewed the baseline CTHA scans of these patients with early recurrence. To ratify immediate ablations of concomitantly detected CRLM, the upper limit of false positives was predefined at 10%. RESULTS: One hundred and fifty-two patients were included. With CTHA, a total of 17 additional tumours in 15 patients were diagnosed and treated immediately, two representing disappeared tumours following systemic chemotherapy. Compared to the conventional contrast-enhanced (ce)CT, ceMRI and 18F-FDG PET-CT, adding CTHA was superior for the detection of CRLM (P < .001). Within 12 months of follow-up 121, new CRLM appeared in 49/152 patients (32.2%); retrospective blinded assessment revealed 56 to already be visible on the baseline CTHA scan (46%); four lesions without substrate on follow-up scans were considered false positives (n = 4/60; 7%). Arterial ring enhancement was the most frequently reported imaging characteristic (n = 45/60; 75%). CONCLUSION: The subsequent use of CTHA has added value for the detection of previously unknown and vanished CRLM. Taking into account the low number of false positives (7%) and the favourable safety profile of percutaneous ablation, we believe that immediate ablation of typical ring-enhancing supplementary tumours is justified and sufficiently validated. LEVEL OF EVIDENCE: Level 3; individual cross-sectional study with consistently applied reference standard and blinding.

Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study.

This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher's exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416-1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249-1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483-1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).

Thermal Ablation versus Stereotactic Ablative Body Radiotherapy to Treat Unresectable Colorectal Liver Metastases: A Comparative Analysis from the Prospective Amsterdam CORE Registry.

Thermal ablation and stereotactic ablative radiotherapy (SABR) are techniques to eradicate colorectal liver metastases (CRLM). This study compares the safety, efficacy and long-term oncological outcomes of these treatment methods. All prospectively registered patients (AmCORE registry) treated with thermal ablation or SABR alone for unresectable CRLM between 2007 and 2020 were analyzed using multivariate Cox-proportional hazard regression. In total 199 patients were included for analysis: 144 (400 CRLM) thermal ablation; 55 (69 CRLM) SABR. SABR patients were characterized by older age (p = 0.006), extrahepatic disease at diagnosis (p = 0.004) and larger tumors (p < 0.001). Thermal ablation patients were more likely to have synchronous disease, higher clinical risk scores (p = 0.030) and higher numbers of CRLMs treated (p < 0.001). Mortality was zero and morbidity low in both groups: no serious adverse events were recorded following SABR (n = 0/55) and nine (n = 9/144 [6.3%]; all CTCAE grade 3) after thermal ablation. SABR was associated with an inferior overall survival (OS) (median OS 53.0 months vs. 27.4 months; HR = 1.29, 95% CI 1.12-1.49; p = 0.003), local tumor progression-free survival (LTPFS) per-tumor (HR = 1.24, 95% CI 1.01-1.52; p = 0.044) and local control per-patient (HR = 1.57, 95% CI 1.20-2.04; p = 0.001) and per-tumor (HR = 1.89, 95% CI 1.44-2.49; p < 0.001). In this study thermal ablation was superior to SABR with regard to OS, LTPFS and local control, albeit at the cost of a limited risk of serious adverse events. Further studies are required to assess whether the worse outcomes following SABR were the effect of true differences in ablative treatment or a result of residual confounding.

Primary Tumor Sidedness, RAS and BRAF Mutations and MSI Status as Prognostic Factors in Patients with Colorectal Liver Metastases Treated with Surgery and Thermal Ablation: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE).

The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan-Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596-0.923) and for RC of 0.760 (95% CI, 0.597-0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.

Thermal Ablation Compared to Partial Hepatectomy for Recurrent Colorectal Liver Metastases: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study.

The aim of this study was to assess safety, efficacy and survival outcomes of repeat thermal ablation as compared to repeat partial hepatectomy in patients with recurrent colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study of two cohorts, repeat thermal ablation versus repeat partial hepatectomy, analyzed 136 patients (100 thermal ablation, 36 partial hepatectomy) and 224 tumors (170 thermal ablation, 54 partial hepatectomy) with recurrent CRLM from May 2002 to December 2020. The primary and secondary endpoints were overall survival (OS), distant progression-free survival (DPFS) and local tumor progression-free survival (LTPFS), estimated using the Kaplan-Meier method, and complications, analyzed using the chi-square test. Multivariable analyses based on Cox proportional hazards model were used to account for potential confounders. In addition, subgroup analyses according to patient, initial and repeat local treatment characteristics were performed. In the crude overall comparison, OS of patients treated with repeat partial hepatectomy was not statistically different from repeat thermal ablation (p = 0.927). Further quantification of OS, after accounting for potential confounders, demonstrated concordant results for repeat local treatment (hazard ratio (HR), 0.986; 95% confidence interval (CI), 0.517-1.881; p = 0.966). The 1-, 3- and 5-year OS were 98.9%, 62.6% and 42.3% respectively for the thermal ablation group and 93.8%, 74.5% and 49.3% for the repeat resection group. No differences in DPFS (p = 0.942), LTPFS (p = 0.397) and complication rate (p = 0.063) were found. Mean length of hospital stay was 2.1 days in the repeat thermal ablation group and 4.8 days in the repeat partial hepatectomy group (p = 0.009). Subgroup analyses identified no heterogeneous treatment effects according to patient, initial and repeat local treatment characteristics. Repeat partial hepatectomy was not statistically different from repeat thermal ablation with regard to OS, DPFS, LTPFS and complications, whereas length of hospital stay favored repeat thermal ablation. Thermal ablation should be considered a valid and potentially less invasive alternative for small-size (0-3 cm) CRLM in the treatment of recurrent new CRLM. While, the eagerly awaited results of the phase III prospective randomized controlled COLLISION trial (NCT03088150) should provide definitive answers regarding surgery versus thermal ablation for CRLM.

A hidden mismatch between experiences of young athletes with overuse injuries of the wrist and sports physicians' perceptions: a focus group study.

BACKGROUND: Although overuse wrist injuries can have serious consequences, young athletes often do not immediately report their injury to a physician. This qualitative study aimed to identify symptoms and limitations related to overuse wrist injuries that young athletes consider important and to compare those with sports physicians' opinions, in order to improve the diagnostic process for early identification of overuse wrist injuries. METHODS: Twenty-one athletes aged 13-25 years in wrist-loading sports (gymnastics, tennis, judo, field hockey, volleyball and rowing) with a (previous) overuse wrist injury were included. In five focus groups, participants discussed important signals and limitations of their injury, as well as a list of relevant items previously composed by sports physicians. Data were grouped into themes and (sub)categories and subsequently coded. RESULTS: Of the resulting 224 signals and 80 limitations, respectively 81 and 20 were labelled important. Athletes considered both pain and limitations during daily life activities important indicators of overuse wrist injury, as well as long pain duration, acute onset of pain, and accompanying symptoms like swelling, cracking and discoloration. All of the sports physicians' items were also considered important by the athletes, but sport-related pain and limitations were regarded by many athletes as a natural part of their sport. CONCLUSIONS: Discrepancies exist between the opinions of young athletes and sports physicians on sport-related pain reporting and competing regardless of pain or limitations. Although clinicians may be inclined to focus on these aspects, they are advised to also inquire specifically about limitations and pain during daily life activities in young athletes with overuse wrist injuries.

Overuse wrist injuries in young athletes: What do sports physicians consider important signals and functional limitations?

This study's objective was to collect items from experienced sports physicians, relating to the presence and severity of overuse wrist injuries in young athletes, for developing a measurement instrument for signals of overuse wrist injury. Seven Dutch elite sports physicians involved in guidance and treatment of young athletes in wrist-loading sports (gymnastics, tennis, judo, field hockey, volleyball and rowing) participated in a focus group. They discussed signals and limitations related to overuse wrist injuries in young athletes. Data were coded and categorised into signals and limitations with subcategories, using an inductive approach. Of the resulting 61 signals and limitations in nineteen (sub)categories, 20 were considered important, forming a comprehensive item set for identifying overuse wrist injury in young athletes. Signals such as pain, "click", crepitations, swelling and limited range of motion were marked useful for early identification of overuse wrist injury. Limitations in movement and performance were considered indicative of severe overuse injury but less relevant for initial injury identification. The focus group provided 17 important signals and 3 important limitations indicative of overuse wrist injury. These provide the basis for a valid measurement instrument for identifying overuse wrist injury in young athletes, with equal emphasis on pain and on other symptoms.